Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.12.015
Elizabeth Krieger MD , Lylie Hinh DO , Amir Toor MD
Allogeneic hematopoietic cell transplantation (allo-HCT) with post-transplant cyclophosphamide (PTCy) is effective in mitigating graft-versus-host disease (GVHD), but the dynamics of T-cell receptor (TCR) repertoire reconstitution under this platform remain unexplored.
We examined TCR α (TRA), β (TRB), γ (TRG), and δ (TRD) receptor diversity and clonality both pre- and early post-HCT in 35 patients with hematologic malignancies who underwent myeloablative allo-HCT with PTCy from matched unrelated (MUD n=25), mismatched unrelated (MMUD n=4), or haploidentical donors (n=6). TCR repertoire metrics including, Shannon diversity, Simpson evenness, clonality indices, and unique clone counts were assessed in peripheral blood at recipient baseline (pre-conditioning), and post-HCT days 30 and 60. The TCR repertoire of the donor product was also assessed.
Across all TCR, we observed an expected early contraction of repertoire diversity after transplant. For example, median TRB Shannon diversity declined sharply from baseline to day 30 (p < 0.001) and remained significantly lower than baseline by day 60 (p < 0.01). Simpson evenness also decreased post-HCT, indicating a less even (more oligoclonal) repertoire, while clonality measures (e.g., Gini–Simpson index and largest clone frequency) increased significantly at day 30 (p < 0.001). Unique TCR clone counts were markedly reduced after transplant (day 30, p < 0.001) with partial recovery by day 60. Notably, donor age influenced γδ T-cell reconstitution at these early transplant time points recipients of grafts from younger donors exhibited higher TRG and TRD diversity than those with older donors (MWU, p = 0.03 and 0.04).
Clinical factors shape post-transplant trajectories. Patients who reactivated CMV developed oligoclonal expansions with rising largest-clone fractions (Fig.1). aGVHD was similarly linked to expanding dominant T-cell clones and falling repertoire evenness (Fig.1) consistent with antigen-driven proliferation.
These findings indicate that PTCy-based allo-HCT induces a profound yet partially reversible narrowing of the T cell receptor (TCR) repertoire during the early post-transplant period. Donor age is a factor associated with greater early γδ TCR diversity. These insights underscore the importance of further investigating early post-transplant TCR reconstitution kinetics to elucidate the mechanisms underlying transplant-related complications and to inform interventions that improve patient outcomes.
{"title":"Early TCR Αβ and Γδ Repertoire Dynamics after Myeloablative Allo-HCT with Post-Transplant Cyclophosphamide","authors":"Elizabeth Krieger MD , Lylie Hinh DO , Amir Toor MD","doi":"10.1016/j.jtct.2025.12.015","DOIUrl":"10.1016/j.jtct.2025.12.015","url":null,"abstract":"<div><div>Allogeneic hematopoietic cell transplantation (allo-HCT) with post-transplant cyclophosphamide (PTCy) is effective in mitigating graft-versus-host disease (GVHD), but the dynamics of T-cell receptor (TCR) repertoire reconstitution under this platform remain unexplored.</div><div>We examined TCR α (TRA), β (TRB), γ (TRG), and δ (TRD) receptor diversity and clonality both pre- and early post-HCT in 35 patients with hematologic malignancies who underwent myeloablative allo-HCT with PTCy from matched unrelated (MUD n=25), mismatched unrelated (MMUD n=4), or haploidentical donors (n=6). TCR repertoire metrics including, Shannon diversity, Simpson evenness, clonality indices, and unique clone counts were assessed in peripheral blood at recipient baseline (pre-conditioning), and post-HCT days 30 and 60. The TCR repertoire of the donor product was also assessed.</div><div>Across all TCR, we observed an expected early contraction of repertoire diversity after transplant. For example, median TRB Shannon diversity declined sharply from baseline to day 30 (p < 0.001) and remained significantly lower than baseline by day 60 (p < 0.01). Simpson evenness also decreased post-HCT, indicating a less even (more oligoclonal) repertoire, while clonality measures (e.g., Gini–Simpson index and largest clone frequency) increased significantly at day 30 (p < 0.001). Unique TCR clone counts were markedly reduced after transplant (day 30, p < 0.001) with partial recovery by day 60. Notably, donor age influenced γδ T-cell reconstitution at these early transplant time points recipients of grafts from younger donors exhibited higher TRG and TRD diversity than those with older donors (MWU, p = 0.03 and 0.04).</div><div>Clinical factors shape post-transplant trajectories. Patients who reactivated CMV developed oligoclonal expansions with rising largest-clone fractions (Fig.1). aGVHD was similarly linked to expanding dominant T-cell clones and falling repertoire evenness (Fig.1) consistent with antigen-driven proliferation.</div><div>These findings indicate that PTCy-based allo-HCT induces a profound yet partially reversible narrowing of the T cell receptor (TCR) repertoire during the early post-transplant period. Donor age is a factor associated with greater early γδ TCR diversity. These insights underscore the importance of further investigating early post-transplant TCR reconstitution kinetics to elucidate the mechanisms underlying transplant-related complications and to inform interventions that improve patient outcomes.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S1-S2"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.12.094
Andrew Paisley MD, MEd , Karla Foster MS, RCEP, RPFT , Iesha Gover MS, RCEP , Samantha Diebold MS , Adam Lane PhD , William Hardie MD , Kristen Ruff MD , Gregory Burg MD , Christopher Towe MD , Pooja Khandelwal MD , Dr. Jane Koo MD , Stella M. Davies MBBS, PhD, MRCP , Kasiani Myers MD
<div><h3>Introduction</h3><div>Pulmonary complications are a cause of morbidity and mortality following hematopoietic stem cell transplant (HSCT) in children. Bronchiolitis obliterans syndrome (BOS) and lung graft versus host disease, a late-phase chronic respiratory complication of HSCT, contributes to decreased exercise tolerance and quality of life. Pulmonary rehabilitation (PR) has demonstrated efficacy in improving functional outcomes in adults with chronic respiratory disease, but pediatric-focused programs remain rare and under-investigated.</div></div><div><h3>Objectives</h3><div>The purpose of this study is to evaluate the characteristics and functional outcomes of pediatric patients with chronic respiratory disease after HSCT who enrolled in a comprehensive pediatric PR program.</div></div><div><h3>Methods</h3><div>This single center, cohort study examined children with chronic respiratory disease after HSCT completing a comprehensive PR program. The study period was March 2017 to September 2025. Eligibility included completion of a baseline exercise evaluation and at least 5 PR sessions. Data were retrospectively abstracted from the electronic medical record, including demographics, reason for HSCT, type of transplant, pulmonary function tests (PFT), six-minute walk tests (6MWT), measures of exercise capacity, patient/caregiver reported quality of life outcomes, and patient/caregiver reported acceptability of the program. PFT outcomes included the forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) presented as z-scores. Data are presented as mean values with a standard deviation and includes comparisons pre- and post-PR.