Pub Date : 2025-01-01DOI: 10.1016/S2666-6367(24)00820-0
{"title":"Officers and Directors of ASTCT","authors":"","doi":"10.1016/S2666-6367(24)00820-0","DOIUrl":"10.1016/S2666-6367(24)00820-0","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 1","pages":"Page A5"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150145","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}
Pub Date : 2025-01-01DOI: 10.1016/j.jtct.2024.09.025
Andrés Noyola-Pérez , Rafaella Ribas-Muratori , Marco A. Vargas-Hernández , Laura Saavedra-Salazar , Cristóbal Frutos , Carmem Bonfim , Fernando Barroso-Duarte , Sebastián Galeano , Gregorio Jaimovich , Amado Karduss , Andrés Gómez-De León , Latin-American Bone Marrow Transplantation Group (LABMT)
Hematopoietic cell transplantation (HCT) is a complex and resource-intensive procedure that has become a critical treatment for certain hematologic conditions. However, in Latin America, access to HCT is limited compared to high-income countries, in part due to a lack of standardized training programs for HCT professionals. To address this gap, the Latin-American Bone Marrow Transplantation Group conducted a cross-sectional study to assess the current state of training programs in HCT and cellular therapy across the region. This study aimed to describe and analyze the availability, characteristics, and challenges of HCT training programs in Latin America, with a focus on identifying barriers and proposing solutions for improvement. A cross-sectional survey was sent to 127 recognized HCT centers across 14 Latin-American countries in December 2022. The survey collected data on institutional characteristics, training program structure, costs, and barriers to program development. Descriptive statistics were used to summarize the data, and comparative analyses were performed using Chi-square and Mann–Whitney tests. Of the 127 centers surveyed, 50 (39%) responded, with the majority located in Brazil (34%) and Mexico (30%). Among the respondents, 64% (n = 32) offered formal training programs lasting 6 months or longer. The most significant barriers reported were lack of funding (n = 21), limited number of transplant procedures (n = 15), and a shortage of qualified professors (n = 11). Proposed solutions included increasing student mobility opportunities (n = 28), enhancing program quality (n = 27), and improving access to funding (n = 15). Only 6% of programs offered exposure to CAR-T therapy, and fewer than half of the centers provided international rotations. This study highlights significant disparities in HCT training programs across Latin America, with most countries lacking access to formalized training. While Brazil and Mexico serve as regional hubs, other nations have limited or no training opportunities. Addressing these gaps through increased funding, international collaborations, and standardized curricula is essential to improving HCT training and ultimately patient care in the region.
{"title":"Training in Transplantation and Cellular Therapy in Latin America: A Cross-Sectional Study of the LABMT","authors":"Andrés Noyola-Pérez , Rafaella Ribas-Muratori , Marco A. Vargas-Hernández , Laura Saavedra-Salazar , Cristóbal Frutos , Carmem Bonfim , Fernando Barroso-Duarte , Sebastián Galeano , Gregorio Jaimovich , Amado Karduss , Andrés Gómez-De León , Latin-American Bone Marrow Transplantation Group (LABMT)","doi":"10.1016/j.jtct.2024.09.025","DOIUrl":"10.1016/j.jtct.2024.09.025","url":null,"abstract":"<div><div>Hematopoietic cell transplantation (HCT) is a complex and resource-intensive procedure that has become a critical treatment for certain hematologic conditions. However, in Latin America, access to HCT is limited compared to high-income countries, in part due to a lack of standardized training programs for HCT professionals. To address this gap, the Latin-American Bone Marrow Transplantation Group conducted a cross-sectional study to assess the current state of training programs in HCT and cellular therapy across the region. This study aimed to describe and analyze the availability, characteristics, and challenges of HCT training programs in Latin America, with a focus on identifying barriers and proposing solutions for improvement. A cross-sectional survey was sent to 127 recognized HCT centers across 14 Latin-American countries in December 2022. The survey collected data on institutional characteristics, training program structure, costs, and barriers to program development. Descriptive statistics were used to summarize the data, and comparative analyses were performed using Chi-square and Mann–Whitney tests. Of the 127 centers surveyed, 50 (39%) responded, with the majority located in Brazil (34%) and Mexico (30%). Among the respondents, 64% (<em>n</em> = 32) offered formal training programs lasting 6 months or longer. The most significant barriers reported were lack of funding (<em>n</em> = 21), limited number of transplant procedures (<em>n</em> = 15), and a shortage of qualified professors (<em>n</em> = 11). Proposed solutions included increasing student mobility opportunities (<em>n</em> = 28), enhancing program quality (<em>n</em> = 27), and improving access to funding (<em>n</em> = 15). Only 6% of programs offered exposure to CAR-T therapy, and fewer than half of the centers provided international rotations. This study highlights significant disparities in HCT training programs across Latin America, with most countries lacking access to formalized training. While Brazil and Mexico serve as regional hubs, other nations have limited or no training opportunities. Addressing these gaps through increased funding, international collaborations, and standardized curricula is essential to improving HCT training and ultimately patient care in the region.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 1","pages":"Pages 47.e1-47.e9"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475655","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}
Pub Date : 2025-01-01DOI: 10.1016/j.jtct.2024.10.010
Giovanna Melica , Alejandro Luna de Abia , Gunjan L. Shah , Sean Devlin , Magdalena Corona , Joshua Fein , Parastoo B. Dahi , Sergio A. Giralt , Richard J. Lin , M. Lia Palomba , Allison Parascondola , Jae Park , Gilles Salles , Amethyst Saldia , Michael Scordo , Roni Shouval , Miguel-Angel Perales , Susan K. Seo
Patients undergoing CD19 chimeric antigen receptor (CAR)–T cell therapy exhibit multiple immune deficits that may increase their susceptibility to infections. Invasive fungal infections (IFIs) are life-threatening events in the setting of hematologic diseases. However, there is ongoing debate regarding the optimal role and duration of antifungal prophylaxis in this specific patient population. The objective of this study was to provide a comprehensive overview of the evolution of IFI prophylactic strategies over time and to assess IFI incidence rates in a cohort of patients with relapsed or refractory (R/R) lymphoma treated with CAR-T cell therapy. A single-center retrospective study was conducted on a cohort of patients with R/R B cell lymphoma treated with CD19 CAR-T cell therapy between April 2016 and March 2023. Group A (April 2016–August 2020) consisted of patients primarily treated with fluconazole, irrespective of their individual IFI risk profile. In Group B (September 2020–March 2023) antifungal prophylaxis was recommended only for high-risk patients. Overall, 330 patients were included. Antifungal prophylaxis was prescribed to 119/142 (84%) patients in Group A and 58/188 (31%) in Group B (P < .001). Anti-mold azoles were prescribed to 8 (5.6%) patients in Group A and 21 (11.2%) patients in Group B. In Group A, 42 (29%) patients were switched to another antifungal, 9 (21%) because of toxicity, with 6 cases of transaminitis and 3 cases of prolonged QTc. In Group B, 21 (11.2%) patients were switched to the antifungal drug, mainly from fluconazole or micafungin to a mold-active agent following revised guidelines. No difference was found in liver toxicity between the two groups at infusion, day 10, and day 30. No significant differences were observed between the groups. IFIs following CAR-T cell therapy were rare, with 1 case of cryptococcal meningoencephalitis in group A (.7%) and 1 case of invasive aspergillosis in Group B (.5%), both occurring in patients on micafungin prophylaxis. In this large single-center cohort of patients with R/R lymphoma treated with CAR-T cells, we show that individualized prophylaxis, alongside careful management of CAR-T cell–related toxicities such as CRS, was associated with a very low IFI rate, avoiding the risk of unnecessary toxicities, drug–drug interactions, and high costs.
{"title":"Shift from Widespread to Tailored Antifungal Prophylaxis in Lymphoma Patients Treated with CD19 CAR T Cell Therapy: Results from a Large Retrospective Cohort","authors":"Giovanna Melica , Alejandro Luna de Abia , Gunjan L. Shah , Sean Devlin , Magdalena Corona , Joshua Fein , Parastoo B. Dahi , Sergio A. Giralt , Richard J. Lin , M. Lia Palomba , Allison Parascondola , Jae Park , Gilles Salles , Amethyst Saldia , Michael Scordo , Roni Shouval , Miguel-Angel Perales , Susan K. Seo","doi":"10.1016/j.jtct.2024.10.010","DOIUrl":"10.1016/j.jtct.2024.10.010","url":null,"abstract":"<div><div>Patients undergoing CD19 chimeric antigen receptor (CAR)–T cell therapy exhibit multiple immune deficits that may increase their susceptibility to infections. Invasive fungal infections (IFIs) are life-threatening events in the setting of hematologic diseases. However, there is ongoing debate regarding the optimal role and duration of antifungal prophylaxis in this specific patient population. The objective of this study was to provide a comprehensive overview of the