Transplantation and Cellular Therapy最新文献

{"title":"To Save a Life - If You Save a Life, Then You are Responsible for That Life","authors":"Smita Bhatia","doi":"10.1016/j.jtct.2025.05.010","DOIUrl":"10.1016/j.jtct.2025.05.010","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 6","pages":"Pages 341-344"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212717","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}

{"title":"Immune Reconstitution After Allogeneic Stem Cell Transplantation: Time Alone Does Not Heal All Wounds","authors":"Matthias Eyrich","doi":"10.1016/j.jtct.2025.05.011","DOIUrl":"10.1016/j.jtct.2025.05.011","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 6","pages":"Pages 345-346"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212890","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}

{"title":"Allogeneic Stem Cell Transplantation in Participants With Hematologic Malignancies Following Pembrolizumab Therapy","authors":"John Kuruvilla ,&nbsp;Philippe Armand ,&nbsp;Alex F. Herrera ,&nbsp;Vincent Ribrag ,&nbsp;Catherine Thieblemont ,&nbsp;Bastian von Tresckow ,&nbsp;Guoqing Wang ,&nbsp;Patricia Marinello ,&nbsp;Samhita Chakraborty ,&nbsp;Robert Orlowski ,&nbsp;Pier Luigi Zinzani","doi":"10.1016/j.jtct.2025.02.022","DOIUrl":"10.1016/j.jtct.2025.02.022","url":null,"abstract":"<div><div>The safety and efficacy of allogeneic stem cell transplantation (allo-SCT) following antiprogrammed cell death protein 1 (PD-1) therapy in participants with hematologic malignances is of high clinical interest. The objective of the study is to present outcomes in participants enrolled in 4 clinical trials who underwent allo-SCT within 2 years of their last dose of pembrolizumab therapy. This analysis included participants from the phase 1b KEYNOTE-013 study (n = 20), the phase 2 KEYNOTE-087 study (n = 31), the phase 2 KEYNOTE-170 study (n = 5), and the phase 3 KEYNOTE-204 study (n = 14). Outcomes of interest included acute and chronic graft-versus-host disease (GVHD), progression-free survival (PFS) and overall survival (OS), transplant-related mortality (TRM), and relapse. Of 70 participants included in the analysis, 57 had classical Hodgkin lymphoma (cHL) and the remainder had B-cell non-Hodgkin lymphoma, multiple myeloma, and myelodysplastic syndrome. Overall, 31 participants (44%) were in remission at first allo-SCT. The median duration of treatment with pembrolizumab was 5.3 months (range, 0.7 to 29.6), and the median time from last dose of pembrolizumab to allo-SCT was 4.6 months (range, 1 to 20). The estimated 6-month cumulative incidence of grade II-IV acute GVHD was 41% (95% confidence interval [CI], 30% to 53%); the estimated 6-month cumulative incidence of grade III-IV acute GVHD was 20% (95% CI, 12% to 30%). The estimated 1-year incidence of chronic GVHD was 19% (95% CI, 11% to 29%). After a median follow-up of 40.1 months, both the estimated median PFS and median OS after allo-SCT were not reached; the 40-month PFS rate was 56.8% and the 40-month OS rate was 76.5%. The estimated 40-month cumulative incidence of TRM and relapse was 17% (95% CI, 9% to 27%) and 27% (95% CI, 16% to 38%), respectively. Among participants with cHL (median follow-up, 39.5 months), both the estimated median PFS and median OS after allo-SCT were not reached; the 40-month PFS rate was 59.7% and the 40-month OS rate was 83.4%. The estimated 40-month cumulative incidence of TRM and relapse in participants with cHL was 12% (95% CI, 5% to 23%) and 23% (95% CI, 12% to 36%), respectively. Overall, the incidences of acute and chronic GVHD in this cohort were within the expected ranges. PFS and OS outcomes were favorable, and the rates of TRM and relapse were low. These results support allo-SCT as a useful and feasible salvage option after anti–PD-1 therapy.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 6","pages":"Pages 357.e1-357.e11"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568322","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}