</div></div><div><h3>Results</h3><div>A total of 20 unique patients were enrolled in PR. The cohort included 9 males and 11 females. The mean age of participants at the start of PR enrollment was 15.5 years (SD 4.3). The mean time from HSCT to PR enrollment was 1,202 days (SD 1,372). The most common respiratory diagnosis at time of PR referral was BOS (N=13, 65%). The baseline lung function at PR enrollment was FEV1 z-score -3.82 (SD 1.29) and FVC z-score -2.80 (1.39). The 6MWT distance at PR enrollment was 1,289 feet (SD 361). Among participants with a paired post-PR 6MWT (N=18), distance walked increased to 1,469 feet (SD 441). Improvements were seen in other assessments of functional exercise performance (table 1). The PR program was favorably viewed by all the participating patients and caregivers (table 2).</div></div><div><h3>Conclusions</h3><div>Children with chronic respiratory disease after HSCT improved their 6MWT distance and other measures of functional exercise performance and muscle strength following participation in a pediatric-specific PR program. Importantly, the participants and their caregivers had high satisfaction with the program, supporting its acceptability and feasibility. This data provides a foundation for future study on the impact of PR and exercise interventions on
{"title":"Pediatric Pulmonary Rehabilitation after Hematopoietic Stem Cell Transplantation","authors":"Andrew Paisley MD, MEd , Karla Foster MS, RCEP, RPFT , Iesha Gover MS, RCEP , Samantha Diebold MS , Adam Lane PhD , William Hardie MD , Kristen Ruff MD , Gregory Burg MD , Christopher Towe MD , Pooja Khandelwal MD , Dr. Jane Koo MD , Stella M. Davies MBBS, PhD, MRCP , Kasiani Myers MD","doi":"10.1016/j.jtct.2025.12.094","DOIUrl":"10.1016/j.jtct.2025.12.094","url":null,"abstract":"<div><h3>Introduction</h3><div>Pulmonary complications are a cause of morbidity and mortality following hematopoietic stem cell transplant (HSCT) in children. Bronchiolitis obliterans syndrome (BOS) and lung graft versus host disease, a late-phase chronic respiratory complication of HSCT, contributes to decreased exercise tolerance and quality of life. Pulmonary rehabilitation (PR) has demonstrated efficacy in improving functional outcomes in adults with chronic respiratory disease, but pediatric-focused programs remain rare and under-investigated.</div></div><div><h3>Objectives</h3><div>The purpose of this study is to evaluate the characteristics and functional outcomes of pediatric patients with chronic respiratory disease after HSCT who enrolled in a comprehensive pediatric PR program.</div></div><div><h3>Methods</h3><div>This single center, cohort study examined children with chronic respiratory disease after HSCT completing a comprehensive PR program. The study period was March 2017 to September 2025. Eligibility included completion of a baseline exercise evaluation and at least 5 PR sessions. Data were retrospectively abstracted from the electronic medical record, including demographics, reason for HSCT, type of transplant, pulmonary function tests (PFT), six-minute walk tests (6MWT), measures of exercise capacity, patient/caregiver reported quality of life outcomes, and patient/caregiver reported acceptability of the program. PFT outcomes included the forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) presented as z-scores. Data are presented as mean values with a standard deviation and includes comparisons pre- and post-PR.</div></div><div><h3>Results</h3><div>A total of 20 unique patients were enrolled in PR. The cohort included 9 males and 11 females. The mean age of participants at the start of PR enrollment was 15.5 years (SD 4.3). The mean time from HSCT to PR enrollment was 1,202 days (SD 1,372). The most common respiratory diagnosis at time of PR referral was BOS (N=13, 65%). The baseline lung function at PR enrollment was FEV1 z-score -3.82 (SD 1.29) and FVC z-score -2.80 (1.39). The 6MWT distance at PR enrollment was 1,289 feet (SD 361). Among participants with a paired post-PR 6MWT (N=18), distance walked increased to 1,469 feet (SD 441). Improvements were seen in other assessments of functional exercise performance (table 1). The PR program was favorably viewed by all the participating patients and caregivers (table 2).</div></div><div><h3>Conclusions</h3><div>Children with chronic respiratory disease after HSCT improved their 6MWT distance and other measures of functional exercise performance and muscle strength following participation in a pediatric-specific PR program. Importantly, the participants and their caregivers had high satisfaction with the program, supporting its acceptability and feasibility. This data provides a foundation for future study on the impact of PR and exercise interventions on","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S63"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.09.030
Valentina Ardila , Lynn Onstad , Paul Carpenter , Joseph Pidala , Carrie Kitko , Najla El Jurdi , Stephanie J. Lee , Betty K. Hamilton
Obesity is increasing in prevalence and has been linked to inflammation, leading to worse outcomes in various disease states. Preclinical studies have demonstrated deleterious effects of obesity on graft-versus-host disease (GVHD). Several retrospective clinical studies have investigated the impact of obesity on allogeneic hematopoietic cell transplantation (HCT); however, with varying results and more limited data on the impact on chronic GVHD. We aimed to investigate the association of obesity on organ involvement, severity, and response to chronic GVHD therapy in a multicenter cohort of patients with chronic GVHD, as well as its impact on overall survival (OS), nonrelapse mortality (NRM), failure-free survival (FFS), and quality of life (QOL). We conducted a retrospective study of patients enrolled from 2007 to 2019 in two prospective longitudinal observational studies from the Chronic GVHD Consortium. Obesity was defined as a body mass index (BMI) ≥ 30, as calculated based on height and weight at the time of enrollment. Grade, organ involvement, and response to chronic GVHD therapy were compared between obese (BMI ≥ 30) and nonobese (BMI < 30) patients. Secondary outcomes included OS, NRM, FFS, and QOL measurement with the Lee symptom scale, Functional Assessment of Cancer Therapy, and Medical Outcomes Study Short Form 36. Among 487 patients identified with newly diagnosed chronic GVHD within 3 mo of study enrollment, 114 (23.4%) had BMI ≥ 30. The only significant difference between obese and nonobese patients was the presence of diabetes as a comorbidity. There were no significant differences in affected organs, grade, overall response to treatment, or organ-specific response to treatment between obese and nonobese patients. Chronic lung GVHD was more common in obese compared to nonobese patients (24.6% versus 13.9% for mild, 5.3% versus 4.8% for moderate, and 0.9% versus 0.8% for severe lung GVHD, P = .047), however, small case numbers and the lack of between group differences in OS, NRM, or FFS limit this interpretation. QOL analyses revealed greater patient-reported symptom burden and worse QOL in obese patients at enrollment and after 6 mo. We found obesity is associated with worse QOL but not with chronic GVHD phenotypes, responsiveness to treatment, or survival outcomes in a multicenter cohort of allogeneic HCT recipients. Given the increasing evidence of a multi-factorial role for obesity as a modulator of immune processes, additional studies investigating more accurate measures of obesity and body composition are needed to further understand their role in chronic GVHD.
