Transplantation and Cellular Therapy最新文献

{"title":"Nephrotoxicity in CAR-T cell therapy.","authors":"Karol Sadowski, Weronika Ploch, Alicja Downar, Wiktoria Giza, Dorota Szcześ, Wioletta Olejarz, Wiesław W Jędrzejczak, Jolanta Malyszko, Grzegorz Basak","doi":"10.1016/j.jtct.2025.03.007","DOIUrl":"https://doi.org/10.1016/j.jtct.2025.03.007","url":null,"abstract":"<p><p>Chimeric antigen receptor-T (CAR-T) cell therapy is a novel therapy for the treatment of different hematological malignancies. Besides its efficiency, CAR-T cell therapy is associated with significant toxicity, primarily manifested as cytokine release syndrome (CRS) and neurotoxicity. However, there are reports that CAR-T cell therapy is also nephrotoxic and this aspect attracted so far less attention. In this review, we focus on the incidence and association between CAR-T cell therapy and kidney injury. Here, we describe risk factors, biomarkers, and potential reasons for acute kidney injury (AKI) and chronic kidney disease (CKD) related to CAR-T cell therapy to shed light on pathomechanisms leading to renal impairment, as well as to the association of kidney failure with other side effects of CAR-T cell therapy. We also review the toxicity of different types of CAR-T cell products, the impact of nephrotoxicity on CAR-T cell therapy efficacy, and the safety of lymphodepletion in patients with baseline AKI or CKD.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664619","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":"Clinical effects of granulocyte colony-stimulating factor administration and the timing of its initiation on allogeneic hematopoietic cell transplantation outcomes for myelodysplastic syndrome.","authors":"Takaaki Konuma, Machiko Fujioka, Kyoko Fuse, Hiroki Hosoi, Yosuke Masamoto, Noriko Doki, Naoyuki Uchida, Masatsugu Tanaka, Masashi Sawa, Tetsuya Nishida, Jun Ishikawa, Noboru Asada, Hirohisa Nakamae, Yuta Hasegawa, Makoto Onizuka, Takeshi Maeda, Takahiro Fukuda, Koji Kawamura, Yoshinobu Kanda, Marie Ohbiki, Yoshiko Atsuta, Hidehiro Itonaga","doi":"10.1016/j.jtct.2025.03.010","DOIUrl":"https://doi.org/10.1016/j.jtct.2025.03.010","url":null,"abstract":"<p><strong>Background: </strong>Granulocyte colony-stimulating factor (G-CSF) accelerates neutrophil recovery after allogeneic hematopoietic cell transplantation (HCT). However, the optimal use of G-CSF and the timing of its initiation after allogeneic HCT for myelodysplastic syndrome (MDS) according to graft type have not been determined.</p><p><strong>Objective: </strong>This retrospective study aimed to investigate the effects of using G-CSF administration and the timing of its initiation on transplant outcomes in adult patients with MDS undergoing allogeneic HCT.</p><p><strong>Study design: </strong>Using Japanese registry data, we retrospectively investigated the effects of G-CSF administration and the timing of its initiation on transplant outcomes among 4,140 adults with MDS after bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT), or single-unit cord blood transplantation (CBT) between 2013 and 2022.</p><p><strong>Results: </strong>Multivariate analysis showed that early (days 0-4) and late (days 5-10) G-CSF administration significantly accelerated neutrophil recovery compared with no G-CSF administration following BMT, PBSCT, and CBT, but there was no benefit of early G-CSF initiation for early neutrophilic recovery regardless of graft type. Late G-CSF initiation was significantly associated with a higher risk of overall chronic GVHD following PBSCT (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.18 to 2.24; P = 0.002) and CBT (HR, 2.09; 95% CI, 1.21 to 3.60; P = 0.007) compared with no G-CSF administration. Late G-CSF initiation significantly improved OS compared with no G-CSF administration only following PBSCT (HR, 0.74; 95% CI, 0.58 to 0.94; P = 0.015). However, G-CSF administration and the timing of its initiation did not affect acute GVHD, relapse, or non-relapse mortality, irrespective of graft type.</p><p><strong>Conclusion: </strong>These results suggest that G-CSF administration significantly accelerated neutrophil recovery after BMT, PBSCT, and CBT, but increased risk of overall chronic GVHD after PBSCT and CBT. However, the effect of early and late G-CSF initiation on transplant outcomes needs further study in adult patients with MDS.