Transplantation and Cellular Therapy最新文献

{"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":"https://doi.org/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 non-relapse mortality (NRM) for the entire cohort were 73%, 60%, 27% and 13% respectively. While 3-year OS (78% vs 70%), EFS (56% vs. 63%) and NRM (10% vs 14%) rates were similar for IDH1mut and IDH2mut patients, relapse incidence was numerically higher in IDH1mut patients (34% vs. 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":"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":"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":"https://doi.org/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":"https://doi.org/10.1016/j.jtct.2025.02.026","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>This study aimed to assess the feasibility and clinical efficacy of UCBT as a potential treatment for pediatric patients with CAEBV.</p><p><strong>Study design: </strong>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.</p><p><strong>Results: </strong>Eight patients, including four males and four females, with a diagnosis age of 4 (1-8) years and a transplantation age of 4 (2-8) years, were enrolled in this study. The mean time from diagnosis to transplantation was 5 (2-14) 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% confidence interval [CI]: 0.529-0.994). The 3-year EFS rate was estimated to be 75% (95% CI: 0.409-0.956). The estimated 3-year GRFS rate was also 75.0% (95% CI: 0.409-0.956).</p><p><strong>Conclusions: </strong>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":"https://doi.org/10.1016/j.jtct.2025.02.023","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>Characterize the impact of pomalidomide on motor and functional outcomes in patients with cGVHD.</p><p><strong>Study design: </strong>Thirty-four adult patients with cGVHD were enrolled in a randomized and unblinded trial. Pomalidomide was administered orally at two dose levels: low (0.5mg/d) or high (initial 0.5 mg/d, escalating 0.5 mg/d every 2 weeks to a maximum 2mg/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).</p><p><strong>Results: </strong>Compared to baseline, the pooled sample of study participants at 6 months showed improvement in hand skills (MAM, P = 0.01), upper extremity (UE) function (DASH, P = 0.01), and health related quality of life (SF-36 Physical Component Summary score (PCS), P = 0.02). 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.</p><p><strong>Conclusions: </strong>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-Transplant 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":"https://doi.org/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 2-4 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 2-4 aGVHD incidence at 150 days post alloBMT between weekly IS levels &lt;10 ng/mL versus ≥10 ng/mL throughout the four 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 four 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% vs 8%, p&lt;0.001). When evaluating survival outcomes, post-alloBMT week 1 tacrolimus levels ≥10 ng/mL were associated with decreased OS (HR 3.84, 95% CI [1.16-12.67]; p=0.027), but no correlation was seen in RFS (HR 1.62, 95% CI [0.56-4.72]; p=0.377), or GRFS (HR 1.56, 95% CI [0.89-2.74]; p=0.124). Post-alloBMT week 1 sirolimus ≥10 ng/mL levels were associated with decreased OS (HR 2.74, 95% CI [1.37-5.48]; p=0.004) and GRFS (HR 1.93, 95% CI [1.19-3.12]; p=0.007), but not RFS (HR 1.60, 95% CI [0.78-3.30]; p=0.202). 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 levels &lt;10 ng/mL may be optimal when","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}

{"title":"Allogeneic Stem Cell Transplantation in Participants With Hematologic Malignancies Following Pembrolizumab Therapy.","authors":"John Kuruvilla, Philippe Armand, Alex F Herrera, Vincent Ribrag, Catherine Thieblemont, Bastian von Tresckow, Guoqing Wang, Patricia Marinello, Samhita Chakraborty, Robert Orlowski, Pier Luigi Zinzani","doi":"10.1016/j.jtct.2025.02.022","DOIUrl":"https://doi.org/10.1016/j.jtct.2025.02.022","url":null,"abstract":"<p><strong>Background: </strong>The safety and efficacy of allogeneic stem cell transplantation (allo-SCT) following anti-programmed cell death protein 1 (PD-1) therapy in participants with hematologic malignances is of high clinical interest.</p><p><strong>Objective: </strong>To present outcomes in participants enrolled in 4 clinical trials who underwent allo-SCT within 2 years of their last dose of pembrolizumab therapy.</p><p><strong>Study design: </strong>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.</p><p><strong>Results: </strong>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%. 