{"title":"Obesity Associations with Chronic Graft-Versus-Host Disease","authors":"Valentina Ardila , Lynn Onstad , Paul Carpenter , Joseph Pidala , Carrie Kitko , Najla El Jurdi , Stephanie J. Lee , Betty K. Hamilton","doi":"10.1016/j.jtct.2025.09.030","DOIUrl":"10.1016/j.jtct.2025.09.030","url":null,"abstract":"<div><div>Obesity is increasing in prevalence and has been linked to inflammation, leading to worse outcomes in various disease states. Preclinical studies have demonstrated deleterious effects of obesity on graft-versus-host disease (GVHD). Several retrospective clinical studies have investigated the impact of obesity on allogeneic hematopoietic cell transplantation (HCT); however, with varying results and more limited data on the impact on chronic GVHD. We aimed to investigate the association of obesity on organ involvement, severity, and response to chronic GVHD therapy in a multicenter cohort of patients with chronic GVHD, as well as its impact on overall survival (OS), nonrelapse mortality (NRM), failure-free survival (FFS), and quality of life (QOL). We conducted a retrospective study of patients enrolled from 2007 to 2019 in two prospective longitudinal observational studies from the Chronic GVHD Consortium. Obesity was defined as a body mass index (BMI) ≥ 30, as calculated based on height and weight at the time of enrollment. Grade, organ involvement, and response to chronic GVHD therapy were compared between obese (BMI ≥ 30) and nonobese (BMI < 30) patients. Secondary outcomes included OS, NRM, FFS, and QOL measurement with the Lee symptom scale, Functional Assessment of Cancer Therapy, and Medical Outcomes Study Short Form 36. Among 487 patients identified with newly diagnosed chronic GVHD within 3 mo of study enrollment, 114 (23.4%) had BMI ≥ 30. The only significant difference between obese and nonobese patients was the presence of diabetes as a comorbidity. There were no significant differences in affected organs, grade, overall response to treatment, or organ-specific response to treatment between obese and nonobese patients. Chronic lung GVHD was more common in obese compared to nonobese patients (24.6% versus 13.9% for mild, 5.3% versus 4.8% for moderate, and 0.9% versus 0.8% for severe lung GVHD, <em>P</em> = .047), however, small case numbers and the lack of between group differences in OS, NRM, or FFS limit this interpretation. QOL analyses revealed greater patient-reported symptom burden and worse QOL in obese patients at enrollment and after 6 mo. We found obesity is associated with worse QOL but not with chronic GVHD phenotypes, responsiveness to treatment, or survival outcomes in a multicenter cohort of allogeneic HCT recipients. Given the increasing evidence of a multi-factorial role for obesity as a modulator of immune processes, additional studies investigating more accurate measures of obesity and body composition are needed to further understand their role in chronic GVHD.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages 177.e1-177.e10"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.09.035
Darren Wijaya , Riyan Bittar , Pranati Shah , Farris Al-Manaseer , Adam Hagele , Isaiah Courtad , Mengni Guo , Mojtaba Akhtari
The COVID-19 pandemic led to the widespread adoption of cryopreserved peripheral blood stem cell (PBSC) grafts in allogeneic hematopoietic stem cell transplantation (HSCT), diverging from the traditional preference for fresh grafts. Although cryopreservation ensures graft availability during logistical disruptions, its impact on transplantation outcomes remains uncertain. Existing studies report mixed findings, and no consensus has been established regarding long-term outcomes. In the present study, we compared clinical outcomes of fresh versus cryopreserved allogeneic PBSC grafts in patients undergoing HSCT, with a focus on engraftment and survival outcomes, and evaluated the consistency of reported effects across studies, through a meta-analysis and systematic review of retrospective cohort studies published between 2005 and 2025. PubMed and Embase were searched through May 10, 2025. Primary outcomes included composite, primary, and secondary graft failure; secondary outcomes included engraftment times, overall survival (OS), and relapse-free survival (RFS). Random-effects and fixed-effects models were conducted using R, and Kaplan–Meier curves were digitized when necessary. Thirteen studies were included in the meta-analysis, and 19 studies were included in the systematic review. Fresh grafts were associated with significantly lower odds of composite graft failure (odds ratio [OR], 0.58), primary graft failure (OR, 0.60), and secondary graft failure (OR, 0.46), all with low heterogeneity. Neutrophil and platelet engraftment times were similar, although platelet engraftment showed a nonsignificant trend favoring fresh grafts (–1.34 days; P = .058). One-year and 2-year OS favored fresh grafts in fixed-effects models (OR, 1.15 and 1.16, respectively), but these associations were not significant under random-effects models owing to substantial heterogeneity. One-year RFS also favored fresh grafts in the fixed-effects model (OR, 1.25) but lost significance in the random-effects model. In contrast, 2-year RFS consistently favored fresh grafts across both models (OR, 1.21; 95% CI, 1.08 to 1.35; I² = 0%). Our findings indicate that fresh PBSC grafts are associated with significantly lower rates of graft failure and may confer long-term survival benefits compared to cryopreserved grafts. While survival outcomes varied by statistical model because of heterogeneity, no studies reported superior outcomes with cryopreserved products. These findings support the preferential use of fresh grafts when feasible. Preclinical and clinical studies are needed to further improve the cryopreservation process. Subgroup analyses also may help identify patient populations most likely to benefit from fresh grafts.
{"title":"Comparison of Fresh Versus Frozen Allogenic Peripheral Blood Stem Cell Grafts in Hematopoietic Stem Cell Transplantation: A Meta-Analysis and Systematic Review","authors":"Darren Wijaya , Riyan Bittar , Pranati Shah , Farris Al-Manaseer , Adam Hagele , Isaiah Courtad , Mengni Guo , Mojtaba Akhtari","doi":"10.1016/j.jtct.2025.09.035","DOIUrl":"10.1016/j.jtct.2025.09.035","url":null,"abstract":"<div><div>The COVID-19 pandemic led to the widespread adoption of cryopreserved peripheral blood stem cell (PBSC) grafts in allogeneic hematopoietic stem cell transplantation (HSCT), diverging from the traditional preference for fresh grafts. Although cryopreservation ensures graft availability during logistical disruptions, its impact on transplantation outcomes remains uncertain. Existing studies report mixed findings, and no consensus has been established regarding long-term outcomes. In the present study, we compared clinical outcomes of fresh versus cryopreserved allogeneic PBSC grafts in patients undergoing HSCT, with a focus on engraftment and survival outcomes, and evaluated the consistency of reported effects across studies, through a meta-analysis and systematic review of retrospective cohort studies published between 2005 and 2025. PubMed and Embase were searched through May 10, 2025. Primary outcomes included composite, primary, and secondary graft failure; secondary outcomes included engraftment times, overall survival (OS), and relapse-free survival (RFS). Random-effects and fixed-effects models were conducted using R, and Kaplan–Meier curves were digitized when necessary. Thirteen studies were included in the meta-analysis, and 