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S1083879120300033 | Chimeric antigen receptor engineered T cells are a promising new treatment option for patients with multiply relapsed and refractory diffuse large B cell lymphoma . Because of the favorable outcome data reported for CART cells uncertainty is emerging if there is still a role for allogeneic hematopoietic cell transplantation in the treatment of R R DLBCL . This article provides an overview of available evidence and theoretical considerations to put these 2 types of cellular immunotherapy into perspective . Altogether current data suggest that CART cells are preferred now over transplantation as first choice CI in many clinical situations . However the majority of patients will fail CART therapy resulting in an unmet medical need where allo HCT could be beneficial . In contrast employing allo HCT instead of CART cells as first CI should be presently restricted to situations where CART cell therapy is deemed not feasible or useful such as patients with refractory cytopenia or incipient myelodysplastic syndrome . However allo HCT remains a standard treatment option as first CI for patients with chemosensitive R R DLBCL when CARTs are not available or transplantation is preferred by the patient . Continuous collection and analysis of CI outcome data by professional registries appear to be of key importance for developing rational strategies of CI allocation and sequencing . | This article addresses the possible role of allogeneic hematopoietic cell transplantation allo HCT for relapsed and refractory diffuse large B cell lymphoma in the chimeric antigen receptor engineered T CART cell era. Allo HCT should be explored for patients failing CART therapy. Allo HCT should be considered when CART therapy is not feasible or available. Allo HCT and CART outcome data should be collected and analyzed in registries. |
S1083879120300045 | Autologous hematopoietic stem cell transplantation is a complex procedure that can be performed in both inpatient and outpatient care settings . We examined reimbursement service utilization and patient financial responsibility among Medicare beneficiaries with multiple myeloma who underwent auto HCT in the IP and OP settings using a merged dataset of the Center for International Blood and Marrow Transplant Research observational database and Centers for Medicare Medicaid Services Medicare administrative claims data . Selection criteria included first auto HCT time from diagnosis to auto HCT 18 months and continuous enrollment in Medicare Parts A and B for 30 days before HCT index claims and 100 days post HCT or until death . Total reimbursement and patient responsibility were adjusted for patient and disease characteristics using a weighted generalized linear model . The final cohort comprised 1640 patients 1445 who received IP HCT and 195 who received OP HCT . The adjusted total mean reimbursement was higher for IP HCT compared with OP HCT versus 46 824 | Hospital reimbursement patient financial responsibility and service utilization patterns vary by inpatient or outpatient transplantation setting for Medicare beneficiaries with multiple myeloma. Mean total reimbursement is 35 544 higher for inpatient autologous hematopoietic stem cell transplantation auto HCT recipients and the mean patient responsibility is 2208 higher for outpatient auto HCT recipients. The subsequent admission rate for planned outpatient auto HCT recipients is 55 . |
S1083879120300112 | In most clinical oncology trials time to first event analyses are used for efficacy assessment which often do not capture the entire disease process . Instead the focus may be on more complex time to event endpoints such as the course of disease after the first event or endpoints occurring after randomization . We propose relapse and immunosuppression free survival as an innovative and clinically relevant outcome measure for assessing treatment success after hematopoietic stem cell transplant . To capture the time dynamic relationship of multiple episodes of immunosuppressive therapy during follow up relapse and nonrelapse mortality a multistate model was developed . The statistical complexity is that the probability of RIFS is nonmonotonic over time thus standard time to first event methodology is inappropriate for formal treatment comparisons . Instead a generalization of the Kaplan Meier method was used for probability estimation and simulation based resampling was suggested as a strategy for statistical inference . We reanalyzed data from a recently published phase III trial in 201 leukemia patients after SCT . The study evaluated long term treatment success of standard graft versus host disease prophylaxis plus a pretransplant antihuman T lymphocyte immunoglobulin compared with standard prophylaxis alone . Results suggested that treatment increased the long term probability of RIFS by approximately 30 during the entire follow up period which complements the original findings . This article highlights the importance of complex endpoints in oncology which provide deeper insight into the treatment and disease process over time . Multistate models combined with resampling are highlighted as a promising tool to evaluate treatment success beyond standard endpoints . An example code is provided in the Supplementary Materials . | Relapse and immunosuppression free survival were novel endpoints after transplant. These endpoints were formulated and statistically analyzed by multistate methodology and resampling. A randomized clinical trial was conducted on GVHD prophylaxis. The difference between treatment groups was estimated as approximately 30 over 8 years. An R code was provided to promote our methods to the transplant community. |
S1083879120300124 | Patients with severe thalassemia commonly have a survival that is significantly shorter than that of the general population . Allogeneic hematopoietic stem cell transplantation is the only established treatment that is potentially curative but it is limited by the availability of donors and the medical condition of the patient . To expand the donor pool to include haploidentical related donors we introduced a program consisting of a pharmacologic pretransplant immune suppression phase and 2 courses of dexamethasone and fludarabine followed by pretransplant conditioning with fludarabine i.v . busulfan and post transplant graft versus host disease prophylaxis with cyclophosphamide tacrolimus and mycophenolate mofetil . We transplanted 83 consecutive transfusion dependent patients with thalassemia with a minimum follow up of 6 months the 3 year projected overall and event free survival is over 96 and there have been no secondary graft failures . Of the first 31 patients we had 2 graft failures both of them occurring in patients with extremely high titers of anti donor specific HLA antibodies but after adjusting the PTIS to include bortezomib and rituximab for patients with high titers of anti DSAs and using pharmacologic dose guidance for busulfan we had no graft failures in the last 52 patients . Six of 83 patients developed severe GVHD . We conclude that this is a safe and efficacious approach to allogeneic SCT in thalassemia yielding results comparable to those available for patients with fully matched donors . | Allogeneic stem cell transplant SCT is curative for patients with severe thalassemia. It can be safely performed with a sequence of a pretransplant immunosuppressive therapy PTIS of pulse fludarabine and dexamethasone followed by a reduced intensity regimen of fludarabine and i.v. busulfan as well as peripheral blood progenitor transplant with post transplant cyclophosphamide based immunosuppression. Patients with very high titers of anti donor specific antibodies 1 3000 further benefited from the addition of bortezomib and Rituxan to the PTIS phase to alleviate antibody mediated graft rejection. With this approach SCT now be safely carried out using both matched and mismatched aka haploidentical donors with a 3 year event free and overall survival of 95 regardless of donor type and without having any increased risk for mortality in patients who are older than 7 years and having hepatomegaly i.e. the Lucarelli group III high risk subset . This demonstrates that there is no reason to take the risk s of total body irradiation to secure engraftment in this group of patients who are at high risk for graft failure. |
S1083879120300136 | Allogeneic hematopoietic cell transplantation is recommended in high risk patients with T cell acute lymphoblastic leukemia . For patients without an HLA identical donor haploidentical HCT is becoming the leading source of stem cell donation . However data are scarce on predictive factors for outcome in that setting . We identified 122 adults with T ALL who underwent haplo HCT with post transplantation cyclophosphamide between 2010 and 2017 . The median duration of follow up of living patients was 23 months . The 2 year incidences of relapse and nonrelapse mortality were 45 and 21 respectively . The 2 year leukemia free survival overall survival and graft versus host disease relapse free survival were 34 42 and 27 respectively . The 2 year LFS and OS were highly influenced by disease status at transplantation being 49 and 55 respectively for patients in first complete remission 34 and 50 respectively for those in second CR and 8 and 12 respectively for patients with active disease . On multivariate analysis only disease status was found to affect LFS and OS . Transplantation in CR2 negatively affected LFS whereas active disease at the time of haplo HCT negatively affected LFS and OS . In conclusion haplo HCT with ptCy produced encouraging results in this challenging disease particularly when performed in patients in CR . Despite the limitation of the small sample size our results were not affected by the type of conditioning calling into question the need for total body irradiation based myeloablative conditioning in that setting . | Outcomes of 122 haploidentical hematopoietic cell transplantations with post transplantation cyclophosphamide for T cell acute lymphoblastic leukemia are reported. Survival was mostly affected by disease status being significantly better in first complete remission. Outcomes were not affected by conditioning calling into question the need for total body irradiation. |
S1083879120300148 | Acute graft versus host disease continues to be a major cause of morbidity and mortality after allogeneic hematopoietic cell transplant in pediatric patients and limits broader application of the therapy . Pediatric HCT patients have faced major obstacles to access clinical trials that test new agents for GVHD prevention and treatment . According to a recent search only 6 clinical trials of interventions for prevention or treatment of acute GVHD were conducted specifically in pediatric patients in the United States over the past decade with 8 internationally . In this review we summarize the studies that were performed and specifically enrolled and reported on pediatric patients after allogeneic HCT and provide a listing of studies currently under way . | Acute graft versus host disease GVHD continues to be a major cause of morbidity and mortality after allogeneic hematopoietic cell transplant HCT in pediatric patients. Pediatric HCT patients have faced major obstacles to access clinical trials that test new agents for GVHD prevention and treatment. Clinical trials in which adult and pediatric endpoints are the same succeed in meeting their primary endpoint more often than trials that do not combine all ages. |
S108387912030015X | Serious viral infections due to delayed immune reconstitution are a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation . Thus many transplant centers prospectively track cellular immune recovery by evaluating absolute cell numbers and the phenotypic profile of reconstituting T cell subsets to identify individuals who are at highest risk of infection . Conventional assessments however fail to measure either the antigen specificity or functional capacity of reconstituting cellsboth factors that correlate with endogenous antiviral protection . In this pilot study we sought to address this limitation by prospectively investigating the tempo of endogenous immune reconstitution in a cohort of 23 pediatric HSCT patients using both quantitative and qualitative measures which we correlated with either the presence or absence of infections associated with cytomegalovirus adenovirus Epstein Barr virus BK virus human herpes virus 6 respiratory syncytial virus parainfluenza influenza and human metapneumovirus . We present data spanning 12 months post transplant demonstrating the influence of conditioning on immune recovery and highlighting the differential impact of active viral replication on the quantity and quality of reconstituting cells . Judicious use of standard and novel monitoring strategies can help guide the clinical care and personalized management of allogenic HSCT recipients with infections . | A combination of phenotypic and functional immune assays enables risk stratification of patients with viral infections after transplant. Functional immune monitoring can help identify patients in need of additional antiviral intervention. |
S1083879120300161 | The incidence of hepatitis B virus infection is high in the Asian population . Increasing attention is being given to the risk of HBV reactivation in hepatitis B core antibody positive patients during immunosuppressive therapy . Knowledge of HBV reactivation in hematopoietic stem cell transplantation is limited . Moreover the effect of hepatitis B surface antibody on HBV reactivation in HBcAb patients during HSCT remains uncertain . We sought to investigate the role of HBsAb and the need for prophylactic antiviral treatment in hepatitis B surface antigen negative HBcAb patients during HSCT . We classified 665 HBsAg HSCT recipients into 4 groups HBcAbHBsAb HBcAbHBsAb HBcAbHBsAb and HBcAbHBsAb . HBV reactivation was identified in 16 patients after HSCT . The median time to HBV reactivation was 645 days after transplantation . The cumulative HBV reactivation rate was significantly higher in the HBcAbHBsAb group compared with the HBcAbHBsAb HBcAbHBsAb and HBcAbHBsAb groups respectively | Hepatitis B core antibody HBcAb and hepatitis B surface antibody HBsAb play protective roles in patients with resolved hepatitis B virus HBV infection undergoing hematopoietic stem cell transplantation HSCT . The risk of HBV reactivation was significantly higher in HBcAb HBsAb patients compared with HBcAb HBsAb patients. HBV reactivation in HBcAb HBsAb patients following HSCT was a rare and late complication. Prophylactic anti HBV treatment might not be mandatory for hepatitis B surface antigen negative HBsAg HBcAb HBsAb patients following HSCT. |
S1083879120300185 | A multicenter retrospective study was performed to evaluate the prognostic factors in 104 patients with relapsed or refractory acute lymphoblastic leukemia who underwent allogeneic hematopoietic cell transplantation between 2005 and 2015 . The median age was 38 and the median blast fraction in peripheral blood and bone marrow was 1 and 52 respectively . With a median follow up of 47 months overall survival nonrelapse mortality and relapse mortality at 1 year were 25 44 and 31 respectively . Multivariate analysis demonstrated independent predictors for poor OS including nuclear cell count in the bone marrow 1010 | Prognostic factors for relapsed refractory acute lymphoblastic leukemia in allogeneic hematopoietic cell transplantation HCT recipients were evaluated. Higher nuclear cell count in bone marrow is one of the independent predictors for poor survival. The scoring may be useful in identifying patients who will receive the least benefit from HCT. |
S1083879120300197 | With increasing focus on the importance of long term survivorship care after allogeneic hematopoietic cell transplantation more institutions have been establishing long term follow up clinics . Currently however with varying volumes of HCT procedures and resources there is no standardized operation of these clinics in HCT centers . We conducted a nationwide questionnaire survey to characterize the current operation of LTFU clinics in Japan . We targeted 271 HCT centers that registered allo HCT cases to the national transplant registry database . The response rate was 69 and 117 of the 188 participating centers had an established LTFU clinic . The most frequent reason cited for not operating an LTFU clinic was a lack of human resources especially nurses . Most centers with an LTFU clinic targeted allo HCT recipients although autologous HCT survivors were followed up at 18 of adult centers and 48 of pediatric centers . Ninety two percent of centers did not terminate LTFU at a specific time point and 56 recommended that patients visit the LTFU clinic beyond 5 years after HCT . Fifteen of 20 pediatric centers indicated that they did not routinely refer survivors who underwent HCT at a young age to an adult HCT center for their adulthood LTFU . We found that staffing and standard practices varied widely among centers and that most centers continued to see long term HCT survivors at their own outpatient clinics . The development of common LTFU tools may help standardize LTFU practices and facilitate efficient transitions . | The establishment rate of long term follow up LTFU clinics was 62 among participating centers in Japan. The most frequently cited reason for not operating an LTFU clinic was a lack of human resources especially nurses. Transplantation centers with an LTFU clinic had various staff compositions and practice approaches. Most centers continued to follow up long term HCT survivors at their own outpatient clinic. The development of common nationwide LTFU tools may help reduce the burden on healthcare staff and facilitate standardized interventions and efficient transitions. |
S1083879120300203 | Although long term antiviral prophylaxis is recommended to prevent varicella zoster virus infection in seropositive recipients of allogeneic and autologous hematopoietic cell transplantation studies of VZV infections in pediatric auto HCT recipients are rare . This study aimed to investigate the incidence and characteristics of VZV infection in pediatric auto HCT recipients and explore the risk factors of VZV infection and its effect on survival outcomes . This study included all pediatric patients who underwent auto HCT at Samsung Medical Center Seoul Korea between January 1998 and December 2013 . Before 2006 short term acyclovir prophylaxis was provided until neutrophil engraftment thereafter routine prophylaxis was not provided . Patients who developed either herpes zoster or chickenpox within 2 years from transplantation were identified and a chart review was performed . A total of 413 recipients and 698 auto HCTs were included . Sixty one episodes of VZV infections were identified in 54 patients . Fourteen cases of VZV infection occurred within 30 days after auto HCT . The cumulative incidence of the first episode of VZV infection at 2 years after transplantation was 14 7.9 to 22.8 in all recipients and 9 in VZV seronegative patients . Notably the VZV infection rate increased with age and the VZV infection rate in patients age 15 to 19 years was almost three times higher than in patients age 0 to 4 years 28 versus 10 | Even long term antiviral prophylaxis in hematopoietic cell transplantation HCT recipients was recommend as standard preventive stratagem for varicella zoster virus VZV infection epidemiology of VZV infection in pediatric autologous HCT recipients is uncertain. The incidence of VZV infection differs by age. Difference of VZV infection was evaluated between single and tandem autologous HCTs. We explored the risk factors for severe VZV infection in the pediatric autologous HCT population. |