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664614","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, Michiho Shindo, Satoshi Yamasaki, Koji Kato, Satoshi Yoshihara, Go Yamamoto, Keisuke Kataoka, Takashi Ikeda, Hikaru Kobayashi, Kentaro Serizawa, Yasuo Mori, Nobuyuki Takayama, Hideyuki Nakazawa, Ayumu Ito, Yuta Katayama, Yoshinobu Kanda, Makoto Yoshimitsu, Takahiro Fukuda, Yoshiko Atsuta, Eisei Kondo","doi":"10.1016/j.jtct.2025.03.008","DOIUrl":"10.1016/j.jtct.2025.03.008","url":null,"abstract":"<p><p>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%; P < .01). The 3-year cumulative relapse rate was comparable for FluBu4 and FluMel140 (40.1% versus 38.5%; P = .65). However, 3-year nonrelapse mortality was significantly higher for FluBu4 than for FluMel140 (35.3% versus 22.5%; P = .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%; P = .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.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-15","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, André Airosa Pardal, Santiago de Cossio, Aitana Balaguer-Roselló, Juan Montoro, Marta Villalba, Eva María González, María Dolores Gómez, Inés Gómez, Pilar Solves, Marta Santiago, Pedro Asensi, Pablo Granados, Alberto Louro, Paula Rebollar, Aurora Perla, Miguel Salavert, Javier de la Rubia, Miguel A Sanz, Jaime Sanz","doi":"10.1016/j.jtct.2025.02.027","DOIUrl":"10.1016/j.jtct.2025.02.027","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Despite the high incidence of diarrhea in hematopoietic cell transplant (HCT) recipients, data on infectious enterocolitis with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis remain limited. Evaluate the characteristics, incidence, risk factors, and impact on outcomes 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. 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 a median onset and duration of 83 and 13 days, respectively, 20% were nosocomial and 58% were managed ambulatorily. The 1-year cumulative incidence was 19% and was similar for Clostridioides difficile infection (CDI; 7%), non-CDI bacterial (8%), and viral enterocolitis (6%), with no differences in clinical features. Bone marrow HCT significantly increased the risk of overall infectious enterocolitis, while moderate-severe chronic GVHD increased all-cause and viral enterocolitis incidence. Finally, infectious enterocolitis did not significantly impact overall survival, GVHD disease-free relapse-free survival, and non-relapse mortality. Our findings suggest approximately one-fifth of PTCy-based HCT recipients develop infectious enterocolitis in the first year, typically resolving within 2 weeks, while not impacting HCT outcomes. The incidence is higher among bone marrow recipients and moderate-severe chronic GVHD. EXTENDED ABSTRACT: 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 ","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-09","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":"Temporal evolution of functional immune reconstitution after allogeneic HSCT.","authors":"William Mouton, Léa Aguilhon, Vincent Alcazer, Mathilde Carrer, Priscille Franc, Caroline Dupre, Guy Oriol, Hélène Labussière-Wallet, Sophie Ducastelle-Leprêtre, Fiorenza Barraco, Marie Balsat, Gaëlle Fossard, Florence Ader, Sophie Trouillet-Assant, Anne Conrad","doi":"10.1016/j.jtct.2025.03.001","DOIUrl":"https://doi.org/10.1016/j.jtct.2025.03.001","url":null,"abstract":"<p><strong>Background: </strong>Immune reconstitution (IR) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently monitored by measuring the absolute number of immune effectors. However, this approach does not capture functional immune capacities. In this study, we aimed to evaluate the temporal evolution of functional IR alongside traditional immune cell counts measurements.