{"title":"Fludarabine Plus Myeloablative Dose of Busulfan Regimen Was Associated with High Nonrelapse Mortality in Allogeneic Hematopoietic Stem Cell Transplantation for Malignant Lymphoma: A Propensity Score-Matched Comparison Study with Fludarabine Plus High-Dose Melphalan","authors":"Akihito Shinohara ,&nbsp;Michiho Shindo ,&nbsp;Satoshi Yamasaki ,&nbsp;Koji Kato ,&nbsp;Satoshi Yoshihara ,&nbsp;Go Yamamoto ,&nbsp;Keisuke Kataoka ,&nbsp;Takashi Ikeda ,&nbsp;Hikaru Kobayashi ,&nbsp;Kentaro Serizawa ,&nbsp;Yasuo Mori ,&nbsp;Nobuyuki Takayama ,&nbsp;Hideyuki Nakazawa ,&nbsp;Ayumu Ito ,&nbsp;Yuta Katayama ,&nbsp;Yoshinobu Kanda ,&nbsp;Makoto Yoshimitsu ,&nbsp;Takahiro Fukuda ,&nbsp;Yoshiko Atsuta ,&nbsp;Eisei Kondo","doi":"10.1016/j.jtct.2025.03.008","DOIUrl":"10.1016/j.jtct.2025.03.008","url":null,"abstract":"<div><div>In recent years, there have been notable advancements in the treatment of malignant lymphoma. However, a certain percentage of patients are unlikely to achieve a cure through chemotherapy alone. Therefore, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a crucial curative treatment for malignant lymphoma. FluBu4, comprising fludarabine (Flu) combined with a myeloablative dose of intravenous busulfan (Bu; 12.8 mg/kg in total), is a widely used conditioning regimen for allo-HSCT, but its usefulness in malignant lymphoma (ML) has not been fully investigated. The objective of this study was to evaluate the efficacy and safety of FluBu4 in allo-HSCT for lymphoma by comparing the outcomes of two conditioning regimens: FluBu4 and FluMel140. We used a Japanese national database from the Transplant Registry Unified Management Program to retrospectively analyze the first allo-HSCT for ML in patients aged ≥16 years. Allo-HSCT cases treated with posttransplant cyclophosphamide were excluded. Two groups, namely FluBu4 and FluMel140 were selected by propensity score matching (PSM) with a case ratio of 1:2. From 921 cases, 113 were selected by PSM for the FluBu4 group and 226 for the FluMel140 group. The median age was 54 (19 to 68) years, the median observation period of survivors was 33.8 months, and 145 (42.7%) had a history of autologous HSCT. There were no significant differences in patients’ backgrounds between the two groups after PSM. Three-year overall survival (OS) was significantly worse for FluBu4 than for FluMel140 (28.0% versus 48.6%; <em>P</em> &lt; .01). The 3-year cumulative relapse rate was comparable for FluBu4 and FluMel140 (40.1% versus 38.5%; <em>P</em> = .65). However, 3-year nonrelapse mortality was significantly higher for FluBu4 than for FluMel140 (35.3% versus 22.5%; <em>P</em> = .02). There was no significant difference between the two treatment groups in the cumulative incidence of acute graft-versus-host disease (aGVHD) at day 100 after allo-HSCT and the 3-year cumulative incidence of chronic GVHD. While the common and major cause of death was the relapse of lymphoma, aGVHD, and noninfectious lung complications were observed more frequently with FluBu4 than with FluMel140. One-year cumulative incidence of interstitial pneumonia was significantly higher for FluBu4 than for FluMel140 (5.3% versus 0.4%; <em>P</em> = .03). FluBu4 use was associated with worse nonrelapse mortality (NRM) and OS in allo-HSCT for ML compared with FluBu4 and FluMel140 adjusted by PSM. Patients treated with FluBu4 had a higher incidence of noninfectious pulmonary complications and an increased number of associated deaths. A higher rate of NRM in the patients treated with FluBu4 was particularly evident in patients aged ≥60, and its use should be avoided in this patient population.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 6","pages":"Pages 382.e1-382.e17"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650972","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}