S1083879120300215 | Allogeneic hematopoietic cell transplantation is the only curative treatment modality for primary myelofibrosis and related myeloproliferative neoplasms . Older age at diagnosis and age related comorbidities make most patients ineligible for allo HCT given concerns for nonrelapse mortality .Here we report the outcomes of 37 consecutive recipients of allo HCT for MF performed at a single center between 2009 and 2018 with a standardized institutional protocol . Most patients received ruxolitinib before HCT and those with splenomegaly 22 cm received pretransplantation splenic irradiation . The median age at HCT was 60 years and 68 of the cohort carried a | Allogeneic hematopoietic cell transplantation HCT is the only curative treatment modality for myelofibrosis MF . However the presence of comorbidities advanced age and increased risk of graft failure after allogeneic HCT decrease the probability of long term survival. Pretransplantation JAK inhibitor therapy use of fludarabine busulfan based conditioning and splenic management are keys to improved transplantation outcomes in patients with MF. Graft rejection is a recognized post transplantation complication monitoring donor chimerism and liberal use of immune suppression JAK inhibitors and donor leukocyte infusion can be preventative. Post transplantation ruxolitinib can improve survival outcomes by managing graft versus host disease especially in steroid refractory cases. |
S1083879120300227 | Severe aplastic anemia is most frequently immune mediated however rare inherited bone marrow failure syndromes such as Fanconi anemia may be causal and can present as aplastic anemia . FA is primarily an autosomal recessive disorder caused by the presence of 2 pathogenic variants in a single FA BRCA DNA repair pathway gene . Patients with SAA often undergo genetic testing during clinical evaluation that may identify single deleterious alleles in FA pathway genes . We quantified the rate of germline single deleterious alleles in 22 FA genes using both a general population database and in a cohort of patients with SAA undergoing hematopoietic cell transplantation . The variants were classified as deleterious using in silico tools and database resources . We found similar rates of single deleterious alleles in FA genes in both groups . The presence of a single deleterious variant in a gene for FA in SAA HCT recipients did not affect the overall survival after HCT hazard ratio 0.85 95 CI 0.37 to 1.95 | There is a similar rate of single deleterious Fanconi anemia FA gene variants in patients with severe aplastic anemia SAA and the general population. In patients with SAA a single FA variant does not affect overall survival after hematopoietic cell transplantation HCT . There is no increased risk of cancer in patients with SAA and a single FA gene variant after HCT. |
S1083879120300458 | Incidence and outcome of infections after allogeneic hematopoietic stem cell transplantation with post transplant cyclophosphamide as graft versus host disease prophylaxis are largely unknown . Study aims were to estimate the incidence of pre engraftment bloodstream infections and viral infections adenovirus human herpes virus 6 and BK polyomavirus hemorrhagic cystitis their predictive factors and infection related mortality after HSCT with PT Cy . We analyzed 235 patients 62 21 and 17 received haploidentical matched unrelated donor and matched related donor respectively . Overall 72 patients had 77 PE BSI episodes at a median time of 13 days after HSCT cumulative incidence function at 28 days was 32 without differences among donor types | This cohort analysis evaluates the incidence risk factors and mortality of pre engraftment bloodstream infections BSIs and double strand DNA viral infections VIs after hematopoietic stem cell transplantation HSCT with post transplant cyclophosphamide PT Cy platform among different donor sources. Allogeneic HSCT with PT Cy showed a 32 incidence of pre engraftment BSIs and donor type did not affect their occurrence. VIs are common in the early phase but immune reconstitution after PT Cy transplant is broad and fast allowing to handle them. |
S108387912030046X | The present study was conducted to investigate cellular and molecular features of chronic graft versus host disease fibroblasts and to assess the effectiveness of nilotinib as a fibrosis modulator . Growth kinetics phenotype and differentiation of cultured skin biopsy derived GVHD Fbs were compared with normal fibroblasts from both a dermal cell line and healthy individuals undergoing cosmetic surgery . Collagen genes and p SMAD2 expression were assessed by real time PCR and immunofluorescence . The in vivo effects of nilotinib on chronic GVHD affected skin were investigated by immunohistochemistry the relationship to TGF plasma levels was assessed . Although the morphology phenotype and differentiation of cultured GVHD Fbs were comparable to normal fibroblasts growth was slower and senescence was reached earlier . The expression of COL11 and COL12 mRNAs was respectively 4 and 1.6 times higher in cGVHD Fbs | Chronic graft versus host disease cGVHD fibroblasts grow slower and become senescent earlier than normal fibroblasts. Collagen mRNA expression and TGF levels are elevated in patients with cGVHD. Nilotinib reduces TGF levels and collagen production by cGVHD fibroblasts. Nilotinib induced TGF inhibition is associated with an intracellular p Smad2 decrease. TGF pathway inhibition is a basic antifibrotic mechanism of nilotinib in vivo. |
S1083879120300471 | Cytomegalovirus DNAemia occurs frequently in allogeneic hematopoietic stem cell transplant recipients . There is limited information about the incidence features and clinical impact of CMV DNAemia blips in this setting . In this retrospective study 225 consecutive adult patients undergoing any modality of allo HSCT at our center between May 2012 and July 2019 were included . Plasma CMV DNA load was monitored using a highly sensitive real time PCR assay . In all 187 of 225 patients had CMV DNAemia through day 365 after allo HSCT . Eighty three of the 187 patients had 1 or more blips . Blips occurred as a first episode of CMV DNAemia as opposed to prolonged CMV DNAemia in 47 patients in 20 of these patients blips represented the only documented episode throughout the study period and in 27 patients blips preceded a prolonged CMV DNAemia episode . In the remaining 36 patients blips developed as recurrences . Blips presenting as initial episodes occurred more frequently | Cytomegalovirus CMV DNAemia blips occur frequently in allogeneic hematopoietic stem cell transplant recipients. CMV DNAemia recurrences develop frequently following blips. Initial CMV DNA load does not reliably predict the course of CMV DNAemia episodes. Receipt of an allograft from a CMV seropositive donor was associated with the occurrence of blips. |
S1083879120300483 | Graft versus host disease is an important challenge and a major cause of morbidity and mortality in children after hematopoietic stem cell transplant . Herein we report our institution s experience of goal oriented Bayesian monitoring for cyclosporine used alone as GVHD prophylaxis during the post transplant period in pediatric patients with thalassemia major or sickle cell anemia undergoing HLA matched HSCT . We also studied evolution of chimerism . Twenty six consecutive patients underwent matched sibling donor HSCT from 2004 to 2014 . All patients received a myeloablative conditioning regimen . GVHD prophylaxis consisted of 20 mg kg antithymocyte globulin in the conditioning regimens and then CsA alone in the post transplant period . Target CsA trough blood concentration was 150 20 ng mL . At last follow up all patients were alive and free of disease even in cases of mixed chimerism . Engraftment occurred in all patients . No patient developed grades II to IV acute GVHD 4 patients developed acute grade I skin GVHD and only 1 presented with chronic pulmonary GVHD . A better control of GVHD and immunosuppression by a strict monitoring of CsA TBC as described herein is promising and could play a crucial role . Further investigations are required but this study opens new perspectives to improve survival and safety of HSCT from alternative donors in TM and SCA to levels compatible with that obtained with MSDs . | HLA matched transplant in pediatric patients with hemoglobinopathy is reported. Close monitoring of cyclosporine A CsA with a goal oriented Bayesian method is described. GVHD prophylaxis using antithymocyte globulin in the conditioning regimen and then CsA alone is effective. No graft rejection low rate of GVHD 100 overall survival and 100 disease free survival are reported. This study opens new perspectives to improve efficacy of transplant. |
S1083879120300513 | Steroid refractory acute graft versus host disease following hematopoietic cell transplantation is associated with poor clinical outcomes . Currently there are no safe and effective therapies approved for use in the pediatric population under the age of 12 years . Accordingly there is an urgent need for new treatments that are safe well tolerated and effective in managing this debilitating and potentially fatal complication of HSCT . In early phase clinical trials mesenchymal stromal cells have demonstrated efficacy in the treatment of acute GVHD in pediatric patients . We now report the results of a phase 3 prospective single arm multicenter study in 54 children with primary SR aGVHD who were naive to other immunosuppressant therapies for aGVHD treated with MSC product dosed at 210 | This is the first mesenchymal stromal cell study in acute graft versus host disease aGVHD to meet a primary efficacy endpoint. There are no approved therapies for aGVHD in children younger than 12 years. Day 28 overall response was 69.1 74.5 and 68.5 were alive at days 100 and 180 respectively. Day 28 overall response strongly predicted day 100 survival. Remestemcel L is a promising therapy in pediatric steroid refractory aGVHD. |
S1083879120300537 | A major cause of morbidity and mortality for patients who undergo hematologic stem cell transplantation is acute graft versus host disease a mostly T cell mediated disease . Examination of the T cell receptor repertoire of HSCT recipients and the use of next generation nucleotide sequencing have raised the question of whether features of TCR repertoire reconstitution might reproducibly associate with aGVHD . | Using MCA and a data reduction model we were able to show that not only were clones shared across patient samples but also there are specific TRBV families that were seen predominantly in those who responded to steroids. We found a statistically significant decreasing trend in diversity measures over time. We offer an honest discussion that better reflects the current literature and our study limitations and its merits. |
S1083879120300550 | Graft versus host disease is a major cause of morbidity and mortality after allogeneic stem cell transplantation . These patients face a unique challenge due to the complexity of GVHD and the toxicity of treatments received . GVHD has significant impact on quality of life but this is not routinely evaluated formally . Despite the availability of patient reported outcome measures to assess QOL there is currently no consensus regarding the optimal PROMs that should be used to evaluate the impact of GVHD . We undertook a systematic review to determine the current evidence for the use of PROMs in assessment of QOL symptom burden and disease severity of patients with GVHD . A comprehensive systematic review based on the COSMIN guidelines was conducted to identify studies using PROMs in acute and chronic GVHD patients . The following databases were searched OVID Medline AMED CINAHL Embase PROQOLID ProQuest PsychINFO and Social Sciences Citation Index from inception to May 2018 . Hand searches updated the search to December 2018 . Articles were screened by 2 independent reviewers with discrepancies resolved by a third independent reviewer . Included articles were critically appraised using the COSMIN Risk of Bias tool and relevant data on measurement properties for the included PROMs were extracted from within the target population . A total of 4545 articles were identified and 64 articles reporting on 27 PROMs were included in this review . PROMs were separated into 5 groups generic patient reported measures cancer specific measures bone marrow transplantspecific measures cGVHD specific measures and dimension specific measures . Three PROMs had evidence to support strong reliability responsiveness and aspects of validity within the cGVHD population . Only 5 included PROMs were used in patients with acute GVHD . This review summarizes the current evidence regarding the use of 27 included PROMs in the context of GVHD . The choice of the most optimal PROM depends on the clinical or research context of use . Future research should comprehensively validate these tools in the GVHD population including the testing and possible development of a PROM for use in acute GVHD which remains a current critical gap in the existing literature . | This systematic review used the COSMIN methodology to identify PROMs for use in GVHD. Twenty seven PROMs were identified with varying levels of supportive psychometric evidence. Three PROMs had evidence to support reliability responsiveness and validity for chronic GVHD. Few PROMs had psychometric validation for acute GVHD. Future research should include comprehensive psychometric testing of PROMs for GVHD. |
S1083879120300586 | Permanent impairment of vital organs is one of the transplantation related health problems affecting the quality of life and morbidity even in patients who do not develop graft versus host disease after allogeneic hematopoietic stem cell transplantation but no data are available on PI of multiple organs . This retrospective study aimed to estimate a novel composite endpoint of PI free relapse free survival in 164 allo HCT recipients . We defined PI as 26 to 30 impairment of the whole person in 6 vital organs using the whole person impairment rating . Conventional GVHD free relapse free survival and PIRFS at 5 years were 33.8 26.5 to 41.3 and 40.6 respectively . In the whole cohort PIRFS was higher than GRFS at any time after allo HCT . However PIRFS was lower than GRFS after day 397 post transplantation in patients who underwent umbilical cord blood transplantation . In UCBT recipients 5 year GRFS and PIRFS were 47.6 and 39.2 respectively . The cumulative incidence of PI after 5 years was 20.9 in patients surviving for 6 months without relapse . The multivariate analysis revealed that high disease risk 1.91 95 CI 1.26 to 2.88 | We estimated permanent impairment of 6 vital organs in allogeneic transplantation. The 5 year permanent impairment free relapse free survival PIRFS was 40.6 . PIRFS is an endpoint to assess long term transplantation success from a novel perspective. |
S1083879120300598 | Clinical outcomes in children with steroid refractory acute graft versus host disease are generally poor with a high mortality rate and limited therapeutic options . Here we report our updated investigational experience with mesenchymal stromal cell therapy with remestemcel L in a multicenter expanded access protocol in 241 children with aGVHD who failed to respond to steroids with or without other secondary and tertiary immunosuppressive therapies . A total of 241 children with grade B D SR aGVHD were enrolled at 50 sites in 8 countries and received 8 biweekly i.v . infusions of human MSCs 210 | There are no approved therapies for acute graft versus host disease aGVHD in children 12 years. A total of 241 children with steroid refractory aGVHD received remestemcel L as salvage therapy. Day 28 overall response was achieved by 65.1 66.9 were alive at day 100. Day 28 overall response strongly predicted day 100 survival. Remestemcel L is a promising therapy for steroid refractory aGVHD in children. |
S1083879120300604 | Letermovir potently inhibits the cytomegalovirus terminase complex . Letermovir primary prophylaxis given for the first 3 months after allogeneic hematopoietic cell transplantation has been shown to reduce clinically significant CMV infection and is well tolerated . Until now only case reports or small retrospective series have been published on the use of letermovir for a secondary prophylaxis of CMV infection or diseases after HCT . Here we report the outcome of 80 consecutive CMV seropositive adult patients included in the French compassionate program and who received letermovir as a SP after at least 1 CMV episode since HCT . Letermovir was initiated at a median of 170 days after transplant and given orally for a median of 118 days at the usual daily dose of 480 mg once daily and adjusted to 240 mg once daily when coadministered with cyclosporine . The donors were seronegative in 53 of the cases . Fifty patients had a current or previous graft versus host disease and 14 had experienced CMV disease since transplant . Four patients developed CMV breakthrough infections or diseases after the initiation of letermovir . In 3 of these 4 patients further investigation of virologic resistance showed a CMV UL56 mutation C325Y or W conferring the high level letermovir resistance . One or more adverse reactions were declared by the local investigator in 15 patients . Only 2 patients stopped letermovir SP because of an adverse reaction . In our experience letermovir given as a SP may prevent a new CMV reactivation in a high risk patient population and can be administered for several weeks providing a bridge between the pre emptive or therapeutic treatment of a CMV episode and CMV specific immune reconstitution giving time for tapering immunosuppressants . Prospective studies are required to confirm these results . | Letermovir was used for cytomegalovirus CMV secondary prophylaxis after allogeneic hematopoietic cell transplantation HCT in a compassionate program. Letermovir was given from day 170 median for 118 days median . The drug was well tolerated. Only 4 of 80 patients developed a CMV recurrence during letermovir prophylaxis. Secondary prophylaxis of CMV recurrence is feasible with letermovir after allogeneic HCT. |
S1083879120300616 | Fluid overload grade 2 has recently been recognized as an important toxicity associated with a high rate of nonrelapse mortality in recipients of allogeneic hematopoietic cell transplantation . The causes for FO remain unclear . We hypothesized that endothelial damage possibly due to treatments received prior to AHCT may be associated with this toxicity and sought to determine whether the Endothelial Activation and Stress Index creatinine platelets 10 | High Endothelial Activation and Stress Index EASIX score at time of admission predicts the occurrence of grade 2 fluid overload toxicity in recipients of allogeneic stem cell transplantation. For haploidentical transplants independently of EASIX score older patients with lower weight had an increased risk of grade 2 fluid overload toxicity. For HLA matched transplants independently of EASIX score diabetics had an increased risk of grade 2 fluid overload toxicity. |