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.</p><p><strong>Conclusions: </strong>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.</p>","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":"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":"Pretransplant Chromosome Genomic Array Testing Improves Prognostication for Myelofibrosis Patients Undergoing Transplantation","authors":"Xiaoyu Qu ,&nbsp;Emily Stevens ,&nbsp;Matthew P. Fitzgibbon ,&nbsp;Lan Beppu ,&nbsp;Tim M. Monahan ,&nbsp;Cecilia Yeung ,&nbsp;Derek L. Stirewalt ,&nbsp;David Wu ,&nbsp;Jerald P. Radich ,&nbsp;H. Joachim Deeg ,&nbsp;Min Fang","doi":"10.1016/j.jtct.2024.12.018","DOIUrl":"10.1016/j.jtct.2024.12.018","url":null,"abstract":"<div><h3>Background</h3><div>Despite its known superior diagnostic yield for chromosomal anomalies compared with karyotype and fluorescence in situ hybridization (FISH) studies, chromosome genomic array testing (CGAT) is not used as a routine clinical test for myelofibrosis. Although many prognostic systems exist that risk stratify patients at diagnosis, limited tools are available to prognosticate transplant outcome.</div></div><div><h3>Objective</h3><div>The current study aimed at testing whether CGAT results obtained before transplantation improves prognosis of post-transplant outcome in patients with myelofibrosis compared with current risk categorization systems, for example, DIPSS plus (Dynamic International Prognostic Scoring System).</div></div><div><h3>Study Design</h3><div>We studied patients with myelofibrosis who underwent hematopoietic cell transplantation between 2000 and 2017 at our center (N = 44). We assessed the prognostic significance of CGAT, DIPSS plus, and the total count of gene mutations for post-transplant clinical outcomes, including relapse-free survival (RFS), overall survival (OS), and graft-versus-host-disease (GVHD).</div></div><div><h3>Results</h3><div>Abnormal CGAT results were seen in 24 patients (55%), including 18 with copy-neutral loss of heterozygosity (cnLOH, 41%). With a median follow-up of 91 (range 2-258) months starting from the CGAT sample date, RFS was 59% and OS was 68%. The outcome analysis showed significant prognostic implication from CGAT (normal vs. abnormal), specifically for patients with intermediate risk by DIPSS-plus scores and those with 0∼2 mutations. CGAT alone significantly stratified the patients’ RFS outcome (<em>P</em> = .03). The addition of CGAT to DIPSS-plus improved the significance from a <em>P</em> value of .08 to .003, whereas the addition of CGAT to mutation count improved the <em>P</em> value from .02 to .01. The best stratification system for RFS was achieved when CGAT, DIPSS-plus, and mutation count were all considered (<em>P =</em> 1e-08). The current study also confirmed individual anomalies that are prognostically significant, including <em>U2AF1</em> mutation (n = 5, <em>P</em> = .03) and 1q gain (n = 3, <em>P</em> = .01), which were associated with worse RFS. <em>ASXL1</em> mutations (n = 14) appeared to associate with a later onset of chronic GVHD (<em>P</em> =.03).</div></div><div><h3>Conclusion</h3><div>Pretransplant CGAT analysis augments the existing risk stratification tools and may be considered as routine clinical testing for myelofibrosis.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 170.e1-170.e8"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898500","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":"Oxidative Stress Early After Hematopoietic Stem Cell Transplant","authors":"Eleanor Cook ,&nbsp;Lucille Langenberg ,&nbsp;Nathan Luebbering ,&nbsp;Azada Ibrahimova ,&nbsp;Kasiani C. Myers ,&nbsp;Anthony Sabulski ,&nbsp;Christopher Dandoy ,&nbsp;Kelly Lake ,&nbsp;Assem Ziady ,&nbsp;Adam Lane ,&nbsp;Aaron Webster ,&nbsp;Sheyar Abdullah ,&nbsp;Sonata Jodele ,&nbsp;Stella M. Davies","doi":"10.1016/j.jtct.2025.01.880","DOIUrl":"10.1016/j.jtct.2025.01.880","url":null,"abstract":"<div><div>HSCT conditioning regimens cause massive lysis of hematopoietic cells with release of toxic intracellular molecules into the circulation. To describe the response to oxidative stress early after hemopoietic stem cell transplantation (HSCT) and assess the association of early oxidative stress with later transplant outcomes. Key components of in the body's physiological response to oxidative stress were studied in a cohort of 122 consecutive pediatric allogeneic HSCT recipients. Glutathione reductase (GSR), glutathione peroxidase (GPX) and glutathione synthetase protein expression was measured using ELISA and reduced and oxidized glutathione (GSH and GSSG) levels were quantified using mass spectrometry. GSR is an inducible enzyme which catalyzes the regeneration of reduced glutathione (GSH). Levels of GSR increased by more than 5-fold between start of conditioning chemotherapy and day 0 (median 87ng/mL to 459ng/mL, <em>P &lt; .