evolution of IFI prophylactic strategies over time and to assess IFI incidence rates in a cohort of patients with relapsed or refractory (R/R) lymphoma treated with CAR-T cell therapy. A single-center retrospective study was conducted on a cohort of patients with R/R B cell lymphoma treated with CD19 CAR-T cell therapy between April 2016 and March 2023. Group A (April 2016–August 2020) consisted of patients primarily treated with fluconazole, irrespective of their individual IFI risk profile. In Group B (September 2020–March 2023) antifungal prophylaxis was recommended only for high-risk patients. Overall, 330 patients were included. Antifungal prophylaxis was prescribed to 119/142 (84%) patients in Group A and 58/188 (31%) in Group B (<em>P</em> < .001). Anti-mold azoles were prescribed to 8 (5.6%) patients in Group A and 21 (11.2%) patients in Group B. In Group A, 42 (29%) patients were switched to another antifungal, 9 (21%) because of toxicity, with 6 cases of transaminitis and 3 cases of prolonged QTc. In Group B, 21 (11.2%) patients were switched to the antifungal drug, mainly from fluconazole or micafungin to a mold-active agent following revised guidelines. No difference was found in liver toxicity between the two groups at infusion, day 10, and day 30. No significant differences were observed between the groups. IFIs following CAR-T cell therapy were rare, with 1 case of cryptococcal meningoencephalitis in group A (.7%) and 1 case of invasive aspergillosis in Group B (.5%), both occurring in patients on micafungin prophylaxis. In this large single-center cohort of patients with R/R lymphoma treated with CAR-T cells, we show that individualized prophylaxis, alongside careful management of CAR-T cell–related toxicities such as CRS, was associated with a very low IFI rate, avoiding the risk of unnecessary toxicities, drug–drug interactions, and high costs.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 1","pages":"Pages 36-44"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508738","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}
Pub Date : 2025-01-01DOI: 10.1016/j.jtct.2024.10.014
Manmeet Kaur , Mary M. Horowitz , Adam Mendizabal , Min Chen , Amy Foley , Jeffery J. Auletta , Steven Devine , Anita D'Souza
Underrepresentation by race and ethnicity in oncology clinical trials, including those of hematopoietic cell transplantation (HCT), is a known challenge. This analysis studied accrual on Blood and Marrow Transplant Clinical Trials Network (BMT CTN) trials conducted in 2014 to 2020 by race/ethnicity, age, and sex, comparing these characteristics with those of potentially eligible patients identified from the Surveillance, Epidemiology, and End Results (SEER) and Center for International Blood and Marrow Transplant Research (CIBMTR) databases for the disease, age, and years of interest of BMT CTN studies. Five BMT CTN trials met the inclusion criteria, including 1 autologous HCT trial and 4 allogeneic HCT trials. Two studies focused on multiple myeloma (BMT CTN 1302 and 1401), 2 studies focused on graft-versus-host disease (GVHD) treatment (BMT CTN 1301 and 1501), and 1 study focused on post-HCT maintenance therapy in FLT3+ acute myelogenous leukemia (BMT CTN 1506). A decline in the proportion of patients from minority racial and ethnic groups was seen from the SEER population to trial enrollees, with the largest drop seen between the SEER population and all patients who underwent HCT (on or off trial) at US transplant centers. Allogeneic HCT trials that allowed alternative donor graft sources had less decrease from the SEER population. No decrease in clinical trial enrollment was seen with respect to older age and female HCT recipients. This study provides insight into the underrepresentation of racial and ethnic minority patients in BMT CTN clinical trials, owing largely to lack of access to HCT in general. Pathways expanding access to donors and improving the outreach of HCT programs to underserved populations are needed to improve access to clinical trials.
{"title":"Representativeness of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Trial Participants","authors":"Manmeet Kaur , Mary M. Horowitz , Adam Mendizabal , Min Chen , Amy Foley , Jeffery J. Auletta , Steven Devine , Anita D'Souza","doi":"10.1016/j.jtct.2024.10.014","DOIUrl":"10.1016/j.jtct.2024.10.014","url":null,"abstract":"<div><div>Underrepresentation by race and ethnicity in oncology clinical trials, including those of hematopoietic cell transplantation (HCT), is a known challenge. This analysis studied accrual on Blood and Marrow Transplant Clinical Trials Network (BMT CTN) trials conducted in 2014 to 2020 by race/ethnicity, age, and sex, comparing these characteristics with those of potentially eligible patients identified from the Surveillance, Epidemiology, and End Results (SEER) and Center for International Blood