S1083879120300628 | Historically outcomes of adult patients with relapsed acute lymphoblastic leukemia who fail to enter remission with conventional chemotherapy are very poor . Blinatumomab a bispecific CD3 CD19 antibody has shown remarkable activity in relapsed refractory ALL . Although allogeneic hematopoietic cell transplant is the recommended consolidation therapy for patients with r r ALL who respond to salvage therapy HCT and toxicity outcomes for those who received blinatumomab salvage and HCT remain largely unknown . We treated 89 patients with r r ALL with blinatumomab of whom 43 patients achieved remission . Here we describe our single center experience in the subset of patients who responded to blinatumomab salvage therapy for eradication of either gross or minimal residual disease before HCT . Overall survival at 1 and 2 years after allogeneic HCT was 77 and 52 respectively . Leukemia free survival at 1 and 2 years were 65 and 40 respectively . Additionally with blinatumomab administration pre HCT no unusual toxicities such as delayed neutrophil platelet engraftment or graft failure were observed . Acute grades II to IV graft versus host disease at day 100 post HCT was at 43 and 2 year chronic GVHD was 36 both comparable with historic control subjects . Finally results of our subset analysis based on pre HCT minimal residual disease status indicated no significant difference in survival outcomes among patients undergoing transplant in MRD negative status and the entire cohort . In conclusion based on results of this study blinatumomab may be considered as a safe and effective agent for r r ALL patients before HCT . | HCT outcomes were analyzed in r r ALL patients after salvage with blinatumomab. Pre HCT blinatumomab was given for morphologic n 24 or MRD positive disease n 11 . No unusual toxicities or delayed engraftment was observed post HCT. Subgroup analysis MRD cytogenetics showed no significant difference in survival. Blinatumomab may be considered as a safe and effective salvage therapy pre HCT. |
S108387912030063X | Measles can be a life threatening infection in immunocompromised patients especially after allogeneic hematopoietic cell transplantation because of the corresponding loss of immunity . However measles vaccines are live attenuated which is why measles vaccinations are recommended only in seronegative HCT recipients and in specific conditions . However little data exist on the rates of seroprotection to measles with the current conditioning regimens and in long term follow up . The objectives of this study were to assess measles immunity before considering vaccination in a cohort of allogeneic HCT long term survivors and to identify the factors associated with seropositivity seroprotection . One hundred and twenty six patients who underwent transplantation between 1 and 39 years earlier were assessed for measles immunity . Measles IgG titers were determined with an automated chemiluminescent immunoassay . Seropositivity seroprotection was defined by an IgG titer 16.5 UA mL . Patients underwent transplantation with a reduced intensity conditioning or nonmyeloablative conditioning in 46 of cases mainly for acute leukemia . Seventy eight of the 126 patients were seropositive seroprotected for measles . Among the seropositive patients the patients who had been vaccinated before transplantation had a lower median IgG titer compared with those who had not . Myeloproliferative disorder RIC or NMA conditioning and absence of acute grade II graft versus host disease were associated with seropositivity seroprotection . With a 62 rate of seropositivity seroprotection for measles at a median of 9 years after transplantation our findings strongly support a systematic assessment of anti measles antibody titers to avoid unnecessary vaccination in seroprotected patients . | In a cohort of 126 allogeneic HCT recipients who underwent transplantation between 1 and 39 years ago 62 were seropositive seroprotected for measles before any vaccination since transplantation. The seropositivity seroprotection was associated with myeloproliferative disorder reduced intensity or nonmyeloablative conditioning and absence of acute grade 2 graft versus host disease. Our findings strongly support a systematic assessment of antimeasles antibody titers to avoid unnecessary vaccination in seroprotected patients. |
S1083879120300872 | Clinical trials have shown that nivolumab has remarkable activity against relapsed refractory classical Hodgkin lymphoma . However the role of allogeneic hematopoietic stem cell transplantation as consolidation therapy in these patients remains controversial . We performed a retrospective analysis of data from 74 patients treated with nivolumab . The overall response rate was 58 . Treatment related adverse events were reported in 56.8 of patients . The main reasons for nivolumab discontinuation were referral for transplantation and disease progression . The 2 year overall survival rate was 52 for the entire series . Ultimately 39 patients underwent allo HSCT . The cumulative incidence of grade II IV acute graft versus host disease was 33.3 . The cumulative incidence of nonrelapse mortality was 13.2 . Among the patients who responded to nivolumab the 2 year OS and progression free survival were higher in patients who underwent consolidation with allo HSCT 77.5 versus 42.6 | The efficacy and safety of nivolumab in real life for the treatment of relapsed refractory Hodgkin lymphoma are comparable to those reported in clinical trials. The main reasons for nivolumab discontinuation were referral for transplantation and disease progression. Based on a median follow up of 18 months our results show that consolidation with allogeneic hematopoietic stem cell transplantation is associated with favorable progression free survival and overall survival. |
S1083879120300896 | A matched pair analysis of transplant related outcomes was carried out in 116 of 255 consecutive patients who received transplants from an HLA identical sibling or haploidentical related donor . The 2 patient series were matched with 9 variables period of transplant patient and donor age sex diagnosis disease phase conditioning regimen donor recipient sex and cytomegalovirus status combinations . As graft versus host disease prophylaxis all patients received the standard cyclosporine and methotrexate association with the addition of anti thymocyte globulins mycophenolate mofetil and basiliximab in haploidentical unmanipulated bone marrow recipients . Anti infectious management transfusion policy and supportive care were identical for all patients . By comparing the 2 patient series no statistically significant difference was observed for the cumulative incidence of advanced acute and extensive chronic GVHD transplant related mortality and relapse . With a median follow up of 3.5 years the 5 year disease free survival was 37 6 and 36 6 for HLA identical sibling and haploidentical recipients respectively . The results of transplant from HLA identical siblings and haploidentical donors are comparable . Regardless of the HLA matching other factors known to affect the transplant outcomes such as donor recipient age sex and CMV status combinations might drive the search for the best donor . | Comparable outcomes between HLA identical sibling and haploidentical transplants. Similar incidence of advanced graft versus host disease with prophylaxis not including post transplant cyclophosphamide CTX . Combined donor recipient characteristics more important than HLA matching. |
S1083879120300902 | Treatment for relapse of chronic myeloid leukemia following hematopoietic cell transplantation includes tyrosine kinase inhibitors with or without donor lymphocyte infusions but the most effective treatment strategy is unknown . This study was performed through the Center for International Blood and Marrow Transplant Research database . We retrospectively reviewed all patients reported to the CIBMTR registry from 2002 to 2014 who underwent HCT for CML and were alive 30 days postrelapse . A total of 215 HCT recipients relapsed and were analyzed in the following groups TKI alone TKI with DLI and DLI without TKI . In multivariate analysis disease status prior to HCT had a significant effect on overall survival . Patients who received a DLI alone compared with a TKI with a DLI had inferior survival hazard ratio 2.28 95 confidence interval 1.23 to 4.24 | In the setting of chronic myeloid leukemia CML relapse after hematopoietic cell transplantation HCT tyrosine kinase inhibitors TKIs are an effective treatment strategy. Donor lymphocyte infusions DLIs added to TKIs do not appear to add benefit. DLIs alone when compared with TKIs alone have inferior survival in patients with CML relapsing after HCT. |
S1083879120300914 | Central venous catheters are extensively used in patients undergoing allogeneic hematopoietic cell transplantation . In these patients CVC are placed routinely either via the internal jugular vein or the subclavian vein . Purpose of this study was to systematically analyze complications of CVC at different insertion sites in HCT recipients . In this retrospective analysis all consecutive patients who received a CVC due to allogeneic HCT at our institution between January 2011 and June 2013 were included . Three lumen standard nontunneled CVCs were placed via either the IJV or the SCV . Study endpoints were time to local inflammation at the insertion site time to fever time to a combined endpoint of inflammation and fever central line associated bloodstream infection duration of catheterization catheter lumen obstruction deep vein thrombosis pneumothorax and catheter related death . The median duration of catheterization per CVC was almost identical for the IJV and SCV sites 18 days versus 17 days | Rates of central line associated bloodstream infections are the same in internal jugular vein IJV and subclavian vein SCV central venous catheters CVCs after allogeneic hematopoietic cell transplantation HCT . The strongest risk factor for local inflammation or fever is 6 neutropenic CVC days. The time to local inflammation is longer with CVCs placed in the IJV. CVC placement in the SCV is not superior to placement in the IJV in allogeneic HCT. A clear recommendation for a preferred CVC insertion site is not supported in allogeneic HCT. |
S108387912030094X | Isavuconazole is a broad spectrum triazole approved for treatment of invasive fungal infections . In this open label single arm study we evaluated isavuconazole for antifungal prophylaxis after allogeneic hematopoietic cell transplantation . Adult patients admitted for first HCT received micafungin 150 mg i.v . daily from admission through day 7 post transplantation followed by isavuconazole prophylaxis through maximum D 98 post HCT . Patients were followed through D 182 . The primary endpoint was prophylaxis failure defined as discontinuation of prophylaxis for proven probable IFI systemic antifungal therapy for 14 days for suspected IFI toxicity leading to discontinuation or an adverse event . Between June 2017 and October 2018 99 patients were enrolled in the study of whom 95 were included in our analysis . The median patient age was 57 years 50 to 66 years . Sixty four patients received peripheral blood 17 received bone marrow and 14 received a cord blood allograft for acute leukemia lymphoma myelodysplastic syndrome or another hematologic disease . One third of patients underwent CD34 | Isavuconazole as primary antifungal prophylaxis after allogeneic HCT was safe and effective in our study cohort. Seven patients 7.4 stopped prophylaxis due to treatment emergent toxicity. Three patients 3.1 developed breakthrough candidemia while on isavuconazole therapy. |
S1083879120300951 | While allogeneic hematopoietic stem cell transplantation currently offers the only curative option for patients with myelodysplastic syndrome there is still a high risk of relapse or transplant related complications . We collected data on all patients who had undergone allo HCT at our center between 2000 and 2018 . In total 215 patients with MDS or chronic myelomonocytic leukemia were included . Estimated 1 year overall survival was 70.3 64.2 to 77.0 and the median survival was 7.7 years . There was a significant improvement in OS over time | Overall survival improved after the introduction of fludarabine and treosulfan FluTreo conditioning. FluTreo patients had a median age of 59 years and hematopoietic stem cell transplantation specific comorbidity index of 2 higher than standard myeloablative conditioning. Nonrelapse mortality was lower with FluTreo. The incidence of acute and chronic graft versus host disease was lower with FluTreo. |
S1083879120300963 | Peripheral blood stem cells have been increasingly used for allogeneic hematopoietic cell transplantation instead of bone marrow stem cells . Current National Marrow Donor Program policy recommends 5 days of daily filgrastim followed by either 1 or 2 days of apheresis for unrelated donors depending on collection center choice . To date there are no published studies comparing the differences in donor experience between 1 day and 2 days of apheresis . We examined 22 348 adult unrelated donor collections in 184 centers between 2006 and 2016 . Of these 22 348 donors 20 004 had collection on 1 day and the other 2344 had collection over 2 days . Information on why donors underwent apheresis in 1 day or 2 days was not available . Donors who underwent apheresis in 1 day were more likely to be male 67 versus 46 | Donors who undergo collection in 1 day have less apheresis related toxicity and fewer hospitalizations compared with donors with collection over 2 days. In donors with collection over 2 days the apheresis yield of mononuclear cells was greater on the second day compared with the first day. Although there are statistically significant differences in the incidence of modified toxicity criteria and skeletal pain during apheresis these differences might not be clinically significant. |
S1083879120300975 | Chimeric antigen receptor T cell therapy using engineered cytotoxic T cells has shown promising responses in various hematologic malignancies . Cytokine release syndrome and immune effector cell associated neurologic syndrome are recognized toxicities of CAR T whereas kidney injury remains less well recognized . The objective of the present study was to identify the incidence of acute kidney injury after CAR T cell therapy potential risk factors and recovery of kidney function . We performed a retrospective review of 46 adult patients with non Hodgkin lymphoma treated with CAR T therapy between February 2018 and February 2019 at our institution . Serum creatinine values before CAR T therapy through day 100 were used to assess AKI as defined by the Kidney Disease Improving Global Outcomes criteria grade 1 1.5 to 2 fold of baseline grade 2 2 to 3 fold of baseline grade 3 3 fold of baseline . CRS and ICANS were graded using the consensus criteria of the American Society of Transplantation and Cellular Therapy . The overall incidence of CRS was 78.3 66 to 90.5 of whom 13 developed grade 3 4 CRS whereas the overall incidence of ICANS was lower at 45.7 . The cumulative incidence of any grade AKI by day 100 was 30 with a grade 1 AKI incidence of 21.7 and a grade 2 3 AKI incidence of 8.7 . No patients developed severe AKI necessitating renal replacement therapy . Patients with previous autologous or allogeneic stem cell transplantation those requiring intensive care unit level care and with grade 3 4 CRS had a higher incidence of AKI . Most patients recovered with kidney function returning to baseline within 30 days . We conclude that with early recognition and management of CAR T complications the incidence of AKI is low the severity of injury is mild and most patients recover kidney function within 30 days . | The incidence of acute kidney injury following chimeric antigen receptor T cell CAR T cell therapy is low. Previous hematopoietic cell transplantation intensive care unit admission and grade 3 4 cytokine release syndrome after CAR T therapy may increase the risk of acute kidney injury AKI . Most patients who experience AKI after CAR T therapy recover kidney function. |
S1083879120300987 | Despite advances in transplantation medicine psychological distress and quality of life and functional deficits continue to compromise survivorship after hematopoietic stem cell transplantation . With increasing numbers of HSCT survivors supportive oncology interventions that target health related outcomes in HSCT survivorship are needed . Here we aimed to test the feasibility and acceptability of a group format phone delivered positive psychology intervention in HSCT survivors . This is a one arm pilot study design that adapted and tested an individual PP intervention used in cardiac disease to a phone delivered group based program for HSCT survivors who were .4 to 39 years post transplantation . All participants received an 8 session weekly PP intervention . We assessed feasibility by the enrollment and intervention completion rates . We examined acceptability on a 10 point Likert scale of ease and utility . Unstructured qualitative interviews were used to obtain participant feedback on the intervention for future application in a larger trial . Self reported assessments on psychological functional and quality of life outcomes were administered at baseline and at follow up . Of 64 eligible participants 29 enrolled in the study . For the main aim of intervention feasibility and acceptability participants completed 96 of all PP sessions and rated the ease and utility of sessions highly . Of the self reported assessments obtained the PP intervention resulted in improvements in the resilience scale mean difference 2.4 5.4 | A telephone administered group positive psychology intervention was feasible and well received by hematopoietic stem cell transplantation survivors. |
S1083879120300999 | Familial hemophagocytic lymphohistiocytosis is a potentially fatal disorder of immune regulation . Management includes chemotherapy followed by hematopoietic stem cell transplantation . T cell depleted haploidentical HSCT could be an option for those patients who do not have HLA matching family donor . The objective of this study was to report on the outcome of TCD haploidentical HSCT in patients with FHLH who underwent transplantation at Sultan Qaboos University Hospital . This is a retrospective report on 12 patients with FHLH who received TCD haploidentical HSCT at SQUH between August 2010 and December 2018 . Epidemiologic characteristics and details on the transplantation procedures and complications were collected from patients electronic records . Twelve patients with FHLH received TCD haploidentical HSCT after a myeloablative conditioning regimen composed of treosulfan thiotepa fludarabine anti thymocyte globulin and rituximab . The mean age at transplantation was 11.67 8 months . All patients had | Hemophagocytic lymphohistiocytosis is curable only by stem cell transplantation. For patients with no matching donors haploidentical transplantation was offered. A disease free survival was 58.3 at around 3 years after transplantation. A low incidence of graft versus host disease was encountered while infectious complications were common. Cytomegalovirus antigenemia was the most frequent infectious complication. |
S1083879120301014 | Analysis of specific leukocyte subsets for post transplantation monitoring of chimerism provides greater sensitivity and clinical informativeness on dynamic changes in donor and recipient derived cells . Limitations of the most commonly used approach to chimerism testing relying on PCR based analysis of microsatellite markers prompted us to assess the applicability of digital droplet PCR amplification of deletion insertion polymorphisms for lineage specific chimerism testing in the related stem cell transplantation setting where the identification of informative markers facilitating the discrimination between donor derived and recipient derived cells can be challenging . We analyzed 100 genetically related patient donor pairs by ddPCR analysis using commercially available DIP kits including large sets of polymorphic markers . At least 1 informative marker was identified in all related pairs analyzed and 2 or more discriminating markers were detected in the majority of instances . The achievable detection limit is dependent on the number of cells available for analysis and was as low as 0.1 in the presence of 20 000 leukocytes available for DNA extraction . Moreover the reproducibility and accuracy of quantitative chimerism analysis compared favorably to highly optimized microsatellite assays . Thus the use of ddPCR based analysis of DIP markers is an attractive approach to lineage specific monitoring of chimerism in any allogeneic transplantation setting . | Analysis of deletion insertion polymorphisms DIPs by digital droplet dd PCR represents a powerful technique for the sensitive and quantitative detection of overall and lineage specific chimerism. The DIP marker panel used was demonstrated to be informative in any donor recipient constellation including the related transplant setting. Analysis of specific cell subsets isolated by flow sorting had a detection limit of .1 . In terms of quantitative analysis the results of ddPCR analysis were highly comparable to those of short tandem repeat PCR which has been considered the gold standard in post transplantation diagnostic testing of chimerism. |
