Transplantation and Cellular Therapy最新文献

{"title":"Impact of Underlying Disease and Total Body Irradiation on the Incidence of Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation","authors":"Robert Puckrin ,&nbsp;Megan Kinzel ,&nbsp;Douglas Stewart ,&nbsp;Ahsan Chaudhry ,&nbsp;Kareem Jamani ,&nbsp;Jan Storek","doi":"10.1016/j.jtct.2024.12.024","DOIUrl":"10.1016/j.jtct.2024.12.024","url":null,"abstract":"<div><div>Multiple factors have been described to influence the risk of acute or chronic graft-versus-host disease (aGVHD or cGVHD) after allogeneic hematopoietic cell transplantation (HCT), including underlying chronic myeloid leukemia (CML) and high-dose total body irradiation (TBI). However, the impact of the underlying disease or low-dose TBI on the risk of GVHD in the modern era has not been determined. The objective of this study was to determine risk factors for GVHD in the modern era in the setting of antithymocyte globulin (ATG)-based GVHD prophylaxis. This retrospective study included 1219 patients with hematologic malignancy who underwent first peripheral blood allogeneic HCT using myeloablative fludarabine and busulfan conditioning ± low-dose total body irradiation, along with ATG, cyclosporine, and methotrexate as GVHD prophylaxis. The adjusted cumulative incidence of GVHD was compared between patient subgroups using multivariable competing risks regression. When disregarding the underlying disease, risk factors for grade 2-4 aGVHD were donor type other than matched sibling donor (non-MSD) and lack of low-dose TBI (non-TBI). Risk factors for grade 3-4 aGVHD were non-MSD, non-TBI, and CMV donor negative/recipient positive serostatus (D-R+). Risk factors for moderate-severe cGVHD were ≤9/10 HLA match, non-male/male donor/recipient sex, and non-TBI. In models including the underlying disease, additional significant risk factors were chronic lymphocytic leukemia (CLL) for grade 2 to 4 aGVHD (sub-hazard ratio over acute myeloid leukemia [SHR] 3.16, 95% CI 1.97-5.08, <em>P</em> &lt; .001); CLL and acute lymphoblastic leukemia (ALL) for grade 3-4 aGVHD (SHR for CLL 3.54, 95% CI 1.54-8.17, <em>P</em> = .003 and SHR for ALL 2.26, 95% CI 1.26-4.04, <em>P =</em> .006); and myelofibrosis (MF) for moderate-severe cGVHD (SHR 2.14, 95 CI 1.34-3.41, <em>P =</em> .001). In the modern era when using ATG for GVHD prophylaxis, newly identified risk factors include CLL and non-TBI for grade 2-4 aGVHD; CLL, ALL, and non-TBI for grade 3-4 aGVHD; and MF and non-TBI for moderate-severe cGVHD. These findings, if confirmed in a separate cohort, should be taken into consideration when tailoring the prophylaxis and monitoring of GVHD.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 176.e1-176.e8"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966616","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":"The Cure of Thalassemia and the Angst of a Junior Attending","authors":"Keith M. Sullivan ,&nbsp;Jean E. Sanders","doi":"10.1016/j.jtct.2025.02.006","DOIUrl":"10.1016/j.jtct.2025.02.006","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 113-117"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511133","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 Amphiregulin Expression in Intestinal Biopsies of Pediatric Patients with Severe Acute Graft-Versus-Host Disease.","authors":"Fjolla Zeka, Silvia Angori, Dorothea Rutishauser, Holger Moch, Carsten Posovszky, Khalid Amin, Shernan Holtan, Tayfun Güngör, Daniel Drozdov","doi":"10.1016/j.jtct.2025.02.020","DOIUrl":"10.1016/j.jtct.2025.02.020","url":null,"abstract":"<p><p>Acute graft-versus-host disease (GvHD) is a major complication of hematopoietic cell transplantation (HCT). Despite of recent advances in prophylaxis, diagnosis and treatment it is still a serious cause of morbidity and mortality after HCT. Amphiregulin (AREG) is an epidermal growth factor receptor ligand known for restoring damaged intestinal tissue. AREG has been studied as a blood biomarker in acute GvHD and was found predictive of steroid response and mortality. However, the expression of AREG in intestinal tissue in pediatric patients with acute GvHD is unknown. The aim of this study is to analyze and evaluate AREG expression in intestinal tissue biopsies of pediatric patients with GvHD, in comparison to patients with inflammatory bowel disease (IBD) and a control group with no pathological findings to provide insights in the biological tissue expression of this potential diagnostic and prognostic biomarker. We performed a retrospective study with pediatric patients who had an intestinal biopsy performed after HCT between 2010 and 2021, patients who had a diagnosis of IBD and patients with normal findings at the University Children's Hospital Zurich. Intestinal biopsies were stained for AREG. We used a semi-quantitative score ranging from 0 (not present) to 3 (intense) to grade the AREG expression. The