{"title":"Infectious Enterocolitis in Hematopoietic Cell Transplant with Post-Transplant Cyclophosphamide","authors":"Pedro Chorão ,&nbsp;André Airosa Pardal ,&nbsp;Santiago de Cossio ,&nbsp;Aitana Balaguer-Roselló ,&nbsp;Juan Montoro ,&nbsp;Marta Villalba ,&nbsp;Eva María González ,&nbsp;María Dolores Gómez ,&nbsp;Inés Gómez ,&nbsp;Pilar Solves ,&nbsp;Marta Santiago ,&nbsp;Pedro Asensi ,&nbsp;Pablo Granados ,&nbsp;Alberto Louro ,&nbsp;Paula Rebollar ,&nbsp;Aurora Perla ,&nbsp;Miguel Salavert ,&nbsp;Javier de la Rubia ,&nbsp;Miguel A. Sanz ,&nbsp;Jaime Sanz","doi":"10.1016/j.jtct.2025.02.027","DOIUrl":"10.1016/j.jtct.2025.02.027","url":null,"abstract":"<div><div>Despite the high incidence of diarrhea in hematopoietic cell transplant (HCT) and the frequent involvement of infections, evidence concerning patients receiving post-transplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis in the molecular diagnostic era is limited. This study aimed to evaluate the characteristics, incidence, risk factors, and outcomes impact of infectious enterocolitis in patients with hematologic malignancies undergoing HCT from matched sibling, matched unrelated, and haploidentical donors using PTCy as GVHD prophylaxis. Retrospective analysis of infectious enterocolitis episodes in 399 patients undergoing HCT at a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus, and mycophenolate mofetil was given, irrespective of donor type or conditioning intensity. Levofloxacin was used prophylactically until myeloid engraftment. Infectious enterocolitis episodes were diagnosed by both molecular-based techniques and stool cultures. Infectious enterocolitis affected 21% of patients, with 19% having more than one episode. The median onset and duration was of 83 and 13 days, respectively, 20% were nosocomial and 58% were managed ambulatorily. The 1-year cumulative incidence was 19%, with 39% occurring beyond day 100, and was similar for <em>Clostridioides difficile</em> infection (CDI; 7%)<em>,</em> non-CDI bacterial (8%), and viral enterocolitis (6%), with no differences in clinical features. However, toxin-positive CDI lasted longer (22 days) than toxin-negative cases (10 days, <em>P</em> = .03) Bone marrow HCT significantly increased the risk of overall infectious enterocolitis, while moderate-severe chronic GVHD increased all-cause and viral enterocolitis incidence. Infectious enterocolitis did not significantly impact overall survival, GVHD disease-free relapse-free survival, and non-relapse mortality. Approximately one-fifth of PTCy-based HCT recipients develop infectious enterocolitis in the first year, typically resolving within 2 weeks, with higher incidence in bone marrow recipients and those with moderate-severe chronic GVHD. CDI, non-CDI bacterial, and viral infections had similar incidences and clinical features. While infectious enterocolitis does not significantly impact transplant outcomes, its diagnosis remains challenging.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 6","pages":"Pages 392.e1-392.e11"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606504","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}

{"title":"Efficacy of Pomalidomide on Motor Performance and Functional Abilities in Patients with Steroid Refractory Chronic Graft Versus Host Disease: A Randomized Clinical Study","authors":"Jessica J. Jorgensen ,&nbsp;Galen O. Joe ,&nbsp;Rafael Jiménez-Silva ,&nbsp;Pei-Shu Ho ,&nbsp;Tiara Dunigan ,&nbsp;Sandra A. Mitchell ,&nbsp;Steven Z. Pavletic ,&nbsp;Lauren M. Curtis ,&nbsp;Leora E. Comis","doi":"10.1016/j.jtct.2025.02.023","DOIUrl":"10.1016/j.jtct.2025.02.023","url":null,"abstract":"<div><div>Deficits in motor performance and functional abilities represent a severe complication for individuals with steroid refractory chronic graft versus host disease (cGVHD) and is associated with decreased survival and high morbidity. The objective of this study was to characterize the impact of pomalidomide on motor and functional outcomes in patients with cGVHD. Thirty-four adult patients with cGVHD were enrolled in a randomized and unblinded trial. Pomalidomide was administered orally at two dose levels: low (0.5 mg/d) or high (initial 0.5 mg/d, escalating 0.5 mg/d every 2 weeks to a maximum 2 mg/d). Efficacy was assessed primarily by the Activity Card Sort (ACS), 2 Minute Walk Test (2MWT), Medical Outcomes Study Short Form 36 (SF-36), Active Range of Motion (AROM), Disabilities of the Arm, Shoulder, and Hand (DASH), and Manual Abilities Measure 36 (MAM). Compared to baseline, the pooled sample of study participants at 6 months showed improvement in hand skills (MAM, <em>P</em> = .01), upper extremity (UE) function (DASH, <em>P</em> = .01), and health related quality of life (SF-36 Physical Component Summary score (PCS), <em>P</em> = .02). Though no statistically meaningful differences between the two dose groups were found, the low-dose group had greater improvements in AROM, walk distance, UE and hand function, and in the high-demand physical leisure and social subdomains of the ACS as compared to the high-dose group. Responders to pomalidomide performed better than nonresponders on most measures at the 6-month endpoint. The study suggests pomalidomide, at both dose levels, may improve several aspects of motor and functional abilities. However, further study is warranted to determine if the trends found in this study, are sustained over time in larger, and in more diverse cGVHD populations. The findings highlight the potential utility of administering functional and motor tests, such as the ACS, DASH, and MAM, to patients with cGVHD, to fully elucidate the efficacy of treatment options for persons with steroid refractory cGVHD.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 6","pages":"Pages 361.e1-361.e15"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587010","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}