S1083879120301026 | Hematopoietic stem cell transplantation survivors are burdened by a high prevalence and early onset of chronic diseases . Healthy dietary patterns have been associated with lower risks of chronic health conditions in the general population . HCT survivors are susceptible to multiple complications that may result in chronic illness . Unfortunately no study to date has comprehensively documented the adherence of HCT survivors to the Dietary Guidelines for Americans which are designed specifically to provide guidance for making healthy food choices . The primary aim of this study was to evaluate diet quality and nutrient intake adequacy of HCT survivors . A secondary aim was to assess these survivors willingness to take part in a future dietary intervention . The dietary intake of adults who had undergone autologous or allogeneic HCT for a hematologic disease and were at least 1 year post transplantation was assessed using the Block 2014 food frequency questionnaire and diet quality was estimated using the Healthy Eating Index 2015 . Nutrient intake adequacies of the group were estimated by the estimated average requirement cutpoint method . Survivors HEI 2015 scores averaged 61.6 1.1 . Adherence to a good quality diet was reported by only 10 of survivors . Intakes of vitamins A C and D as well as magnesium and calcium suggested inadequacy . Fiber intake at 8.9 g per 1000 kcal day fell below the recommended adequate intake . Change in taste was associated with lower quality of diet | Long term survivors of hematopoietic stem cell transplantation HCT reported less than optimal adherence to the 2015 2020 Dietary Guidelines for Americans and had numerous short fall nutrient intakes. The majority of survivors reported willingness to receive nutritional advice and participate in a nutrition program or dietary intervention. These findings reinforce the need to incorporate nutrition assessment and awareness into HCT survivor care. |
S1083879120301038 | We aimed to investigate the frequency risk factors and outcome of active tuberculosis after allogeneic hematopoietic stem cell transplantation . This retrospective nested case control study reviewed data from 6236 patients who received allo HSCT from January 2008 to December 2018 at a single center thirty three patients with active TB and 99 controls without active TB after allo HSCT were identified . We performed propensity score matching by randomly selecting 3 controls for each identified active TB patient according to the time of transplantation and follow up period . History of pretransplant active TB previously treated and inactive at time of transplantation | The frequency of active tuberculosis TB following allogeneic hematopoietic stem cell transplantation allo HSCT was 0.5 . TB infection history was an independent risk factor for active TB after allo HSCT. The prognosis was similar between patients with or without post transplant active TB. This study includes the largest cohort of recipients with active TB after allo HSCT. The impact of the anti TB regimen for prophylaxis and treatment is described. |
S1083879120301063 | Many patients with multiple myeloma eventually relapse even after allogeneic hematopoietic cell transplantation for curative intent.Over the past decade outcomes for patients with MM have improved significantly with the availability of new therapies including next generation proteasome inhibitors immunomodulatory agents and more recently monoclonal antibodies . Although several published studies have evaluated the outcomes of alloHCT for MM the data on survival outcomes in patients with MM experiencing disease relapse following alloHCT are limited . In addition the predictors for postrelapse survival in these patients are not known . In this study we examined the outcomes of a single center cohort of 60 patients with MM who experienced relapse or progression after alloHCT . In addition we evaluated the use of salvage regimens for treatment of relapsed MM and analyzed the predictors for improved postrelapse survival . After a median follow up of 2.2 years from the time of relapse the median duration of postrelapse survival was 1.8 years 1.2 to 5.0 years . Patients received a median of 3 lines of therapy for treatment of MM beyond the post alloHCT relapse progression . Multivariate analysis identified cytogenetic risk .34 P .01 time to relapse after alloHCT 12 months versus 12 months HR .41 | Long term survival is feasible in high risk patients with multiple myeloma MM who relapse after allogeneic hematopoietic cell transplantation alloHCT . This is best achieved using combination treatment and donor lymphocyte infusion DLI . DLI can be incorporated without a significantly increased risk of graft versus host disease GVHD . Cytogenetic risk time to relapse after alloHCT development of acute GVHD before relapse impact survival after relapse in allogeneic transplant recipients. There is a continued need to improve GVHD prophylaxis and treatment strategies. The risk of GVHD after MM relapse post alloHCT is associated with the use of immunomodulatory drugs and checkpoint inhibitors. There are limited data to support the use of checkpoint inhibitors in this population. |
S1083879120301105 | Allogeneic stem cell transplantation is applied to patients suffering from hematologic malignancies to replace the diseased hematopoietic system with cells derived from a donor stem cell graft . The majority of 10 10 matched unrelated donors are HLA DP mismatched and this may result in varying degrees of the graft versus leukemia effect with or without the occurrence of graft versus host disease . Allo HLA reactive T cells are commonly present in the donor T cell repertoire and thus a very profound alloreactive immune response can be provoked in the HLA DP mismatched setting . The magnitude and the diversity of the allo HLA DP specific immune response likely dictates the balance between the occurrence of GVL and or GVHD after transplantation . To understand the nature of the allo HLA DP specific immune response provoked under different stimulatory conditions immune responses were induced from both the nave and memory T cell compartments using either HLA DP mismatched professional antigen presenting cells or HLA DP mismatched nonprofessional APCs as stimulator cells . In this study we observed that allo HLA DP reactive T cells could be provoked from both the nave and memory compartments by both types of APCs . However the magnitude of the allo HLA DP specific immune response was greater when stimulation was performed with allo DCs . Moreover we found that the frequency of allo HLA DP reactive T cells was greater in the nave T cell compartment compared with the memory T cell compartment but we observed a comparable lineage specificity of these allo HLA DP specific reactivities . Overall the data from this study illustrate that the presence of professional APCs of recipient origin will mostly dictate the magnitude of the allo HLA DP specific immune response derived from both the nave and memory T cell compartments but does not exclusively mediate the induction of these immune responses . | Allo HLA DP responses can be provoked from both the nave and memory T cell compartments. Professional hematopoietic antigen presenting cells dendritic cells DCs dictate the magnitude of allo HLA DP responses. DCs are not pivotal for provoking allo HLA DP responses from the nave T cell compartment. Frequencies of allo HLA DP reactive T cells are higher in the nave T cell compartment. |
S1083879120301117 | Acute kidney injury is nearly universally associated with worse outcomes especially among children after hematopoietic stem cell transplant . Our objective was to examine urinary immune biomarkers of AKI after HCT to provide insights into novel mechanisms of kidney injury in this population . Studying patients undergoing allogeneic HCT provides a unique opportunity to examine immune markers of AKI because the risk of AKI is high and the immune system newly develops after transplant . Children and young adults undergoing their first allogeneic HCT and enrolled in a prospective observational cohort study at 2 large children s hospitals had urine collected pre HCT and monthly for the first 4 months after HCT . Urine samples at each monthly time point were assayed for 8 immune related biomarkers . AKI was defined as a 1.5 fold increase in the monthly serum creatinine value which was recorded 1 day from when the research urine sample was obtained as compared with the pre HCT baseline . Generalized estimating equation regression analysis evaluated the association between the monthly repeated measures . A total of 176 patients were included from 2 pediatric centers . Thirty six patients from 1 center were analyzed as a discovery cohort and the remaining 140 patients from the second center were analyzed as a validation cohort . AKI rates were 18 to 35 depending on the monthly time point after HCT . Urine CXCL10 and CXCL9 concentrations were significantly higher among children who developed AKI compared with children who did not | Urine CXCL10 and CXCL9 are associated with acute kidney injury among children after hematopoietic stem cell transplant. Cell line data demonstrate production of CXCL10 and CXCL9 in the kidney. These promising biomarkers could guide management strategies for acute kidney injury in this high risk population. |
S1083879120301129 | Disease relapse is the most common cause of therapy failure in patients with non Hodgkin lymphoma undergoing reduced intensity conditioning allogeneic hematopoietic cell transplantation . It is not known whether or not increasing total body irradiation dose from 2 to 4 Gy in a RIC platform can provide improved disease control without increasing nonrelapse mortality . Using the Center for International Blood Marrow Transplant Research database we evaluated the outcomes of patients with NHL receiving RIC allo HCT with either fludarabine 2 Gy TBI versus Flu 4 Gy TBI . In the CIBMTR registry 413 adult patients with NHL underwent a first allo HCT using either a matched related or unrelated donor between 2008 and 2017 using a RIC regimen with either Flu 2 Gy TBI or Flu 4 Gy TBI . The primary endpoint was overall survival . Secondary endpoints included acute and chronic graft versus host disease NRM relapse progression and progression free survival . At baseline the Flu 2 Gy TBI cohort had significantly fewer patients with Karnofsky performance status 90 and significantly more patients had a higher HCT comorbidity index . On multivariate analysis the 2 conditioning cohorts were not significantly different in terms of risk of grade 3 to 4 aGVHD or cGVHD . Compared to Flu 2 Gy TBI the Flu 4 Gy TBI conditioning was associated with a significantly higher risk of NRM 1.79 95 confidence interval 1.11 to 2.89 | Augmentation of total body irradiation TBI dose from 2 to 4 Gy for patients with non Hodgkin lymphoma undergoing reduced intensity conditioning allogeneic hematopoietic cell transplantation is associated with higher nonrelapse mortality and inferior overall survival. Higher dose of TBI does not result in improved disease control. |
S1083879120301130 | Antithymocyte globulin is used to reduce the incidence and severity of graft versus host disease with hematopoietic cell transplantation yet optimum dosing has yet to be determined . We have previously demonstrated that 2.5 mg kg ATG in conditioning can reduce the incidence of GVHD in unrelated donor transplants . Recent literature has suggested that ATG dosing based on absolute lymphocyte count could lead to more optimum exposure of the drug . We sought to determine if ALC at the time of transplant could impact clinical outcomes . We conducted a retrospective single center study analyzing all consecutive patients at The Ottawa Hospital who received a matched unrelated donor stem cell transplant with ATG between 2009 and 2014 . Patients received rabbit ATG at 0.5 mg kg on day 2 and 2.0 mg kg on day 1 . Univariate and multivariate analyses were used to determine if any patient or transplant related factors including weight ALC and total ATG dose given impacted GVHD relapse or mortality . In total 111 patients met inclusion with a median age of 50 years . The most common diagnoses were acute myelogenous leukemia Myelodysplasia myeloproliferative neoplasms and lymphoma . The median weight at time of conditioning was 80.3 kg . The median ALC on the first day of ATG administration was 0.110 | Weight based dosing of antithymocyte globulin ATG at 2.5 mg kg as part of graft versus host disease GVHD prophylaxis leads to similar GVHD outcomes as lymphocyte count based ATG dosing. Absolute lymphocyte count in this single center retrospective analysis was not associated with GVHD relapse or survival outcomes. Prospective comparisons of low weight based versus lymphocyte count based ATG dosing are still warranted. |
S1083879120301427 | The health and outcomes of long term survivors after hematopoietic cell transplant are areas of evolving interest as short term transplant outcomes improve . Because recent changes in transplant practice have likely changed the survivor population we sought to assess the survival of a contemporary cohort of patients who were alive and free of disease 2 years after HCT . Data were extracted from first transplants documented between 2002 and 2011 in the Australasian Bone Marrow Transplant Recipient Registry on patients who received an allogeneic HCT for acute myeloid leukemia acute lymphoblastic leukemia chronic myeloid leukemia non Hodgkin lymphoma and myelodysplastic syndromes or an autologous HCT for myeloma or lymphoma . Patients were included if they had survived at least 2 years without disease relapse or progression . Mortality rates were compared with standard Australian and New Zealand populations using relative survival analysis . A total of 1562 allogeneic and 3822 autologous HCT patients were included with a median follow up of 5.6 years . Compared with a matched group of patients from our previous study from 1992 to 2001 the contemporary cohort of allogeneic HCT recipients was older and more likely to receive peripheral blood stem cells and from unrelated donors . Allogeneic HCT for AML increased wheresa transplants for CML fell from 32 to 8 . Increasing use of reduced intensity conditioning and unrelated donors was also seen . Long term survival after allogeneic and autologous HCT were very similar to the previous 1992 to 2001 cohort despite changes in practice over time . Recipients of autologous HCT for myeloma demonstrated substantially lower overall survival than HCT for other indications with no clear plateau . Annual relative survival for survivors of allogeneic HCT was 96 to 99 of the general population but only 89 to 96 of the general population for recipients of autologous HCT . Late deaths were primarily due to nonrelapse causes after allogeneic HCT but relapse or disease progression remained prominent for recipients of autologous HCT particularly for myeloma . The management of late HCT effects is important to improve long term survival of transplant recipients but should be tailored to the risks specific to the primary disease and transplant type . Future planning should account for the impact of the expected increase in transplant activity and number of survivors on resource utilization . | Recent 2 year survivors after hematopoietic stem cell transplant are older than previous transplant generations. Survivors are more likely to have received peripheral blood stem cells and from unrelated donors. Despite this long term outcomes of 2 year allogeneic and autologous transplant survivors 2002 to 2011 cohort are similar to a 1992 to 2001 cohort. Relative survival is close to but still reduced compared with the general population in Australasia and screening for late effects remains important. |
S1083879120301439 | High dose chemotherapy and autologous stem cell transplantation have provided effective treatment for patients with newly diagnosed multiple myeloma for more than 3 decades however which patients will benefit from tandem ASCT compared with single ASCT remains unclear . Here we retrospectively analyzed 978 trial and nontrial patients who underwent single or tandem ASCT in Heidelberg or other German Speaking Myeloma Multicenter Group centers . Our results show that response improvement after first ASCT is a significant prognostic factor for progression free survival benefit from tandem versus single ASCT multivariable analysis | Which myeloma patients benefit from tandem autologous stem cell transplantation ASCT compared with single ASCT. Depth of response after first ASCT is not a survival factor in tandem versus single ASCT. Response improvement after first ASCT leads to a survival benefit from tandem ASCT. |
S1083879120301464 | Allogeneic hematopoietic cell transplantation has the capacity to cure numerous malignant and nonmalignant disorders . A dreaded complication is graft failure as it puts patients at high risk of infection and disease relapse . There are few contemporary data on the risks outcomes and economic burden of GF in pediatric patients . In this study we address this gap by focusing on 14 years of transplant at our single center for which data are compared in 2 time periods 2005 to 2010 and 2011 to 2018 . In the 290 patients studied the median age was 9.33 years and 50.3 had malignant versus nonmalignant disease . Cell source included bone marrow cord blood unmanipulated peripheral blood stem cells and CD34 selected PBSCs . Twenty one percent of patients had reduced intensity conditioning and 54.8 of transplants were fully HLA matched . Most patients received serotherapy with rabbit anti thymocyte globulin or alemtuzumab . The incidence of neutropenic and non neutropenic GF was 6.6 and 3.8 respectively . Multivariate analysis demonstrated alemtuzumab 6.256 | Graft failure was associated with alemtuzumab reduced intensity conditioning and unrelated donor grafts. Intermediate scheduling of alemtuzumab had the highest incidence of graft failure. Costs and outcomes of graft failure have improved over time but remain a significant burden. |