19 studies were included in the systematic review. Fresh grafts were associated with significantly lower odds of composite graft failure (odds ratio [OR], 0.58), primary graft failure (OR, 0.60), and secondary graft failure (OR, 0.46), all with low heterogeneity. Neutrophil and platelet engraftment times were similar, although platelet engraftment showed a nonsignificant trend favoring fresh grafts (–1.34 days; <em>P</em> = .058). One-year and 2-year OS favored fresh grafts in fixed-effects models (OR, 1.15 and 1.16, respectively), but these associations were not significant under random-effects models owing to substantial heterogeneity. One-year RFS also favored fresh grafts in the fixed-effects model (OR, 1.25) but lost significance in the random-effects model. In contrast, 2-year RFS consistently favored fresh grafts across both models (OR, 1.21; 95% CI, 1.08 to 1.35; <em>I</em>² = 0%). Our findings indicate that fresh PBSC grafts are associated with significantly lower rates of graft failure and may confer long-term survival benefits compared to cryopreserved grafts. While survival outcomes varied by statistical model because of heterogeneity, no studies reported superior outcomes with cryopreserved products. These findings support the preferential use of fresh grafts when feasible. Preclinical and clinical studies are needed to further improve the cryopreservation process. Subgroup analyses also may help identify patient populations most likely to benefit from fresh grafts.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages 215.e1-215.e14"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.10.002
Caden Chiarello , Sihath Singhabahu , Mats Remberger , Carol Chen , Tommy Alfaro Moya , Eshrak Al-Shaibani , Armin Gerbitz , Dennis Dong Hwan Kim , Rajat Kumar , Wilson Lam , Arjun Datt Law , Jeffrey H. Lipton , Fotios V. Michelis , Igor Novitzky-Basso , Auro Viswabandya , Jonas Mattsson , Ivan Pasic
<div><div>Allogeneic hematopoietic cell transplantation (HCT) relies on careful donor selection to optimize outcomes and minimize complications such as graft-versus-host disease (GVHD). While human leukocyte antigen matching remains central to donor selection, secondary characteristics such as age, sex, cytomegalovirus serostatus, and donor-recipient weight difference have become increasingly relevant. Previous studies have demonstrated a relationship between donor-recipient weight ratio and stem cell dose, which may, in turn, influence outcomes including engraftment, survival, relapse, and GVHD. Despite evidence suggesting that donor weight affects CD34<sup>+</sup> cell dose per unit of recipient weight, the specific impact of donor-recipient weight difference on transplant outcomes remains unclear. This study aims to evaluate the effect of donor-recipient weight disparity on post-transplant outcomes in adult allogeneic HCT, thereby informing donor selection when multiple suitable donors are available. This retrospective cohort study included 841 consenting patients 18 yr of age or older who underwent allogeneic HCT using peripheral blood stem cells (PBSC) as the source of graft at the Princess Margaret Hospital Cancer Centre between January 1, 2018, and April 30, 2023. Collected variables included patient and donor weight, clinical and demographic characteristics, transplant regimen details, engraftment time, stem cell dose, survival outcomes, incidence of GVHD, and secondary complications. Conditioning regimens and GVHD prophylaxis varied by donor type, with protocol changes implemented during the study period. Primary outcomes included overall survival (OS), relapse-free survival (RFS), nonrelapse mortality (NRM), cumulative incidence of relapse, and incidence of GVHD, cytomegalovirus (CMV) and Epstein-Barr virus reactivation, and bloodstream infections. Statistical analyses included Mann-Whitney U test, chi-squared test, Kaplan-Meier survival estimates with log-rank testing, and Cox proportional hazards modeling for univariate and multivariate analysis. All analyses were conducted using TIBCO Statistica 13.5. Among 841 patients, the median donor-recipient weight difference was 1.3 kg (range: −82 kg to +128 kg). When donor-recipient weight difference was analyzed as a continuous variable, the use of heavier donors was associated with higher CD34<sup>+</sup> dose (r = .2956, <em>P</em> < .001) and increased risk of chronic GVHD (HR 1.07, <em>P</em> = .036). Weight difference was not significantly associated with OS, RFS, relapse, or risk of acute GVHD. The use of heavier donors was associated with decreased risk of NRM in univariate (HR .93, <em>P</em> = .05) and multivariate (HR .93, <em>P</em> < .05) analyses. The use of heavier donors in PBSC allogeneic HCT is associated with higher CD34<sup>+</sup> cell dose, but its impact on transplant outcomes is limited, being associated only with a small decrease in the incidence of NRM and incr
{"title":"Size Does Not Always Matter: Limited Impact of Donor-recipient Weight Difference on Outcomes of Adult Allogeneic Peripheral Blood Stem Cell Hematopoietic Cell Transplantation","authors":"Caden Chiarello , Sihath Singhabahu , Mats Remberger , Carol Chen , Tommy Alfaro Moya , Eshrak Al-Shaibani , Armin Gerbitz , Dennis Dong Hwan Kim , Rajat Kumar , Wilson Lam , Arjun Datt Law , Jeffrey H. Lipton , Fotios V. Michelis , Igor Novitzky-Basso , Auro Viswabandya , Jonas Mattsson , Ivan Pasic","doi":"10.1016/j.jtct.2025.10.002","DOIUrl":"10.1016/j.jtct.2025.10.002","url":null,"abstract":"<div><div>Allogeneic hematopoietic cell transplantation (HCT) relies on careful donor selection to optimize outcomes and minimize complications such as graft-versus-host disease (GVHD). While human leukocyte antigen matching remains central to donor selection, secondary characteristics such as age, sex, cytomegalovirus serostatus, and donor-recipient weight difference have become increasingly relevant. Previous studies have demonstrated a relationship between donor-recipient weight ratio and stem cell dose, which may, in turn, influence outcomes including engraftment, survival, relapse, and GVHD. Despite evidence suggesting that donor weight affects CD34<sup>+</sup> cell dose per unit of recipient weight, the specific impact of donor-recipient weight difference on transplant outcomes remains unclear. This study aims to evaluate the effect of donor-recipient weight disparity on post-transplant outcomes in adult allogeneic HCT, thereby informing donor selection when multiple suitable donors are available. This retrospective cohort study included 841 consenting patients 18 yr of age or older who underwent allogeneic HCT using peripheral blood stem cells (PBSC) as the source of graft at the Princess Margaret Hospital Cancer Centre between January 1, 2018, and April 30, 2023. Collected variables included patient and donor weight, clinical and demographic characteristics, transplant regimen details, engraftment time, stem cell dose, survival outcomes, incidence of GVHD, and secondary complications. Conditioning regimens and GVHD prophylaxis varied by donor type, with protocol changes implemented during the study period. Primary outcomes included overall survival (OS), relapse-free survival (RFS), nonrelapse mortality (NRM), cumulative incidence of relapse, and incidence of GVHD, cytomegalovirus (CMV) and Epstein-Barr virus reactivation, and bloodstream infections. Statistical analyses included Mann-Whitney U test, chi-squared test, Kaplan-Meier survival estimates with log-rank testing, and Cox proportional hazards modeling for univariate and multivariate