and Marrow Transplant Research (CIBMTR) databases for the disease, age, and years of interest of BMT CTN studies. Five BMT CTN trials met the inclusion criteria, including 1 autologous HCT trial and 4 allogeneic HCT trials. Two studies focused on multiple myeloma (BMT CTN 1302 and 1401), 2 studies focused on graft-versus-host disease (GVHD) treatment (BMT CTN 1301 and 1501), and 1 study focused on post-HCT maintenance therapy in FLT3<sup>+</sup> acute myelogenous leukemia (BMT CTN 1506). A decline in the proportion of patients from minority racial and ethnic groups was seen from the SEER population to trial enrollees, with the largest drop seen between the SEER population and all patients who underwent HCT (on or off trial) at US transplant centers. Allogeneic HCT trials that allowed alternative donor graft sources had less decrease from the SEER population. No decrease in clinical trial enrollment was seen with respect to older age and female HCT recipients. This study provides insight into the underrepresentation of racial and ethnic minority patients in BMT CTN clinical trials, owing largely to lack of access to HCT in general. Pathways expanding access to donors and improving the outreach of HCT programs to underserved populations are needed to improve access to clinical trials.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 1","pages":"Pages 49-57"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569178","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}
Pub Date : 2025-01-01DOI: 10.1016/j.jtct.2024.12.014
Kristine A. Karvonen
{"title":"Challenging the Status Quo: Multi-level Solutions for Equitable Hematopoietic Cell Transplantation Clinical Trial Representation","authors":"Kristine A. Karvonen","doi":"10.1016/j.jtct.2024.12.014","DOIUrl":"10.1016/j.jtct.2024.12.014","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 1","pages":"Pages 7-9"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012349","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}
Pub Date : 2025-01-01DOI: 10.1016/j.jtct.2024.12.012
Joanne Kurtzberg
{"title":"Profile of a Pioneer: Eliane Gluckman","authors":"Joanne Kurtzberg","doi":"10.1016/j.jtct.2024.12.012","DOIUrl":"10.1016/j.jtct.2024.12.012","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 1","pages":"Pages 1-3"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012351","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}
Pub Date : 2025-01-01DOI: 10.1016/j.jtct.2024.10.008
Jean Roy , Sandra Cohen , Guy Sauvageau , Imran Ahmad , Valentyn Fournier , Rafik Terra , Pierre Caudrelier , Stéphanie Thiant , Gabrielle Thauvette , Nadia Bambace , Jean-Sébastien Delisle , Silvy Lachance , Thomas Kiss , Léa Bernard , Denis Claude Roy , Olivier Veilleux , Richard LeBlanc
<div><div>Multiple myeloma (MM) remains associated with a poor outcome, particularly in patients with advanced disease and high-risk (HR) cytogenetics. To date, the only curative treatment is allogeneic (allo) hematopoietic cell transplantation (HCT), but high incidences of graft versus host disease (GVHD), nonrelapse mortality (NRM) and disease progression remain important obstacles. Cord blood (CB) transplantation has been associated with low rates of relapse and chronic (c) GVHD, but its use has declined because of high incidences of infections, severe acute GVHD and high NRM. In other hematologic malignancies, UM171-expanded CB transplants have led to improved outcomes, allowing for the selection of smaller, better HLA-matched units. We aimed to investigate the safety and feasibility of single UM171-expanded single CB unit transplantation in frontline tandem auto/allo HCT for HR/ultra-HR MM patients. Newly diagnosed MM patients ≤ 65 years with an ISS stage II/III and del(17p), t(4;14), t(14;16), t(14;20), del(1p) or +1q, R-ISS 3, ≥ 2 cytogenetic abnormalities, or plasma cell leukemia without a sibling donor and availability of a 5-7/8 matched CB graft with ≥ 0.5 x 10<sup>5</sup> CD34+/kg and ≥ 1.5 x 10<sup>7</sup> TNCs/kg were eligible to this phase I/II prospective study (ClinicalTrials.gov NCT03441958). After induction and autologous HCT, patients received a reduced intensity conditioning regimen and were infused with 7-day UM171-expanded CD34+ cells, along with the lymphocytes contained in the CD34-negative fraction. The primary endpoints were feasibility of UM171 expansion, safety, kinetics of engraftment, incidences and maximum grades of acute and cGVHD at 1 and 2 years, assessment of measurable residual disease (MRD) and quality of life (QoL). Between 05/2018 and 11/2021, 20 patients were enrolled. One patient had an unsuccessful CB expansion with UM171, leaving 19 patients with a median age of 56 years. Median CD34+ cell dose infused after expansion was 4.62 x 10<sup>6</sup>/kg (range: 0.79 to 5.76). Median times to achieve absolute neutrophil counts of 0.1 and 0.5 x 10<sup>9</sup>/L