S1083879120301488 | Veno occlusive disease sinusoidal obstruction syndrome is a potentially life threatening complication of hematopoietic cell transplantation that is traditionally diagnosed using Baltimore or modified Seattle criteria . Whereas the Baltimore criteria require the presence of hyperbilirubinemia for a diagnosis of VOD SOS the modified Seattle criteria do not . Before approval by the US Food and Drug Administration defibrotide was available in the United States through an expanded access study . The T IND protocol initially required post HCT diagnosis of VOD SOS by the Baltimore criteria or biopsy but was later amended to include patients diagnosed using the modified Seattle criteria . This post hoc analysis examined the incidence of VOD SOS with a bilirubin level 2 mg dL before and after Day 21 post HCT in T IND patients enrolled following the amendment allowing for diagnosis by the modified Seattle criteria . Survival of adult and pediatric patients with or without hyperbilirubinemia and with or without multiorgan dysfunction was also evaluated . Of 803 post HCT patients with VOD SOS enrolled following the protocol amendment 181 had a bilirubin level 2 mg dL and would not have been diagnosed if hyperbilirubinemia was required . The bilirubin level at diagnosis was 2 mg dL in 165 of 331 patients diagnosed by the modified Seattle criteria and in 16 of 23 patients diagnosed by biopsy . VOD SOS with a bilirubin level 2 mg dL was more common in pediatric patients although it also occurred in adult patients . Patients with hyperbilirubinemia had lower Day 100 survival and a higher incidence of MOD . The incidence of treatment emergent adverse events and serious adverse events was lower in patients with a bilirubin level 2 mg dL . These results indicate that anicteric VOD SOS occurs in both adult and pediatric patients post HCT and can be diagnosed before and after Day 21 in both groups . The worse survival in patients with bilirubin 2 mg dL suggests that requiring hyperbilirubinemia may result in a progressed disease stage associated with worse outcomes . Taken together these results highlight the importance of awareness and the possibility of VOD SOS in the absence of elevated bilirubin level . | Anicteric veno occlusive disease sinusoidal obstruction syndrome VOD SOS bilirubin 2 mg dL occurred in pediatric and adult patients. VOD SOS with hyperbilirubinemia was associated with worse Day 100 survival. Hyperbilirubinemia resulted in more treatment emergent and serious adverse events. Diagnosis according to the Baltimore criteria could result in missed VOD SOS diagnoses. |
S108387912030149X | Chronic hepatitis E virus infection in hematopoietic stem cell transplantation recipients is an emerging threat . The aim of this study was to provide data on the HEV burden in an Italian cohort of HSCT recipients and analyze risk factors for HEV seropositivity . This retrospective study reports data from 596 HSCT recipients compiled between 2010 and 2019 . It included patients who underwent transplantation between 2010 and 2015 for whom pretransplantation and post transplantation serum samples were available and tested retrospectively as well as patients in whom prospective HEV testing was performed during the standard care pre HSCT IgG screening in 144 pre HSCT HEV RNA screening in addition to IgG screening in 60 and HEV RNA testing in case of clinical suspicion of HEV infection in 59 . The rate of pre HSCT HEV IgG positivity was 6.0 . Older age was an independent risk factor for seropositivity | Chronic hepatitis E virus HEV infection in hematopoietic stem cell transplantation HSCT recipients is an emerging problem of unknown extent. HEV IgG positivity of 6 was found in our cohort in pre HSCT screening and the incidence increased with recipient age. Two patients were diagnosed with chronic HEV hepatitis with HEV RNA performed after an increase in alanine aminotransferase ALT was detected and both were HEV IgG negative. The rate of HEV infection in HSCT recipients in Italy is low and the benefit of screening pre HSCT seems absent. HEV RNA testing is mandatory in the event of an ALT increase. |
S1083879120301506 | Latent tuberculosis infection affects one fourth of the worlds population . Hematopoietic stem cell transplantation recipients are at an elevated risk of developing active tuberculosis infection . In this retrospective study of donors and HSCT recipients who underwent transplantation between February 2000 and June 2018 our aim was to determine the prevalence of LTBI and ATBI and to describe diagnostic and therapeutic strategies in an HSCT population in an endemic region . The cohort of 409 participants included 125 allogeneic HSCT recipients 165 autologous HSCT recipients and 119 HSCT donors . Patients were evaluated pre HSCT with tuberculin skin test and thoracic imaging . LTBI was diagnosed in 26.2 of the cohort . Cases represented 20 of the auto HSCT population 20 of the allo HSCT population and 41.2 of the donor population . Pre HSCT evaluation to rule out ATBI was performed in 62.6 of the cohort all results were negative . Isoniazid was administered to 73.3 of those with LTBI . Within subgroups 91.7 of HSCT recipients and 51 of donors received treatment . The median duration of therapy pre HSCT was 70 days in recipients and 48 days in donors . The incidence of post HSCT ATBI was 0 at 1 year follow up . The incidence of LTBI in our population was higher than expected and still might have been underestimated owing to diagnostic test limitations . The absence of incident ATBI suggests that recipients as opposed to donors must receive LTBI treatment . Prevention of infectious complications in the HSCT population should be prioritized to improve clinical outcomes . Prospective data from collaborative working groups is needed to determine the best diagnostic and therapeutic approaches in this vulnerable patient population . | Infectious complications represent an important limitation for hematopoietic stem cell transplantation HSCT outcomes. Host immunity and diagnostic limitations make latent tuberculosis infection LTBI an underestimated problem. Recipients diagnosed with LTBI could benefit from pre HSCT treatment. Prospective data is required to define the best strategies for LTBI in the HSCT setting. |
S1083879120301518 | Potentially curative but high risk trials of gene therapy or stem cell transplantation for sickle cell disease pose new opportunities for adults with SCD many of whom experience significant disease burden and complications with few treatment options as well as stigma and disparities in care . We explored motivations and decision making processes of enrollees and decliners of such trials . Semistructured interviews were conducted with a purposive sample of 20 enrollees and 6 decliners . Interviews explored participants SCD experiences motivations and decision making about trial participation understanding of research related information and retrospective reflections . Interviews were analyzed with content analysis . Most identified the purpose of research risks and uncertainties of participation . Both enrollees and decliners described deliberative weighing of study risks and potential benefits with heavy factoring of their SCD status experiences and desire for a better life . Despite the influence of spirituality religion and support of family and friends all described the decision about participation as their own . In some patients the primary outcome status defined by the trial did not match the patients perceived outcomes . Patients with negative experiences expressed a desire for greater emphasis on risks and possible outcomes during informed consent . This cohort of adults with SCD were thoughtfully deliberative in their decisions about gene therapy or PBSCT trials . Future participants decision making may be enhanced by emphasizing that successful scientific outcomes can still involve complications or symptoms and be facilitated by referrals to former research participants and anticipatory discussions . | Adults with sickle cell disease SCD correctly identified research purpose risks and uncertainties of gene therapy or stem cell transplantation trials. Patients engaged in deliberative individualized weighing of study risks and potential benefits in light of their SCD experiences. Family friends and religion played a supportive but not decisive role. Patients subjective experiences did not always coincide with objective trial outcomes. |
S108387912030152X | Pulmonary complications are fatal adverse events after allogeneic hematopoietic cell transplantation . On the other hand smoking is a well known risk factor for various pulmonary diseases and also increases the incidence of pulmonary complications and overall mortality in allo HCT recipients . In this study we retrospectively assessed the impact of smoking intensity on survival outcomes . This study included consecutive allo HCT recipients at our center between June 2007 and May 2019 whose smoking profiles were available they were divided into high and low pack years groups . In univariate analyses nonrelapse mortality and overall survival were significantly inferior in the high pack years group 1 year NRM 26.6 versus 13.9 | High pack years were associated with inferior survival especially in males. High pack years were related to a high incidence of death due to pulmonary events. Total body irradiation dose did not affect survival in the high pack years recipients. Current and ex smokers showed equivalent survival outcomes. |
S1083879120301531 | Hematopoietic stem cell transplantation is the only curative option available for patients with thalassemia major in India with increasing access to alternate donor transplantation for patients with no matched family donor . We aimed to analyze the impact of family and alternate donor HSCT on morbidity and mortality post HSCT . We conducted a retrospective study in the department between July 2007 and December 2018 where all children who underwent HSCT for thalassemia major were included . A total of 264 children were included with a median age of 6 years . The graft source was matched related donor and matched unrelated donor . All children received a myeloablative conditioning regimen with treosulfan thiotepa fludarabine in 93 and busulfan cyclophosphamide in 7 . The source of stem cells was peripheral blood in 61 bone marrow in 38 and umbilical cord blood in 3 . The incidence of bacteremia was 14 versus 25 in MRD versus MUD groups . There was a higher incidence of posterior reversible encephalopathy syndrome in the MUD group . Engraftment occurred in 97 with a higher trend toward mixed chimerism in the MRD group . When indicated whole blood donor lymphocyte infusion was used to ensure complete chimerism in children in the MRD group . A statistically significant difference was found in the incidence of graft versus host disease both acute and chronic between the MUD versus MRD groups 60 versus 20 and 41 versus 17 respectively | With advances in supportive care and a higher index of suspicion for adverse effects early interventions can help provide equivalent overall survival rates of 93 in children undergoing family and alternative donor hematopoietic stem cell transplantation HSCT for thalassemia major. Immediate complications like infections 25 versus 21 are similar but the incidence of posterior reversible encephalopathy syndrome is higher 10 versus 3 in matched unrelated donor MUD children and they require short term intensive care support. Newer steroid sparing agents for graft versus host disease GVHD reducing the dose of CD34 to less than 510. kilogram and slow tapering of immunosuppression after the first 18 months help reduce morbidity and mortality due to GVHD and help optimize outcomes among the MUD HSCT recipients. |
S1083879120301762 | Allogeneic hematopoietic cell transplant is often the only curative therapy for patients with nonmalignant diseases however many patients do not have an HLA matched donor . Historically poor survival has been seen after HLA haploidentical HCT because of poor immune reconstitution increased infections graft versus host disease and graft failure . Encouraging results have been reported using a nonmyeloablative T cellreplete HLA haploidentical transplant approach in patients with hematologic malignancies . Here we report the outcomes of 23 patients with various nonmalignant diseases using a similar approach . Patients received HLA haploidentical bone marrow or granulocyte colony stimulating factormobilized peripheral blood stem cell grafts after conditioning with cyclophosphamide 50 mg kg fludarabine 150 mg m | Modified nonmyeloablative conditioning has a low toxicity profile. Rates of overall survival of 91 and event free survival of 78 were found. There was a high incidence of acute and chronic GHVD. |
S1083879120301774 | ganciclovir or foscarnet as preemptive therapy for cytomegalovirus after allogeneic hematopoietic cell transplantation is associated with myelosuppression and nephrotoxicity respectively . We analyzed a cohort of CMV seropositive R | We assessed toxicities by day 100 associated with preemptive therapy PET in a cohort of cytomegalovirus seropositive hematopoietic cell transplantation recipients. Neutropenia occurred in 41.8 of PET versus 28.6 of no PET patients. .0009 . Acute kidney injury AKI occurred in 10.2 of PET versus 7.8 of no PET patients. .19 . In multivariate models PET increased the risk of neutropenia and AKI by 1.8 and 2.8 fold respectively. |
S1083879120301786 | Optimal conditioning regimens for older patients with myelofibrosis undergoing allogeneic hematopoietic cell transplant are not known . Likewise the role of dose intensity is not clear . | Myeloablative pharmacokinetic guided i.v. busulfan is safe in older myelofibrosis patients. It reduced relapse without increasing NRM even in older patients. Intermediate 2 DIPSS plus risk has better outcomes than high risk disease. |
S1083879120302032 | As the world of cellular therapy expands to include immune effector cell products such as commercial chimeric antigen receptor T cells quality management professionals are faced with creating either new IEC stand alone programs or expand existing hematopoietic cell transplantation programs to promote patient safety and be aligned with quality regulatory and accreditation requirements . The team professionals at City of Hope recently expanded the quality HCT program to include IEC products and in doing so implemented new regulatory infrastructure while maintaining high quality patient care . At COH we developed the quality structure of our cellular therapy program through collaborations between quality regulatory and CAR T patient care committees which included physicians and nurse coordinators . To ensure the quality of our program we monitor data collection and reporting perform quarterly proactive audits of for example outcome analysis and measure selected end points for benchmarking purposes . QM professionals play a critical role in the monitoring and evaluation processes and provide guidance on how to implement accreditation requirements and what impact the requirements may have on care management . Here we describe the process by which COH expanded our HCT QM program to include IEC therapy . We share examples of how we developed our overall program structure and other key items such as how we addressed patient care management and accreditation to apprise other programs that wish to create and or expand existing programs . | Establishing a quality program for immune effector cell IEC therapy requires a multidisciplinary approach. Considerations such as standardization of patient care management and data management are crucial for a new IEC quality program. IEC quality programs must align accreditation and federal requirements with institutional policies. Auditing and reporting are essential elements of IEC quality programs. |
S1083879120302056 | Hematopoietic cell transplantation is physically and psychologically challenging potentially exposing patients to quality of life impairments . Adolescent and young adults are a vulnerable cohort facing multiple hurdles due to dynamic changes in several aspects of their lives . The AYA population may be particularly prone to QoL issues during HCT . We hypothesized that due to the unique psychosocial challenges faced by AYAs they would have an inferior quality of life . We studied QoL differences between AYA and older adult allogeneic HCT recipients before and after HCT . Additionally we determined if pre HCT QoL for AYA transplant recipients changed over time . QoL data were collected prospectively before and after transplant on 431 recipients aged 15 to 60 years from June 2003 through December 2017 using the Functional Assessment of Cancer Therapy Bone Marrow Transplantation questionnaire . Repeated measures analysis of variance was used to assess differences among age groups . Pearson correlation | Adolescent and young adults AYAs had comparable quality of life QoL compared to older adults during the hematopoietic cell transplantation period. AYAs have improved QoL over time during transplant since 2003. Improvements in AYA QoL are driven by a domain that mainly addressed psychosocial concerns. |
S1083879120302068 | The aim of this study was to evaluate the incidence risk factors and outcomes of primary prolonged isolated thrombocytopenia after haploidentical hematopoietic stem cell transplant . We retrospectively analyzed patients who received haplo HSCT for various hematologic malignancies at Peking University Institute of Hematology between January 2015 and December 2016 . Of the 918 patients 93 developed primary PT . We designed a propensity score method based study . For each primary PT patient control subjects were selected using a propensity scorematching method . A total of 372 recipients were enrolled in the study 93 in the PT group and 279 in the control group . Multivariate analysis showed that age older than 25 years | This study represents the first specific report on the incidence risk factors and outcomes of primary PT after haplo HSCT. The incidence of primary PT after haplo HSCT was 10.1 . Primary PT was associated with poorer survival and higher TRM along with older age grades II to IV acute GVHD and EBV infection after haplo HSCT. |
S1083879120302081 | Hematopoietic stem cell transplantation is firmly established as an important curative therapy for patients with hematologic malignancies and other blood disorders . Apart from finding HLA matched donors during the HSCT process donor availability remains a key consideration as the time taken from diagnosis to transplant is recognized to adversely affect patient outcome . In this study we aimed to develop and validate a machine learning approach to predict the availability of stem cell donors . We retrospectively collected a data set containing 10 258 verification typing requests made during the HSCT process in the British Bone Marrow Registry between January 1 2013 and December 31 2018 . Three machine learning algorithms were implemented and compared including boosted decision trees logistic regression and support vector machines . Area under the receiver operating characteristic curve was primarily used to assess the algorithms . The experimental results showed that BDTs performed better in predicting the availability of BBMR donors . The overall predictive power of the model using AUC on the test cohort of 2052 records was found to be 0.826 . Our findings show that machine learning can predict the availability of donors with a high degree of accuracy . We propose the use of the BDT machine learning approach to predict the availability of BBMR donors and use the predictive scores during the HSCT process to ensure patients with blood cancers or disorders receive a transplant at the optimum time . | Unavailability of stem cell donors remains a considerable issue during the stem cell transplantation process. Machine learning can predict the availability of donors with a high degree of accuracy. Availability predictive score can be useful to assist the donor selection process to ensure patients will be provided with a transplant in a timely fashion. It would also be an advantage for patients requiring urgent transplantation. |
