Transplantation and Cellular Therapy最新文献

{"title":"Changes in Chronic Graft-versus-Host Disease Treatment Over Time: A 15-Years Survey Within Allogeneic Hematopoietic Stem Cell Transplant Centers in Germany, Austria, and Switzerland.","authors":"Alexander Denk, Matthias Alexander Fante, Silke Heidenreich, Hildegard T Greinix, Eva-Maria Wagner Drouet, Katharina Egger-Heidrich, Julia Marx, Darina Kodzhabasheva, William Krüger, Gesine Bug, Claudia Wehr, Joerg Halter, Irene Teichert von Lüttichau, Lutz Peter Mueller, Olaf Penack, Inken Hilgendorf, Guido Kobbe, Stefan Klein, Anita Lawitschka, Jochen Frietsch, Julia Winkler, Daniel Wolff","doi":"10.1016/j.jtct.2025.04.017","DOIUrl":"10.1016/j.jtct.2025.04.017","url":null,"abstract":"<p><strong>Background: </strong>Chronic graft-versus-host disease (cGVHD) represents a major complication after allogeneic stem cell transplantation (alloHSCT). In 2009 and 2018 a survey among German, Austrian, and Swiss transplant centers showed a homogeneous 1<sup>st</sup>-line treatment practice, while 2nd-line treatment as well as management of progressive onset type and bronchiolitis obliterans syndrome (BOS) displayed significant heterogeneity. Since the last survey, ruxolitinib (rux) has been approved and other new agents are explored in treatment of cGVHD.</p><p><strong>Objective: </strong>We conducted a follow-up survey in 2024 to document the impact of recent approvals and new agents on treatment pattern focusing on management of 2nd-line treatment, progressive onset type, BOS, and sclerotic manifestations.</p><p><strong>Study design: </strong>A paper-and-pencil-based questionnaire was sent electronically to 60 German speaking centers performing alloHSCT. 20 centers responded, representing 45% of the patients receiving an alloHSCT in 2023 in Germany, Austria, and Switzerland.</p><p><strong>Results: </strong>In 1<sup>st</sup>-line treatment of classic standard risk cGVHD, single agent prednisone represents standard of care (14/20 centers) which may be combined with calcineurin inhibitor (CNI) (4/20), while rux is used in selected cases only. In 2nd-line treatment rux is now used by the majority of centers (19/20). In the presence of cytopenia, rux remains the preferred agent (12/20) while use of extracorporeal photopheresis (ECP) is considered by 8 of 20 centers. In case of active infections, ECP is preferred by 15 of 20 centers and both agents are regarded as steroid-sparing agents in 2nd-line treatment of steroid-dependent cGVHD. Rux would be applied in the presence of active infections by 5/20 centers only. Moreover, rux (15/20) and ECP (6/20) are also preferred treatment modalities in treatment of progressive onset cGVHD. For BOS, systemic and inhalative corticosteroids, montelukast and azithromycin (FAM, 13/20), rux (15/20), ECP (17/20) and CNI (10/20) are frequently applied agents, while abatacept (8/20), belumosudil (7/20), imatinib (5/20), mycophenolate mofetil (MMF) (5/20), everolimus (4/20) and ibrutinib (3/20) are used as salvage options in selected patients only. In case of new sclerotic manifestations after failure of 2nd-line treatment including steroids, CNI and rux, most centers would use ECP (14/20), whereas subsequent or alternative salvage treatment of sclerotic manifestations remains heterogenous comprising belumosudil (13/20), ibrutinib (5/20), imatinib (5/20), rituximab (4/20), cyclosporine (3/20), tacrolimus (3/20), everolimus (3/20), sirolimus (3/20), methotrexate (3/20) and MMF (3/20). The preferred taper sequence of immunosuppressive agents in case of response applied in 12/20 centers is initial taper of steroids, followed by taper of CNI and final termination of rux.</p><p><strong>Conclusion: </strong>The surve","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036410","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":"Out-of-Pocket Expenditures and Financial Hardship Among Patients With Myelodysplastic Syndrome Undergoing Allogeneic Transplant or Hypomethylating Agent / Supportive Care (BMT CTN 1102).","authors":"Christopher T Su, Wael Saber, Aasthaa Bansal, Li Li, Ryotaro Nakamura, Corey Cutler, Joshua A Roth, Winona Wright, Lotte Steuten, Scott D Ramsey","doi":"10.1016/j.jtct.2025.04.015","DOIUrl":"10.1016/j.jtct.2025.04.015","url":null,"abstract":"<p><strong>Introduction: </strong>The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1102 trial demonstrated that allogeneic hematopoietic cell transplantation (HCT) was associated with superior overall survival compared to non-HCT approaches among elderly patients with higher-risk myelodysplastic syndrome (MDS). The trial included an ancillary cost diary component to assess the out-of-pocket (OOP) expenditures and financial hardship in the post-HCT period through 3 phased surveys for up to 19 months after enrollment.