</em>0001). GPX catalyzes removal of toxic reactive oxygen species (ROS) by oxidation of GSH. GPX4 levels fell briskly by day 0 (median 20.3 ng/mL prior to HSCT to 7.4ng/mL at day 0, <em>P &lt; .</em>0001), likely indicating consumption of the enzyme as cell lysis and subsequent oxidative stress occurred. Levels of the antioxidant substrate reduced glutathione stayed stable from pre-HSCT through day 14, likely maintained by increased glutathione synthesis by the enzyme glutathione synthetase, whose median levels increased from 38.8ng/mL before conditioning to 54ng/mL at day 21 (<em>P = .</em>02). GSR levels were associated with patient outcomes. Median GSR levels were significantly elevated through days 0-21 in those who died in the first year after HSCT compared to those who survived. Similarly, patients who developed high risk transplant-associated thrombotic microangiopathy (TA-TMA) and grade 2 and above graft versus host disease (GVHD) also had significantly higher GSR levels early after HSCT. Our data suggest that the body is for the most part able to mount a brisk and effective response to the oxidative stress associated with lysis of the hematopoietic cell system before HSCT. Our data also suggest that early events in the first 21 days of HSCT may set the scene for later clinical events in the first year after HSCT. It is plausible that patients who are unable to effectively overcome this early period of significant oxidative stress may have increased endothelial injury and activation of complement. Potential therapeutics to augment and optimize the body's response to oxidative stress may improve outcomes.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 135.e1-135.e10"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012402","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 Outcomes of Early WT1 mRNA Reduction After Remission Induction in Newly Diagnosed Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation","authors":"Takafumi Tsushima,&nbsp;Chiharu Kimeda,&nbsp;Natsumi Yoda,&nbsp;Kosuke Matsuo,&nbsp;Kazusuke Tanaka,&nbsp;Yasuhito Hatanaka,&nbsp;Rena Matsumoto,&nbsp;Sonoko Shimoji,&nbsp;Yoshikazu Utsu,&nbsp;Shin-Ichi Masuda,&nbsp;Nobuyuki Aotsuka","doi":"10.1016/j.jtct.2024.12.007","DOIUrl":"10.1016/j.jtct.2024.12.007","url":null,"abstract":"<div><div><em>Wilms’ Tumor 1 (WT1)</em> mRNA is a non-specific marker of measurable residual disease in acute myeloid leukemia (AML). Few studies have focused on the prognostic value of <em>WT1</em> mRNA after initial remission induction of patients with AML who have received transplant treatments. Thus, we retrospectively analyzed the clinical features and prognostic impact of <em>WT1</em> mRNA reduction in patients with AML after initial remission induction at our hospital. We classified the reduction in <em>WT1</em> mRNA levels using logarithmic stratification, with particular focus on the prognostic impact of a 3-log reduction after initial remission induction. This single-center, retrospective, observational study included 71 consecutive patients with AML who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between April 2013 and June 2023 and had <em>WT1</em> mRNA quantified. Patients were grouped based on whether a 3-log reduction was observed during follow-up (N=30) or not (N=41). Among patients who did not achieve a 3-log reduction, European Leukemia Net (ELN) 2022 adverse risk was more common, and fewer patients showed complete hematological responses at transplantation. Patients who reached a 3-log reduction in <em>WT1</em> mRNA after the initial remission induction had significantly longer overall survival (OS) and progression-free survival (PFS) and a lower relapse rate than patients who had not reached a 3-log reduction (2-year OS: 79.7% vs. 27.5%, 2-year PFS: 83.1% vs. 11.7% and 2-year cumulative relapse rate: 5.9% vs. 81.2%). In multivariate analysis, a 3-log reduction in <em>WT1</em> mRNA after initial remission induction and ELN 2022 adverse risk by genetics were significantly associated with OS and PFS. We identified that patients with AML undergoing HSCT with an early and deep 3-log reduction in <em>WT1</em> mRNA after initial remission induction were associated with low relapse rates and better long-term prognosis. Our data highlight the importance of <em>WT1</em> mRNA reduction after initial remission induction.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 168.e1-168.e12"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}