S1083879120302093 | The COVID 19 pandemic has created significant barriers to timely donor evaluation cell collection and graft transport for allogeneic hematopoietic stem cell transplantation . To ensure availability of donor cells on the scheduled date of infusion many sites now collect cryopreserved grafts before the start of pretransplantation conditioning . Post transplantation cyclophosphamide is an increasingly used approach for graft versus host disease prophylaxis but the impact of graft cryopreservation on the outcomes of allo HCT using ptCY is not known . Using the Center for International Blood and Marrow Transplant Research database we compared the outcomes of HCT using cryopreserved versus fresh grafts in patients undergoing HCT for hematologic malignancy with ptCY . We analyzed 274 patients with hematologic malignancy undergoing allo HCT between 2013 and 2018 with cryopreserved grafts and ptCY . Eighteen patients received bone marrow grafts and 256 received peripheral blood stem cell grafts . These patients were matched for age graft type disease risk index and propensity score with 1080 patients who underwent allo HCT with fresh grafts . The propensity score which is an assessment of the likelihood of receiving a fresh graft versus a cryopreserved graft was calculated using logistic regression to account for the following disease histology Karnofsky Performance Score HCT Comorbidity Index conditioning regimen intensity donor type and recipient race . The primary endpoint was overall survival . Secondary endpoints included acute and chronic graft versus host disease non relapse mortality relapse progression and disease free survival . Because of multiple comparisons only P values .01 were considered statistically significant . The 2 cohorts were similar in terms of patient age KPS diagnosis DRI HCT CI donor graft source and conditioning intensity . One year probabilities of OS were 71.1 68.3 to 73.8 with fresh grafts and 70.3 with cryopreserved grafts . Corresponding probabilities of OS at 2 years were 60.6 and 58.7 . In matched pair regression analysis graft cryopreservation was not associated with a significantly higher risk of mortality for cryopreserved versus fresh 1.05 95 CI .86 to 1.29 P .60 . Similarly rates of neutrophil recovery platelet recovery grade III IV acute GVHD NRM and relapse progression were similar with cryopreserved grafts versus fresh grafts . There were somewhat lower rates of chronic GVHD and DFS with graft cryopreservation that were of marginal statistical significance after adjusting for multiple comparisons . Overall our data indicate that graft cryopreservation does not significantly delay hematopoietic recovery increase the risk of acute GVHD or NRM or decrease OS after allo HCT using ptCY . | In post transplantation cyclophosphamide based allogeneic hematopoietic stem cell transplantation graft cryopreservation was not associated with significantly higher mortality. Cryopreserved grafts were not associated with significantly delayed hematopoietic recovery or increased risk of acute graft versus host disease GVHD . Cryopreserved grafts were associated with lower risk of chronic GVHD and inferior disease free survival but these differences were of only borderline statistical significance. |
S108387912030210X | The effects of cytomegalovirus reactivation on cord blood transplant are unclear . We assessed the effect of CMV reactivation in adult single unit CBT without in vivo T cell depletion . Of 3147 eligible cases 2052 were acute myeloid leukemia 643 acute lymphoblastic leukemia and 452 myelodysplastic syndrome . CMV reactivation up to 100 days after CBT was associated with better overall survival compared with no reactivation cases whereas nonrelapse mortality was increased in ALL and standard disease risk 17.1 versus 10.6 | Effect of cytomegalovirus CMV reactivation on cord blood transplant CBT was studied. CMV reactivation is associated with improved overall survival OS in AML and MDS. CMV reactivation is associated with improved OS in high disease risk cases. CMV reactivation reduced the risk of relapse in MDS and high disease risk cases. CMV reactivation adversely affected nonrelapse mortality in standard risk cases. |
S1083879120302111 | Patients with refractory or relapsed B cell acute lymphoblastic leukemia and highly aggressive B cell non Hodgkin lymphoma have a very dismal prognosis and limited treatment options . The advent of chimeric antigen receptor T cell therapy constitutes a milestone in current cell and gene therapies covering the unmet need of treatment of high risk patients and bringing immunotherapies one step closer toward cancer therapeutics including hematologic malignancies . CAR T cells targeting CD19 antigen have shown startling remission rates in heavily pretreated B ALL and B NHL patients in whom CAR T cell therapy may sometimes be their last resort treatment . However a high proportion of these patients evade immune surveillance by CAR T cells losing their initial deep responses which leads to disease recurrence as either CD19 positive or CD19 negative relapse . As a result many investigators have questioned the need for consolidative allogeneic hematopoietic stem cell transplantation after CAR T cell therapy once a patient has achieved remission . There remains much controversy regarding whether CAR T cells should be a bridge therapy to allo HCT or a definitive treatment owing to the paucity of strong evidence based data . In this context here we review the existing data regarding the necessity safety and outcomes of allo HCT performed after autologous anti CD19 CAR T cell therapy in B ALL and B NHL patients . | High initial remission rates are achieved post chimeric antigen receptor CAR T cell therapy in patients with B cell acute lymphoblastic leukemia B ALL and patients with B cell non Hodgkin lymphoma B NHL . A significant proportion of patients will eventually relapse or progress. Allogeneic hematopoietic stem cell transplantation allo HCT should be considered in transplantation nave B ALL patients while in remission. allo HCT should be considered preferably in the progression relapse setting for patients with B NHL. |
S1083879120302159 | Adult T cell leukemia lymphoma is an aggressive peripheral T cell neoplasm caused by infection with human T cell lymphotropic virus type 1 . Its prognosis remains extremely poor . Tax the most important regulatory protein for HTLV 1 is associated with the aggressive proliferation of host cells and is also a major target antigen for CD8 | HTLV 1 Tax is a major target antigen for CD8. cytotoxic T cells. PDR. TCR transduced T cells exert strong anti ATL HTLV 1 effects in vitro and in vivo. Therapy using PDR. TCR transduced T cells has the potential to be a novel immunotherapy for ATL. |
S1083879120302184 | CALGB 100001 was a phase II study evaluating autologous stem cell transplant followed by nonmyeloablative allogeneic stem cell transplant in patients with multiple myeloma who had received no more than 18 months of prior therapy and had experienced no more than 1 prior progression event . Conditioning for ASCT was with high dose melphalan 200 mg m | CALGB Alliance 100001 evaluated tandem autologous allogeneic transplant for myeloma. A fludarabine cyclophosphamide conditioning regimen was associated with a very low treatment related mortality rate. Long term follow up demonstrates a subset of patients who derived benefit from this approach. |
S1083879120302202 | Autologous stem cell transplantation remains the standard of care for transplantation eligible patients with multiple myeloma . Bortezomib with lenalidomide and dexamethasone is the most common triplet regimen for newly diagnosed MM in the United States . Carfilzomib with lenalidomide and dexamethasone has shown promising efficacy and may supplant VRD . We compared stem cell yields and autograft minimal residual disease negativity after VRD and KRD induction . Deeper responses were more common with KRD . Precollection bone marrow cellularity interval from the end of induction therapy to start of stem cell collection and method of stem cell mobilization were similar for the 2 cohorts . Days to complete collection was greater with KRD which more often required 3 days of apheresis . Precollection viable CD34 | Bortezomib Velcade lenalidomide Revlimid and dexamethasone VRD and carfilzomib Kyprolis Revlimid and dexamethasone KRD are effective regimens for multiple myeloma. Deeper responses ie very good partial response or better are more common with KRD. Stem cell collection yields are higher with VRD than with KRD. Differences in stem cell yields between VRD and KRD are associated with Revlimid exposure. Stem cell autograft minimal residual disease negativity is higher with KRD than with VRD. |
S1083879120302226 | Melphalan at a myeloablative dose followed by autologous stem cell transplantation remains the standard of care for transplant eligible patients with myeloma . However therapies such as new immunomodulatory drugs and proteasome inhibitors and more recently monoclonal antibodies and chimeric antigen receptor T cells are challenging the traditional role of ASCT . Which patients benefit from ASCT Can its use be delayed until first relapse The field is moving rapidly as novel agents lead to new patient care strategies . The place of ASCT in this changing landscape will be reviewed and reassessed . | Dramatic improvements have been made in the treatment of myeloma. Monoclonal antibodies are improving the rate and depth of response. New drug combinations and chimeric antigen receptor T cell therapy challenge the role of autologous stem cell transplantation in myeloma. |
S1083879120302251 | Hematopoietic cell transplantation is a well established treatment to control and or cure many malignant and nonmalignant diseases involving the hematopoietic system and some solid tumors . We report information about HCT procedures performed in the United States in 2018 and analyze trends and outcomes of HCT as reported to the Center for International Blood and Marrow Transplant Research . Overall compared with 2017 the number of allogeneic HCTs performed in the United States increased by 1 and the number of autologous HCTs decreased by 5 . Key findings are fewer autologous HCTs performed for non Hodgkin lymphoma and increasing numbers of haploidentical HCTs nearly all of which use post transplantation cyclophosphamide for graft versus host disease prophylaxis . There is a continuing increase in HCT in adults age 70 years particularly for acute myelogenous leukemia and myelodysplastic syndromes . Survival rates by disease disease stage donor type and age are presented . This report prepared annually by the CIBMTR provides a snapshot of current transplant activity in the United States . | We summarize hematopoietic cell transplantation activity in the United States in 2018. Key findings include fewer autologous transplantations performed for non Hodgkin lymphoma and increasing numbers of haploidentical transplantations. There is a continuing increase in transplantation activity in adults age 70 years. |
S1083879120302263 | Anhedonia the loss of the capacity to experience pleasure is subjectively and biologically distinct from depressed mood . Few studies have specifically examined the association of pretransplantation anhedonia with key functional outcomes in patients with hematologic malignancies who have undergone hematopoietic stem cell transplantation . | Anhedonia is defined the diminished interest in activities that were previously perceived as enjoyable. Despite the unique role of anhedonia in psychological distress limited studies have examined its associations on outcomes in hematopoietic stem cell transplantation HSCT . Pretransplantation anhedonia is negatively associated with health related quality of life in HSCT recipients. Likewise pretransplantation anhedonia is negatively associated with fatigue in HSCT recipients. Assessment of anhedonia should be incorporated into psychological distress evaluation and management in HSCT recipients. |
S1083879120302275 | Acute lymphoblastic leukemia is associated with poor survival in older adults and allogeneic hematopoietic cell transplant with reduced intensity conditioning has been an increasingly used strategy in this population . At City of Hope we conducted a retrospective analysis of 72 patients who underwent allogeneic HCT with fludarabine and melphalan as the conditioning regimen between 2005 and 2018 from either a matched sibling or fully matched unrelated donor while in complete remission . Tacrolimus and sirolimus were used as graft versus host disease prophylaxis . Overall survival and progression free survival at 4 years post HCT were 58 and 44 respectively . The cumulative incidences of relapse progression and nonrelapse mortality at 4 years were 34 and 22 respectively . Patients with Philadelphia chromosomepositive ALL had a significantly lower cumulative incidence of relapse progression 20 versus 48 for patients with Ph negative status | HCT outcomes in ALL patients after Flu Mel conditioning Tac Siro GVHD prophylaxis. OS and PFS at 4 years were 58 and 44 respectively. Cumulative incidences of relapse and NRM at 4 years were 34 and 22 respectively. Patients with Philadelphia chromosomepositive Ph status had lower relapse. This regimen had favorable outcomes in adult ALL patients with Ph status. |
S1083879120302305 | Adult T cell leukemia lymphoma is a mature T cell malignancy associated with human T cell leukemia virus type I a retrovirus that is endemic in southwestern Japan . Because of population migration cases of ATL are expected to increase in nonendemic areas . Here to clarify the outcomes of patients with ATL in the nonendemic metropolitan area of Osaka we retrospectively analyzed data from the population based Osaka Cancer Registry from 2010 to 2015 . This analysis included 91 patients age 70 years who received chemotherapy for ATL . With a median follow up of 988 days in surviving patients the probability of 2 year overall survival was 21.9 14.1 to 30.9 and the median OS was 9.8 months . The probability of 2 year OS was 22.2 in the nontransplant group and 21.4 in the transplant group without a statistically significant difference between the 2 groups . Allogeneic transplantation was not a favorable prognostic factor in patients with ATL in propensity score adjusted analysis | The clinical outcomes in transplantation recipients and nonrecipients were poor in a nonendemic metropolitan area of Osaka Japan. Patients who received mogamulizumab before undergoing allogeneic hematopoietic stem cell transplantation had an unacceptably high nonrelapse mortality rate. More clinical studies are needed to improve the clinical outcomes in nonendemic areas. |
S1083879120302317 | In this study we compared the outcomes of patients with acute myelogenous leukemia in complete remission treated with myeloablative conditioning and those treated with reduced intensity conditioning before allogeneic hematopoietic stem cell transplantation . In addition we explored the efficacy of dual T cell depletion using anti thymocyte globulin and post transplantation cyclophosphamide for the prevention of graft versus host disease in patients undergoing RIC allo HCT . Our study cohort comprised 356 adults with AML in complete remission who underwent allo HCT between 2013 and 2018 . One hundred eleven patients received a MAC regimen and 245 received an RIC regimen . One hundred seventy one of the patients who received an RIC regimen received ATG PTCy and cyclosporine for GVHD prophylaxis in accordance with our institutional protocol . Data were collected retrospectively and updated in July 2019 . With a median follow up of 14.5 months 161 patients died and 66 relapsed . Two year overall survival relapse free survival and GVHD free RFS were 55 52.6 and 35 respectively . The intensity of the conditioning regimen with or without ATG PTCY CsA did not have a significant impact on OS and RFS . However RIC in combination with ATG PTCY CsA was associated with a significantly lower cumulative incidence of acute GVHD and chronic GVHD . The use of RIC with ATG PTCy CsA was a significant predictor for higher GRFS secondary to the reduction of clinically relevant GVHD | Dual T cell depletion for graft versus host disease GVHD prophylaxis in reduced intensity conditioning allogeneic hematopoietic stem cell transplantation reduces clinically significant GVHD thereby improving GVHD free relapse free survival GRFS in patients with acute myelogenous leukemia AML . The intensity of the conditioning regimen was not a significant predictor for better post transplantation outcomes overall survival GRFS in patients with AML. |
S1083879120302329 | This study of patients with acute myelogenous leukemia age 60 years analyzed the association between patients performance indicesHematopoietic Stem Cell Transplantation Comorbidity Index Karnofsky Performance Score and European Society for Blood and Marrow Transplantation risk scorebefore undergoing allogeneic hematopoietic stem cell transplantation and quality of life quantified using the Functional Assessment of Cancer Therapy Bone Marrow Transplant Scale in the first year after allo HSCT . Over a period of 7 years 48 evaluable patients underwent reduced intensity conditioning allo HSCT . The median patient age was 65 years with 2 year and 5 year overall survival of 65.8 and 52.3 respectively . A significant improvement across all QoL scores was observed over the 12 months post HSCT . An HCT CI of 0 was associated with improved general QoL score at 6 months compared with patients with an HCT CI of 1 to 2 | Quality of life QoL scores improve up to 12 months post transplantation in patients age 60 years. A Karnofsky Performance Status score of 100 at pretransplantation was correlated with improved QoL at 6 months post transplantation. A lower comorbidity score was associated with improved quality of life post transplantation. |
S1083879120302342 | Systemic glucocorticoids remain the standard treatment for gastrointestinal acute graft versus host disease despite their toxicity and incomplete efficacy . Controlled trials have tested poorly absorbable steroids as adjuncts with systemic glucocorticoids but only small case series have reported treatment with poorly absorbed beclomethasone dipropionate and budesonide alone . Our team has adopted the practice of administering BDP or BDP BUD without systemic glucocorticoids as first line therapy for isolated upper GI aGVHD . We report results in 76 patients treated with BDP alone and in 81 patients treated with BDP BUD with allocation by physician choice . Almost all patients received peripheral blood stem cells from a fully HLA matched related or unrelated donor after myeloablative conditioning for acute leukemia myelodysplastic syndrome non Hodgkin lymphoma or another hematopoietic disorders . After 28 days of treatment with BDP 46 of the patients had a complete response and 10 had a partial response after 200 days 61 patients were alive 34 maintained a CR and 3 maintained a PR whereas 53 required additional immunosuppression . After 28 days of treatment with BDP BUD 67 had a CR and 10 a PR after 200 days 74 patients were alive 46 maintained a CR and 2 maintained a PR whereas 43 required additional IS . Among the entire cohort of 157 patients 66 were treated successfully without systemic glucocorticoids . This study reports the efficacy of poorly absorbable steroids alone for patients with isolated UGI aGVHD . Prospective trials should test for the potential advantages of BDP and BUD use over systemic glucocorticoids . | Upper gastro intestinal acute GVHD may improve with sole upfront topical steroids. Combined beclomethasone and budesonide are safe in upper gastro intestinal GVHD. Prospective trials should explore the advantages of topical over systemic steroids. |
