Transplantation and Cellular Therapy最新文献

{"title":"Redefining Engraftment Syndrome after Post-Transplant Cyclophosphamide Allogeneic Hematopoietic Cell Transplantation: A Novel Classification and Impact on Outcomes.","authors":"Rafael Benavente, Juan Montoro, Aitana Balaguer-Roselló, Marta Villalba, Pedro Chorão, Pedro Asensi Cantó, Pablo Granados, Inés Gómez-Seguí, Pilar Solves, Marta Santiago, Brais Lamas, Ana Bataller, Juan Eirís, Alberto Louro, Aurora Perla, Javier de la Rubia, Miguel Á Sanz, Jaime Sanz","doi":"10.1016/j.jtct.2025.06.003","DOIUrl":"https://doi.org/10.1016/j.jtct.2025.06.003","url":null,"abstract":"<p><strong>Background: </strong>Engraftment syndrome (ES) is a non-infectious febrile complication of hematopoietic cell transplantation (HCT), with diagnostic challenges, particularly in the allogeneic setting. The increasing use of post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis highlights the need for a re-examination of ES in this contemporary context.</p><p><strong>Objectives: </strong>To evaluate the incidence and clinical presentation of engraftment syndrome (ES), as well as its impact on transplant outcomes in the era of PTCy-based prophylaxis.</p><p><strong>Study design: </strong>We retrospectively analyzed 552 allogeneic HCT patients receiving PTCy, sirolimus, and mycophenolate mofetil across various donor types. To improve ES diagnosis in this setting, we proposed new criteria in which peri-engraftment fevers (PEFs) (day -4 to day +3 before and after myeloid engraftment) were classified as follows: definite ES (PEF meeting Spitzer, Maiolino, or Grant criteria); probable ES (PEF plus ≥1 additional ES sign); and possible ES (PEF without additional signs).</p><p><strong>Results: </strong>Among the 80 patients (14.5%) who developed PEF, 24 (30%) fulfilled criteria for definite engraftment syndrome (ES), 14 (17.5%) for probable ES, and 42 (52.5%) for possible ES. The 30-day cumulative incidence of overall ES was 15% (95% CI, 12-18), comprising 4.4% (95% CI, 2.9-6.4) for definite ES, 2.6% (95% CI, 1.5-4.2) for probable ES, and 7.8% (95% CI, 5.7-10) for possible ES. In addition to fever, the most frequently observed ES-related symptoms included diarrhea (n = 18), weight gain (n = 14), skin rash (n = 11), hepatic dysfunction (n = 8), and pulmonary infiltrates (n = 7). Risk factors associated with the development of ES were younger age (defined as <40 years), underlying lymphoproliferative neoplasms, haploidentical donor transplantation, and a history of prior cytokine release syndrome. Importantly, ES resolved within 48 hours in 75 of the 80 cases (94%), and no deaths were attributed to PEF or ES episodes. Interestingly, the presence of ES was significantly associated with improved overall survival and event-free survival, potentially reflecting a composite effect of trends toward lower relapse rates and reduced non-relapse mortality in affected patients.</p><p><strong>Conclusions: </strong>ES in PTCy-based allogeneic HCT is frequent but rarely meets traditional criteria, highlighting the potential value of a refined three-category classification. Our findings suggest an unexpected survival benefit, possibly linked to the immunomodulatory effects of PTCy, and underscore the need for further studies to validate this classification and investigate the underlying biological mechanisms.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258917","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":"Malignancies after chimeric antigen receptor T-cell therapy.","authors":"Razan Mohty, Amal Halwani, Talha Badar, Hassan Alkhateeb, Mithun V Shah, Hong Qin, Mohamed A Kharfan-Dabaja","doi":"10.1016/j.jtct.2025.06.001","DOIUrl":"https://doi.org/10.1016/j.jtct.2025.06.001","url":null,"abstract":"<p><p>CAR T-cell therapy is a transformative treatment for relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and multiple myeloma (MM). Recent data brought serious concerns for the development