Transplantation and Cellular Therapy最新文献

{"title":"Reduced Chimeric Antigen Receptor T Cell Expansion Postinfusion Is Associated with Poor Survival in Patients with Large B Cell Lymphoma after Two or More Therapies","authors":"Edward Abadir ,&nbsp;Rebecca Wayte ,&nbsp;Wenlong Li ,&nbsp;Sachin Gupta ,&nbsp;Shihong Yang ,&nbsp;Elizabeth Reaiche ,&nbsp;Katrina Debosz ,&nbsp;Emily Anderson ,&nbsp;James Favaloro ,&nbsp;Esther Aklilu ,&nbsp;Christina Brown ,&nbsp;Christian Bryant ,&nbsp;Scott Dunkley ,&nbsp;Derek McCulloch ,&nbsp;Stephen Larsen ,&nbsp;John E.J. Rasko ,&nbsp;Vinay Vanguru ,&nbsp;P. Joy Ho","doi":"10.1016/j.jtct.2025.01.001","DOIUrl":"10.1016/j.jtct.2025.01.001","url":null,"abstract":"<div><div>CD19-directed chimeric antigen receptor T cell (CAR-T) therapy is now standard of care for relapsed/refractory large B cell non-Hodgkin lymphoma. Despite good overall response rates, many patients still experience disease progression and therefore it is important to predict those at risk of relapse following CAR-T therapy. We performed a prospective study using a flow cytometry assay at a single treatment center to assess early CAR T cell expansion in vivo 6 to 9 days after CAR T cell infusion. Early CAR T cell expansion was used in conjunction with additional clinical risk factors to identify those at greater risk of relapse or treatment failure. Forty-four patients treated with commercial CD19-directed CAR-T therapy were included in the study, with a median follow-up of 306 days. CAR T cell expansion of &gt;30 cells/μL was associated with a lower risk of disease progression or death (hazard ratio, 0.34; <em>P</em> = .048), but did not correlate with the risk of death alone. Patients who had poor early CAR T cell expansion (&lt;30 cells/μL) in addition to high lactate dehydrogenase (LDH) had significantly lower median progression-free survival and overall survival. High LDH level alone was not a statistically significant risk factor for death or disease progression, and thus the interaction between CAR T cell expansion and this clinical risk factor may be important in predicting response. The mean CAR T cell count was higher in patients with grade 2 to 4 cytokine release syndrome (CRS) compared to those with grade 0 to 1 CRS (54.9 cells/μL versus 25.5 cells/μL; <em>P</em> = .01). The methodology of this assay is easily reproducible outside of a clinical trial, allowing for real-life implementation in clinical settings. This study suggests that early assessment of CAR T cell expansion can assist in identifying patients with poor overall survival who may benefit from early intervention or more intensive monitoring.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 159-165"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955613","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":"Early Engraftment and Immune Kinetics Following Allogeneic Transplant Using a Novel Reduced-Toxicity Transplant Strategy in Children/Adolescents with High-Risk Transfusion-Dependent Thalassemia: Early Results of the ThalFAbS Trial","authors":"Enass H Raffa ,&nbsp;Taylor M Harris ,&nbsp;Chane Choed-Amphai ,&nbsp;Melanie Kirby-Allen ,&nbsp;Isaac Odame ,&nbsp;Muhammad Ali ,&nbsp;Joerg Krueger ,&nbsp;Karin G Hermans ,&nbsp;Soumitra Tole ,&nbsp;Jennifer Seelisch ,&nbsp;Robert J Klaassen ,&nbsp;Lesleigh Abbott ,&nbsp;Yogi Raj Chopra ,&nbsp;Donna A Wall ,&nbsp;Kuang-Yueh Chiang","doi":"10.1016/j.jtct.2024.12.016","DOIUrl":"10.1016/j.jtct.2024.12.016","url":null,"abstract":"<div><div>Allogeneic hematopoietic stem cell transplantation is challenging for patients with transfusion-dependent thalassemia who have experienced iron overload and received chronic transfusion support. A transplantation strategy including a reduced-intensity preparative regimen and tailored immunosuppression to support donor engraftment and prevent graft-versus-host disease (GVHD) was developed for this population. The combination of a pretransplantation immunosuppression phase with reduced dosing of fludarabine/prednisone, a treosulfan-based preparative regimen with reduced cyclophosphamide dosing, and introduction of a calcineurin/methotrexate-free GVHD prophylaxis/engraftment supporting regimen with abatacept/sirolimus/antithymocyte globulin was tested. In the ThalFAbS trial, a prospective pilot trial (ClinicalTrials.gov NCT05426252) of a transplantation strategy designed for higher-risk patients with transfusion-dependent thalassemia, 12 pediatric patients (4 with alpha thalassemia, 8 with beta thalassemia) were treated with this strategy. Descriptive statistics were used to characterize transplantation outcomes and immune recovery. With a median follow-up of 12 months (range, 4 to 26 months) post-transplantation, all 12 patients had prompt and durable trilineage donor engraftment with low transplantation-related morbidity and acute GVHD and are alive without transfusion support at the time of this report. GVHD was limited to 1 patient with skin-only grade II acute GVHD and 3 patients with limited oral chronic GVHD. Early hematologic and immunologic recovery was achieved, with low rates of transfusion support and infection. Neutrophil recovery occurred at a median of 18 days (range, 15 to 24 days), and platelet recovery occurred at a median of 18 days (range, 12 to 36 days). No patients experienced veno-occlusive disease, transplantation-associated thrombotic microangiopathy, or sepsis. This platform was sufficient to support haploidentical donor transplantation in 2 patients. The ThalFAbS approach is tailored to meet the unique needs of transfusion-dependent thalassemia patients. Delivery of this novel regimen is feasible, and it shows excellent early engraftment and transplantation outcomes. Further follow-up of this cohort and expansion of patient numbers is needed before the findings can be generalized, but early experience is promising.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 180.e1-180.e12"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898499","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 Standard-Risk Multiple Myeloma Patients Who Undergo Upfront Autologous Hematopoietic Stem Cell Transplantation","authors":"Oren Pasvolsky ,&nbsp;Curtis Marcoux ,&nbsp;Zhongya Wang ,&nbsp;Denái R. Milton ,&nbsp;Babar Pal ,&nbsp;Mark R. Tanner ,&nbsp;Qaiser Bashir ,&nbsp;Samer Srour ,&nbsp;Neeraj Saini ,&nbsp;Paul Lin ,&nbsp;Jeremy Ramdial ,&nbsp;Yago Nieto ,&nbsp;Guilin Tang ,&nbsp;Naureen Syed ,&nbsp;Yosra Aljawai ,&nbsp;Hans C. Lee ,&nbsp;Krina K. Patel ,&nbsp;Melody R. Becnel ,&nbsp;Christine Ye ,&nbsp;Partow Kebriaei ,&nbsp;Muzaffar H. Qazilbash","doi":"10.1016/j.jtct.2024.12.023","DOIUrl":"10.1016/j.jtct.2024.12.023","url":null,"abstract":"<div><div>Patients with multiple myeloma (MM) without high-risk cytogenetic abnormalities are classified as having standard-risk MM (SRMM), and data focusing on their outcomes after autologous hematopoietic stem cell transplantation (autoHCT) are limited. We sought to evaluate survival outcomes for patients with SRMM receiving autoHCT, and to elucidate factors that impact these outcomes. This was a single-center retrospective analysis that included consecutive MM patients who received upfront autoHCT between 2013 and 2021, had available cytogenetic information and had no high-risk chromosomal abnormalities on fluorescence in situ hybridization, defined as t(4;14), t(14;16), del(17p) or 1q21 gain or amplification. A total of 1000 SRMM patients were included, with a median age of 61 years (range 25 to 83), and 61% were male (<em>n</em> = 612). The most common induction regimens were bortezomib/lenalidomide/dexamethasone (VRD; <em>n</em> = 398, 40%) and carfilzomib/lenalidomide/dexamethasone (KRD; <em>n</em> = 212, 21%), and the majority (87%) received single-agent melphalan as conditioning. After induction and before autoHCT, 16% and 57% achieved ≥complete response (CR) and ≥very good partial response (VGPR), respectively. At day 100 post autoHCT, 37% and 77% achieved ≥CR and ≥VGPR, respectively. Sixty-two percent and 89% of patients achieved ≥ CR and ≥VGPR as best response post-transplant. A minimal residual disease (MRD) negative response pre- and post-transplantation was achieved in 43% (401/936) and 64% (199/311) of patients, respectively. After a median follow-up of 42.1 months, the median progression-free survival (PFS) for the entire cohort was 68.3 months (95% CI 60.1 to 72.1), and the median overall survival (OS) was not reached (95% CI 102.3-not reached). The 5-year PFS and OS rates were 55% and 83%, respectively. In multivariable analysis, achieving MRD-negative CR prior to autoHCT (HR 0.65 [95% CI 0.44 to 0.97], <em>P</em> = .033) or as best response (0.52 [0.34 to 0.78], <em>P</em> = .002), and use of post-transplant maintenance (0.69 [0.52 to 0.93], <em>P</em> = .013) and lenalidomide-based combination maintenance (0.68 [0.48 to 0.96], <em>P</em> = .030) were associated with improved PFS, whereas use of an induction regimen other than KRD was associated with worse PFS (1.50 [1.04 to 2.17], <em>P</em> = .031). For OS, post-transplant maintenance (0.48 [0.32 to 0.70], <em>P</em> &lt; .001) was associated with better survival in multivariable analysis, whereas R-ISS stage III, compared with stage I, (2.34 [1.01 to 5.43], <em>P</em> = .047) was associated with worse OS. Patients with SRMM who received upfront autoHCT had a median PFS of &gt;5.5 years, and median OS was not reached. These results highlight the favorable outcomes with upfront autoHCT for patients with SRMM, serving as a benchmark for future therapeutic approaches in this subgroup of MM patients.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 166.e1-166.e9"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923386","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":"Masthead (Purpose and Scope)","authors":"","doi":"10.1016/S2666-6367(25)01026-7","DOIUrl":"10.1016/S2666-6367(25)01026-7","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Page A1"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511129","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":"CAR-T — The Slow and the Spurious","authors":"Vinodh Pillai","doi":"10.1016/j.jtct.2025.02.007","DOIUrl":"10.1016/j.jtct.2025.02.007","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 121-122"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511135","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":"Engraft: A Collaborative Learning Health Network for Enhanced Transplant and Cellular Therapy Outcomes","authors":"Christopher E. Dandoy ,&nbsp;Jeffery J. Auletta ,&nbsp;Priscila Badia ,&nbsp;Alan Bidgoli ,&nbsp;Nancy M. Daraiseh ,&nbsp;Anna M. DeSalvo ,&nbsp;Javier Diaz ,&nbsp;Stella M. Davies ,&nbsp;Kathleen Demmel ,&nbsp;Eleanor Cook ,&nbsp;John A. Craddock ,&nbsp;John Huber ,&nbsp;Megan Sampson ,&nbsp;Taylor J. Fitch ,&nbsp;Karis French ,&nbsp;Sonata Jodele ,&nbsp;Samantha M. Jaglowski ,&nbsp;Malika A. Kapadia ,&nbsp;Nandita Khera ,&nbsp;Georgia R. Kent ,&nbsp;David Hartley","doi":"10.1016/j.jtct.2024.12.017","DOIUrl":"10.1016/j.jtct.2024.12.017","url":null,"abstract":"<div><div>The Engraft Learning Health Network (LHN) aims to improve outcomes for patients undergoing transplant and cellular therapy (TCT) through a collaborative, data-driven approach. Engraft brings together diverse stakeholders, including clinicians, patients, caregivers, and institutions, to standardize best practices and accelerate the dissemination of innovations in TCT care. By establishing a multicenter, real-world clinical registry focused on rapid-cycle quality improvement (QI) and implementation research, Engraft seeks to reduce variability in clinical practice to improve TCT outcomes across centers. Initial efforts have centered on developing QI toolkits, sharing de-identified patient data, and building consensus around best practices to reduce non-relapse mortality and improve survivorship. A distinctive feature of Engraft is its commitment to engaging patients and caregivers as equal partners in the network's direction. This manuscript outlines the network's design, early successes, and future goals.