S1083879120302585 | Although CD19 directed chimeric antigen receptor T cells have been successfully used after a preceding allogeneic stem cell transplant in patients with acute lymphoblastic leukemia little is known about the feasibility and outcome of CAR T cell treatment in patients who have been previously allotransplanted for lymphoma . In a single center retrospective analysis course and outcome of all allografted patients treated with CD19 CAR constructs for B cell lymphoma between October 2018 and November 2019 were studied . CAR therapy consisted either of a third generation CAR or of commercially manufactured axicabtagene ciloleucel . Altogether 10 CAR T cell dosings using recipient leukapheresis products were performed in 8 patients 4 patients received 6 dosings with HD CAR 1 and 4 patients received 4 dosings with axi cel . Overall 6 of 8 patients responded . CAR treatment was well tolerated with grade 3 cytokine release syndrome and neurotoxicity each being observed after 1 of 10 dosings . A single patient had moderate chronic graft versus host disease . Of note 3 of 4 patients who received axi cel had ongoing grade 3 cytopenia 3 months postdosing whereas prolonged cytopenia was not observed in 9 alloHCT naive patients who received axi cel during the same time period . In conclusion CAR T cell treatment from recipient derived leukapheresis products after a prior alloHCT appears to be feasible effective and safe in patients with B cell lymphoma . Protracted cytopenia after axi cel treatment is a matter of concern and requires further exploration . | CAR T cells might be a salvage option for lymphoma relapse after alloHCT. Information on CAR T cells in B cell lymphoma after a prior alloHCT is limited. After prior alloHCT CD19 CAR T cell treatment in lymphoma is feasible and effective. CAR T cells did not induce or exacerbate the risk of acute or chronic GVHD. Protracted cytopenia after CAR T cell treatment is a matter of concern. |
S1083879120302597 | Delayed reconstitution of the immune system is a long recognized complication after allogeneic hematopoietic cell transplantation . Specifically loss of T cell diversity has been thought to contribute to infectious complications graft versus host disease and disease relapse . We performed serial high resolution next generation sequencing of T cell receptor in 99 related or unrelated donor allogeneic HCT recipients during the first 3 months after HCT using the immunoSEQ Assay . We measured T cell fraction clonality and Daley Smith richness from recipient samples at multiple time points . In agreement with previous studies we found that although absolute T cell numbers recover relatively quickly after HCT T cell repertoire diversity remains diminished . Restricted diversity was associated with conditioning intensity use of antithymocyte globulin and donor type . Increased number of expanded clones compared to donor T cell clones at day 30 was associated with the incidence of acute GVHD 1.11 | After allogeneic hematopoietic cell transplantation T cell repertoire diversity lags behind quantitative T cell recovery. An increase in the number of expanded clones at day 30 is associated with an increased risk of acute graft versus host disease. The use of antithymocyte globulin results in prolonged T cell anomalies including increased clonality 1 Peilou s evenness and decreased Daley Smith richness despite a nearly equivalent T cell fraction. |
S1083879120302834 | Hemorrhagic cystitis is an important complication after haploidentical hematopoietic stem cell transplantation with post transplantation cyclophosphamide . Sodium 2 mercaptoethanesulfonate can prevent bladder injury when given with PT CY . However the best way to deliver MESNA is not known . This study assessed the incidence of HC after haplo HSCT with PT CY with 2 different methods of MESNA administration . The cumulative incidence of HC was lower in patients who received MESNA as a continuous infusion compared with those who received it as an intermittent bolus 5.6 versus 27.8 | Hemorrhagic cystitis is a common complication after haploidentical hematopoietic stem cell transplantation with post transplantation cyclophosphamide. This study evaluated two different regimens of sodium 2 mercaptoethanesulfonate MESNA administration. A continuous infusion of MESNA lowered the incidence of hemorrhagic cystitis. Adverse events were similar regardless of the administration scheme. |
S1083879120302846 | We report the outcomes of hematopoietic stem cell transplantation for 52 patients with Shwachman Diamond syndrome who underwent transplantation between 2000 and 2017 . The median age at transplantation was 11 years and the median duration of follow up was 60 months . The indication for HSCT was bone marrow failure in 39 patients and myelodysplasia acute myelogenous leukemia in 13 patients . The donor type was an HLA matched sibling for 18 patients an HLA matched or mismatched relative for 6 patients and an HLA matched or mismatched unrelated donor for 28 patients . Preparative regimens for BMF were myeloablative in 13 patients and reduced intensity in 26 . At the time of this report 29 of the 39 patients with BMF were alive and the 5 year overall survival was 72 . Graft failure and graft versus host disease were the predominant causes of death . Preparative regimens for patients with MDS AML were myeloablative in 8 and reduced intensity in 5 . At the time of this report only 2 of 13 patients were alive with relapse the predominant cause of death . Survival after transplantation for SDS related BMF is better compared with historical reports but strategies are needed to overcome graft failure and graft versus host disease . For SDS related MDS or AML transplantation does not extend survival . Rigorous surveillance and novel treatments for leukemia are urgently needed . | The 5 year survival of 72 after transplantation for Shwachman Diamond syndrome SDS related bone marrow failure is superior to historical reports. Transplantation for SDS related myelodysplasia MDS or acute myelogenous leukemia AML does not extend survival. A standardized approach to screening may identify patients for transplantation before the onset of MDS or AML. |
S1083879120302858 | High dose chemotherapy and autologous blood stem cell transplantation represent the standard of care in multiple myeloma for transplantation eligible patients . Up to 3 HD CHT ABSCT treatments may be administered during the course of disease including during late onset relapse . Transplantation centers routinely collect more than 1 peripheral blood stem cell graft however subsequent HD CHT ABSCT treatments are often not performed for various reasons . Currently little is known about the actual utilization rate of stored PBSCs . The collection storage and disposal of PBSC products was analyzed in a large cohort of patients with MM over a 12 year period with a minimum follow up of 6 years . The final dataset analysis was performed in March 2019 which was set as the reference date . Based on institution specific charges the costs for PBSC collection processing and storage were estimated . | Up to 3 high dose chemotherapy and autologous blood stem cell transplantation treatments may be administered in patients with multiple myeloma MM . Therefore several peripheral blood stem cell PBSC grafts are collected in MM patients. Considerable discrepancies between PBSC collection and utilization were identified. This was associated with significant efforts and costs. Guidelines for the reevaluation of stored PBSC grafts are warranted. |
S108387912030286X | Post transplant cyclophosphamide has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft versus host disease . Given its increasing use we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation using PTCy . Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia acute lymphoblastic leukemia myelodysplastic syndrome or chronic myeloid leukemia who underwent PTCy based haplo HCT were analyzed and categorized into 4 groups based on myeloablative or reduced intensity conditioning and bone marrow or peripheral blood graft source . In total 646 patients were identified . The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA PB followed by RIC PB MA BM and RIC BM | In haploidentical hematopoietic cell transplant with post transplant cyclophosphamide conditioning intensity and graft source impact graft versus host disease GVHD . In reduced intensity conditioning peripheral blood compared to bone marrow is significantly associated with chronic GVHD. Older donor age is associated with higher risk of acute GVHD and nonrelapse mortality. |
S1083879120302925 | Hematopoietic stem cell transplantation is increasingly being applied globally . Cases in which healthy HSCT donors are chronically infected with hepatitis B virus are relatively common in areas where HBV is endemic . Recipients of stem cells from such hepatitis B surface antigen positive donors are at risk of viral infection and thus may develop HBV related hepatitis . Given the lack of standardized approach to minimizing the risk of such infections from HBsAg | We developed a strategy comprising antiviral treatment for detectable hepatitis B virus HBV DNA hepatitis B surface antigen HBsAg positive donors passive immunity in HBsAg. recipients and prophylactic antiviral treatment of HBsAg. recipients to deal with allogeneic hematopoietic stem cell transplantation allo HSCT accepting stem cells from HBsAg. donors. Groups of recipients accepting cells from HBsAg. and HBsAg. donors showed a similar incidence of HBV related hepatitis. The strategy may increase the treatment options for patients in need of allo HSCT in HBV endemic areas by expanding the donor pool to including HBsAg. individuals. |
S1083879120302950 | Despite a well established risk of chronic kidney disease after allogeneic hematopoietic cell transplant the benefits of using nephrotoxic anti infective agents to treat serious peritransplant infections often outweigh this risk . While there is no consensus on the optimal management of post allo HCT human herpes virus 6 reactivation the nephrotoxic drug foscarnet is often used although its long term impact on renal function has not been established . We retrospectively reviewed 987 adult patients who underwent transplantation between 2002 and 2016 of whom 45.3 were exposed to foscarnet . The most frequent indications for foscarnet treatment were cytomegalovirus and HHV6 . In the first 3 months post transplant patients exposed versus unexposed had similar rates of acute kidney injury and acute kidney failure 61.6 versus 58.7 | This was a retrospective study evaluating the impact of foscarnet on long term renal function after allogeneic hematopoietic cell transplant allo HCT . Acute kidney injury is observed in most patients but is partially reversible. Foscarnet administration results in chronic irreversible kidney injury. Foscarnet should be used judiciously following allo HCT due to the lasting negative impact on renal function. |
S1083879120302962 | Patients presenting for treatment of hematologic cancers may be at increased risk for cognitive dysfunction before allogeneic hematopoietic stem cell transplantation due to advanced age previous chemotherapy treatment deconditioning and fatigue . Cognitive dysfunction may affect treatment decision making ability to recall or follow post HSCT treatment recommendations and overall survival . A total of 448 patients admitted for HSCT between 2011 and 2014 were administered the Montreal Cognitive Assessment by occupational therapists during admission before transplantation and 260 were reassessed following transplantation and before discharge . We examined select predictor variables including age Karnofsky Performance Status sex disease type psychotropic medications and select outcome variables including OS and nonrelapse mortality . Before transplantation 36.4 of patients met criteria for cognitive dysfunction . Age was found to be a significant predictor along with disease type myeloproliferative disorder . No significant association was found between cognitive dysfunction and OS or NRM . Longitudinal analysis from pretransplantation to post transplantation indicated significant decline following HSCT . Notably one third of the study cohort showed cognitive dysfunction at hospital discharge . A significant proportion of HSCT candidates present with cognitive dysfunction with older patients and those diagnosed with MDS and MPD at greatest risk in this cohort . Attention to cognitive dysfunction before transplantation may alert the treatment team to high risk cases that require increased oversight inclusion by caregivers and referral to occupational therapy at discharge . Longitudinal follow up studies are needed to clarify the specific effect of HSCT on cognitive dysfunction and the impact of cognitive dysfunction on transplantation outcomes . | Before hematopoietic stem cell transplantation 36 of patients meet criteria for cognitive dysfunction. Age and disease type are risk factors for cognitive dysfunction. Post transplantation 33 of patients meet criteria for cognitive dysfunction. |
S1083879120302974 | Male gonadal dysfunction is a frequent late effect after pediatric hematopoietic stem cell transplantation but detailed insight into patterns of male gonadal function at long term is limited by retrospective studies without semen sample data . In this study we investigated the risk of azoospermia and testosterone deficiency the diagnostic value of markers of spermatogenesis and paternity at long term follow up after pediatric allogeneic HSCT . All male HSCT survivors age 18 years transplanted in Denmark or Finland between 1980 and 2010 were invited to participate in this cross sectional study . Examinations included a semen sample measurements of reproductive hormones and testicular volume and screening for chronic graft versus host disease . Cumulative treatment doses were calculated . Of 181 eligible patients 98 participated at a median 18 years after undergoing HSCT . Sperm was found in 30 patients azoospermia in 42 and azoospermia during testosterone substitution in 24 . A higher cumulative testicular irradiation dose was associated with increased risk of azoospermia and testosterone substitution per 1 Gy 1.27 95 confidence interval 1.14 to 1.46 | Azoospermia and testosterone deficiency were frequent after pediatric hematopoietic stem cell transplantation. The cumulative testicular irradiation dose was the main risk factor. Testis irradiation of 12 Gy led to azoospermia and irradiation of 16 Gy led to testosterone substitution. Prepubertal stage at transplantation increased the risk of testosterone deficiency. Inhibin B was an accurate surrogate marker of azoospermia in adulthood. |
S1083879120302986 | Accumulating evidence points toward a protective role of intestinal microbiota diversity in allogeneic hematopoietic cell transplantation . The purpose of this systematic review and meta analysis is to determine the effect of antibiotic mediated disruption of microbiota on main allo HCT outcomes treatment related mortality overall survival . Following literature search 2 reviewers screened eligible studies and assessed risk of bias . Meta analysis was performed using Review Manager Software . Among 443 screened references 18 were eligible for meta analysis . In studies with genomic markers grade II to IV acute GVHD was significantly reduced in patients not receiving gut decontamination 1.56 95 confidence interval 1.20 to 2.04 . In subgroup analysis prophylaxis with systemic antibiotics conferred an increased risk of acute GVHD . When we incorporated RoB we found a positive correlation of intestinal GVHD with GD . Patients with higher microbiota diversity presented increased OS 1.58 95 CI 1.19 to 2.09 and lower TRM . Our findings confirm that GD and prophylaxis with systemic antibiotics increase acute and intestinal GVHD . Importantly our meta analysis was the first to show a significant effect of microbiota diversity on TRM and OS . | This is the first meta analysis on impact of antibiotic related microbiota disruption on allogeneic hematopoietic cell transplantation outcomes. Grade II to IV acute and intestinal graft versus host disease GVHD was reduced in patients not receiving gut decontamination. Prophylaxis with systemic antibiotics conferred an increased risk of acute GVHD. Higher microbiota diversity was related to higher overall survival and lower treatment related mortality. Further trials using standardized microbiota scores will improve certainty in our estimates. |
S1083879120303128 | To date there are no data focusing on outcomes of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic myeloproliferative neoplasms unclassifiable . This study aimed to evaluate outcomes and prognostic factors in patients with MDS MPN U after allo HSCT using Japanese nationwide registry data . The primary endpoint was 3 year overall survival secondary endpoints included the cumulative incidence of relapse and nonrelapse mortality . We evaluated the prognostic factors for 3 year OS by univariate analysis using the log rank test . In our cohort of 86 patients with MDS MPN U we found a 3 year OS of 48.5 cumulative incidence of relapse of 23.7 and NRM of 26.3 . The 3 year OS was significantly worse in patients age 50 years compared with those age 50 years 38.1 versus 65.0 | This study provides the first data on outcomes of allogeneic stem cell transplantation allo HSCT in patients with myelodysplastic myeloproliferative neoplasms unclassifiable MDS MPN U . The 3 year overall survival OS was 48.5 in MDS MPN U patients undergoing allo HSCT. Age and disease status were significantly associated with OS of MDS MPN U patients. |
S108387912030313X | New interventions are needed in advanced chronic graft versus host disease . In a phase II single arm multicenter trial we examined the efficacy of ixazomib in patients with chronic GVHD who had progressed after at least 1 previous line of systemic immunosuppressive therapy . Ixazomib was given as a 4 mg oral dose weekly on days 1 8 and 15 of a 28 day cycle for up to 6 total cycles . The primary endpoint was 6 month treatment failure a composite endpoint including death relapse and requirement for an additional line of systemic IS therapy . A total of 50 subjects were enrolled at 6 institutions . The median time from the onset of chronic GVHD to enrollment was 2.8 years . The degree of chronic GVHD at enrollment was National Institutes of Health defined moderate or severe predominantly classic with 52 of patients having involvement of 4 or more organs . The patients were heavily pretreated with 39 receiving 3 or more previous lines of systemic therapy for chronic GVHD . Of the 50 patients treated 26 completed 6 months of planned therapy . The 6 month treatment failure rate was significantly lower than the historical benchmark 28 versus 44 | Oral ixazomib therapy was associated with decreased treatment failure compared with a historical benchmark in a national phase II trial. The 2014 National Institutes of Health response criteria defined overall response rate was 40 at 6 months in a cohort with advanced chronic graft versus host disease. |