analysis. All analyses were conducted using TIBCO Statistica 13.5. Among 841 patients, the median donor-recipient weight difference was 1.3 kg (range: −82 kg to +128 kg). When donor-recipient weight difference was analyzed as a continuous variable, the use of heavier donors was associated with higher CD34<sup>+</sup> dose (r = .2956, <em>P</em> < .001) and increased risk of chronic GVHD (HR 1.07, <em>P</em> = .036). Weight difference was not significantly associated with OS, RFS, relapse, or risk of acute GVHD. The use of heavier donors was associated with decreased risk of NRM in univariate (HR .93, <em>P</em> = .05) and multivariate (HR .93, <em>P</em> < .05) analyses. The use of heavier donors in PBSC allogeneic HCT is associated with higher CD34<sup>+</sup> cell dose, but its impact on transplant outcomes is limited, being associated only with a small decrease in the incidence of NRM and incr","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages 195.e1-195.e13"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div><div>Ethnic minority donors are essential in international donor registries to ensure access to all patients requiring allogeneic stem cell transplantation. Current literature regarding bone marrow (BM) donation-associated pain and toxicity in donors with sickle cell trait (ST), a condition that disproportionally affects minorities, is very limited. Improved communication with potential donors with ST about donation-associated toxicities is important to address misconceptions about donation and may increase the likelihood of participation by minority donors. The aim of this study was to determine the impact of ST on pericollection pain and toxicities experienced by unrelated BM donors. The study population comprised first-time unrelated donors with ST and a subset of unrelated donors without ST from the United States whose BM donation was facilitated by the National Marrow Donor Program (NMDP) between 2010 and 2019. Donors in the control group (ie, donors without ST) were selected for propensity score matching based on age categories, sex, race/ethnicity, and predonation skeletal pain. Logistic regression models were conducted to compare the donors with and without ST for pain and toxicities associated with donation after adjusting for differences in donor characteristics. Descriptive statistics were used to report serious adverse events. Univariate probabilities of complete recovery from donation were calculated using the Kaplan-Meier estimator. A total of 346 BM donors (87 with ST and 259 without ST) were included in this study. The majority of the donors in both cohorts were male (52%), African American (64%) and overweight or obese (77%). Stem cell collection parameters, including BM harvest volume, requirement for autologous blood transfusion postharvest, and duration of anesthesia were comparable between the 2 cohorts. At 2 days postdonation, 68.9% of BM donors with ST and 83.1% of BM donors without ST experienced skeletal pain (<em>P</em> < .01). Although grade 1 pain was more common in donors without ST (51.4% vs 35.6%), grade 2-4 pain was comparable between the 2 cohorts (<em>P</em> = .98). At 1 month postdonation, the incidence of grade 2-4 pain was also comparable between the 2 cohorts (<em>P</em> = .25). By 6 months postdonation, the rates of persistent pain were low, at 5.7% in donors with ST and 6.5% in donors without ST. Donation-related modified toxicity criteria (MTC) at 2 days postdonation were comparable between the 2 cohorts (<em>P</em> = .59). The median time to recovery was 23.5 days in donors with ST and 22.0 days in donors without ST. The rate of reported AEs was slightly higher in donors with ST (2.29% versus 1.59%). BM donation appeared to be well tolerated in donors with ST, with similar rates of postdonation pain and general symptoms as seen in donors without ST. Moreover, BM donation carries a low risk of perioperative mortality, comparable to that observed in donors without ST. This report provides, to our kn
{"title":"Acute Toxicities of Bone Marrow Donation in Unrelated Donors with Sickle Cell Trait: A Center for International Blood and Marrow Transplantation Research Analysis","authors":"Nosha Farhadfar , Stephanie Bo-Subait , Gabrielle Schmidt , Brent Logan , Mahmoud Aljurf , Sherif Badawy , Amer Beitinjaneh , Lohith Gowda , Kimberly A. Kasow , Matthew Seftel , Akshay Sharma , Hemalatha G. Rangarajan , Megan Herr , Minoo Battiwalla , Bronwen E. Shaw , Heather E. Stefanski","doi":"10.1016/j.jtct.2025.10.007","DOIUrl":"10.1016/j.jtct.2025.10.007","url":null,"abstract":"<div><div>Ethnic minority donors are essential in international donor registries to ensure access to all patients requiring allogeneic stem cell transplantation. Current literature regarding bone marrow (BM) donation-associated pain and toxicity in donors with sickle cell trait (ST), a condition that disproportionally affects minorities, is very limited. Improved communication with potential donors with ST about donation-associated toxicities is important to address misconceptions about donation and may increase the likelihood of participation by minority donors. The aim of this study was to determine the impact of ST on pericollection pain and toxicities experienced by unrelated BM donors. The study population comprised first-time unrelated donors with ST and a subset of unrelated donors without ST from the United States whose BM donation was facilitated by the National Marrow Donor Program (NMDP) between 2010 and 2019. Donors in the control group (ie, donors without ST) were selected for propensity score matching based on age categories, sex, race/ethnicity, and predonation skeletal pain. Logistic regression models were conducted to compare the donors with and without ST for pain and toxicities associated with donation after adjusting for differences in donor characteristics. Descriptive statistics were used to report serious adverse events. Univariate probabilities of complete recovery from donation were calculated using the Kaplan-Meier estimator. A total of 346 BM donors (87 with ST and 259 without ST) were included in this study. The majority of the donors in both cohorts were male (52%), African American (64%) and overweight or obese (77%). Stem cell collection parameters, including BM harvest volume, requirement for autologous blood transfusion postharvest, and duration of anesthesia were comparable between the 2 cohorts. At 2 days postdonation, 68.9% of BM donors with ST and 83.1% of BM donors without ST experienced skeletal pain (<em>P</em> < .01). Although grade 1 pain was more common in donors without ST (51.4% vs 35.6%), grade 2-4 pain was comparable between the 2 cohorts (<em>P</em> = .98). At 1 month postdonation, the incidence of grade 2-4 pain was also comparable between the 2 cohorts (<em>P</em> = .25). By 6 months postdonation, the rates of persistent pain were low, at 5.7% in donors with ST and 6.5% in donors without ST. Donation-related modified toxicity criteria (MTC) at 2 days postdonation were comparable between the 2 cohorts (<em>P</em> = .59). The median time to recovery was 23.5 days in donors with ST and 22.0 days in donors without ST. The rate of reported AEs was slightly higher in donors with ST (2.29% versus 1.59%). BM donation appeared to be well tolerated in donors with ST, with similar rates of postdonation pain and general symptoms as seen in donors without ST. Moreover, BM donation carries a low risk of perioperative mortality, comparable to that observed in donors without ST. This report provides, to our