of second primary malignancies (SPM), whether second myeloid neoplasms (SMN) or second non-hematological malignancies (SNHM), or T-cell cancers. Pertaining SPMs after CAR T-cell therapy, studies report an incidence ranging from 2.3% to 11.3% with a higher trend in patients 65 years of age or older, those with higher number of prior therapies, and with longer follow-up. In the case of SMNs, myelodysplastic syndrome is the most common ranging from 0.3% to 4.2%, followed by acute myeloid leukemia in 0.2% to 1.1% of cases. In SNHM, the incidence ranges from 0.6% to 11.6% and does not appear limited to a particular diagnosis or CAR T-cell product. Establishing a causal association between CAR T-cell therapy and development of T-cell malignancies is challenging. Notwithstanding the possibility of underreporting, the incidence of T-cell cancers after commercially approved CAR T-cell therapies ranges from 0.03% to 1%, occurring at 1 to 36 months post- infusion, with only a handful of reports confirming CAR transgene integration. We believe that therapeutic benefits of CAR T-cell therapies in R/R B-cell NHL, B-cell ALL, CLL and MM outweigh their potential risks of developing SPMs and T-cell cancers. More work is needed to help better understand the corresponding contributions of CAR T-cell therapy per se as opposed to other factors including pre-existing somatic or germline mutations, chemotherapy and/or radiotherapy acquired CH, and their ultimate effect on developing SPMs.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249775","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":"Pilot Study of Low-Dose Splenic Irradiation and Transplantation in JAK Inhibitor-Refractory Myelofibrosis With Splenomegaly.","authors":"Kristin Rathje, Nico Gagelmann, Artur Schneider, Johanna Richter, Christina Rautenberg, Catherina Lueck, Christine Wolschke, Hans Christian Reinhardt, Francis Ayuk, Thomas Schroeder, Nicolaus Kröger","doi":"10.1016/j.jtct.2025.05.023","DOIUrl":"10.1016/j.jtct.2025.05.023","url":null,"abstract":"<p><p>Splenomegaly is a hallmark feature of myelofibrosis, driven by extramedullary hematopoiesis due to progressive bone marrow fibrosis. Enlarged spleens cause significant symptoms, impair quality of life, and complicate hematopoietic stem cell transplantation (HSCT) by increasing the risk of delayed engraftment, graft failure, and relapse. While Janus kinase (JAK) inhibitors can reduce spleen size, some patients remain refractory or lose response over time. Splenic irradiation has emerged as an alternative strategy, though optimal protocols and safety profiles remain unclear. In this bicentric observational study, we evaluated the safety and efficacy of a standardized low-dose splenic irradiation protocol administered immediately prior to HSCT in patients with myelofibrosis and refractory splenomegaly. We included 11 patients with primary or secondary myelofibrosis who underwent first HSCT from 2020 to 2025. Patients received standardized low-dose splenic irradiation of 3.0 Gy fractionated into three or six daily sessions using volumetric modulated arc therapy (VMAT), administered either shortly before or partially concurrently with the conditioning regimen. We systematically monitored spleen size, hematologic parameters, molecular clearance of driver mutations, donor chimerism, and transplant-related outcomes. Median spleen size before irradiation was 25 cm, which significantly decreased to 22 cm postirradiation (median reduction: 3 cm) and further reduced to 17.7 cm by engraftment (median additional reduction: 4.3 cm). All patients achieved neutrophil engraftment within a median of 12 days and platelet engraftment was achieved by 82% within 14 days. Isolated hyperbilirubinemia occurred transiently in 82% of patients without significant clinical consequences. No occurrences of veno-occlusive disease, thrombotic microangiopathy, or hemorrhagic complications were reported. At days 30 and 100 