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 123-134"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915658","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":"Donor Type Does Not Impact Late Graft Failure Following Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis","authors":"Cindy Lynn Hickey ,&nbsp;Mei-Jie Zhang ,&nbsp;Mariam Allbee-Johnson ,&nbsp;Rizwan Romee ,&nbsp;Navneet S. Majhail ,&nbsp;Monzr M. Al Malki ,&nbsp;Joseph H. Antin ,&nbsp;Cara L. Benjamin ,&nbsp;Christopher Bredeson ,&nbsp;Saurabh Chhabra ,&nbsp;Michael R. Grunwald ,&nbsp;Yoshihiro Inamoto ,&nbsp;Christopher G. Kanakry ,&nbsp;Filippo Milano ,&nbsp;Robert J. Soiffer ,&nbsp;Scott R. Solomon ,&nbsp;Stephen R. Spellman ,&nbsp;Claudio G. Brunstein ,&nbsp;Corey Cutler","doi":"10.1016/j.jtct.2024.12.021","DOIUrl":"10.1016/j.jtct.2024.12.021","url":null,"abstract":"<div><h3>Background</h3><div>Post-transplant cyclophosphamide (PTCy) is a commonly used graft-vs-host disease (GVHD) prophylaxis, particularly in the setting of haploidentical (haplo) hematopoietic cell transplantation (HCT). The rate of graft failure has been reported to be as high as 12% to 20% in haplo-HCT recipients using PTCy. The objective of this study was to determine whether donor type influenced the risk of late graft failure following reduced-intensity conditioning (RIC) HCT using PTCy-based GVHD prophylaxis.</div></div><div><h3>Study Design</h3><div>A retrospective cohort analysis using the Center for International Blood and Marrow Transplant Research (CIBMTR) database among adult patients who underwent first RIC haplo or 8/8 matched unrelated donor (MUD) HCT between 2011 and 2018 for acute myeloblastic leukemia (AML), acute lymphoblastic leukemia (ALL) or myelodysplastic syndrome (MDS) with PTCy GVHD prophylaxis. The primary outcome was incidence of late graft failure, defined as secondary graft loss in the absence of relapse or poor graft function requiring a cellular therapy intervention.</div></div><div><h3>Results</h3><div>A total of 1336 patients met the eligibility criteria (1151 haplo, 185 MUD). Patients in the MUD group were older (65 vs. 61 years), less ethnically diverse (95% vs. 72% White), received fewer bone marrow grafts (45% vs. 16%), and had younger donors (median age, 28 vs. 37 years old). Conditioning regimens were predominately fludarabine, cyclophosphamide, and total body irradiation (TBI; 87% haplo and 38% MUD). At 2 years, the adjusted probabilities of late graft failure for the haplo group was 6.5% (95% confidence interval [CI], 5.2-8.0) versus 5.9% (95% CI, 2.7%–10.9%) for the MUD group (<em>P</em> = .79). Multivariate analysis for risk factors associated with late graft failure found associations with a diagnosis of MDS (HR, 1.98; 95% CI, 1.22–3.20; <em>P</em> = .005), and earlier year of HCT (2015–2018 vs. 2011–2014; HR, 0.39; 95% CI, 0.24-0.64; <em>P</em> = .0002). A post-hoc sensitivity analysis was performed to evaluate the effect of donor age and use of peripheral blood stem cell (PBSC) grafts. Graft failure did not differ between haplo and MUD HCT (HR, 1.19; <em>P</em> = .67) when adjusted for donor age nor when restricted to PBSC grafts only (HR, 0.85; <em>P</em> = .70).</div></div><div><h3>Conclusion</h3><div>In this registry-based analysis of patients undergoing RIC HCT for AML, ALL, or MDS using GVHD prophylaxis with PTCy, there was no significant difference in late graft failure rates between haplo and MUD donors. Overall rates of late graft failure were high.