{"title":"Corrigendum to 'Graft-versus-Host Disease Causes Broad Suppression of Hematopoietic Primitive Cells and Blocks Megakaryocyte Differentiation in a Murine Model' Biology of Blood and Marrow Transplantation Therapy 20 (2014) 1290 - 1300.","authors":"Yan Lin, Xiaoxia Hu, Hui Cheng, Yakun Pang, Libing Wang, Lin Zou, Sheng Xu, Xiaomeng Zhuang, Chuanhe Jiang, Weiping Yuan, Tao Cheng, Jianmin Wang","doi":"10.1016/j.jtct.2025.03.016","DOIUrl":"10.1016/j.jtct.2025.03.016","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051019","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}

{"title":"Letermovir Primary and Secondary Prophylaxis in Pediatric Recipients of Allogeneic Haematopoietic Stem Cell Transplant.","authors":"Francesca Vendemini, Paola De Lorenzo, Francesca Romani, Sandro Maria Ivano Malandrin, Marta Verna, Sonia Bonanomi, Maria Grazia Valsecchi, Giovanna Lucchini, Adriana Balduzzi","doi":"10.1016/j.jtct.2025.05.021","DOIUrl":"10.1016/j.jtct.2025.05.021","url":null,"abstract":"<p><strong>Background: </strong>CMV reactivation represents one of the most frequent infectious complications post HSCT. Letermovir is a viral terminate inhibitor which has been approved in adults for the prophylaxis of post HSCT CMV reactivation. Its use in pediatric HSCT recipient was recently approved by US FDA but data on the use of letermovir in children remain limited.</p><p><strong>Objective(s): </strong>We aimed at comparing the incidence of CMV reactivation in a more recent cohort of pediatric HSCT recipients receiving primary or secondary prohylaxis with letermovir with a previous cohort of children receiving no prophylaxis. We analyzed the risk factors for CMV reactivation among IgG seropositive recipients and the role of CMV reactivation on treatment related mortality/overall survival.</p><p><strong>Study design: </strong>This is a single center retrospective study which enrolled all consecutive patients aged <21 years who underwent allogeneic HSCT between 1 January 1, 2014 and October 31, 2023 at the pediatric HSCT Unit of the Fondazione IRCCS San Gerardo dei Tintori in Monza RESULTS: 287 patients who received 308 HSCT were analyzed. Three months cumulative incidence of CMV reactivation was 29.5% (95% CI: 24.3-35) in the standard cohort versus 3.7% (95% CI: 0.3-16.3) in the cohort of patients receiving letermovir as primary prophylaxis (P = .0029). The use of letermovir as well as the use of a HLA-identical donor with no serotherapy, bone marrow as a source of stem cell and the absence of acute GVHD were statistically significant protective factors against CMV reactivation at multivariate analysis. At 3 months after discontinuation of preemptive therapy, the cumulative incidence of CMV reactivation was 0% for the 15 patients receiving letermovir as secondary prophylaxis versus 34.7% (SE 5.8, 95% CI: 23.7-46.0) for the 72 patients not receiving secondary prophylaxis.</p><p><strong>Conclusions: </strong>Letermovir is safe and efficacious in preventing CMV reactivation in pediatric patients undergoing HSCT in both primary and secondary prophylaxis.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175012","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}