</p><p><strong>Objective: </strong>The purpose of the study is to assess the OOP costs and financial hardship experienced by participants of BMT CTN 1102.</p><p><strong>Study design: </strong>BMT CTN 1102 assigned participants to Donor and No-Donor arms based on donor availability. Participants could additionally enroll in the ancillary cost diary component, with a total of 138 participants returning 267 surveys across 3 survey waves at 1-, 7-, and 19-months after enrollment. As participants who underwent HCT returned 78% (207/267) of the total surveys, we report on the collected data descriptively.</p><p><strong>Results: </strong>Participants who underwent HCT had high levels of monthly OOP expenditure ($1126, $812, $442) and financial hardship (47%, 53%, 57%) across the 3 survey waves. For reference, participants who did not undergo HCT generally reported lower levels of OOP expenditure ($478, $845, $256) and financial hardship (37%, 55%, 46%).</p><p><strong>Conclusion: </strong>Among BMT CTN 1102 participants, those who underwent HCT reported high levels of OOP expenditures and financial hardship for up to 19 months after enrollment. Ongoing routine assessment of patient-level OOP expenditures and financial burden may be helpful in the post-HCT survivorship period.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020440","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":"What's Best? Transformative Therapies for Adults with Sickle Cell Disease","authors":"John J Strouse ,&nbsp;Adetola Kassim","doi":"10.1016/j.jtct.2025.04.004","DOIUrl":"10.1016/j.jtct.2025.04.004","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 5","pages":"Pages 279-281"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903372","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":"Unravelling T Cell Immunity in CAR-T Therapy: Implications for Influenza Vaccination","authors":"Adam G Stewart ,&nbsp;Roy F Chemaly","doi":"10.1016/j.jtct.2025.04.003","DOIUrl":"10.1016/j.jtct.2025.04.003","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 5","pages":"Pages 282-284"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Masthead (Purpose and Scope)","authors":"","doi":"10.1016/S2666-6367(25)01161-3","DOIUrl":"10.1016/S2666-6367(25)01161-3","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 5","pages":"Pages A1-A2"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904500","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":"Outcome of Patients With IDH-Mutated AML Following Allogeneic Stem Cell Transplantation—A Retrospective Analysis on Behalf of the German Registry for Hematopoietic Stem Cell Transplantation and Cell Therapy, DRST","authors":"Thomas Schroeder ,&nbsp;Sarah Flossdorf ,&nbsp;Claudia Schuh ,&nbsp;Caroline Pabst ,&nbsp;Michael Stadler ,&nbsp;Johannes Schetelig ,&nbsp;Claudia Wehr ,&nbsp;Matthias Stelljes ,&nbsp;Elisa Sala ,&nbsp;Andreas Burchert ,&nbsp;Julia Winkler ,&nbsp;H. Christian Reinhardt ,&nbsp;Nicolaus Kröger ,&nbsp;Katharina Fleischhauer ,&nbsp;Christina Rautenberg","doi":"10.1016/j.jtct.2025.02.018","DOIUrl":"10.1016/j.jtct.2025.02.018","url":null,"abstract":"<div><div>Mutations in isocitrate dehydrogenase 1 and 2 genes (<em>IDH1</em> and <em>IDH2</em>) are found in 15% to 20% of patients with acute myeloid leukemia (AML). <em>IDH</em> inhibitors have been introduced as targeted treatment and are currently under investigation as maintenance therapy after allogeneic transplantation (allo-SCT). Since reports about the outcome of <em>IDH1</em>- and <em>IDH2</em>-mutated (<em>IDH</em>mut) AML after allo-SCT are limited, we retrospectively analyzed 356 <em>IDH</em>-mutated AML patients (<em>IDH1</em> 40%, <em>IDH2</em> 60%). Ten patients (4%) had received an <em>IDH</em> inhibitor prior transplantation, but none had received maintenance with <em>IDH</em> inhibitors. After a median follow-up of 24 months 3-year probabilities of overall (OS) and event-free (EFS) survival, relapse and nonrelapse mortality (NRM) for the entire cohort were 73%, 60%, 27% and 13% respectively. While 3-year OS (78% versus 70%), EFS (56% versus 63%) and NRM (10% versus 14%) rates were similar for <em>IDH1</em>mut and <em>IDH2</em>mut patients, relapse incidence was numerically higher in <em>IDH1</em>mut patients (34% versus 24%) and landmark analysis suggested a continuous rise of relapse incidence preferentially in <em>IDH1</em>mut AML also beyond the first year. Concordantly, <em>IDH2</em> mutation was associated with superior EFS and by trend with lower relapse incidence. The strongest risk factor for adverse outcomes, however, was AML not in CR. This analysis provides benchmarks for interpretation of results emerging from post-transplant maintenance trials in <em>IDH</em>mut AML and suggest that maintenance strategies may further optimize the promising outcome in this molecularly defined subgroup by reducing relapse risk, especially for patients whose AML is not in remission at time of alloHCT.