were D+6 and D+10.5; median time to reach ≥ 20 x 10<sup>9</sup>/L platelets was D+36. Full donor chimerism was achieved in all cell lineages by D+120 in recipients of reduced intensity conditioning. Cumulative incidences of grade II-IV, grade III-IV acute GVHD and moderate/severe cGVHD at 12 months were 68.4% (95% CI: 46 to 90), 5.3% (95% CI: 0% to 16%), and 10.5% (95% CI: 0% to 25%), respectively. With a median follow-up of 2.9 years (range: 0.46 to 5.3), cumulative incidences of relapse, PFS, OS and NRM at 3 years were 36.8% (95% CI: 14 to 59), 47.4% (95% CI: 29 to 76), 68.4% (95% CI: 50 to 93) and 15.8% (95%CI: 0 to 33), respectively. Median time to complete immunosuppression discontinuation was D+238. No unexpected adverse events were observed. Only one of 7 patients alive at 2 years with negative MRD at transplant has relapsed. Non-relapsing patients
背景：多发性骨髓瘤（MM多发性骨髓瘤（MM）的预后仍然很差，尤其是晚期患者和高危（HR）细胞遗传学患者。迄今为止，唯一可治愈的治疗方法是异基因（allo）造血细胞移植（HCT），但移植物抗宿主疾病（GVHD）、非复发死亡率（NRM）和疾病进展的高发病率仍是重要障碍。脐带血（CB）移植的复发率和慢性（c）移植物抗宿主疾病（GVHD）发生率较低，但由于感染、严重急性GVHD和高NRM发生率较高，脐带血移植的使用已经减少。在其他血液系统恶性肿瘤中，UM171扩增的CB移植改善了预后，可以选择更小、HLA匹配更好的单位：我们的目的是研究在一线串联自体/异体 HCT 治疗 HR/ultra-HR MM 患者时进行单个 UM171 扩增的单个 CB 单位移植的安全性和可行性：研究设计：新诊断的MM患者，年龄≤65岁，ISS II/III期，del17p、t4,14、t14,16、t14,20、del1p或+1q、R-ISS 3、≥2细胞遗传学异常，或浆细胞白血病，无同胞供者，有5-7/8匹配的CB移植物，CD34+/kg≥0.5 x 105 CD34+/kg且≥ 1.5 x 107 TNCs/kg的患者有资格参加这项I/II期前瞻性研究（ClinicalTrials.gov NCT03441958）。诱导和自体造血干细胞移植后，患者接受强度降低的调理方案，并输注7天的UM171扩增CD34+细胞以及CD34阴性部分所含的淋巴细胞。主要终点是UM171扩增的可行性、安全性、移植动力学、1年和2年后急性和cGVHD的发生率和最大分级、可测量残留疾病（MRD）的评估以及生活质量（QoL）：结果：在2018年5月至2021年11月期间，共有20名患者入组。一名患者使用 UM171 进行 CB 扩增失败，剩下 19 名患者，中位年龄为 56 岁。扩增后输注的 CD34+ 细胞剂量中位数为 4.62 x 106/kg（范围：0.79-5.76）。中性粒细胞绝对计数达到0.1和0.5 x 109/L的中位时间分别为D+6和D+10.5；血小板达到≥20 x 109/L的中位时间为D+36。在减低强度调理的受者中，所有细胞系的供体嵌合率在D+120前均已达到。12个月时，II-IV级、III-IV级急性GVHD和中度/重度cGVHD的累积发生率分别为68.4%（95% CI：46-90）、5.3%（95% CI：0-16%）和10.5%（95% CI：0-25%）。中位随访时间为 2.9 年（范围：0.46-5.3），3 年时复发、PFS、OS 和 NRM 的累积发生率分别为 36.8%（95% CI：14-59）、47.4%（95% CI：29-76）、68.4%（95% CI：50-93）和 15.8%（95%CI：0-33）。完全停用免疫抑制剂的中位时间为 D+238。未观察到意外不良事件。在移植时MRD为阴性且存活2年的7名患者中，只有1人复发。未复发患者移植后的生活质量与普通人群相似：UM171扩增CB移植在HR/超HR骨髓瘤患者中是可行的，而且可以使用单个CB单位，发生cGVHD的风险较低。移植前MRD阴性的患者可能会从UM171扩增CB移植中获益最多。
{"title":"A Pilot Study of UM171-Expanded Cord Blood Grafts for Tandem Auto/Allogeneic Hematopoietic Cell Transplant in High and Ultra-High-Risk Myeloma Patients","authors":"Jean Roy , Sandra Cohen , Guy Sauvageau , Imran Ahmad , Valentyn Fournier , Rafik Terra , Pierre Caudrelier , Stéphanie Thiant , Gabrielle Thauvette , Nadia Bambace , Jean-Sébastien Delisle , Silvy Lachance , Thomas Kiss , Léa Bernard , Denis Claude Roy , Olivier Veilleux , Richard LeBlanc","doi":"10.1016/j.jtct.2024.10.008","DOIUrl":"10.1016/j.jtct.2024.10.008","url":null,"abstract":"<div><div>Multiple myeloma (MM) remains associated with a poor outcome, particularly in patients with advanced disease and high-risk (HR) cytogenetics. To date, the only curative treatment is allogeneic (allo) hematopoietic cell transplantation (HCT), but high incidences of graft versus host disease (GVHD), nonrelapse mortality (NRM) and disease progression remain important obstacles. Cord blood (CB) transplantation has been associated with low rates of relapse and chronic (c) GVHD, but its use has declined because of high incidences of infections, severe acute GVHD and high NRM. In other hematologic malignancies, UM171-expanded CB transplants have led to improved outcomes, allowing for the selection of smaller, better HLA-matched units. We aimed to investigate the safety and feasibility of single UM171-expanded single CB unit transplantation in frontline tandem auto/allo HCT for HR/ultra-HR MM patients. Newly diagnosed MM patients ≤ 65 years with an ISS stage II/III and del(17p), t(4;14), t(14;16), t(14;20), del(1p) or +1q, R-ISS 3, ≥ 2 cytogenetic abnormalities, or plasma cell leukemia without a sibling donor and availability of a 5-7/8 matched CB graft with ≥ 0.5 x 10<sup>5</sup> CD34+/kg and ≥ 1.5 x 10<sup>7</sup> TNCs/kg were eligible to this phase I/II prospective study (ClinicalTrials.gov NCT03441958). After induction and autologous HCT, patients received a reduced intensity conditioning regimen and were infused with 7-day UM171-expanded CD34+ cells, along with the lymphocytes contained in the CD34-negative fraction. The primary endpoints were feasibility of UM171 expansion, safety, kinetics of engraftment, incidences and maximum grades of acute and cGVHD at 1 and 2 years, assessment of measurable residual disease (MRD) and quality of life (QoL). Between 05/2018 and 11/2021, 20 patients were enrolled. One patient had an unsuccessful CB expansion with UM171, leaving 19 patients with a median age of 56 years. Median CD34+ cell dose infused after expansion was 4.62 x 10<sup>6</sup>/kg (range: 0.79 to 5.76). Median times to achieve absolute neutrophil counts of 0.1 and 0.5 x 