grading was performed by a pathologist blinded to the group allocation. Lerner scores were also performed. The median AREG scores between the groups were compared using multivariable linear regression with age and sex as confounders. The study protocol was approved by the Ethical committee of Canton Zürich, Switzerland, number 2022-01037. Overall, 59 biopsies were stained for AREG, 20 after HCT (6 patients with severe GvHD, 5 with mild GvHD and 9 without GvHD), 19 with IBD and 20 controls. The median for the AREG overall grade for control group was 2, for the HCT with severe GvHD group 2.5 (P = .060) and for the IBD group 2.5 (P = .007). The results for the AREG epithelium and lamina propria grades were similar. There were no differences in survival between patients with GvHD with overall AREG scores below and greater or equal to the median of 2.5. This study showed that AREG scores were higher in intestinal biopsies from patients with severe GvHD and IBD compared to controls and patients with mild or no GvHD. Consequently, AREG staining could potentially be used as an additional marker for severe inflammation as seen in GvHD and IBD.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524529","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":"Two Nonmyeloablative HLA-Matched Related Donor Allogeneic Hematopoietic Cell Transplantation Regimens in Patients with Severe Sickle Cell Disease.","authors":"Zaina Inam, Neal Jeffries, Mary Link, Wynona Coles, Priscilla Pollack, Christina Luckett, Oswald Phang, Elizabeth Harvey, Triscia Martin, Tiffani Farrey, John F Tisdale, Matthew M Hsieh","doi":"10.1016/j.jtct.2025.02.021","DOIUrl":"10.1016/j.jtct.2025.02.021","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Nonmyeloablative (NMA) conditioning is being used increasingly with success in matched related donor (MRD) and alternative donor allogeneic hematopoietic cell transplantation (allo-HCT) in individuals with sickle cell disease (SCD). Advantages include decrease toxicity and applicability in patients otherwise unable to tolerate conditioning regimens due to end-organ damage or age. We aimed to add to published data outcomes of two similar NMA conditioning protocols, termed Protocol 1 (ClinicalTrials.gov ID NCT00061568) and Protocol 2 (ClinicalTrials.gov ID: NCT02105766)) in mainly adult patients with SCD to evaluate the safety, toxicity, and success of these regimens in individuals at high-risk for poor transplantation-related outcomes. We also evaluated the tolerability and outcomes of Protocol 2, which included preconditioning immunodepletion, in patients at even higher risk of T cell-mediated rejection or plasma/B cell-mediated anti-donor erythrocyte antibody production-the latter due to ABO incompatibility or recipient RBC alloimmunization to a donor antigen. Finally, we evaluated the incidence and trajectory of mixed donor myeloid chimerism over time following allo-HCT. In this retrospective analysis of the 2 prospective phase 2 NMA transplant protocols, 91 individuals with SCD or transfusion-dependent β-thalassemia underwent MRD allo-HCT at the National Heart, Lung, and Blood Institute; regimens contained alemtuzumab, low-dose radiation, and sirolimus for graft-versus-host disease (GVHD) prophylaxis with or without preconditioning immunodepletion with pentostatin and oral cyclophosphamide (Protocol 2). In the total cohort of 91 transplantation recipients, outcomes were favorable with timely neutrophil and platelet engraftment (median, 21 days [range, 7 to 67 days] and 21 days [range, 10 to 112 days], respectively), minimal high-grade acute GVHD and no chronic GVHD, overall survival of 90%, sickle-free survival of 85%, and mixed donor myeloid chimerism in 43% at a median follow up of 7.3 years (range, 0.8 to 20 years). Most patients with mixed myeloid chimerism at 2-years post-HCT remained stable in their values. In analyzing each protocol separately, outcomes were comparable except for higher cytomegalovirus reactivation necessitating treatment in Protocol 2 without an associated increase in graft failure. In the combined cohort, graft failure occurred in 11 patients, and hematologic malignancy or abnormal cytogenetics on bone marrow evaluation developed in 7 patients. In a subanalysis of factors that may implicate transplantation outcomes, the number of RBC units transfused post-HCT was significantly higher in recipients with pre-HCT history of alloimmunization to donor RBC antigens. There was no difference in the number of RBC units transfused, duration of transfusion, or red cell engraftment in those with major ABO incompatibility; preconditioning immunodepletion and pretreatment with rituximab likely were helpful. Both NMA allo-HCT ","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516916","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, Liora M Schultz","doi":"10.1016/j.jtct.2025.02.016","DOIUrl":"10.1016/j.jtct.2025.02.016","url":null,"abstract":"<p><p>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 <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.