post-transplant, full donor chimerism was achieved in 91% and 80%, with driver mutation clearance observed in 70% and 80%, respectively. With a median follow-up of 5.5 months, overall survival was 91%, with two cases of early relapse and two instances of acute graft-versus-host disease. Two patients experienced poor graft function, one requiring stem cell boost. Our study demonstrates that low-dose splenic irradiation prior to HSCT is an effective and safe adjunct treatment for managing splenomegaly in myelofibrosis patients. The standardized protocol resulted in substantial spleen size reduction, favorable engraftment kinetics, and acceptable toxicity profiles. These promising outcomes highlight splenic irradiation as a viable, less invasive alternative to splenectomy, warranting further exploration in larger prospective trials to refine protocols and confirm long-term benefits.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226818","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":"Tisagenlecleucel in Practice: Real-World Lessons in Pediatric and Young Adult B-ALL","authors":"Kevin O. McNerney ,&nbsp;Liora M. Schultz","doi":"10.1016/j.jtct.2025.02.016","DOIUrl":"10.1016/j.jtct.2025.02.016","url":null,"abstract":"<div><div>The global multi-institutional registration trial (ELIANA) of CD19.41BB.zeta chimeric antigen receptor (CAR) T cell therapy forged the path to the first FDA-approved CAR T product, tisagenlecleucel. Since its approval, extensive post-market experience with CAR T cells in children and young adults has amassed, allowing several multi-institutional efforts to leverage real-world data. Real-world data has validated clinical trial findings and provided insights into CAR T-cell use in patient groups not included in early clinical trials, such as children &lt;3 years, patients with active CNS and isolated extramedullary disease, and patients treated in first relapse. Data from multi-centered consortia has also identified cohorts who experienced inferior outcomes post-tisagenlecleucel, informing high-risk groups for whom further treatment optimization is needed, and delineating treatment variables, such as CAR T cell dose and lymphodepleting chemotherapy pharmacokinetics, that impact outcomes. In this early stage of CAR T-cell therapies, real-world experience provides an increasingly rich data reservoir and an invaluable resource to investigate and address clinical gaps for CAR T recipients. This review highlights key insights gained from post-market studies that have informed clinical use of CAR T-cell therapy for children and young adults with B-ALL.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 6","pages":"Pages 351.e1-351.e11"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493845","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 ,&nbsp;Léa Aguilhon ,&nbsp;Vincent Alcazer ,&nbsp;Mathilde Carrer ,&nbsp;Priscille Franc ,&nbsp;Caroline Dupre ,&nbsp;Guy Oriol ,&nbsp;Hélène Labussière-Wallet ,&nbsp;Sophie Ducastelle-Leprêtre ,&nbsp;Fiorenza Barraco ,&nbsp;Marie Balsat ,&nbsp;Gaëlle Fossard ,&nbsp;Florence Ader ,&nbsp;Sophie Trouillet-Assant ,&nbsp;Anne Conrad","doi":"10.1016/j.jtct.2025.03.001","DOIUrl":"10.1016/j.jtct.2025.03.001","url":null,"abstract":"<div><div>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 count measurements. Whole-blood stimulation with TruCulture tubes (Myriad Rbm, Austin, TX, USA) 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 (NanoString Technologies, Seattle, WA, USA) . The temporal follow-up of functional immune profiles was analyzed over time according to demographics, clinical characteristics, and immune cell counts. 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, eg. 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. 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 immune functional assay (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.