</p><p><strong>Methods: </strong>Whole-blood stimulation with TruCulture® tubes containing lipopolysaccharides or Staphylococcal enterotoxin B was performed on 55 allo-HSCT recipients at 6- and 12-months post-transplant, and on 10 healthy volunteers. The expression of 144 immune-related genes was quantified using NanoString® technology. The temporal follow-up of functional immune profiles was analyzed over time according to demographic, clinical characteristics, and immune cell counts.</p><p><strong>Results: </strong>The evaluation of IR in allo-HSCT recipients up to 12-months post-transplant showed a significant discrepancy between quantitative and qualitative assessments. While immune cell counts improved, e.g. the proportion of recipients reaching normal CD4⁺ T-cell values, increasing from 25% to 46%, transcriptomic profiles showed persistent functional alterations. More than 78% of less-induced genes observed at 6-months still exhibited a reduced expression at 12-months post-transplant. Transcriptomic immune profiling divulged diverse functional outcomes linked to clinical characteristics, which were not reflected by cell count assessments alone.</p><p><strong>Conclusions: </strong>Herein, we emphasize that quantitative assessment of immune effectors alone is not informative enough to classify allo-HSCT recipients regarding functional immune capacity. Our findings highlight the value of implementing IFA as an additional tool for a comprehensive understanding of functional IR post-allo-HSCT, which could serve as a straightforward and efficient method for enabling personalized post-transplant management.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587141","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":"Outcome of Patients With IDH-Mutated AML Following Allogeneic Stem Cell Transplantation-A Retrospective Analysis on Behalf of the German Registry for Hematopoietic Stem Cell Transplantation and Cell Therapy, DRST.","authors":"Thomas Schroeder, Sarah Flossdorf, Claudia Schuh, Caroline Pabst, Michael Stadler, Johannes Schetelig, Claudia Wehr, Matthias Stelljes, Elisa Sala, Andreas Burchert, Julia Winkler, H Christian Reinhardt, Nicolaus Kröger, Katharina Fleischhauer, Christina Rautenberg","doi":"10.1016/j.jtct.2025.02.018","DOIUrl":"10.1016/j.jtct.2025.02.018","url":null,"abstract":"<p><p>Mutations in isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) are found in 15% to 20% of patients with acute myeloid leukemia (AML). IDH inhibitors have been introduced as targeted treatment and are currently under investigation as maintenance therapy after allogeneic transplantation (allo-SCT). Since reports about the outcome of IDH1- and IDH2-mutated (IDHmut) AML after allo-SCT are limited, we retrospectively analyzed 356 IDH-mutated AML patients (IDH1 40%, IDH2 60%). Ten patients (4%) had received an IDH inhibitor prior transplantation, but none had received maintenance with IDH inhibitors. After a median follow-up of 24 months 3-year probabilities of overall (OS) and event-free (EFS) survival, relapse and nonrelapse mortality (NRM) for the entire cohort were 73%, 60%, 27% and 13% respectively. While 3-year OS (78% versus 70%), EFS (56% versus 63%) and NRM (10% versus 14%) rates were similar for IDH1mut and IDH2mut patients, relapse incidence was numerically higher in IDH1mut patients (34% versus 24%) and landmark analysis suggested a continuous rise of relapse incidence preferentially in IDH1mut AML also beyond the first year. Concordantly, IDH2 mutation was associated with superior EFS and by trend with lower relapse incidence. The strongest risk factor for adverse outcomes, however, was AML not in CR. This analysis provides benchmarks for interpretation of results emerging from post-transplant maintenance trials in IDHmut AML and suggest that maintenance strategies may further optimize the promising outcome in this molecularly defined subgroup by reducing relapse risk, especially for patients whose AML is not in remission at time of alloHCT.