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 174.e1-174.e12"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928471","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":"Tumor-Infiltrating Lymphocyte Therapy: A New Frontier","authors":"Diane Tseng ,&nbsp;Sylvia Lee","doi":"10.1016/j.jtct.2024.11.014","DOIUrl":"10.1016/j.jtct.2024.11.014","url":null,"abstract":"<div><div>In recent years, the successful use of tumor-infiltrating lymphocyte (TIL) therapy to treat melanoma not only culminated in a landmark Food and Drug Administration approval, but has also fueled the emergence of a new, rapidly growing field in TIL cellular immunotherapy surrounding novel enhancements in TIL design, refined manufacturing strategies to enrich for more potent TIL populations, as well as numerous clinical trials now investigating TIL therapy in additional solid tumor types beyond melanoma. This review provides a summary of the latest advances in TIL therapy and what lies ahead for the field. The first section explores several solid cancers that demonstrate the greatest potential for future indications of TIL therapy. The second section provides insight into the promising innovations for designing the next generation of TIL with greater specificity, persistence, safety, and function.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages S599-S609"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610673","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}

{"title":"T Cell Immune Response to Influenza Vaccination When Administered Prior to and Following Autologous Chimeric Antigen Receptor-Modified T Cell Therapy.","authors":"Hannah Kinoshita, Carla S Walti, Kathleen Webber, Gloria Pezzella, Mariah Jensen-Wachspress, Haili Lang, Kiel Shuey, Jim Boonyaratanakornkit, Steven A Pergam, Helen Y Chu, Catherine M Bollard, Michael D Keller, Joshua A Hill","doi":"10.1016/j.jtct.2025.02.019","DOIUrl":"10.1016/j.jtct.2025.02.019","url":null,"abstract":"<p><p>Chimeric antigen receptor-modified T (CAR-T) cell therapies are gaining wider use in relapsed and refractory malignancies. However, data on vaccination in this population is lacking. We evaluated T cell responses in an established cohort of CAR-T recipients and healthy controls before and after 2019 to 2020 influenza vaccination. Peripheral blood mononuclear cells were isolated from healthy controls and patients who received the 2019 to 2020 influenza vaccine pre- or post-CD19, CD20, or B cell maturation antigen CAR-T. T cells were expanded in vitro for 10 days with peptide libraries for hemagglutinin (HA) and nucleoprotein from the 2019 to 2020 vaccine influenza A strains and analyzed by flow cytometry following interferon-γ/tumor necrosis factor-α (IFNγ/TNFα) intracellular staining. Antibody response was evaluated by a hemagglutination inhibition assay. Twenty-nine participants, including eight immunocompetent adults, seven pre-CAR-T, and 14 post-CAR-T patients, were evaluated. IFNγ⁺/TNFα⁺ T cell responses after influenza vaccination in healthy controls varied with an increased response to HA-Kansas after vaccination in 7/8 individuals. In the pre-CAR-T cohort, there was a rise in CD4+ T cell response to HA-Brisbane in 6/7 patients after vaccination that remained detectable in 3/4 evaluable patients 90 days post-CAR-T. Five of six patients who lacked an antibody response nonetheless demonstrated a T cell response to HA-Brisbane. There was no association between time since CAR-T administration, baseline immunoglobulin G, or absolute lymphocyte count and change in CD4+ T cell IFNγ⁺/TNFα⁺ response pre- to postvaccine for the post-CART cohort. These data demonstrate that cell-mediated immunity to the influenza vaccine can be elicited in patients vaccinated pre-CAR-T and sustained post-CAR-T, filling an important gap from lack of humoral responses.