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 6","pages":"Pages 367-381"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","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":"High Melphalan Exposure Increases the Risk of Graft-Versus-Host Disease in Pediatric Patients Undergoing Alpha-Beta T-Cell Depleted Haploidentical Transplantation","authors":"Christopher C. Dvorak ,&nbsp;Soohee Cho ,&nbsp;Gabriel Salinas Cisneros ,&nbsp;Christine S. Higham ,&nbsp;Julia Chu ,&nbsp;Lena E. Winestone ,&nbsp;William C. Temple ,&nbsp;Sandhya Kharbanda ,&nbsp;Kristin A. Shimano ,&nbsp;Serine Avagyan ,&nbsp;Philip T. Pauerstein ,&nbsp;James N. Huang ,&nbsp;Geoffrey Cheng ,&nbsp;Nahal Lalefar ,&nbsp;Paibel Aguayo-Hiraldo ,&nbsp;Ron J. Keizer ,&nbsp;Michael A. Pulsipher ,&nbsp;Janel R. Long-Boyle","doi":"10.1016/j.jtct.2025.03.020","DOIUrl":"10.1016/j.jtct.2025.03.020","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Melphalan is often used as the backbone agent for conditioning prior to A/B-T-cell depleted (A/B-TCD) hematopoietic cell transplant (HCT) due to lower rates of organ toxicity compared to busulfan or total-body irradiation, albeit with significant mucosal injury. Traditional dosing based on body-surface-area (BSA) may result in non-optimal melphalan exposure among certain patient subsets.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;As mucosal injury is linked to initiation of alloreactivity, we hypothesized that high exposure of melphalan predicted via a pharmacokinetic (PK) model would be associated with an increased risk of acute graft-versus-host disease (aGVHD).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study Design&lt;/h3&gt;&lt;div&gt;We performed an analysis of 85 patients who underwent A/B-TCD haploidentical HCT on 2 prospective trials using melphalan-based conditioning for treatment of malignancy at 3 centers from 2015 to 2024. Most patients (61.2%) received a total dose of melphalan at 140 mg/m&lt;sup&gt;2&lt;/sup&gt; using actual body weight; others received a dose adjusted for obesity or age &lt;2 years. We analyzed outcomes based on whether melphalan exposure was above or below the median exposure for the group.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The 100-day cumulative incidences of engraftment syndrome (ES), grade II-IV aGVHD, and grade III-IV aGVHD were 34.2%, 24.8%, and 17.1%, respectively. The 3-year cumulative incidence of chronic GVHD (cGVHD), non-relapse mortality (NRM), and relapse were 17.5%, 8.7%, 21.8%, respectively. The 3-year cumulative incidence of disease-free survival (DFS) and severe GVHD-relapse-free survival (GRFS) were 71.4% and 55.6%, respectively. ES was significantly associated with the subsequent development of aGVHD, both grade II-IV (41.4% vs. 17.3% in those with and without ES, &lt;em&gt;P =&lt;/em&gt; .01) and grade III-IV (34.5% vs. 8.5% in those with and without ES; &lt;em&gt;P =&lt;/em&gt; .003). Chronic GVHD occurred at significantly higher rates in patients with prior Grade II-IV (66.7% vs. 0% for Grade 0-I; &lt;em&gt;P &lt;&lt;/em&gt; .001) and Grade III-IV aGVHD (75% vs. 4.3% for Grade 0-II; &lt;em&gt;P &lt;&lt;/em&gt; .001). Compared to non-obese patients, the PK model predicted lower melphalan exposure (&lt;em&gt;P =&lt;/em&gt; .02) in obese patients where adjusted ideal body weight was utilized, suggesting overcorrection of the dose. There was no impact of melphalan exposure on immunologic rejection. The median melphalan exposure was 6.81 mg*hr/L (range, 4.4-8.8). Compared to a melphalan exposure ≤6.8 mg*hr/L, a melphalan exposure &gt;6.8 mg*hr/L was associated with a higher incidence of ES (48.8% vs. 19.1%; &lt;em&gt;P =&lt;/em&gt; .005), grade II-IV aGVHD (39.3% vs. 10.1%; &lt;em&gt;P =&lt;/em&gt; .002), and grade III-IV aGVHD (31.5% vs. 2.5%; &lt;em&gt;P &lt;&lt;/em&gt; .001). The 3-year incidence of cGVHD was 27.2% in those with high predicted melphalan exposure compared to 7.4% for low exposure (&lt;em&gt;P =&lt;/em&gt; .03); with no difference in 3-year NRM incidence (9.2% vs. 