Transplantation and Cellular Therapy最新文献

{"title":"Phototherapy for the Treatment of Acute and Chronic Cutaneous Graft versus Host Disease.","authors":"Ian Nykaza, Anna Chen, Stephanie Gu, Stephen Dusza, Brian Shaffer, Esperanza Papadopoulos, Doris M Ponce, Andrew C Harris, Alina Markova","doi":"10.1016/j.jtct.2026.10.028","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.10.028","url":null,"abstract":"<p><strong>Background: </strong>Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT) and commonly exhibits cutaneous involvement. Topical and systemic therapies are frequently utilized to treat cutaneous GVHD, however these treatments are often limited by toxicity, incomplete response, and poor tolerability. Phototherapy has shown potential benefit as an adjunct treatment for cutaneous GVHD, although prior research has been limited to small retrospective studies.</p><p><strong>Objective: </strong>Evaluate the efficacy and safety of ultraviolet (UV)-based phototherapy in the treatment of cutaneous acute GVHD (aGVHD) and chronic GVHD (cGVHD).</p><p><strong>Study design: </strong>Retrospective cohort study of allo-HCT recipients with cutaneous GVHD treated with phototherapy at Memorial Sloan Kettering Cancer Center from 2009-2024. Patients received either narrow-band UVB or UVA1 and were followed for response to phototherapy based on NIH scoring criteria, body surface area involvement, and physician notes.</p><p><strong>Results: </strong>Forty-six patients were evaluated, including 25 (54%) with aGVHD and 21 (46%) with cGVHD. Most patients received narrow-band UVB (94%). For aGVHD, complete response (CR) occurred in 48% and partial response (PR) in 44%, with an overall response rate (ORR) of 92%. For patients with cGVHD, CR occurred in 43% and PR in 48%, with an ORR of 91%. Median time to best response was 48 days for acute GVHD and 42 days for chronic GVHD. Systemic treatments, including corticosteroids and ruxolitinib, were commonly tapered during phototherapy. Adverse events occurred in 22% of patients, most commonly burning, with 9% discontinuing due to toxicity. Four patients developed skin cancer during follow-up, however three patients had a prior history of nonmelanoma skin cancer, and the remaining patient received concurrent extracorporeal photopheresis leading up to the diagnosis of melanoma in-situ.</p><p><strong>Conclusions: </strong>Phototherapy is an effective and well-tolerated treatment for cutaneous GVHD, achieving high response rates and facilitating tapering of systemic immunosuppression. Given its favorable safety profile and rapid time to response, phototherapy should be considered as an adjunctive or steroid-sparing option for cutaneous GVHD, particularly in patients with extensive or treatment-refractory disease.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228489","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":"Beta-2 adrenergic receptor in CD8+ T cells inhibits GVHD through transcriptional modulation of differentiation and exhaustion.","authors":"Sayon Basu, Rachel Massalee, Habeebat Aderonke Mustapha, Mohammad Alzubi, Chang-Yong Choi, Xiaoxuan Fan, Xuefang Cao","doi":"10.1016/j.jtct.2026.10.029","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.10.029","url":null,"abstract":"<p><p>Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective therapy for selected hematologic diseases. However, graft-versus-host disease (GVHD) limits broader application of allo-HCT. The catecholaminergic sympathetic nervous system modulates immune cells. Beta-2 adrenergic Receptor (β2AR) acts as an immune checkpoint, yet its role in CD8+ T cells remains poorly understood. We used an MHC-mismatched model of acute GVHD to study how β2AR activity on donor CD8+ T cells affects GVHD severity. Host mice receiving β2AR+/+ (WT) CD8+ T cells demonstrated less severe GVHD, lower inflammatory cytokines in peripheral circulation, decreased donor CD8+ T cell expansion, and reduced central memory formation compared to host mice receiving β2AR-/- (KO) CD8+ T cells. Single cell RNA-seq and flow cytometry analyses revealed that donor-derived KO CD8+ T cells had an increased Tc1/Tc17 signature (T-Bet, IFNγ, TNFα, RORγT, and IL23r), expressed lower levels of Eomes and Gata3, and expressed inhibitory PD1, Tim3, Lag3, and CTLA4 less frequently than β2AR WT counterparts. In addition, host mice receiving KO CD8+ T cells exhibit a stronger graft-versus-lymphoma effect than host mice receiving β2AR WT CD8+ T cells. Together, these results indicate that β2AR activity in donor CD8+ T cells inhibits GVHD through transcriptional modulation of T cell differentiation and exhaustion, including a T-Bet/Eomes and PD1 relevant process.