Pub Date : 2025-03-01DOI: 10.1016/S2666-6367(25)01026-7
{"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}
Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2025.02.007
Vinodh Pillai
{"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}
Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2024.12.017
Christopher E. Dandoy , Jeffery J. Auletta , Priscila Badia , Alan Bidgoli , Nancy M. Daraiseh , Anna M. DeSalvo , Javier Diaz , Stella M. Davies , Kathleen Demmel , Eleanor Cook , John A. Craddock , John Huber , Megan Sampson , Taylor J. Fitch , Karis French , Sonata Jodele , Samantha M. Jaglowski , Malika A. Kapadia , Nandita Khera , Georgia R. Kent , David Hartley
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.
{"title":"Engraft: A Collaborative Learning Health Network for Enhanced Transplant and Cellular Therapy Outcomes","authors":"Christopher E. Dandoy , Jeffery J. Auletta , Priscila Badia , Alan Bidgoli , Nancy M. Daraiseh , Anna M. DeSalvo , Javier Diaz , Stella M. Davies , Kathleen Demmel , Eleanor Cook , John A. Craddock , John Huber , Megan Sampson , Taylor J. Fitch , Karis French , Sonata Jodele , Samantha M. Jaglowski , Malika A. Kapadia , Nandita Khera , Georgia R. Kent , 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}
Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2024.12.021
Cindy Lynn Hickey , Mei-Jie Zhang , Mariam Allbee-Johnson , Rizwan Romee , Navneet S. Majhail , Monzr M. Al Malki , Joseph H. Antin , Cara L. Benjamin , Christopher Bredeson , Saurabh Chhabra , Michael R. Grunwald , Yoshihiro Inamoto , Christopher G. Kanakry , Filippo Milano , Robert J. Soiffer , Scott R. Solomon , Stephen R. Spellman , Claudio G. Brunstein , Corey Cutler
Background
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.
Study Design
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.
Results
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 (P = .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; P = .005), and earlier year of HCT (2015–2018 vs. 2011–2014; HR, 0.39; 95% CI, 0.24-0.64; P = .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; P = .67) when adjusted for donor age nor when restricted to PBSC grafts only (HR, 0.85; P = .70).
Conclusion
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.
背景：移植后环磷酰胺（PTCy）是一种常用的移植物抗宿主病（GVHD）预防药物，特别是在单倍同型（haplo）造血细胞移植（HCT）的情况下。据报道，在使用PTCy的单倍hct受体中，移植失败率高达12-20%。本研究的目的是确定供体类型是否影响基于ptc的GVHD预防RIC HCT后移植失败的风险。研究设计：使用CIBMTR研究数据库，对2011年至2018年间接受首次降低强度调节（RIC）单倍体或8/8 MUD HCT治疗AML、ALL或MDS的PTCy GVHD预防的成年患者进行回顾性队列分析。主要结局是晚期移植物衰竭的发生率，定义为在没有复发的情况下继发性移植物丧失，或移植物功能差需要细胞治疗干预。结果：共有1336例患者符合入选标准（haplo 1151例，MUD 185例）。MUD组患者年龄较大（65岁vs 61岁），种族差异较小（95% vs 72%高加索人），接受骨髓移植较少（45% vs 16%），并且供者年龄较年轻（中位年龄28岁vs 37岁）。调理方案主要为氟达拉滨、环磷酰胺和全身照射（87%为单倍率，38%为单倍率）。在2年时，haplo组晚期移植物失败的调整概率为6.5%(95%可信区间（CI） 5.2-8.0)，而MUD组为5.9% (95% CI 2.7-10.9) （p=0.79）。晚期移植物衰竭相关危险因素的多因素分析发现与MDS诊断相关(HR 1.98；95% ci 1.22-3.20；p=0.005)，早期HCT (2015-2018 vs. 2011-2014；人力资源0.39;95% ci 0.24-0.64；p = 0.0002)。进行了事后敏感性分析，以评估供体年龄和使用PBSC移植物的影响。移植失败在haplo和MUD HCT之间没有差异(HR 1.19；p=0.67)，当调整供者年龄时，也当仅限于PBSC移植物时(HR 0.85；p = 0.70)。结论：在这项基于注册表的分析中，接受RIC HCT治疗AML、ALL或MDS的患者使用PTCy预防GVHD，单倍体供体和MUD供体的晚期移植失败率没有显著差异。晚期移植物衰竭的总体发生率很高。
{"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 , Mei-Jie Zhang , Mariam Allbee-Johnson , Rizwan Romee , Navneet S. Majhail , Monzr M. Al Malki , Joseph H. Antin , Cara L. Benjamin , Christopher Bredeson , Saurabh Chhabra , Michael R. Grunwald , Yoshihiro Inamoto , Christopher G. Kanakry , Filippo Milano , Robert J. Soiffer , Scott R. Solomon , Stephen R. Spellman , Claudio G. Brunstein , 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}
Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2025.02.019
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
Background: 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 2019-2020 influenza vaccination.
Methods: Peripheral blood mononuclear cells were isolated from healthy controls and patients who received the 2019-2020 influenza vaccine pre- or post-CD19, CD20 or B cell maturation antigen (BCMA) CAR-T. T cells were expanded in vitro for 10 days with peptide libraries for hemagglutinin (HA) and nucleoprotein (NP) from the 2019-2020 vaccine influenza A strains and analyzed by flow cytometry following IFNγ/TNFα intracellular staining. Antibody response was evaluated by a hemagglutination-inhibition (HAI) assay.