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-22","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":"Infections in Patients with Solid Tumors Undergoing Adoptive Cellular Therapy.","authors":"Viswatej Avutu, Jumanah N Algazaq, Kenneth Seier, Rhoena Desir-Camille, Li-Xuan Qin, Olayode Babatunde, Prasad S Adusumilli, Christopher A Klebanoff, Ritesh R Kotecha, Alexander N Shoushtari, Susan Slovin, Allison Betof Warner, Jae H Park, Adam J Schoenfeld, Roisin O'Cearbhaill, Sandra D'Angelo, Susan K Seo","doi":"10.1016/j.jtct.2025.02.017","DOIUrl":"10.1016/j.jtct.2025.02.017","url":null,"abstract":"<p><p>Adoptive cellular therapy (ACT) is an increasingly widely used treatment approach for malignancy. While infectious complications of ACT have been well described in patients with hematologic malignancies, limited data are available on the epidemiology of infections in patients with solid tumors. The purpose of this study was to describe the epidemiology of infections occurring within the first 180 days in adult patients with solid tumors treated with ACT and to identify risk factors predisposing these patients to infection. Data on 132 adult patients with solid tumors undergoing ACT between August 2014 and November 2021 at Memorial Sloan Kettering Cancer Center were collected. Infections were documented from the day of ACT infusion through day 180 postinfusion. Overall, 28 of 132 patients (21.2%) experienced 33 infections within the first 30 days of ACT, and 17 of 131 surviving patients (13%) were diagnosed with 24 infections between day 31 and day 180. Infection-related mortality was low. The majority of infections were bacterial. While male gender, older age, Eastern Cooperative Oncology Group (ECOG) performance status (PS) at time of ACT infusion, tocilizumab receipt, and cytokine release syndrome treated with tocilizumab were associated with shorter time to first infection on univariable analysis, only ECOG PS and tocilizumab receipt remained independent risk factors in the multivariable analysis. The proportion of patients with solid tumors experiencing early or late infections after ACT was lower compared to that reported among patients with B cell malignancies after chimeric antigen receptor T cell therapy. Most observed infections were primarily bacterial with low infection-related mortality; the incidence of viral and fungal infections was low. Based on the low frequency and timing of infections relative to neutropenia, antibacterial and antifungal prophylaxis are not likely to be beneficial. ECOG PS ≥2 and tocilizumab receipt were identified as significant predictors for infection after ACT, likely signaling an individual's debilitated state that predisposes to infection. Additional work to parse out confounders is needed to better identify risk factors for infection.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493836","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":"Plasma Nucleosome Levels and Risk of Acute Graft-Versus-Host Disease After Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Cohort Study.","authors":"Sune Holm Hansen, Sisse Rye Ostrowski, Niels Smedegaard Andersen, Lone Smidstrup Friis, Brian Kornblit, Søren Lykke Petersen, Ida Schjødt, Henrik Sengeløv, Lars Klingen Gjærde","doi":"10.1016/j.jtct.2025.02.015","DOIUrl":"10.1016/j.jtct.2025.02.015","url":null,"abstract":"<p><p>Circulating nucleosomes are representative of cell death, which is a feature of acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). We explored whether plasma nucleosome levels were prognostic for acute GVHD. We examined the level of circulating nucleosomes in 131 patients who underwent a myeloablative allo-HSCT between June 2015 and August 2018. The measurements were made using quantitative photometric sandwich-ELISA on stored plasma samples obtained pretransplantation (at a median of day -23) and around days +7, +14, and +28 after allo-HSCT. The median plasma nucleosome level remained constant until day +28, where they increased significantly (P < .001 compared to all other times of measurement). The plasma nucleosome level at day +28 was inversely associated with the risk of later grade II to IV acute GVHD (odds ratio [OR] 0.86 per 5 arbitrary unit [AU] increase [95% confidence intervals (CI): 0.66 to 0.99], P = .03), also after adjustment for risk factors of acute GVHD (OR 0.78 per 5 AU increase [95% CI: 0.56 to 0.96], P = .01). We found no support for an association between the plasma level of nucleosomes measured pretransplantation or around day +7 or +14 and the risk of subsequent grade II to IV acute GVHD. We observed a positive correlation between nucleosomes, suppressor of tumorigenesis 2, and C-reactive protein at day +28 (Spearman's ρ = 0.522, P < .001; and Spearman's ρ = 0.386, P < .001; respectively). A lower level of plasma nucleosomes at day +28 after HSCT was associated with a higher risk of subsequent acute GVHD. Additional studies are needed to validate circulating nucleosomes as a prognostic biomarker of acute GVHD.