10<sup>9</sup>/L were D+6 and D+10.5; median time to reach ≥ 20 x 10<sup>9</sup>/L platelets was D+36. Full donor chimerism was achieved in all cell lineages by D+120 in recipients of reduced intensity conditioning. Cumulative incidences of grade II-IV, grade III-IV acute GVHD and moderate/severe cGVHD at 12 months were 68.4% (95% CI: 46 to 90), 5.3% (95% CI: 0% to 16%), and 10.5% (95% CI: 0% to 25%), respectively. With a median follow-up of 2.9 years (range: 0.46 to 5.3), cumulative incidences of relapse, PFS, OS and NRM at 3 years were 36.8% (95% CI: 14 to 59), 47.4% (95% CI: 29 to 76), 68.4% (95% CI: 50 to 93) and 15.8% (95%CI: 0 to 33), respectively. Median time to complete immunosuppression discontinuation was D+238. No unexpected adverse events were observed. Only one of 7 patients alive at 2 years with negative MRD at transplant has relapsed. Non-relapsing patients ","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 1","pages":"Pages 34.e1-34.e14"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475642","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}
Pub Date : 2025-01-01DOI: 10.1016/j.jtct.2024.12.013
Gemma K. Reynolds , Monica A. Slavin
{"title":"The bottom line of CAR-T fungal risk: low incidence, high stakes and the need for individualised antifungal prophylaxis","authors":"Gemma K. Reynolds , Monica A. Slavin","doi":"10.1016/j.jtct.2024.12.013","DOIUrl":"10.1016/j.jtct.2024.12.013","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 1","pages":"Pages 4-6"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012354","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}
Pub Date : 2025-01-01DOI: 10.1016/j.jtct.2024.08.009
Anmol Baranwal , Kimberly J. Langer , Mohamed A. Kharfan-Dabaja , Ernesto Ayala , James Foran , Hemant Murthy , Vivek Roy , Madiha Iqbal , Jeanne Palmer , Lisa Z. Sproat , Saurabh Chhabra , Nandita Khera , Urshila Durani , Mehrdad Hefazi , Abhishek Mangaonkar , Mithun V. Shah , Mark R. Litzow , William J. Hogan , Hassan B. Alkhateeb
Post-transplant cyclophosphamide (PT-Cy) is becoming the standard of care for preventing graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplant (alloHCT). Cyclophosphamide is associated with endothelial injury. We hypothesized that the endothelial activation and stress index (EASIX) score, being a marker of endothelial dysfunction, will predict non-relapse mortality (NRM) in alloHCT patients receiving PT-Cy for GVHD prophylaxis. We evaluate the prognostic ability of the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and EASIX scores, and report other factors influencing survival, in patients with hematologic malignancies undergoing alloHCT and receiving PT-Cy-based GVHD prophylaxis. Adult patients with hematologic malignancies who underwent alloHCT and received PT-Cy for GVHD prophylaxis at the three Mayo Clinic locations were included in this study. We retrospectively reviewed the Mayo Clinic database and the available electronic medical records to determine the patient, disease, and transplant characteristics. An HCT-CI score of ≥3 was considered high. The EASIX score was calculated from labs available between day –28 (of alloHCT) to the day of starting conditioning and analyzed on log2 transformed values. A log2-EASIX score ≥2.32 was considered high. The cumulative incidence of NRM was determined using competing risk analysis, with relapse considered as competing risk. Overall survival (OS) from transplant was determined using Kaplan–Meier and log-rank methods. Cox-proportional hazard method was used to evaluate factors impacting survival. A total of 199 patients were evaluated. Patients with a high log2-EASIX score had a significantly higher cumulative incidence of NRM at 1 year after alloHCT (34.5% versus 12.3%, P = .003). Competing risk analysis showed that a high log2-EASIX score (HR 2.92, 95% CI 1.38 to 6.17, P = .005) and pre-alloHCT hypertension (HR 2.15, 95% CI 1.06 to 4.36, P = .034) were independently predictive of 1 year-NRM. Accordingly, we combined the two factors to develop a composite risk model stratifying patients in low, intermediate, and high-risk groups: 111 (55.8%) patients were considered low-risk, 76 (38.2%) were intermediate and 12 (6%) were high-risk. Compared to patients in the low-risk group, the intermediate (HR 2.38, 95% CI 1.31 to 4.33, P = .005) and high-risk (HR 5.77, 95% CI 2.31 to 14.39, P < .001) groups were associated with a significantly inferior 1-year OS. Multiorgan failure (MOF) was among the common causes of NRM (14/32, 43.8%) particularly among patients with prior pulmonary comorbidities [7 (50%) patients]. Our study shows that EASIX score is predictive of survival after PT-Cy. The novel EASIX-HTN composite risk model may stratify patients prior to transplant. MOF is a common cause of NRM in patients receiving PT-Cy, particularly among patients with pulmonary comorbidities.