kn","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages 217.e1-217.e12"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div><div>Autologous stem cell transplantation (ASCT) is a cornerstone treatment for multiple myeloma (MM). Implementing outpatient ASCT in lower- and middle-income countries (LMICs) remains challenging due to elevated infection risks, socioeconomic limitations, and logistical hurdles. Due to the limited number of high-efficiency particulate air (HEPA)-filtered rooms for ASCT in Thailand, an early step-down ward model could be an important innovation to increase the number of patients receiving timely ASCT. We performed an observational cohort study of all MM patients undergoing ASCT between January 2017 and October 2023. We compared the rates of infectious complications, engraftment outcomes, and treatment-related mortality (TRM) among patients after implementing the early step-down ward model, the step-down group, to those before its implementation, the pre-step-down group. Two hundred- and fifty-two-MM patients were analyzed, including 114 pre-stepdown group and 138 step-down group patients. The rate of ASCTs comparing the pre-step-down and step-down groups was 30-40/year and 85-100/year, respectively. The univariable cumulative mean infection rates were similar between the pre-step-down and step-down groups (1.27 per patient; 95% CI 1.02, 1.52 versus 1.18 per patient; 95% CI 1.07, 1.28, respectively). The adjusted relative density of infections comparing the groups was not different at 1.02 (95% CI 0.89, 1.17; <em>P = .</em>75). The 30- and 100-day TRM rates were 0% in both groups. Engraftment outcomes were similar in both groups. Rates of mold infections, severe infections, and intensive care unit admissions during admission for ASCT and 14-day re-admissions for infectious complications in the early step-down ward model patients were low and were comparable to or lower than the pre-stepdown group. Infectious complication rates and TRM rates were similar between patients exclusively staying in HEPA-filtered rooms post-ASCT and those under the early step-down-ward model. The model is feasible and safe for implementation in resource-limited LMICs. Keeping multiple myeloma patients in high-efficiency particulate air-filtered rooms after autologous stem cell transplant limits the number of patients undergoing transplantation in resource-limited settings, and may not be necessary for good infection control. We implemented an early step-down ward model, moving patients early from high-efficiency particulate air-filtered rooms to a step-down ward a few days after transplantation. Our model had similar rates of infectious complications, engraftment outcomes and treatment-related mortality comparing patients staying only in high-efficiency particulate air-filtered rooms. The early stepdown-ward model demonstrates safety and efficacy in reducing length of stay in transplantation units while increasing access to autologous stem cell transplantation for multiple myeloma patients in resource-limited settings. Furthermore, this approach can be implemented
背景：自体干细胞移植（ASCT）是多发性骨髓瘤（MM）的基础治疗方法。由于感染风险升高、社会经济限制和后勤障碍，在中低收入国家（LMICs）实施门诊ASCT仍然具有挑战性。由于泰国用于ASCT的高效微粒空气（HEPA）过滤房间数量有限，早期降压病房模式可能是增加及时接受ASCT的患者数量的重要创新。方法：我们对2017年1月至2023年10月期间接受ASCT的所有MM患者进行了一项观察性队列研究。我们比较了实施早期降压病房模型（降压组）和实施前降压组（降压组）患者的感染并发症、植入结果和治疗相关死亡率（TRM）。结果：共分析mm患者252例，其中降压前组114例，降压组138例。降压前组和降压组的asct发生率分别为30-40例/年和85-100例/年。降压前组和降压组的单变量累积平均感染率相似（1.27 /例；95%CI分别为1.02、1.52和1.18 /例；95%CI分别为1.07、1.28）。两组校正后的感染相对密度为1.02，差异无统计学意义（95%CI 0.89, 1.17; p = 0.75）。两组30天和100天的TRM率均为0%。两组移植结果相似。早期降压病房模型患者在ASCT入院期间的霉菌感染、严重感染和重症监护病房入院率以及14天内因感染并发症再次入院率都很低，与降压前组相当或更低。结论：asct后仅住在hepa过滤房间的患者与早期降压模式患者的感染并发症发生率和TRM率相似。该模型适用于资源有限的中低收入国家。关于该主题的已知信息：在自体干细胞移植后，将多发性骨髓瘤患者留在高效微粒空气过滤的房间中，限制了在资源有限的情况下接受移植的患者数量，并且可能不是良好感染控制所必需的。这项研究补充的内容：我们实施了一个早期降压病房模型，在移植后几天，将患者从高效微粒空气过滤病房早期转移到降压病房。与只住在高效微粒空气过滤房间的患者相比，我们的模型具有相似的感染并发症、植入结果和治疗相关死亡率。该研究可能对研究、实践或政策产生的影响：在资源有限的情况下，早期的逐步下降模型证明了在减少移植单位住院时间的同时增加多发性骨髓瘤患者自体干细胞移植的安全性和有效性。此外，这种方法可以在没有hepa过滤的房间中实施自体干细胞移植，为没有hepa过滤设施的中低收入国家提供了一种可行的解决方案。
{"title":"Optimizing Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma: Early Step-Down Ward Versus HEPA-Filtered Rooms: A Practical Approach for Resource-Limited Settings","authors":"Chutima Kunacheewa , Sukanpuk Niwatkittipon , Suparat Atakulreka , Nawapotch Donsakul , Smith Kungwankiattichai , Ekapun Karoopongse , Jane Jianthanakanon , Narupon Sonsak , Pongthep Vittayawacharin , Utairat Meeudompong , Natchanon Sathapanapitagkit , Kamolchanok Kulchutisin , Weerapat Owattanapanich","doi":"10.1016/j.jtct.2025.10.018","DOIUrl":"10.1016/j.jtct.2025.10.018","url":null,"abstract":"<div><div>Autologous stem cell transplantation (ASCT) is a cornerstone treatment for multiple myeloma (MM). Implementing outpatient ASCT in lower- and middle-income countries (LMICs) remains challenging due to elevated infection risks, socioeconomic limitations, and logistical hurdles. Due to the limited number of high-efficiency particulate air (HEPA)-filtered rooms for ASCT in Thailand, an early step-down ward model could be an important innovation to increase the number of patients receiving timely ASCT. We performed an observational cohort study of all MM patients undergoing ASCT between January 2017 and October 2023. We compared the rates of infectious complications, engraftment outcomes, and treatment-related mortality (TRM) among patients after implementing the early step-down ward model, the step-down group, to those before its implementation, the pre-step-down group. Two hundred- and fifty-two-MM patients were analyzed, including 114 pre-stepdown group and 138 step-down group patients. The rate of ASCTs comparing the pre-step-down and step-down groups was 30-40/year and 85-100/year, respectively. The univariable cumulative mean infection rates were similar between the pre-step-down and step-down groups (1.27 per patient; 95% CI 1.02, 1.52 versus 1.18 per patient; 95% CI 1.07, 1.28, respectively). The adjusted relative density of infections comparing the groups was not different at 1.02 (95% CI 0.89, 1.17; <em>P = .</em>75). The 30- and 100-day TRM rates were 0% in both groups. Engraftment outcomes were similar in both groups. Rates of mold infections, severe infections, and intensive care unit admissions during admission for ASCT and 14-day re-admissions for infectious complications in the early step-down ward model patients were low and were comparable to or lower than the pre-stepdown group. Infectious complication rates and TRM rates were similar between patients exclusively staying in HEPA-filtered rooms post-ASCT and those under the early step-down-ward model. The model is feasible and safe for implementation in resource-limited LMICs. Keeping multiple myeloma patients in high-efficiency particulate air-filtered rooms after autologous stem cell transplant limits the number of patients undergoing transplantation in resource-limited settings, and may not be necessary for good infection control. We implemented an early step-down ward model, moving patients early from high-efficiency particulate air-filtered rooms to a step-down ward a few days after transplantation. Our model had similar rates of infectious complications, engraftment outcomes and treatment-related mortality comparing patients staying only in high-efficiency particulate air-filtered rooms. The early stepdown-ward model demonstrates safety and efficacy in reducing length of stay in transplantation units while increasing access to autologous stem cell transplantation for multiple myeloma patients in resource-limited settings. Furthermore, this approach can be implemented ","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages 175.e1-175.e14"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.10.033