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228497","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":"Application of UCB microtransplantation combined with venetoclax and azacitidine in salvage therapy for R/R MN who are not suitable for intensive chemotherapy: clinical efficacy and analysis of changes in the immune microenvironment.","authors":"Chenxiao Du, Shiqin Luo, Yuhui Zhang, Huiqin Zhang, Guangshuai Teng, Yan Wang, Yanqi Li, Lan Peng, Xiaojing Wei, Weiping Yuan, ErLie Jiang, Bing Chen, Jie Bai","doi":"10.1016/j.jtct.2026.10.023","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.10.023","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224833","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":"Favorable survival for older adults treated with Axi-cel and Tisa-cel CD19 CAR-T therapy for relapsed/refractory DLBCL: a U.S. multicenter comparative analysis.","authors":"Marie Hu, Qing Cao, David L Porter, Stephen J Schuster, Sairah Ahmed, Paolo Strati, Miguel-Angel Perales, Peter A Riedell, Michael R Bishop, Joseph P McGuirk, Richard T Maziarz, Smith Kungwankiattichai, Olalekan O Oluwole, Veronika Bachanova","doi":"10.1016/j.jtct.2026.09.014","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.09.014","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Diffuse large B-cell lymphoma (DLBCL) commonly affects older patients &gt; 65 years old, with chimeric antigen receptor T-cell (CAR-T) therapy becoming an increasingly valuable treatment modality for relapsed/refractory (R/R) disease. Real world data on safety, efficacy, and management practices of CAR-T for older patients are important to inform clinical practice and referral.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To compare efficacy and toxicities of axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) in younger (age &lt;65) and older (age ≥ 65) patients with R/R DLBCL, and to describe clinical management practices for delivery of care to older patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design: &lt;/strong&gt;We conducted a retrospective, multicenter analysis of 351 adult patients with R/R DLBCL using data from the Cell Therapy Consortium registry. Patients who underwent apheresis for commercial axi-cel or tisa-cel products from early 2018 to late 2021 were compared by age: 194 patients &lt; 65 years old and 157 patients ≥ 65 years old. Survival was estimated using the Kaplan-Meier method with 95% confidence intervals and compared using the log-rank test. Univariate and multivariate Cox proportional hazards regression was performed to identify factors associating with progression-free survival (PFS) and overall survival (OS).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;328 patients (93.5%) were infused with CAR-T product. Combining all CAR-T products, younger and older groups yielded similar overall response rates (ORR, 61% vs 64%) and complete response rates (CR, 43% vs 49%). When evaluating only those who received axi-cel (n = 65), the older group had improved ORR (82% vs 65%, p = 0.02) and CR rates (63% vs 47%, p = 0.04) compared to younger patients. Median PFS (4.4 months in younger vs 6.8 months in older, p=0.44) and OS (22 months in younger vs 18 months in older, p=0.85) were similar between the two groups. In this cohort, 70% developed cytokine release syndrome (CRS, 6% grade &gt; 3) with no significant difference by age overall or within same CAR-T product. In total, 71 patients (38%) developed immune effector cell-associated neurotoxicity syndrome (ICANS) with 23% being grade ≥ 3. There was no difference in any grade ICANS between younger and older patients. On multivariate analysis, overall mortality was increased in patients with high IPI (HR 1.71, p &lt; 0.01) and bulky disease (HR 1.96, p &lt; 0.01). Age group or CAR-T product were not associated with PFS or OS at 2 years. Rates of early infection, severe (grade &gt;3) cytopenias at 3 months, and 100-day and 1-year non-relapse mortality (NRM) were also similar between younger and older patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Data from our Cell Therapy Consortium retrospective analysis demonstrate that CAR-T recipients older than 65 yrs experience favorable outcomes and manageable toxicity similar to younger patients. Our results support the practice that age alone should not be a