S1083879120303141 | Allogeneic hematopoietic stem cell transplantation may be associated with significant morbidity and mortality resulting in increased healthcare utilization . To date no multicenter comparative cost analyses have specifically evaluated alloHCT in children with acute leukemia . In this retrospective cohort study we examined the relationship between survival and HCU while investigating the hypothesis that matched sibling donor alloHCT has significantly lower inpatient HCU with unrelated donor alloHCT and that among URDs umbilical cord blood alloHCT will have higher initial utilization but lower long term utilization . Clinical and transplantation outcomes data from the Center for International Blood and Marrow Transplant Research were merged with inpatient cost data from the Pediatric Health Information System database using a probabilistic merge methodology . The merged dataset comprised US patients age 1 to 21 years who underwent alloHCT for acute leukemia between 2004 and 2011 with comprehensive CIBMTR data at a PHIS hospital . AlloHCT was analyzed by donor type with specific analysis of utilization and costs using PHIS claims data . The primary outcomes of overall survival leukemia free survival and inpatient costs were evaluated using Kaplan Meier curves and Cox and Poisson models . A total of 632 patients were identified in both the CIBMTR and PHIS data . The 5 year LFS was 60 for MSD alloHCT 47 for well matched matched unrelated donor bone marrow alloHCT 48 for mismatched unrelated donor alloHCT and 45 for UCB alloHCT | Matched sibling donor transplants have a survival and cost advantage over unrelated donor transplants. Matched unrelated donor and unrelated cord blood transplants have similar survival outcomes. Among unrelated donor transplants matched unrelated donor transplants have a cost advantage. |
S1083879120303153 | Almost one half of patients developing graft versus host disease will not respond to standard first line steroid treatment . Alpha 1 antitrypsin is able to induce tolerance in preclinical models of GVHD . AAT alters the cytokine milieu promotes a tolerogenic shift of dendritic cells and skews effector T cells toward regulatory T cells . Gastrointestinal steroid refractory GVHD is a protein losing enteropathy that might represent the optimal setting in which to use AAT . Here we analyze the outcomes of 16 patients treated with human derived AAT in advanced stage gut SR GVHD with two thirds of the patients having failed at least 1 treatment for SR GVHD . The overall response rate was 44 with a complete response rate of 27 . Gastrointestinal response was observed in 61 of patients . The median time to best response was 21 days . At day 56 after AAT treatment all CRs were maintained and the ORR was 39 . The 1 year overall survival was 48 . Ancillary studies showed that AAT serum levels were in the normal range at the beginning of treatment whereas fecal loss was elevated . AAT levels consistently rose after exogenous administration but no correlation was found between serum levels and response . REG3 and IL 33 levels were associated with response while in contrast to previous reports regulatory T cells decreased during AAT treatment . This retrospective analysis supports a previous report of AAT as a promising agent in the management of gut SR GVHD and should prompt its evaluation at an earlier stage . | Steroid refractory SR gastrointestinal graft versus host disease GVHD has a dismal outcome. Gastrointestinal GVHD is a protein losing enteropathy with fecal loss of alpha 1 antitrypsin AAT . AAT has tolerogenic immunomodulatory and anti inflammatory properties. AAT administration was safe and effective in a cohort of high risk SR GVHD patients. |
S1083879120303414 | Delayed neutrophil engraftment has been reported in cord blood transplantation compared with other stem cell transplantation methods . The numbers of total nucleated cells CD34 | Splenomegaly and infused CD34. cell dose had a significant impact on neutrophil engraftment. Cord blood units with .810. kg CD34. cells may still be a suitable choice for patients without splenomegaly. Cord blood transplantation may be a viable option for a patient with splenomegaly when the cord blood unit has a high CD34. cell doses. |
S1083879120303426 | The specific description risk factors and outcomes of chronic graft versus host disease in pediatric patients with hematologic malignancies after T cell replete myeloablative haploidentical hematopoietic stem cell transplantation with antithymocyte globulin granulocyte colony stimulating factor have not been previously well described . We retrospectively analyzed the incidence risk factors and outcomes of cGVHD documented according to the 2014 National Institutes of Health consensus criteria in 292 consecutive pediatric patients with hematologic malignancies after TCR myeloablative haplo HSCT with ATG G CSF between January 2015 and December 2017 . A total of 170 patients experienced cGVHD . The 3 year cumulative incidence of total cGVHD and mild moderate and severe cGVHD was 57.9 27.5 18.8 and 11.9 respectively . Multivariate analysis showed that acute GVHD grade II IV hazard ratio 1.578 | This study represents the first report on the incidence risk factors and outcomes of chronic graft versus host disease cGVHD applying the 2014 National Institutes of Health consensus criteria in pediatric patients with hematologic malignancies after unmanipulated T cell replete myeloablative haploidentical hematopoietic stem cell transplantation haplo HSCT with antithymocyte globulin granulocyte colony stimulating factor. The incidence of severe cGVHD in pediatric haplo HSCT was acceptable. Previous aGVHD grade II IV was a risk factor for the occurrence of cGVHD. Only mild or moderate cGVHD was associated with a lower risk of relapse translating into improved disease free survival and overall survival in pediatric haplo HSCT. |
S1083879120303438 | Cytomegalovirus infection and graft versus host disease remain the major causes of nonrelapse mortality in patients following alternative donor hematopoietic stem cell transplantation . Mizoribine showed an anti CMV effect in addition to its immunosuppressive effect in patients with renal transplantation . In this study we aimed to evaluate the efficacy and safety of MZR combined with a calcineurin inhibitor as a method of prophylactic immunosuppression in recipients following alternative donor HCT . Eighty patients were enrolled in the study and randomized to the MZR or MMF cohort before transplantation conditioning . Analyses involved a comparison of the outcomes between the 2 cohorts as well as risk analyses of early nonrelapse mortality and severe CMV infection . In contrast to MMF MZR was associated with a lower but statistically nonsignificant median CMV DNA peak load | A high cytomegalovirus CMV DNA peak load predicts a persistent and refractory disease course. Treatment with mizoribine MZR can reduce the severity of CMV infection in the presence of ganciclovir. MZR shows good immunosuppressive as well as antiviral effects in the setting of hematopoietic stem cell transplantation. |
S1083879120303451 | Bloodstream infections from oral organisms are a significant cause of morbidity and mortality in hematopoietic stem cell transplantation recipients . There are no proven strategies to decrease BSIs from oral organisms . The aim of this study was to evaluate the impact of daily xylitol wipes in improving oral health decreasing BSI from oral organisms and modulating the oral microbiome in pediatric HSCT recipients . This was a single center 1 1 randomized controlled trial in pediatric HSCT recipients age 2 years . Age matched healthy children were enrolled to compare the oral microbiome . The oral hygiene standard of care group continued to receive the standard oral hygiene regimen . The xylitol group received daily oral xylitol wipes in addition to the SOC . The intervention started from the beginning of the transplantation chemotherapy regimen and extended to 28 days following transplantation . The primary outcome was oral health at interval time points and secondary outcomes included BSIs from oral organisms in the first 30 days following transplantation oral microbiome abundance and diversity and oral pathogenic organism abundance . The study was closed early due to efficacy after an interim analysis of the first 30 HSCT recipients was performed . The xylitol group had a significantly lower rate of gingivitis at days 7 14 and 28 following transplantation | Bloodstream infections BSIs from oral organisms are a significant cause of morbidity and mortality in hematopoietic stem cell transplantation HSCT recipients. The addition of xylitol to standard oral care significantly improves gingivitis and dental plaque in HSCT recipients. The addition of xylitol to standard oral care may be associated with decreased BSIs from oral organisms after HSCT. |
S1083879120303463 | Limited data exist regarding the prevalence and outcome of medication nonadherence in the adult allogeneic hematopoietic stem cell transplantation population . The objective of this cross sectional survey study is to determine the prevalence of medication nonadherence to immunosuppressant and nonimmunosuppressant medications in adult recipients of allo HSCT . An electronic survey using previously validated medication adherence scales was distributed between December 2014 and April 2015 to 200 adult patients with at least 3 months of follow up after allo HSCT . Immunosuppressant serum drug levels and prescription refill records were retrospectively collected to assess correlation with survey responses . In the entire cohort 51 of subjects reported nonadherence to nonimmunosuppressant medications 44.07 to 57.93 on the Morisky Medication Adherence Scale . Of the 153 patients taking oral immunosuppressant medications at the time of the survey 58 reported nonadherence to immunosuppressant therapy as measured by the Immunosuppressant Therapy Adherence Scale . Younger age and distress were associated with medication nonadherence . Nonadherence to immunosuppressant therapy was associated with mild chronic graft vs host disease and a similar trend was observed for moderate cGVHD . Medication nonadherence was found to be highly prevalent for both immunosuppressant and nonimmunosuppressant medications in adult allo HSCT recipient and further study to identify interventions to improve adherence in these patients is warranted . | One half 51 102 of 200 of allogeneic hematopoietic stem cell transplantation recipients reported nonadherence to nonimmunosuppressant medications. More than one third 38 of 153 patients taking oral immunosuppressant medications at the time of survey reported nonadherence to immunosuppressants. Younger age distress and higher number of as needed medications were associated with medication nonadherence. Mediation nonadherence to immunosuppressant therapy was associated with mild chronic graft versus host disease GVHD odds ratio 2.63 95 confidence interval 1.04 to 6.66. .042 with a similar trend for moderate chronic GVHD. We did not find a difference in self reports of nonadherence based on time post transplantation. |
S1083879120303475 | Allogeneic hematopoietic stem cell transplantation is the sole potential cure for paroxysmal nocturnal hemoglobinuria however the data on its utility in PNH are limited . This retrospective analysis of patients with PNH who underwent allo HSCT in 11 Polish centers between 2002 and 2016 comprised 78 patients with PHN including 27 with classic PNH and 51 with bone marrow failure associated PNH . The cohort was 59 male with a median age of 29 years . There was a history of thrombosis in 12 and a history of hemolysis in 81 and 92 required erythrocyte transfusions before undergoing allo HSCT . No patient received eculizumab and 26 received immunosuppressive treatment . The median time from diagnosis to allo HSCT was 12 months . Almost all patients received reduced toxicity conditioning 66 with treosulfan . The stem cell source was peripheral blood in 72 and an identical sibling donor in 24 . Engraftment occurred in 96 of the patients . With a median follow up of 5.1 years in patients with cPNH and 3.2 years in patients with BMF PNH 3 year overall survival was 88.9 in the former and 85.1 in the latter | The 3 year overall survival probability was 88.9 in patients with classic paroxysmal nocturnal hemoglobinuria cPNH and 85.1 in those with bone marrow failure associated PNH BMF PNH . The PNH clone was reduced to 1 in 96 of patients with cPNH and in 95 of patients with BMF PNH. The incidence of acute graft versus host disease GVHD grade II IV was 23 and that of extensive chronic GVHD at 1 year was 9 . Reduced toxicity conditioning with treosulfan was safe and effective. |
S1083879120303499 | The negative impact of iron overload on outcomes of allogeneic hematopoietic cell transplantation is well recognized but its impact on umbilical cord blood transplant outcome is unknown . We retrospectively analyzed outcomes of 150 patients who received UCB HCT at our institution stratified by pre HCT serum ferritin level of 2000 ng mL . Two year overall survival rate among patients with SF 2000 and 2000 ng mL was 26.1 and 52.1 respectively hazard ratio 2.26 95 CI 1.28 to 4.00 | Impact of iron overload serum ferritin SF 2000 ng mL on umbilical cord blood hematopoietic cell transplantation HCT outcomes was examined. Overall survival rate at 2 years was significantly lower in patients with higher pre HCT SF levels. .005 . Nonrelapse mortality was significantly higher in patients with higher SF. .02 . Significantly faster engraftment was seen in patients with lower SF levels. Iron overload is a strong adverse prognostic factor for cord blood transplant. |
S1083879120303505 | Secondary failure of platelet recovery can occur after allogeneic hematopoietic stem cell transplantation and 20 of cases are related to acute graft versus host disease . The underlying mechanisms of this association are unclear however . The aim of the present study was to investigate the potential mechanisms of SFPR secondary to aGVHD which may provide a new therapeutic strategy for these patients . A total of 468 patients with malignant hematologic disease who underwent alloHSCT were included . Sixty six patients developed SFPR after alloHSCT and in 45 of these 66 patients SFPR was secondary to grade II IV aGVHD . Compared with patients with good graft function patients with SFPR had poor overall survival 20.72 versus 88.01 | Patients with secondary failure of platelet recovery SFPR have poor overall survival and grade II IV acute graft versus host disease aGVHD is an independent risk factor for SFPR. Donor derived megakaryopoiesis is suppressed in patients with SFPR aGVHD. The immune microenvironment compromises the proliferation and differentiation potential of hematopoietic primitive cells contributing to SFPR secondary to aGVHD. |
S1083879120303517 | Allogeneic hematopoietic cell transplantation for children with nonmalignant disorders is challenged by potential drug related toxicities and poor engraftment . This retrospective analysis expands on our single pediatric medical center experience with targeted busulfan fludarabine and intravenous alemtuzumab as a low toxicity regimen to achieve sustained donor engraftment . Sixty two patients received this regimen for their first HCT for a nonmalignant disorder between 2004 and 2018 . Donors were matched sibling in 27 8 8 HLA allele matched unrelated in 50 and 7 8 HLA allele mismatched in 23 . Five patients experienced graft failure for a cumulative incidence of 8.4 . In engrafted patients the median donor chimerism in whole blood and CD3 CD14 15 and CD19 subsets at 1 year were 96 90 99 and 99 respectively . Only one patient received donor lymphocyte infusions for poor chimerism . Two patients died following disease progression despite 100 donor chimerism . The 3 year cumulative incidence of treatment related mortality was 10 . Overall survival and event free survival at 3 years were 87 and 80 respectively . The 6 month cumulative incidence of grade II to IV acute graft versus host disease was 7 while the 3 year cumulative incidence of chronic GVHD was 5 . These results suggest that use of targeted busulfan fludarabine and IV alemtuzumab offers a well tolerated option for children with nonmalignant disorders to achieve sustained engraftment with a low incidence of GVHD . | Pediatric patients with nonmalignant diseases need better conditioning options. Targeted busulfan fludarabine and alemtuzumab is an optimal regimen. Incidences of graft failure and transplant related mortality are low. Acute and chronic graft versus host disease is very rare especially with bone marrow. Chimerism is excellent without need for donor lymphocyte infusions. |
S1083879120303608 | The integration of antithymocyte globulin into therapy has significantly reduced the incidence of graft versus host disease and is being actively used in allogeneic hematopoietic stem cell transplantation . The ATG dosage is determined by the recipient s body weight but some insist that this approach does not reflect the actual target of ATG . In this respect weight based dosing may lead to ATG overdose particularly in recipients with a relatively low absolute lymphocyte count . We retrospectively analyzed 84 patients with acute leukemia or myelodysplastic syndrome who underwent matched related donor allo HSCT with reduced intensity conditioning at a single institution . Patients were dichotomized according to the ALC measured on the first day of conditioning to investigate the associations of the ALC with GVHD and survival outcomes . The median duration of follow up was 29 months . The preconditioning ALC was closely correlated with the ALC at the first ATG administration . The cumulative incidences of both acute GVHD and chronic GVHD were significantly lower in the preconditioning ALC 500 L group compared with the ALC 500 L group . There was no significant difference in disease relapse incidence between the 2 groups however mortality was significantly higher in the ALC 500 L group . Multivariate analysis including disease status modified European Blood and Marrow Transplantation score and preconditioning ALC identified disease status and ALC as being independently associated with overall survival . In particular infection was the most common cause of death in the ALC 500 L group . Our data suggest that uniform weight based ATG dosing in MRD allo HSCT with RIC is associated with an increase in nonrelapse mortality and a relatively inferior OS in patients with a significantly low preconditioning ALC . Therefore alternative strategies for the integration of ATG should be considered in allo HSCT at least for patients with a substantially low preconditioning ALC . | We investigated the association between preconditioning absolute lymphocyte count ALC and outcomes in recipients of allogeneic hematopoietic stem cell transplantation who received reduced intensity conditioning and were treated with antithymocyte globulin ATG . Preconditioning ALC 500 L was associated with less graft versus host disease but higher nonrelapse mortality. Preconditioning ALC 500 Lwas a prognostic indicator for overall survival. Conventional ATG dose may harm to those with substantially low preconditioning ALC. |
S108387912030361X | An increased risk of infections has been described after T cell replete haploidentical cell transplantation . Cytokine release syndrome after haploHCT is a known phenomenon but the impact of CRS severity on the risk of infections remains unexplored . We retrospectively evaluated 78 consecutive adult haploHCT recipients from 2012 to 2018 for the development of CRS and examined the incidence and mortality due to infections in correlation with CRS severity . In our study cohort which was stratified into 3 groups by severity of CRS 80 of the patients developed infections within 180 days of HCT . Significantly higher proportions of patients with CRS grade 2 and grade 3 than patients with CRS grade 0 1 had at least 1 infection in the first 100 days | The severity of cytokine release syndrome CRS developing after T cell replete haploidentical hematopoietic cell transplantation is associated with an increased risk of bacterial and viral infections. Severe CRS significantly and independently increases the risk of viral infections but mediates the risk of bacterial infections through an effect on neutrophil recovery. CRS grade is also a significant predictor for infection density overall bacterial and viral after adjusting for other predictors including time to neutrophil engraftment. |
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