7.7%; &lt;em&gt;P =&lt;/em&gt; .82) or 3-year relap","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 6","pages":"Pages 384.e1-384.e15"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789094","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":"Non-myeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Myelofibrosis. A Population-Based Study from Eastern Denmark","authors":"Morten Orebo Holmström ,&nbsp;Lia Minculescu ,&nbsp;Katrine Nørgaard ,&nbsp;Brian Thomas Kornblit ,&nbsp;Ida Schjødt ,&nbsp;Marietta Nygaard ,&nbsp;Niels Smedegaard Andersen ,&nbsp;Henrik Sengeløv ,&nbsp;Helle Bruunsgaard ,&nbsp;Søren Lykke Petersen ,&nbsp;Mette Klarskov Andersen ,&nbsp;Lone Smidstrup Friis","doi":"10.1016/j.jtct.2025.03.006","DOIUrl":"10.1016/j.jtct.2025.03.006","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Myeloablative conditioning (MAC) and reduced intensity conditioning (RIC) regimens are both used before allogeneic hematopoietic stem cell transplantation (allo-HCT) for myelofibrosis (MF). The median age of patients with MF treated with allo-HCT is increasing and a high non-relapse mortality (NRM), especially to MAC, has increased utilization of lesser intense non-myeloablative (NMA) regimens. The NMA regimen is used as the standard conditioning regimen before allo-HCT for MF at all transplantation centers in Denmark. We describe the outcomes of a highly homogenously treated, population-derived cohort of patients with MF who received NMA conditioning prior to allo-HCT and identify factors associated to transplantation outcomes. The study is a retrospective cohort study of patients with MF treated with an NMA regimen prior to allo-HCT at Copenhagen University Hospital, Rigshospitalet from 2007 to 2023. Of 70 patients with MF who were treated with allo-HCT for MF from 2007 to 2023, 67 patients received NMA conditioning with fludarabine 90 mg/m&lt;sup&gt;2&lt;/sup&gt; and total body irradiation of 2 to 4 Gray. These 67 patients had a median age of 61.1 years, 22 patients (33%) had a Karnofsky performance status below 90, and 28 patients (44%) had a hematopoietic stem cell transplantation comorbidity index (HCT-CI) above 2. With a median follow-up time of 3.4 years (range, 0.16–15.58 years), 39 patients (58%) were still alive. Eighteen patients (27%) relapsed and of the 28 patients (42%) who died during the study period, 12 (43%) died from relapse and 16 (57%) from NRM. Median time to neutrophil engraftment, transfusion independency, and platelet engraftment was 21 days (range, 11-119 days), 96 days (range, 0-470 days) and 17 days (range, 0-308 days), respectively, with primary graft failure identified in 13 patients (19.7%). Overall survival (OS) after 1, 3, and 5 years was 77%, 68%, and 61%, respectively, whereas the NRM was 15%, 15%, and 21%, respectively. The cumulative incidence of relapse (CIR) was 24% after 1 year, 28% after 3 years, and 28% after 5 years. Multivariable analysis showed that male sex (hazard ratio (HR) = 5.43, &lt;em&gt;P&lt;/em&gt; &lt; .001), graft from unrelated donor (HR = 3.58, &lt;em&gt;P&lt;/em&gt; = .018) and HCT-CI above 2 (HR = 2.5, &lt;em&gt;P&lt;/em&gt; = .025) remained associated to OS, whereas for progression-free survival, only &lt;em&gt;NRAS&lt;/em&gt; mutations remained as an independent factor (HR = 5.88, &lt;em&gt;P&lt;/em&gt; = .013). Both male sex (HR = 8.41, &lt;em&gt;P&lt;/em&gt; = .037) and graft from unrelated donor (HR = 3.15, &lt;em&gt;P&lt;/em&gt; = .043) were associated to NRM in multivariable analysis. Our analysis shows that NMA conditioning in the form of low dose total body irradiation and fludarabine before allo-HCT for MF is feasible. Patients show low 1-year NRM but a relatively high 1-year CIR. Differentiated conditioning with more intensive RIC regiments for younger and fit patients could be considered to reduce the early relapse rate without increasing NRM. In survival ana","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 