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543350","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":"Incidence, Risk Factors, and Outcomes of BK Hemorrhagic Cystitis in Hematopoietic Stem Cell Transplantation From HLA-Matched and Haploidentical Donors With Post-Transplant Cyclophosphamide","authors":"Pedro Chorão ,&nbsp;Marta Villalba ,&nbsp;Aitana Balaguer-Roselló ,&nbsp;Juan Montoro ,&nbsp;Pablo Granados ,&nbsp;Carmen Gilabert ,&nbsp;Francisca Panadero ,&nbsp;André Airosa Pardal ,&nbsp;Eva María González ,&nbsp;Santiago de Cossio ,&nbsp;Rafael Benavente ,&nbsp;María Dolores Gómez ,&nbsp;Inés Gómez ,&nbsp;Pilar Solves ,&nbsp;Marta Santiago ,&nbsp;Pedro Asensi ,&nbsp;Pilar Lloret ,&nbsp;Juan Eiris ,&nbsp;David Martínez ,&nbsp;Alberto Louro ,&nbsp;Jaime Sanz","doi":"10.1016/j.jtct.2024.12.006","DOIUrl":"10.1016/j.jtct.2024.12.006","url":null,"abstract":"<div><div>BK hemorrhagic cystitis (BK-HC) is a common complication following hematopoietic stem cell transplantation (HSCT), particularly when posttransplant cyclophosphamide (PTCy) is used as graft-versus-host disease (GVHD) prophylaxis. However, comparative studies of BK-HC incidence in matched sibling donors (MSD) and unrelated donors (MUD) often include small haploidentical (HAPLO) donor cohorts and usually lack detailed information on disease evolution, coinfections, management and impact on outcomes. This study aimed to evaluate the incidence, risk factors, and outcomes in patients with hematologic malignancies undergoing HSCT from MSD, MUD, HAPLO donors using PTCy as GVHD prophylaxis. Furthermore, we analyze risk factors for BK-HC and its impact on renal function and transplant outcomes. Retrospective analysis of BK-HC episodes in patients undergoing HSCT from 167 MSD, 129 MUD and 103 HAPLO from a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus and mycophenolate mofetil was given, irrespective of donor type or conditioning intensity, and mesna was used prophylactically with PTCy. The incidence of grade 2-4 BK-HC was 23%, with a higher prevalence of grades 3-4 in HAPLO (19%), compared to MSD (11%) and MUD (8%) recipients (<em>P</em> = .02). BK-HC was diagnosed at a median of 29 days after HSCT and symp toms persisted for a median of 27 days, with longer duration in grade 3-4 cases (<em>P</em> = .02). Additionally, higher grades were associated with a greater transfusion burden (<em>P</em> &lt; .001). JC virus coinfection was detected in 24%, and cytomegalovirus viruria in 17%, which was not treated. BK antiviral treatment beyond supportive care was used in only two patients, while antibacterial treatments were prescribed in 28% for urinary symptoms and in 57% for concomitant infections in other sites. Younger age and HAPLO donors were significant risk factors for developing higher-grade BK-HC. No interaction was seen between age and conditioning intensity. Importantly, BK-HC did not significantly impact overall survival or graft-versus-host disease-free relapse-free survival as a time-dependent variable, as well as non-relapse mortality. Furthermore, BK-HC patients maintained stable creatinine renal clearance at 1-year post-transplant. BK-HC is a relatively early frequent complication in allogeneic HSCT with PTCy, especially in HAPLO recipients, with symptoms typically lasting a median of three weeks. Supportive care remains the mainstay of treatment, while specific antiviral treatments are rarely needed. The role of cidofovir and concomitant CMV viruria treatment are yet to be established. Our findings suggest that BK-HC does not significantly impact transplant outcomes and renal function.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 182.e1-182.e11"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865545","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}