Yadith Karina López-García , Christianne Bourlon-De Los Rios , Perla Rocio Colunga-Pedraza , Luz del Carmen Tarin-Arzaga , Omar Vargas-Serafin , Alberto Vazquez-Mellado , Lourdes Gil-Flores , Héctor A. Vaquera-Alfaro , Nidia K. Moncada-Saucedo , Moises Gallardo-Pérez , David Gomez-Almaguer , Guillermo Ruiz-Argüelles , Andrés Gómez-De León , TCTMX working group
Despite advances in donor availability and transplant techniques, many patients who are eligible for allogeneic hematopoietic cell transplantation (allo-HCT) never undergo the procedure. This gap is particularly pronounced in low- and middle-income countries (LMICs), where structural and clinical barriers may limit access. To identify barriers to undergoing allo-HCT among HLA-typed, transplant-eligible patients, and to assess transplant rates, associated factors, and outcomes. We conducted a multicenter retrospective cohort study of adult patients with hematologic diseases deemed eligible for allo-HCT who underwent HLA typing between January 2015 and March 2020 at 3 referral centers in Mexico. Primary outcome was to identify barriers to transplantation; secondary outcomes included cumulative incidence of allo-HCT, overall survival (OS), and factors associated with undergoing allo-HCT. Analyses were conducted on an intent-to-transplant basis. Among 374 eligible patients, the 2-year cumulative incidence of allo-HCT was 53% (95% CI, 47-58). The most common barrier was disease progression (58%), followed by inpatient bed shortages (35%) and comorbidities (32%). Donor unavailability accounted for only 12% of nontransplant cases. In the multivariate analysis, outpatient care (OR 6.7; 95% CI, 4.1-10.9) and government insurance (OR 1.9; 95% CI, 1.2-3.2) were associated with higher transplant access while high/very high Disease Risk Index (OR 0.4; 95% CI, 0.2-0.7) was associated with reduced likelihood of transplant. The landmark analysis showed improved overall survival (OS) in transplanted patients (30 vs. 12 months; P < .001). Cumulative incidence of transplant-related mortality was 21% at 24 months. In this multicenter intent-to-transplant cohort from a LMIC, disease progression and systemic delays were the leading barriers to allo-HCT. While haploidentical transplantation minimized donor limitations, outpatient transplant models and national insurance coverage emerged as key enablers of access. Expanding outpatient models and strengthening public systems are key to improving equity in transplant delivery.
{"title":"Barriers to Allogeneic Hematopoietic Cell Transplantation in the Haploidentical Era: A Multicenter Intent-to-Transplant Analysis in a Middle-Income Country","authors":"Yadith Karina López-García , Christianne Bourlon-De Los Rios , Perla Rocio Colunga-Pedraza , Luz del Carmen Tarin-Arzaga , Omar Vargas-Serafin , Alberto Vazquez-Mellado , Lourdes Gil-Flores , Héctor A. Vaquera-Alfaro , Nidia K. Moncada-Saucedo , Moises Gallardo-Pérez , David Gomez-Almaguer , Guillermo Ruiz-Argüelles , Andrés Gómez-De León , TCTMX working group","doi":"10.1016/j.jtct.2025.10.033","DOIUrl":"10.1016/j.jtct.2025.10.033","url":null,"abstract":"<div><div>Despite advances in donor availability and transplant techniques, many patients who are eligible for allogeneic hematopoietic cell transplantation (allo-HCT) never undergo the procedure. This gap is particularly pronounced in low- and middle-income countries (LMICs), where structural and clinical barriers may limit access. To identify barriers to undergoing allo-HCT among HLA-typed, transplant-eligible patients, and to assess transplant rates, associated factors, and outcomes. We conducted a multicenter retrospective cohort study of adult patients with hematologic diseases deemed eligible for allo-HCT who underwent HLA typing between January 2015 and March 2020 at 3 referral centers in Mexico. Primary outcome was to identify barriers to transplantation; secondary outcomes included cumulative incidence of allo-HCT, overall survival (OS), and factors associated with undergoing allo-HCT. Analyses were conducted on an intent-to-transplant basis. Among 374 eligible patients, the 2-year cumulative incidence of allo-HCT was 53% (95% CI, 47-58). The most common barrier was disease progression (58%), followed by inpatient bed shortages (35%) and comorbidities (32%). Donor unavailability accounted for only 12% of nontransplant cases. In the multivariate analysis, outpatient care (OR 6.7; 95% CI, 4.1-10.9) and government insurance (OR 1.9; 95% CI, 1.2-3.2) were associated with higher transplant access while high/very high Disease Risk Index (OR 0.4; 95% CI, 0.2-0.7) was associated with reduced likelihood of transplant. The landmark analysis showed improved overall survival (OS) in transplanted patients (30 vs. 12 months; <em>P</em> < .001). Cumulative incidence of transplant-related mortality was 21% at 24 months. In this multicenter intent-to-transplant cohort from a LMIC, disease progression and systemic delays were the leading barriers to allo-HCT. While haploidentical transplantation minimized donor limitations, outpatient transplant models and national insurance coverage emerged as key enablers of access. Expanding outpatient models and strengthening public systems are key to improving equity in transplant delivery.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages 219.e1-219.e10"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145439291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.10.005
Yixian Li , Yau Ki Wilson Chan , Pui Wah Pamela Lee , Ka Leung Daniel Cheuk , Chi Hang Wong , Wing Hang Leung
Background
Viral reactivations, including cytomegalovirus (CMV), Epstein–Barr virus (EBV), adenovirus (ADV), human herpesvirus 6 (HHV-6), and BK virus (BKV), are significant infectious complications following haploidentical hematopoietic stem cell transplant (haplo-HCT). TCRαβ-depletion of haploidentical graft reduces the risk of graft-versus-host disease (GVHD) but may lead to delayed immune recovery and further increases the risk of viral reactivations. Prophylactic infusion of CD45RA-depleted donor memory T lymphocytes (TMDLI) has been reported as a strategy to accelerate recovery of T cell immunity after haplo-HCT.
Objectives
To evaluate the safety and feasibility of therapeutic TMDLI for the treatment of viral infections before immune recovery within 100 days after TCRαβ-depleted haplo-HCT and prophylactic TMDLI administered on Day 0.
Study Design
A retrospective review of patients who had received therapeutic TMDLI for one or more post-transplant viral infection(s) in a tertiary children’s hospital from 2020 to 2023.
Results
A total of 46 therapeutic TMDLIs were administered to 24 patients, with the first dose of infusion given between day 12 to 93 after haplo-HCT. CMV reactivation was the most common indication for TMDLI (n = 32, 69.6%), and the median time to achieve CMV clearance (defined as first negative viral polymerase chain reaction (PCR) test from the time of first therapeutic TMDLI) was 14 days. Other intended-to-treat viral infections or co-infections include ADV (n = 10), EBV (n = 6), BKV (n = 6) and HHV-6 (n = 3). The cumulative incidence of negative viral PCR for all viruses 30 days after the first TMDLI treatment was 75% (18/24 patients). All TMDLIs were well tolerated, with no de novo or recurrence of acute GVHD thereafter. One patient developed de novo moderate chronic GVHD after TMDLI treatment.