barrie","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224827","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":"Outcomes of Allogeneic Stem Cell Transplantation in a North American Adult T Cell Leukemia/Lymphoma Cohort.","authors":"Trent Peng Wang, Julie Nguyen, Leticia Campoverde, Jeremy Ramdial, Luis Malpica, Matthew Hamby, Stefan Klaus Barta, Nyein Nyein Thaw Dar, Jose Sandoval-Sus, Sunwoo Han, Isildinha M Reis, Juan Carlos Ramos, R Alejandro Sica","doi":"10.1016/j.jtct.2026.10.027","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.10.027","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Adult T-cell leukemia/lymphoma (ATLL) is an and aggressive mature T-cell neoplasm driven by human T-cell leukemia virus type 1 (HTLV-1) with dismal prognosis. North American ATLL (NA-ATLL) disproportionately impacts individuals of Afro-Caribbean and Latin American descent who face significant disparities in identifying conventional 8/8 HLA-matched donors in international registries. While allogeneic hematopoietic cell transplantation (HCT) is established in East Asian cohorts, outcomes data in Western populations remain limited. We aimed to evaluate post-HCT survival, toxicities, and prognostic risk factors in NA-ATLL.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The objective of this study was to evaluate HCT clinical outcomes. Our primary outcome was overall survival (OS), and secondary outcomes included progression-free survival (PFS), non-relapse mortality (NRM), and graft-versus-host disease (GVHD). We tested the hypotheses that alternative donor HCT yields comparable survival to matched donor HCT and assessed variables that may dictate post-transplant survival.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design: &lt;/strong&gt;This was a multicenter retrospective registry study evaluating 46 adult patients with NA-ATLL who underwent allogeneic HCT across participating North American centers. Myeloablative conditioning regimens were myeloablative in 21.7%, and alternative donor HCT (without a matched donor) were used in 54.3%. Survival endpoints (OS, PFS) were estimated using the Kaplan-Meier method and compared via log-rank tests. Cumulative incidences of relapse, NRM, acute GVHD, and chronic GVHD were calculated considering competing risks. Independent prognostic variables were evaluated using Cox multivariable proportional hazards regression analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;There was no significant difference in OS or PFS between those who received matched versus alternative donor HCT (OS p = 0.601, PFS p = 0.376). Patients with acute disease subtype had worse OS compared to lymphomatous (logrank p = 0.043, 3-year OS 22.2% versus 52.3%, respectively). Acute GVHD yielded a 1-year cumulative incidence rate of 45.7% (95%CI; 30.7-59.5%) while that of chronic GVHD was 18.5% (95%CI; 8.5-31.5%). Twenty-seven patients were deceased at time of analysis, primarily due to relapse-related causes in 17 patients. In multivariable analysis, lymphomatous disease subtype (HR 0.3, 95%CI 0.1-0.88, p = 0.027) and Karnofsky performance score of ≥80 (HR 0.26, 95%CI 0.09-0.73, p = 0.01) were significant predictors of OS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This is the largest cohort evaluating HCT outcomes in a NA-ATLL population. Alternative donor HCT may expand access to HCT without an apparent increase in non-relapse mortality in this selected cohort. Clinical acute disease subtype shows inferior outcomes compared to lymphomatous subtype. Baseline performance status is a predictor of improved prognosis post-transplant. These data suggest that fit patients sho","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216093","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":"Does Less Than 100 mg/kg Necessarily Represent Reduced Post-Transplant Cyclophosphamide Exposure?","authors":"Bohour AbdulMajeed, Nahla Shihata, Naif I AlJohani","doi":"10.1016/j.jtct.2026.10.004","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.10.004","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208045","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":"External Validation of the CARE-BMT and Modified CARE-BMT Scores for Cardiac Event Prediction After Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia.","authors":"Arnau Torrent, Enric Cascos, Estefanía Pérez-López, Mónica Baile-González, Carlos Martín Rodríguez, María Jesús Pascual Cascón, Marta Luque, Albert Esquirol, Carmen Martín Calvo, Adolfo Jesús Sáez Marín, Sara Fernández-Luis, Juan José Domínguez-García, Sara Villar Fernández, Lucía