6","pages":"Pages 365.e1-365.e13"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664632","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":"Simple, Rapid, Reproducible and Biomarker-Validated Clinical Grading System for Murine Models of Xenogeneic Graft-Versus-Host Disease","authors":"Allan Thiolat ,&nbsp;Cécile Pivert ,&nbsp;Romane Bariseel ,&nbsp;Frédéric Charlotte ,&nbsp;Christine Sedlik ,&nbsp;Eliane Piaggio ,&nbsp;Sébastien Maury ,&nbsp;Mathieu Leclerc ,&nbsp;Jimena Tosello Boari ,&nbsp;José L. Cohen ,&nbsp;Caroline Pilon","doi":"10.1016/j.jtct.2025.03.015","DOIUrl":"10.1016/j.jtct.2025.03.015","url":null,"abstract":"<div><div>Experiment models of xenogeneic graft-versus-host disease (xeno-GVHD), in which human immune cells are injected into immunodeficient mice, are increasingly used to study human immune cell behavior in vivo and to test therapeutic approaches. Today, the main, and more commonly accepted clinical parameters used to characterize xeno-GVHD are weight loss and mortality. These criteria do not provide an accurate and subtle assessment of the disease intensity, nor do they reflect the great variability of xeno-GVHD, which depends on the donor. Relying on previous work in which we described an original clinical grading system for assessing GVHD in mice, we propose an adaptation of this system for xeno-GVHD models. This simple, solid, and reproducible scoring system of xeno-GVHD is constituted of the binary (yes or no) evaluation of 4 easy-to-evaluate parameters that reflect the complexity of the disease without the need to sacrifice the mice. This scoring system is consistent with the gold standard histological grading of human GVHD and with numerous biomarkers characteristic of the disease. We propose this new clinical grading system to evaluate and compare the results obtained with a common tool, regardless of the experimenters and laboratories where the experiments would have been carried out and whatever the therapeutic strategy evaluated.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 6","pages":"Pages 355.e1-355.e13"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754515","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":"A Structured Peer Support Intervention for Patients With Hematologic Malignancies Undergoing Hematopoietic Stem Cell Transplantation: Peer Support Interventionists’ Perspectives","authors":"Michelle Guo ,&nbsp;Emma P. Keane ,&nbsp;Michael Baliousis ,&nbsp;Lisa M. Gudenkauf ,&nbsp;Manfred N. Mate-Kole ,&nbsp;Annabella C. Boardman ,&nbsp;Isabella S. Larizza ,&nbsp;M. Tim Song ,&nbsp;Emma D. Wolfe ,&nbsp;Daniel A. Schaefer ,&nbsp;Corey Cutler ,&nbsp;Heather S. Jim ,&nbsp;Stephanie J. Lee ,&nbsp;Areej El-Jawahri ,&nbsp;Hermioni L. Amonoo","doi":"10.1016/j.jtct.2025.03.017","DOIUrl":"10.1016/j.jtct.2025.03.017","url":null,"abstract":"<div><h3>Background</h3><div>Peer support is emerging as an important component of supportive care for patients with hematologic malignancies, but it has not been robustly implemented in patients undergoing hematopoietic stem cell transplantation (HSCT).</div></div><div><h3>Objectives</h3><div>This qualitative study aimed to explore the experiences of peer support interventionists (participants) delivering a structured, 5-session, phone-delivered peer support intervention, the Supporting Transplant Experiences with Peer Program (STEPP) for patients undergoing HSCT.</div></div><div><h3>Methods</h3><div>Adult patients who underwent allogeneic or autologous HSCT for the treatment of a hematologic malignancy within the past 3 years were eligible to volunteer in this study as trained STEPP interventionists. Semi-structured qualitative interviews were conducted to explore participants’ experiences, including their motivations for volunteering, reflections on intervention delivery and on the impact of peer support, and challenges faced while serving in this role. Interviews were deductively analyzed by 2 coders using framework-guided rapid analysis.