{"title":"Choosing Between HLA-Mismatched Unrelated and Haploidentical Donors: Donor Age Considerations.","authors":"Rohtesh S Mehta, Gabrielle Schmidt, Kirsten Williams, Shyam A Patel, Johannes Schetelig, Bipin Savani, Medhat Askar, Effie Petersdorf, Olle Ringden, Christopher G Kanakry, Jennifer A Kanakry, Heather Stefanski, Esteban Arrieta-Bolaños, Brian Betts, Cara Benjamin, Shahinaz Gadalla, Tao Wang, Jennifer Saultz, Stephen Spellman, Najla El Jurdi, Yung-Tsi Bolon, Stephanie J Lee","doi":"10.1016/j.jtct.2025.05.019","DOIUrl":"10.1016/j.jtct.2025.05.019","url":null,"abstract":"<p><p>Haploidentical donors and HLA-mismatched unrelated donors (MMUDs) are increasingly utilized for hematopoietic cell transplantation (HCT), with post-transplantation cyclophosphamide (PTCy) emerging as an effective graft-versus-host disease (GVHD) prophylaxis strategy. Despite the growing use of these donor types, comparative data to guide donor selection remain limited. Donor age is a known predictor of HCT outcomes, yet its specific impact when choosing between haploidentical and MMUD donors with PTCy-based prophylaxis has not been thoroughly explored. This study aimed to evaluate the influence of donor age on HCT outcomes in patients receiving haploidentical or MMUD HCT with PTCy-based GVHD prophylaxis, hypothesizing that younger donors (<30 years) would be associated with improved outcomes compared to older donors (≥30 years) regardless of donor type. We conducted a retrospective analysis of 7116 patients with hematologic malignancies from the Center for International Blood and Marrow Transplant Research database, transplanted between 2013 and 2021. Donors were categorized into four groups: younger haploidentical (<30 years), older haploidentical (≥30 years), younger MMUD (<30 years), and older MMUD (≥30 years). The primary outcome was GVHD-free relapse-free survival (GRFS), defined as the absence of grade III to IV acute GVHD, chronic GVHD requiring systemic immunosuppressive therapy (IST), relapse, or death. Secondary outcomes included overall survival, treatment-related mortality (TRM), relapse, grade III to IV acute GVHD, overall chronic GVHD, and chronic GVHD requiring IST. Comparisons were made between (1) younger MMUD versus older haploidentical and (2) younger haploidentical versus older MMUD groups using multivariable Cox proportional hazards models. In multivariable analysis, the older MMUD group exhibited inferior GRFS (hazard ratio [HR] 1.20; 95% confidence interval [CI], 1.06 to 1.36; P = .003), higher TRM (HR 1.49; 95% CI, 1.13 to 1.96; P = .005), and increased grade III to IV acute GVHD (HR 2.88; 95% CI, 1.43 to 5.80; P = .003) compared to the younger haploidentical group. The younger MMUD group had modest GRFS improvement over the older haploidentical group (HR 0.87; 95% CI, 0.78 to 0.98; P = .02) and significantly reduced risks of grade II to IV acute GVHD (HR 0.67; 95% CI, 0.51 to 0.88; P = .003) and chronic GVHD (HR 0.78; 95% CI, 0.65 to 0.94; P = .009). Younger donor age is associated with superior HCT outcomes, emphasizing the importance of prioritizing donors aged <30 years regardless of donor type when feasible.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151669","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}

{"title":"Feasibility of a Total Body Irradiation-Augmented Reduced-Toxicity Conditioning Regimen with an Antithymocyte Globulin/Post-Transplantation Cyclophosphamide Combination for Haploidentical Donor Transplantation in Adult Acute Lymphoblastic Leukemia.","authors":"Jaehyun Ahn, Daehun Kwag, Gi June Min, Sung-Soo Park, Silvia Park, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Chang-Ki Min, Seok-Goo Cho, Jae-Ho Yoon","doi":"10.1016/j.jtct.2025.05.017","DOIUrl":"10.1016/j.jtct.2025.05.017","url":null,"abstract":"<p><p>Haploidentical donor transplantation (HIDT) with post-transplantation cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis is a promising alternative donor option for adults with high-risk acute lymphoblastic leukemia (ALL). The optimal conditioning regimen and GVHD prophylaxis strategy in this patient population remain unclear, however. We evaluated a newly optimized reduced-toxicity conditioning regimen consisting of fludarabine 150 mg/m², melphalan 100 mg/m², and low-dose (400 cGy) total body irradiation (FMTBI) with GVHD prophylaxis using an antithymocyte globulin (ATG)/PTCy combination in 26 adult patients with ALL undergoing HIDT. We compared the recipients of the new regimen to 52 historical controls who received fludarabine 150 mg/m² plus busulfan 9.6 mg/kg (FB group) with ATG. Key endpoints included disease-free survival (DFS), overall survival (OS), GVHD-and relapse-free survival (GRFS), relapse, nonrelapse mortality (NRM), and post-transplantation immune reconstitution. At 1 year post-transplantation, the FMTBI group had higher DFS (80.4% versus 51.9%; P = .024) and a trend toward improved GRFS (61.0% versus 34.6%; P = .073). Relapse incidence was slightly lower (11.9% versus 32.7%; P = .059) in the FMTBI group, particularly in the central nervous system. The cumulative incidence of moderate to severe chronic GVHD was lower (0.0% versus 11.5%; P = .074) in the FMTBI group. The rates of OS (82.9% versus 78.8%; P = .465) and NRM (7.7% versus 15.4%; P = .342) were similar in the 2 groups. Natural killer/natural killer T cell recovery was transiently delayed at 3 months after the FMTBI regimen but normalized by 6 months. Compared to the historical FB with ATG alone group, our newly optimized FMTBI and ATG/PTCy combination showed improved DFS and relapse control while reducing chronic GVHD in HIDT for adult ALL.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151704","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}