García, Ana Pilar González-Rodriguez, Tamara Torrado, Silvia Filaferro, Montserrat Rovira, Manuel Jurado Chacón, María Queralt Salas","doi":"10.1016/j.jtct.2026.10.018","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.10.018","url":null,"abstract":"<p><strong>Background: </strong>Cardiac events after allogeneic hematopoietic cell transplantation (allo-HCT) are associated with increased non-relapse mortality (NRM) and inferior survival. The CARE-BMT score predicts cardiovascular events after hematopoietic cell transplantation but does not incorporate post-transplant cyclophosphamide (PTCy). We aimed to externally validate the original CARE-BMT score and a modified version incorporating standard-dose PTCy exposure in patients with acute myeloid leukemia (AML) undergoing allo-HCT.</p><p><strong>Methods: </strong>We conducted a retrospective multicenter study including 809 adults with AML who underwent first allo-HCT across 11 Spanish transplant centers. The original and modified CARE-BMT scores were retrospectively applied. The primary endpoint was the cumulative incidence of post-transplant cardiac events, with relapse and death considered competing risks.</p><p><strong>Results: </strong>Sixty patients developed a cardiac event, corresponding to a cumulative incidence of 6.9% (95% CI, 5.2-8.8). Cardiac events were associated with inferior 3-year overall survival (50.1% vs 62.5%; P = 0.001) and higher 3-year NRM (21.3% vs 6.2%; P = 0.001). Using the original CARE-BMT score, patients were classified as intermediate-risk (n = 246) or high-risk (n = 563), with no low-risk patients identified. Cardiac event incidence was higher in the high-risk group (8.6% vs 3.0%; HR, 2.89; P = 0.005). The modified CARE-BMT score classified patients as low-risk (n = 85), intermediate-risk (n = 558), or high-risk (n = 166), with progressively increasing cardiac event incidence (2.4%, 6.1%, and 11.8%, respectively; P = 0.011). High-risk patients had a significantly greater risk of cardiac events than low-risk patients (HR, 5.37; P = 0.024).</p><p><strong>Conclusions: </strong>In this AML allo-HCT cohort, cardiac events occurred in approximately 7% of patients and were associated with worse survival and increased NRM. Incorporating standard-dose PTCy improved risk stratification, supporting inclusion of transplant-specific variables in cardiovascular risk prediction after allo-HCT.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208043","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":"Comprehensive, simplified, and objective comorbidity assessment before allogeneic hematopoietic cell transplantation: a comparative cohort study.","authors":"Lorenzo Iovino, Ningxin Ma, Chris Davis, Linda Glockling, Ryan Basom, Filippo Milano, Jordan Gauthier, Naveed Ali, Ted Gooley, Marco B Mielcarek, Brenda M Sandmaier, Qian Vicky Wu, Mohamed L Sorror","doi":"10.1016/j.jtct.2026.10.022","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.10.022","url":null,"abstract":"<p><strong>Background: </strong>Pretransplant comorbidity assessment informs risk stratification before allogeneic hematopoietic cell transplantation (allo-HCT), but the optimal balance among comprehensiveness, simplicity, and objectivity of the information captured under the available comorbidity indices (CI) remains uncertain.</p><p><strong>Objective(s): </strong>Here, we are comparing the performance of different CIs of assessing pre-HCT comorbidities and predicting outcomes.</p><p><strong>Study design: </strong>We calculated the HCT-CI, the augmented HCT-CI (augHCT-CI), and the recently proposed simplified comorbidity index (SCI) based on a set of fewer comorbidities. We generated a fourth, objective HCT-CI (objHCT-CI), constructed from the measurable components of the augHCT-CI. We analyzed data from 3,473 consecutive single-center allo-HCT recipients transplanted from 2008-2022. We estimated the Harrell's C-index of the four CIs, their time-dependent ROC (Receiver Operating Characteristic) curve, and their ability of stratifying cumulative incidence of non-relapse mortality (NRM) and overall survival (OS).</p><p><strong>Results: </strong>All four indices significantly stratified NRM and OS (P<0.001). C-indices for NRM were 0.600 for HCT-CI, 0.632 for augHCT-CI, 0.628 for SCI, and 0.610 for objHCT-CI; corresponding C-indices for OS were 0.584, 0.612, 0.587, and 0.591. On the question on comprehensiveness versus simplicity, among 951 patients classified as SCI score 0, the augHCT-CI identified additional risk heterogeneity: 1-year NRM was 5.4%, 8.1%, and 10.9% for augHCT-CI scores 0, 1-2, and ≥3, respectively (Gray P=0.025), and OS differed significantly across these groups (P<0.0001).