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587139","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":"Best Practices in Gene Therapy for Sickle Cell Disease and Transfusion-dependent β-Thalassemia.","authors":"Haydar Frangoul, Amanda Stults, Katie Bruce, Jennifer Domm, Clinton Carroll, Shelby Aide, Morgan Duckworth, Misty Evans, Meghann McManus","doi":"10.1016/j.jtct.2025.02.025","DOIUrl":"10.1016/j.jtct.2025.02.025","url":null,"abstract":"<p><p>Sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT) are inherited blood disorders caused by pathogenic variants of the β-globin gene. Historically, allogeneic hematopoietic stem cell transplantation (HSCT) from human leukocyte antigen (HLA)-matched donors has been the only curative option. However, as most patients with SCD or TDT lack HLA-matched donors, autologous or patient-derived HSCT can provide an alternative, transformative option. Gene therapy-based autologous HSCT for the treatment of SCD and TDT entails a complex patient journey and requires the careful implementation of numerous policies and procedures. As gene therapies for these diseases are now commercially available, there is great value in institutions with developed and implemented approaches sharing their best practices. Here, we describe standardized approaches and best practices for the optimized implementation of gene therapies based on our experience in administering this novel class of medicines.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586978","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":"Clinical Outcome of UCBT for Children With CAEBV: A Retrospective Analysis of a Single Center.","authors":"Zhiyu Fu, Biyun Li, Yujie Chai, Xifeng Guo, Xinghua Chen, Lei Zhang, Jiao Chen, Dao Wang","doi":"10.1016/j.jtct.2025.02.026","DOIUrl":"10.1016/j.jtct.2025.02.026","url":null,"abstract":"<p><p>Chronic active Epstein-Barr virus (CAEBV) infection is a severe, life-threatening condition characterized by persistent Epstein-Barr virus (EBV) infection and the clonal expansion of infected T or NK cells, leading to systemic inflammation, organ damage, and complications such as hemophagocytic lymphohistiocytosis and lymphoma. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only effective treatment for eradicating EBV-infected cells; however, donor availability is limited. Umbilical cord blood stem cell transplantation (UCBT) is a promising alternative owing to its rapid availability and lower complication risk. However, there are fewer existing reports on UCBT in pediatric patients with CAEBV. This study aimed to assess the feasibility and clinical efficacy of UCBT as a potential treatment for pediatric patients with CAEBV. We investigated children with CAEBV who did not have matched donors and underwent UCBT in the First Affiliated Hospital of Zhengzhou University and Zhengzhou People's Hospital, China, between 2016 and 2022. We retrospectively analyzed the clinical characteristics, pretreatment regimens, transplantation-related complications, and clinical outcomes of this group of cases to explore the efficacy of UCBT in CAEBV treatment in children. Eight patients, including four males and four females, with a diagnosis age of 4 (1 to 8) years and a transplantation age of 4 (2-8) years, were enrolled in this study. The mean time from diagnosis to transplantation was 5 (2 to 14) months. The mean follow-up period for surviving patients was 49.75±29.66 months, with a maximum follow-up of 101.0 months. All eight patients exhibited successful engraftment. Acute GVHD was observed in six patients, while chronic GVHD was observed in only one patient, with the case being relatively mild. 2 patients developed CMV reactivation. EBV reactivation and post-transplant lymphoproliferative disease (PTLD) were not observed. Case 4 experienced relapse 10 months post-UCBT and achieved survival following a subsequent haplo-identical HSCT from her father. Case 8 succumbed to thrombotic microangiopathy (TMA) on post-transplant day 50. By the end of the follow-up, the 3-year overall survival rate (OS) was estimated to be 87.5% (95% CI: 0.529 to 0.994). The 3-year EFS rate was estimated to be 75% (95% CI: 0.409 to 0.956). The estimated 3-year GRFS rate was also 75.0% (95% CI: 0.409-0.956). UCBT emerges as a safe and effective treatment for CAEBV in children, serving as a viable alternative for patients without matched donors or emergency transplantation.