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469358","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":"Autologous or Allogeneic Hematopoietic Stem Cell Transplantation as Front-Line Treatment for Adult Secondary Acute Myeloid Leukemia Patients: The PETHEMA Registry Experience.","authors":"Josefina Serrano, David Martínez-Cuadrón, Cristina Gil, Teresa Bernal, Mar Tormo, Pilar Martínez-Sánchez, Carlos Rodríguez-Medina, Pilar Herrera, José A Pérez Simón, María J Sayas, Juan Bergua, Esperanza Lavilla-Rubira, Mariluz Amigo, Celina Benavente, José L López Lorenzo, Manuel M Pérez-Encinas, María B Vidriales, Clara Aparicio-Pérez, Esther Prados de la Torre, Mercedes Colorado, Beatriz de Rueda, Raimundo García-Boyero, Sandra Marini, Julio García-Suárez, María López-Pavía, María I Gómez-Roncero, Víctor Noriega, Aurelio López, Jorge Labrador, Ana Cabello, Claudia Sossa, Lorenzo Algarra, Mariana Stevenazzi, Laura Torres, Blanca Boluda, Joaquín Sánchez-Garcia, Pau Montesinos","doi":"10.1016/j.jtct.2025.02.011","DOIUrl":"10.1016/j.jtct.2025.02.011","url":null,"abstract":"<p><p>It is widely accepted that allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the sole potentially curative option available for secondary acute myeloid leukemia (sAML). However, clinical factors impacting outcomes after allo-HSCT and the potential role of autologous HSCT (auto-HSCT) in real-life series are needed. Previously, the PETHEMA group reported a series of 2310 patients with sAML in the nationwide registry. Of these, 876 were candidates to receive chemotherapy and 274 underwent HSCT (55 auto-HSCT and 219 allo-HSCT). In this study, we analyzed the role of auto-HSCT or allo-HSCT as front-line treatment for sAML patients included in the Spanish PETHEMA AML registry. Here we report an analysis of outcomes as well as prognostic variables in this series of patients undergoing auto-HSCT or allo-HSCT as part of the front-line treatment for sAML. We used the multinational PETHEMA AML registry (Clincial Trials.gov identifier NCT02607059) to identify adult patients (age ≥18 years) with a diagnosis of sAML who underwent auto- or allo-HSCT as front-line treatment in Spanish and Portuguese institutions between August, 1, 1992, and July, 31, 2020. Patient characteristics, diagnostic findings, and management, including treatments, characteristics of HSCT, and outcomes, were retrieved from the PETHEMA AML registry in this retrospective multicenter analysis. With a median follow-up of 32.7 months, better 5-year overall survival (OS) and leukemia-free survival (LFS) were obtained with allo-HSCT in first complete response (CR) (44.5% and 39.9%, respectively) compared with auto-HSCT in CR1 (30% and 20.5%, respectively) but without reaching statistical differences for OS (P = .22 and .03, respectively). The higher incidence of relapse in auto-HSCT is counterbalanced with the significantly lower nonrelapse mortality rate. For allo-HSCT recipients, 5-year outcomes were significantly influenced by the cytogenetic/genetic risk. In multivariate analysis, the adverse cytogenetic/genetic risk group retained statistical significance for all endpoints. We confirmed the role of allo-HSCT as a potential curative option for patients and report that auto-HSCT in CR can still provide a 5-year LFS of 20% in sAML patients. Finally, our results confirm adverse cytogenetic/genetic risk category as an independent negative factor in sAML patients undergoing HSCT.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432767","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":"US Geriatric Assessment Practices for Older Adults Undergoing Hematopoietic Cell Transplantation or Chimeric Antigen Receptor T Cell Therapy: An American Society for Transplantation and Cellular Therapy Physician Survey from the Aging Special Interest Group and Committee on Practice Guidelines.","authors":"Pashna N Munshi, Rebecca L Olin, Sarah Wall, Shannon R McCurdy, Taha Al-Juhaishi, Julie Baker, Vijaya Raj Bhatt, Nora Chokr, Parastoo Dahi, Zachariah DeFilipp, Manuel Espinoza-Gutarra, Shatha Farhan, Lohith Gowda, Betty K Hamilton, Yoshihiro Inamoto, Rena Jayani, Mohamed A Kharfan-Dabaja, Richard Lin, Gabrielle Meyers, Asmita Mishra, Hemant S Murthy, Mariam Nawas, Ashley E Rosko, Marco Ruiz, Mohamed L Sorror, Anthony D Sung, Paul A Carpenter, Mehdi Hamadani, Andrew S Artz","doi":"10.1016/j.jtct.2025.02.014","DOIUrl":"10.1016/j.jtct.2025.02.014","url":null,"abstract":"<p><p>Geriatric assessment (GA) may identify vulnerabilities and promote risk-stratification in older adults predisposed to toxicities after autologous (auto), allogeneic (allo) hematopoietic cell transplantation (HCT) and chimeric antigen T-cell therapies (CAR T). With increased utilization cellular therapies for older adults the American Society for Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines and its Special Interest Group for Aging (SIG) conducted an online cross-sectional survey between April 2023 and August 2023 to determine transplantation and cellular therapy physicians' practice patterns regarding GA in older patients receiving HCT and CAR T-cell therapies. E-mail surveys were sent to 1168 ASTCT physician members and only 96 (8.2%) respondents completed the survey. Most (86%) were affiliated with university/teaching centers and 70% had a combined HCT and cellular therapy practice. More than 50% of respondents were interested in pursuing GA but 68% described barriers. The top two recognized barriers to GA were lack of time (96%) and clinical support staff (90%). Despite interest, only 15% respondents reported to know the domains of GA 'well'. Among those using GA, the minimum age used for routine GA was 65 years for allo-HCT and CAR T in over 91% respondents. Taken together, we recommend the HCT community leadership and GA experts combine efforts to address the gap in GA uptake and implementation.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442143","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":"Awakening from REMS: ASTCT 80/20 Ongoing Recommendations for Safe Use of Chimeric Antigen Receptor T Cells.","authors":"Frederick L Locke, Zahra Mahmoudjafari, Partow Kebriaei, Rebecca A Gardner, Matthew J Frigault, Noelle V Frey, Krishna V Komanduri, Miguel-Angel Perales, Sarah Nikiforow","doi":"10.1016/j.jtct.2025.02.009","DOIUrl":"10.1016/j.jtct.2025.02.009","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The first 6 chimeric antigen receptor T cell (CAR-T) therapies approved in the United States have Risk Evaluation Mitigation Strategies (REMS) programs mandated by the US Food and Drug Administration (FDA). REMS programs aim to ensure the safe use of CAR-T therapy through timely recognition and management of unique severe risks and toxicities that cannot be mitigated by labeling alone, such as cytokine release syndrome and neurotoxicity syndromes. At the launch of each of the first 6 products, CAR-T REMS programs mandated product-specific education and training for clinical staff, patients, and caregivers; adequate access to medications to treat expected toxicities; and reporting of toxicities either to the product manufacturer or to the FDA. Each manufacturer ensures that treatment centers comply with the REMS program for their individual product in different ways, involving time-consuming and often redundant training, testing, and audits. The American Society for Transplantation and Cellular Therapy (ASTCT) 80/20 Subcommittee convened its second workshop in June 2023, inviting approximately 70 cellular therapy stakeholders to discuss whether safety and quality workflows embedded in existing resources within the cellular therapy field could replace FDA-mandated and company-monitored REMS programs. Attendees were clinicians at large academic medical centers experienced in cellular therapy, regulators, members of accrediting bodies and professional societies, and manufacturers of immune effector cell (IEC) therapies at multiple stages of development. Discussion centered on (1) educational requirements for safe delivery and management, (2) goals and mechanisms for data reporting and to whom, and (3) what entities should oversee these quality safeguards around CAR-T administration and management. Broad support was voiced for (1) conducting training programs administered by treatment centers and/or professional societies to replace manufacturers' product training; (2) reporting standardized data points into a central, accessible repository for tracking of safety trends and identification of new signals; and (3) enabling accrediting bodies to attest to programs' quality and ongoing compliance with field safety expectations, thereby replacing intensive manufacturer initial evaluation and ongoing REMS audits. The strong consensus of the second multidisciplinary ASTCT 80/20 Workshop was that such measures would allow elimination, or at least significant reduction and simplification, of current CAR-T REMS programs. Development of educational resources and funding for data reporting outside of a mandated REMS structure were identified as critical, particularly to support treatment centers new to cellular therapy, as were ongoing collaborations with FDA and manufacturers. These consensus recommendations were shared with the FDA at the Cell Therapy Liaison Meeting and in multiple professional society meetings and other public forums with regulators, ma","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426356","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}