</p><p><strong>Conclusion(s): </strong>Performance of all indices was comparable. SCI offers simplicity, but may lose prognostic granularity among patients classified as lowest risk. Future tools should improve reproducibility and automation without sacrificing clinically meaningful comorbidity information.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149196847","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 Pilot Study of Condensed Busulfan, Melphalan, and Fludarabine Myeloablative Conditioning in Ex Vivo CD34-Selected Allogeneic Hematopoietic Cell Transplantation.","authors":"Natalia Tijaro Ovalle, Maria Bromberg, Roni Tamari, Andrew Lin, Vishwamber Talla, Danielle Lutrario, Molly Hogan, Richard Lin, Esperanza B Papadopoulos, Ann Jakubowski, Doris Ponce, Brian C Shaffer, Gagan Raju, Gunjan L Shah, Sarah Samorodnitsky, Miguel-Angel Perales, Sergio A Giralt, Michael Scordo","doi":"10.1016/j.jtct.2026.10.020","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.10.020","url":null,"abstract":"<p><strong>Background: </strong>Myeloablative conditioning (MAC) with busulfan, melphalan, and fludarabine (Bu/Mel/Flu) given over 8 days in combination with rabbit antithymocyte globulin (ATG) and ex vivo CD34+-selected allogeneic hematopoietic cell transplantation (allo-HCT) leads to favorable disease control and consistently low rates of graft-versus-host disease (GVHD) in fit patients with myeloid malignancies. However, early regimen-related toxicity continues to be a major determinant of treatment tolerability, necessitating further optimization of the MAC regimen without compromising the efficacy of this platform.</p><p><strong>Methods: </strong>We conducted a single-center pilot clinical trial evaluating the use of a condensed 5-day (Bu/Mel/Flu) regimen before ex vivo CD34+-selected allo-HCT. The primary analysis focused on patients with myeloid malignancies. A parallel cohort of patients with multiple myeloma was closed early because of slow accrual and is reported descriptively. The primary endpoint of the study was the incidence of CTCAE v5.0 grade 4 non-hematologic toxicity from the start of conditioning through day +30 post-HCT, assessed against a 20% institutional benchmark derived from prior cohorts treated with the sequential 8-day regimen. Secondary endpoints included overall survival (OS), relapse-free survival (RFS), and rates of non-relapse mortality (NRM), CD4+ T cell immune reconstitution, and GVHD.</p><p><strong>Results: </strong>We enrolled 30 participants in the primary cohort of the study. Median age was 53 years (IQR 40-66), 50% were male. The most common underlying diagnosis was acute myeloid leukemia (AML) in 20 of 30 patients (67%). Two of 30 patients (7%) experienced ≥1 grade 4 toxicity from the start of conditioning until day +30 post-HCT, meeting the protocol-defined primary safety endpoint and remaining below the 20% observed rate with the 8-day regimen. With a median follow up time of 3.8 years (IQR 3.6-4.5), median OS and RFS were not reached. OS was 90% (95% CI 80-100) at 1-year and 80% (95% CI 67-96) at 2-years; RFS was 83% (95% CI 71-98) and 73% (95% CI 59-91); NRM was 6.7% (95% CI 1.1-19) at both timepoints. Median times to neutrophil and platelet engraftment were 10 days (IQR 10-11) and 16 days (IQR 15-19), respectively. The cumulative incidence of grade II-IV acute GVHD was 30%, grade III-IV acute GVHD was 10%, and moderate/severe chronic GVHD was 6.7%. CD4+ immune reconstitution by day +100 was achieved in 73% of evaluable patients.</p><p><strong>Conclusions: </strong>Condensed Bu/Mel/Flu before ex vivo CD34+-selected allo-HCT was feasible and met the prespecified safety endpoint in this pilot study primarily conducted in patients with myeloid malignancies. The condensed 5-day regimen was associated with a comparable toxicity profile to the prior sequential 8-day regimen and with favorable survival outcomes supporting further study of this MAC regimen in the context of ex vivo CD34+ selection.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149196792","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":"Does Lower PTCy Dose Increase GVHD?","authors":"Nihar Desai, Gonzalo Bentolila","doi":"10.1016/j.jtct.2026.10.021","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.10.021","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149196809","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}