Conclusion
TMDLI was a safe and feasible treatment for viral infections occurring within 100 days after pediatric TCRαβ-depleted haplo-HCT and prophylactic TMDLI.
{"title":"Memory T Cell Donor Lymphocyte Infusion as a Treatment for Viral Infection After Pediatric Haploidentical Hematopoietic Stem Cell Transplant","authors":"Yixian Li , Yau Ki Wilson Chan , Pui Wah Pamela Lee , Ka Leung Daniel Cheuk , Chi Hang Wong , Wing Hang Leung","doi":"10.1016/j.jtct.2025.10.005","DOIUrl":"10.1016/j.jtct.2025.10.005","url":null,"abstract":"<div><h3>Background</h3><div>Viral reactivations, including cytomegalovirus (CMV), Epstein–Barr virus (EBV), adenovirus (ADV), human herpesvirus 6 (HHV-6), and BK virus (BKV), are significant infectious complications following haploidentical hematopoietic stem cell transplant (haplo-HCT). TCRαβ-depletion of haploidentical graft reduces the risk of graft-versus-host disease (GVHD) but may lead to delayed immune recovery and further increases the risk of viral reactivations. Prophylactic infusion of CD45RA-depleted donor memory T lymphocytes (T<sub>M</sub>DLI) has been reported as a strategy to accelerate recovery of T cell immunity after haplo-HCT.</div></div><div><h3>Objectives</h3><div>To evaluate the safety and feasibility of therapeutic T<sub>M</sub>DLI for the treatment of viral infections before immune recovery within 100 days after TCRαβ-depleted haplo-HCT and prophylactic T<sub>M</sub>DLI administered on Day 0.</div></div><div><h3>Study Design</h3><div>A retrospective review of patients who had received therapeutic T<sub>M</sub>DLI for one or more post-transplant viral infection(s) in a tertiary children’s hospital from 2020 to 2023.</div></div><div><h3>Results</h3><div>A total of 46 therapeutic T<sub>M</sub>DLIs were administered to 24 patients, with the first dose of infusion given between day 12 to 93 after haplo-HCT. CMV reactivation was the most common indication for T<sub>M</sub>DLI (n = 32, 69.6%), and the median time to achieve CMV clearance (defined as first negative viral polymerase chain reaction (PCR) test from the time of first therapeutic T<sub>M</sub>DLI) was 14 days. Other intended-to-treat viral infections or co-infections include ADV (n = 10), EBV (n = 6), BKV (n = 6) and HHV-6 (n = 3). The cumulative incidence of negative viral PCR for all viruses 30 days after the first T<sub>M</sub>DLI treatment was 75% (18/24 patients). All T<sub>M</sub>DLIs were well tolerated, with no de novo or recurrence of acute GVHD thereafter. One patient developed de novo moderate chronic GVHD after T<sub>M</sub>DLI treatment.</div></div><div><h3>Conclusion</h3><div>T<sub>M</sub>DLI was a safe and feasible treatment for viral infections occurring within 100 days after pediatric TCRαβ-depleted haplo-HCT and prophylactic T<sub>M</sub>DLI.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages 156.e1-156.e9"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.10.026
Joseph Pidala , Lynn Onstad , Paul Carpenter , Betty K. Hamilton , Carrie L. Kitko , Mark Juckett , Corey Cutler , Stephanie J. Lee
Late acute and chronic graft-versus-host disease (GVHD) contribute to morbidity and death after allogeneic hematopoietic cell transplantation (HCT). A prior national Chronic GVHD Consortium longitudinal study enrolled patients pre- or early post-HCT and identified the incidence of late acute GVHD, chronic GVHD, and chronic GVHD subtypes of bronchiolitis obliterans syndrome (BOS) and cutaneous sclerosis. We now report 10-yr follow-up from that study in a long-term follow-up analysis (N = 911 subjects). Late acute GVHD occurred in 11% at a median of 5.5 mo. Chronic GVHD in total occurred in 54% with median onset of 7.4 mo. BOS (4% of subjects, median onset 12.6 mo) and cutaneous sclerosis (10% of subjects, median onset of 17.2 mo) were less frequent and had later-onset. The long-term analysis demonstrated additional GVHD events occurring beyond 1 to 2 yr post-HCT. Inter-conversion between GVHD types was common, and notably included new development of BOS and cutaneous sclerosis after initial chronic GVHD presentation without these manifestations. GVHD-free, relapse-free survival (GVHD-DFS, survival without relapse or development of late acute or chronic GVHD) was 22% at 2 yr, 18% at 5 yr, and 15% at 10 yr post-HCT. Non-relapse mortality continued to increase beyond 2 yr, with 10-yr estimates up to 35% (late acute), 31% (chronic GVHD), 62% (BOS), and 36% (cutaneous sclerosis). Durable complete discontinuation of immune suppression was uncommon for all GVHD types. These data suggest that extended surveillance for late acute and chronic GVHD is needed post-HCT due to late occurrences, and that associated mortality is high through 10 yr post-GVHD onset.
{"title":"Longitudinal Study of Late Acute and Chronic Graft-Versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation: A Long-Term Follow-up Study from the Chronic Graft-Versus-Host Disease Consortium","authors":"Joseph Pidala , Lynn Onstad , Paul Carpenter , Betty K. Hamilton , Carrie L. Kitko , Mark Juckett , Corey Cutler , Stephanie J. Lee","doi":"10.1016/j.jtct.2025.10.026","DOIUrl":"10.1016/j.jtct.2025.10.026","url":null,"abstract":"<div><div>Late acute and chronic graft-versus-host disease (GVHD) contribute to morbidity and death after allogeneic hematopoietic cell transplantation (HCT). A prior national Chronic GVHD Consortium longitudinal study enrolled patients pre- or early post-HCT and identified the incidence of late acute GVHD, chronic GVHD, and chronic GVHD subtypes of bronchiolitis obliterans syndrome (BOS) and cutaneous sclerosis. We now report 10-yr follow-up from that study in a long-term follow-up analysis (<em>N</em> = 911 subjects). Late acute GVHD occurred in 11% at a median of 5.5 mo. Chronic GVHD in total occurred in 54% with median onset of 7.4 mo. BOS (4% of subjects, median onset 12.6 mo) and cutaneous sclerosis (10% of subjects, median onset of 17.2 mo) were less frequent and had later-onset. The long-term analysis demonstrated additional GVHD events occurring beyond 1 to 2 yr post-HCT. Inter-conversion between GVHD types was common, and notably included new development of BOS and cutaneous sclerosis after initial chronic GVHD presentation without these manifestations. GVHD-free, relapse-free survival (GVHD-DFS, survival without relapse or development of late acute or chronic GVHD) was 22% at 2 yr, 18% at 5 yr, and 15% at 10 yr post-HCT. Non-relapse mortality continued to increase beyond 2 yr, with 10-yr estimates up to 35% (late acute), 31% (chronic GVHD), 62% (BOS), and 36% (cutaneous sclerosis). Durable complete discontinuation of immune suppression was uncommon for all GVHD types. These data suggest that extended surveillance for late acute and chronic GVHD is needed post-HCT due to late occurrences, and that associated mortality is high through 10 yr post-GVHD onset.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages 205.e1-205.e12"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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