</div></div><div><h3>Results</h3><div>Twenty STEPP interventionists participated in this study. Participants were 65% men, with a median age of 63.5 years. Most (75%) had undergone allogeneic HSCT. Emerging themes from the qualitative interviews highlighted that participants were motivated to serve as interventionists by a sense of gratitude for their transplant care and a desire to share their transplant experiences with others. The impact of the STEPP intervention on interventionists included opportunities to process their transplant journey while also providing support to their peers. Interventionists reported a preference for free-flowing conversations, which were still guided by the structured manual. Challenges included terminating the interventionist-patient relationship at the conclusion of STEPP.</div></div><div><h3>Conclusion</h3><div>Peer support interventions for patients undergoing HSCT have the potential to enhance well-being and provide meaning for both patients preparing to undergo HSCT and HSCT survivors who serve as interventionists. Large-scale randomized clinical trials are needed to test the efficacy of peer support interventions for improving health-related outcomes among patients undergoing HSCT and HSCT survivors serving as interventionists for these interventions.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 6","pages":"Pages 390.e1-390.e13"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789090","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":"Pediatric Transplant and Cellular Therapy Consortium RESILIENT Conference on Pediatric Chronic Graft-versus-Host Disease Survivorship after Hematopoietic Cell Transplantation: Part II. Organ Dysfunction and Immune Reconstitution Considerations for Children with Chronic Graft-versus-Host Disease after Hematopoietic Cell Transplantation","authors":"Blachy J Dávila Saldaña ,&nbsp;Kirk R Schultz ,&nbsp;Archana Ramgopal ,&nbsp;Julie R. Boiko ,&nbsp;Kristen Beebe ,&nbsp;Paul A. Carpenter ,&nbsp;Sherwin S Chan ,&nbsp;Sophie Paczesny ,&nbsp;Paibel Aguayo-Hiraldo ,&nbsp;Geoffrey D.E. Cuvelier ,&nbsp;Seth J. Rotz ,&nbsp;Christine N. Duncan ,&nbsp;Kirsten M Williams","doi":"10.1016/j.jtct.2025.01.885","DOIUrl":"10.1016/j.jtct.2025.01.885","url":null,"abstract":"<div><div>While highly morbid forms of chronic graft versus host disease (cGVHD) and severe late effects of allogeneic hematopoietic cell transplantation (HCT) can impact children and adults alike, unique considerations arise in pediatric cases regarding diagnosis, monitoring, treatment, and likelihood of resolution. As children can present with atypical features of cGVHD and with more significant disease due to inability to communicate symptoms, they may be at increased risk for highly morbid forms of cGVHD and incur greater subsequent late effects, which may be more pronounced in those with underlying chromosomal breakage syndromes, with higher prevalence in pediatric HCT recipients. The long-term effects of cGVHD and its therapies include impaired immune reconstitution, leading to increased risks of infection and secondary malignant neoplasms. However, children also have the greatest potential for full immune reconstitution, due to thymus recovery that could impact the timing of vaccination with respect to tolerance and restoration of optimal immunity. Developing strategies to mitigate the late effects incurred with, and as a result of, cGVHD is of critical importance. The working group recommends surveillance strategies for late effects in patients with cGVHD, increased utilization of emerging diagnostic tools, integration of monitoring for cGVHD treatment response, and development of new treatments and specifies aims of future research endeavors.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 6","pages":"Pages 347.e1-347.e17"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042252","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}