{"title":"Surrogates of Endothelial Injury Predict Survival After Post-transplant Cyclophosphamide","authors":"Anmol Baranwal , Kimberly J. Langer , Mohamed A. Kharfan-Dabaja , Ernesto Ayala , James Foran , Hemant Murthy , Vivek Roy , Madiha Iqbal , Jeanne Palmer , Lisa Z. Sproat , Saurabh Chhabra , Nandita Khera , Urshila Durani , Mehrdad Hefazi , Abhishek Mangaonkar , Mithun V. Shah , Mark R. Litzow , William J. Hogan , Hassan B. Alkhateeb","doi":"10.1016/j.jtct.2024.08.009","DOIUrl":"10.1016/j.jtct.2024.08.009","url":null,"abstract":"<div><div>Post-transplant cyclophosphamide (PT-Cy) is becoming the standard of care for preventing graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplant (alloHCT). Cyclophosphamide is associated with endothelial injury. We hypothesized that the endothelial activation and stress index (EASIX) score, being a marker of endothelial dysfunction, will predict non-relapse mortality (NRM) in alloHCT patients receiving PT-Cy for GVHD prophylaxis. We evaluate the prognostic ability of the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and EASIX scores, and report other factors influencing survival, in patients with hematologic malignancies undergoing alloHCT and receiving PT-Cy-based GVHD prophylaxis. Adult patients with hematologic malignancies who underwent alloHCT and received PT-Cy for GVHD prophylaxis at the three Mayo Clinic locations were included in this study. We retrospectively reviewed the Mayo Clinic database and the available electronic medical records to determine the patient, disease, and transplant characteristics. An HCT-CI score of ≥3 was considered high. The EASIX score was calculated from labs available between day –28 (of alloHCT) to the day of starting conditioning and analyzed on log2 transformed values. A log2-EASIX score ≥2.32 was considered high. The cumulative incidence of NRM was determined using competing risk analysis, with relapse considered as competing risk. Overall survival (OS) from transplant was determined using Kaplan–Meier and log-rank methods. Cox-proportional hazard method was used to evaluate factors impacting survival. A total of 199 patients were evaluated. Patients with a high log2-EASIX score had a significantly higher cumulative incidence of NRM at 1 year after alloHCT (34.5% versus 12.3%, <em>P</em> = .003). Competing risk analysis showed that a high log2-EASIX score (HR 2.92, 95% CI 1.38 to 6.17, <em>P</em> = .005) and pre-alloHCT hypertension (HR 2.15, 95% CI 1.06 to 4.36, <em>P</em> = .034) were independently predictive of 1 year-NRM. Accordingly, we combined the two factors to develop a composite risk model stratifying patients in low, intermediate, and high-risk groups: 111 (55.8%) patients were considered low-risk, 76 (38.2%) were intermediate and 12 (6%) were high-risk. Compared to patients in the low-risk group, the intermediate (HR 2.38, 95% CI 1.31 to 4.33, <em>P</em> = .005) and high-risk (HR 5.77, 95% CI 2.31 to 14.39, <em>P</em> < .001) groups were associated with a significantly inferior 1-year OS. Multiorgan failure (MOF) was among the common causes of NRM (14/32, 43.8%) particularly among patients with prior pulmonary comorbidities [7 (50%) patients]. Our study shows that EASIX score is predictive of survival after PT-Cy. The novel EASIX-HTN composite risk model may stratify patients prior to transplant. MOF is a common cause of NRM in patients receiving PT-Cy, particularly among patients with pulmonary comorbidities.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 1","pages":"Pages 16.e1-16.e9"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000736","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}
Pub Date : 2025-01-01DOI: 10.1016/j.jtct.2024.10.007
Yamuna Naik , Uday Kulkarni , Sharon Lionel , Sushil Selvarajan , Anup J. Devasia , Anu Korula , Kavitha M. Lakshmi , Fouzia N. Aboobacker , Rajesh Balakrishnan , Selvamani Backianathan , Vikram Mathews , Aby Abraham , Biju George