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586981","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, Galen O Joe, Rafael Jiménez-Silva, Pei-Shu Ho, Tiara Dunigan, Sandra A Mitchell, Steven Z Pavletic, Lauren M Curtis, Leora E Comis","doi":"10.1016/j.jtct.2025.02.023","DOIUrl":"10.1016/j.jtct.2025.02.023","url":null,"abstract":"<p><p>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. 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, P = .01), upper extremity (UE) function (DASH, P = 0.01), and health related quality of life (SF-36 Physical Component Summary score (PCS), P = .02). Though no statistical 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 high-demand 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.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-05","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":"Evaluation of Immunosuppression Levels and Risk of Graft-Versus-Host Disease in Allogeneic Blood or Marrow Transplantation With Post-Transplantation Cyclophosphamide.","authors":"John J Lee, Haval Norman, Jamie E Ziggas, Javier Bolaños-Meade, Timothy J Porter","doi":"10.1016/j.jtct.2025.02.024","DOIUrl":"10.1016/j.jtct.2025.02.024","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Post-transplantation cyclophosphamide (PTCy) is standard graft-versus-host disease (GVHD) prophylaxis for allogeneic blood or marrow transplantation (alloBMT), although optimal therapeutic levels of immunosuppression (IS) therapy combined with PTCy remain contested. Previously, with tacrolimus and methotrexate GVHD prophylaxis, week 1 tacrolimus levels &gt;12 ng/mL were associated with a decreased incidence of grade 2 to 4 acute GVHD (aGVHD). We evaluated if associations between aGVHD and early IS levels were observed amongst patients receiving PTCy. This retrospective single-center study consisted of 349 patients who received PTCy and mycophenolate mofetil, with either tacrolimus (n = 185) or sirolimus (n = 164) from September 1, 2017, to September 30, 2019. The median age of patients receiving tacrolimus and sirolimus were 58 and 54 years, respectively. The primary diagnosed diseases for both cohorts were acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, and lymphoma. While most patients receiving tacrolimus were bone marrow graft sourced (78.4%), the majority of patients receiving sirolimus were peripheral blood sourced (80.5%). All patients were transplanted with FluCyTBI as the conditioning regimen. The primary outcome was grade 2 to 4 aGVHD incidence at 150 days post alloBMT between weekly IS levels &lt;10 ng/mL versus ≥10 ng/mL throughout the 4 weeks post-alloBMT. Secondary endpoints included moderate to severe chronic GVHD (cGVHD) incidence, median overall survival (OS), relapse-free survival (RFS), and GVHD-free relapse-free survival (GRFS) at 2 years and the correlation between weekly IS levels &lt;10 ng/mL versus ≥10 ng/mL throughout 4 weeks post-alloBMT. Patients receiving tacrolimus were compared to others in the tacrolimus cohort, and similarly for sirolimus. No correlation was found between IS levels at any individual week and cumulative aGVHD incidence for either tacrolimus or sirolimus. In the sirolimus cohort, no correlation for moderate to severe cGVHD was observed. However, at week 4, patients in the tacrolimus cohort with levels ≥10 ng/mL experienced significantly higher incidence of moderate to severe chronic GVHD than patients with weekly levels &lt;10 ng/mL (20% versus 8%, P &lt; .001). When evaluating survival outcomes, post-alloBMT week 1 tacrolimus levels ≥10 ng/mL were associated with decreased OS (HR 3.84, 95% CI [1.16 to 12.67]; P = .027), but no correlation was seen in RFS (HR 1.62, 95% CI [0.56 to 4.72]; P = .377), or GRFS (HR 1.56, 95% CI [0.89 to 2.74]; P = .124). Post-alloBMT week 1 sirolimus ≥10 ng/mL levels were associated with decreased OS (HR 2.74, 95% CI [1.37 to 5.48]; P = .004) and GRFS (HR 1.93, 95% CI [1.19 to 3.12]; P = .007), but not RFS (HR 1.60, 95% CI [0.78 to 3.30]; P = .202). Overall, early IS levels in patients receiving PTCy-based GVHD prophylaxis did not correlate with aGVHD incidence, although IS levels ≥10 ng/mL were associated with compromised outcomes. Targeting IS lev","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568325","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}