Results: 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 IgG or absolute lymphocyte count and change in CD4+ T cell IFNγ+/TNFα+ response pre- to post-vaccine for the post-CART cohort.
Conclusion: 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.
{"title":"T cell immune response to influenza vaccination when administered prior to and following autologous CAR-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><strong>Background: </strong>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 2019-2020 influenza vaccination.</p><p><strong>Methods: </strong>Peripheral blood mononuclear cells were isolated from healthy controls and patients who received the 2019-2020 influenza vaccine pre- or post-CD19, CD20 or B cell maturation antigen (BCMA) CAR-T. T cells were expanded in vitro for 10 days with peptide libraries for hemagglutinin (HA) and nucleoprotein (NP) from the 2019-2020 vaccine influenza A strains and analyzed by flow cytometry following IFNγ/TNFα intracellular staining. Antibody response was evaluated by a hemagglutination-inhibition (HAI) assay.</p><p><strong>Results: </strong>Twenty-nine participants, including eight immunocompetent adults, seven pre-CAR-T and 14 post-CAR-T patients, were evaluated. IFNγ<sup>+</sup>/TNFα<sup>+</sup> 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 IgG or absolute lymphocyte count and change in CD4+ T cell IFNγ<sup>+</sup>/TNFα<sup>+</sup> response pre- to post-vaccine for the post-CART cohort.</p><p><strong>Conclusion: </strong>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}
Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2024.12.006
Pedro Chorão , Marta Villalba , Aitana Balaguer-Roselló , Juan Montoro , Pablo Granados , Carmen Gilabert , Francisca Panadero , André Airosa Pardal , Eva María González , Santiago de Cossio , Rafael Benavente , María Dolores Gómez , Inés Gómez , Pilar Solves , Marta Santiago , Pedro Asensi , Pilar Lloret , Juan Eiris , David Martínez , Alberto Louro , Jaime Sanz
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 (P = .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 (P = .02). Additionally, higher grades were associated with a greater transfusion burden (P < .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.
{"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 , Marta Villalba , Aitana Balaguer-Roselló , Juan Montoro , Pablo Granados , Carmen Gilabert , Francisca Panadero , André Airosa Pardal , Eva María González , Santiago de Cossio , Rafael Benavente , María Dolores Gómez , Inés Gómez , Pilar Solves , Marta Santiago , Pedro Asensi , Pilar Lloret , Juan Eiris , David Martínez , Alberto Louro , 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> < .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}
Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2024.12.024
Robert Puckrin , Megan Kinzel , Douglas Stewart , Ahsan Chaudhry , Kareem Jamani , Jan Storek
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, P < .001); CLL and acute lymphoblastic leukemia (ALL) for grade 3-4 aGVHD (SHR for CLL 3.54, 95% CI 1.54-8.17, P = .003 and SHR for ALL 2.26, 95% CI 1.26-4.04, P = .006); and myelofibrosis (MF) for moderate-severe cGVHD (SHR 2.14, 95 CI 1.34-3.41, P = .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.
多种因素影响同种异体造血细胞移植（HCT）后急性或慢性移植物抗宿主病（aGVHD或cGVHD）的风险，包括潜在的慢性髓性白血病（CML）和高剂量全身照射（TBI）。然而，在现代，基础疾病或低剂量TBI对GVHD风险的影响尚未确定。在以抗胸腺细胞球蛋白（ATG）为基础的GVHD预防的背景下，确定现代GVHD的危险因素。这项回顾性研究纳入了1219例血液恶性肿瘤患者，他们接受了首次外周血异体HCT，使用清髓性氟达拉滨和布硫凡调节±低剂量全身照射，以及ATG、环孢素和甲氨蝶呤作为GVHD预防。采用多变量竞争风险回归比较患者亚组间调整后的GVHD累积发病率。当不考虑潜在疾病时，2-4级aGVHD的危险因素是供体类型而不是匹配的兄弟姐妹供体（非msd）和缺乏低剂量TBI（非TBI）。3-4级aGVHD的危险因素为非msd、非tbi和CMV供体阴性/受体阳性血清状态（D-R+）。中重度cGVHD的危险因素为HLA配型≤9/10、非男性/男性、非tbi。在包括基础疾病的模型中，2至4级aGVHD的其他显著危险因素是慢性淋巴细胞白血病（CLL）（亚危险比超过急性髓性白血病[SHR] 3.16, 95% CI 1.97-5.08, P < .001）；CLL和急性淋巴细胞白血病（ALL）的3-4级aGVHD (CLL的SHR为3.54,95% CI 1.54 ~ 8.17, P = 。ALL的SHR为2.26,95% CI 1.26-4.04, P = 0.006)；中重度cGVHD患者的骨髓纤维化（SHR 2.14, 95 CI 1.34-3.41, P = .001）。在现代使用ATG预防GVHD时，新发现的危险因素包括2-4级aGVHD的CLL和非tbi；3-4级aGVHD的CLL、ALL和非tbi；中重度cGVHD为MF和非tbi。这些发现，如果在一个单独的队列中得到证实，在调整GVHD的预防和监测时应予以考虑。
{"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 , Megan Kinzel , Douglas Stewart , Ahsan Chaudhry , Kareem Jamani , 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> < .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}
Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2025.02.006
Keith M. Sullivan , Jean E. Sanders
{"title":"The Cure of Thalassemia and the Angst of a Junior Attending","authors":"Keith M. Sullivan , 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}
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.
{"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}
Pub Date : 2025-02-24DOI: 10.1016/j.jtct.2025.02.021
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
<p><p>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
{"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":"<p><p>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}
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