Total marrow and lymphoid irradiation (TMLI) can deliver higher doses of irradiation without increased toxicity. This study evaluated TMLI and cyclophosphamide in patients undergoing stem cell transplantation for acute lymphoblastic leukemia (ALL). A total of 58 patients underwent matched related, unrelated, or haplo-identical donor transplantation using TMLI. The graft source was peripheral blood stem cells (PBSCs) in ALL whereas graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine with methotrexate or post-transplant cyclophosphamide. The median age was 20 years (range: 5-49 years) and included 20 children. Engraftment occurred in 56 (96.5%) at a median of 15 days (range: 12-23) with 2 early deaths. Sinusoidal obstruction syndrome (SOS) was seen in 10 patients whereas hemorrhagic cystitis and cardiac dysfunction occurred in 2 patients each. Cumulative incidence (CI) of grades II-IV acute GVHD was 23.6% whereas the CI of grades III-IV was 10.9%. Chronic GVHD was seen in 46.9% whereas relapse was seen in 10 patients (17.2%). The 2-year overall survival (OS) was 65.9% ± 6.8% and the 2-year disease-free survival (DFS) was 59% ± 6.7%. Outcomes were compared with 52 patients who received either Cy/TBI or Flu/Bu4 for conditioning during the same period. Engraftment rates and time to engraftment were similar. Acute GVHD (P = .002), regimen-related toxicity (P = .043) and day 100 non-relapse mortality (P = .020) were significantly lower with TMLI. TMLI was associated with better OS (P = .004) and DFS (P = .005) for haplo-identical transplants. Better DFS was seen with TMLI in patients with high-risk disease (P = .007) and disease status > CR1 (P = .041). The use of TMLI and cyclophosphamide is associated with good outcomes in patients undergoing hematopoietic stem cell transplantation for ALL, especially with haplo-identical stem cell transplants.
{"title":"Total Marrow and Lymphoid Irradiation (TMLI) Is Associated with Good Early Outcomes in Patients Undergoing Matched Sibling Donor and Haplo-identical Transplants for Acute Lymphoblastic Leukemia","authors":"Yamuna Naik , Uday Kulkarni , Sharon Lionel , Sushil Selvarajan , Anup J. Devasia , Anu Korula , Kavitha M. Lakshmi , Fouzia N. Aboobacker , Rajesh Balakrishnan , Selvamani Backianathan , Vikram Mathews , Aby Abraham , Biju George","doi":"10.1016/j.jtct.2024.10.007","DOIUrl":"10.1016/j.jtct.2024.10.007","url":null,"abstract":"<div><div>Total marrow and lymphoid irradiation (TMLI) can deliver higher doses of irradiation without increased toxicity. This study evaluated TMLI and cyclophosphamide in patients undergoing stem cell transplantation for acute lymphoblastic leukemia (ALL). A total of 58 patients underwent matched related, unrelated, or haplo-identical donor transplantation using TMLI. The graft source was peripheral blood stem cells (PBSCs) in ALL whereas graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine with methotrexate or post-transplant cyclophosphamide. The median age was 20 years (range: 5-49 years) and included 20 children. Engraftment occurred in 56 (96.5%) at a median of 15 days (range: 12-23) with 2 early deaths. Sinusoidal obstruction syndrome (SOS) was seen in 10 patients whereas hemorrhagic cystitis and cardiac dysfunction occurred in 2 patients each. Cumulative incidence (CI) of grades II-IV acute GVHD was 23.6% whereas the CI of grades III-IV was 10.9%. Chronic GVHD was seen in 46.9% whereas relapse was seen in 10 patients (17.2%). The 2-year overall survival (OS) was 65.9% ± 6.8% and the 2-year disease-free survival (DFS) was 59% ± 6.7%. Outcomes were compared with 52 patients who received either Cy/TBI or Flu/Bu4 for conditioning during the same period. Engraftment rates and time to engraftment were similar. Acute GVHD (<em>P</em> = .002), regimen-related toxicity (<em>P</em> = .043) and day 100 non-relapse mortality (<em>P</em> = .020) were significantly lower with TMLI. TMLI was associated with better OS (<em>P</em> = .004) and DFS (<em>P</em> = .005) for haplo-identical transplants. Better DFS was seen with TMLI in patients with high-risk disease (<em>P</em> = .007) and disease status > CR1 (<em>P</em> = .041). The use of TMLI and cyclophosphamide is associated with good outcomes in patients undergoing hematopoietic stem cell transplantation for ALL, especially with haplo-identical stem cell transplants.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 1","pages":"Pages 22.e1-22.e10"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475654","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}
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