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 5","pages":"Pages 303.e1-303.e9"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587139","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":"Belumosudil for Chronic Graft-Versus-Host Disease: Analysis of Long-Term Results from the KD025-208 and ROCKstar Studies.","authors":"Stephanie J Lee, Steven Pavletic, Bruce R Blazar, Yu Yao, Ran Ji, Kathy Marshall, Corey Cutler","doi":"10.1016/j.jtct.2025.04.020","DOIUrl":"10.1016/j.jtct.2025.04.020","url":null,"abstract":"<p><p>Belumosudil is an oral selective rho-associated coiled-coil-containing protein kinase-2 (ROCK2) inhibitor approved for the treatment of chronic graft-versus-host disease (cGVHD) following an allogeneic hematopoietic cell transplant in patients aged ≥12 years after failure of ≥2 prior systemic lines of therapy. The KD025-208 (NCT02841995) and KD025-213 (ROCKstar; NCT03640481) studies demonstrated that belumosudil was well tolerated, with clinically meaningful responses in patients with cGVHD. KD025-217 (NCT05305989) is a follow-up study that evaluated extended treatment with belumosudil in patients enrolled in the parent studies, KD025-208 and ROCKstar. This pooled analysis reports the long-term follow-up (overall median follow-up duration of 31.4 months) results from these studies in patients with cGVHD. The study included a total of 208 patients across 3 cohorts. Cohort 1 (n = 95) received belumosudil 200 mg once daily, cohort 2 (n = 92) received belumosudil 200 mg twice daily, and cohort 3 (n = 21) received belumosudil 400 mg once daily. The primary endpoint was best overall response rate (ORR). Duration of response (DOR), failure-free survival (FFS), and time to next treatment (TTNT) were also evaluated in this analysis. The best ORR in the modified intent-to-treat (mITT) population was 72%. The median DOR for the responder population was 62.3 weeks (range, 36.1 to 82.6 weeks). The median FFS in the mITT population was 15.1 months (range, 11.3 to 20.6 months). The 1- and 2-year FFS rates were 56% and 40%, respectively. The median TTNT was 22.1 months (range, 15.2 to 40.3 months), where 47% of patients received a new systemic therapy for cGVHD by 36 months. When compared with the published data, the long-term results from this pooled analysis of these two phase 2 studies demonstrated belumosudil was associated with durable responses, and it remained well tolerated with no new safety concerns.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033703","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 ,&nbsp;Sisse Rye Ostrowski ,&nbsp;Niels Smedegaard Andersen ,&nbsp;Lone Smidstrup Friis ,&nbsp;Brian Kornblit ,&nbsp;Søren Lykke Petersen ,&nbsp;Ida Schjødt ,&nbsp;Henrik Sengeløv ,&nbsp;Lars Klingen Gjærde","doi":"10.1016/j.jtct.2025.02.015","DOIUrl":"10.1016/j.jtct.2025.02.015","url":null,"abstract":"<div><div>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 (<em>P</em> &lt; .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], <em>P</em> = .03), also after adjustment for risk factors of acute GVHD (OR 0.78 per 5 AU increase [95% CI: 0.56 to 0.96], <em>P</em> = .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 <em>ρ</em> = 0.522, <em>P</em> &lt; .001; and Spearman's <em>ρ</em> = 0.386, <em>P</em> &lt; .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.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 5","pages":"Pages 301.e1-301.e10"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","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":"Profile of a Pioneer: Carl H. June","authors":"David L. Porter ,&nbsp;Stephan A. Grupp","doi":"10.1016/j.jtct.2025.04.002","DOIUrl":"10.1016/j.jtct.2025.04.002","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 5","pages":"Pages 273-278"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903371","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":"Co-designing a Novel Ordinal Endpoint for an Adaptive Platform Trial, BANDICOOT, in Pediatric Hematopoietic Stem Cell Transplant","authors":"Hannah Walker ,&nbsp;Lorna McLeman ,&nbsp;Deborah Meyran ,&nbsp;Li-yin Goh ,&nbsp;Peter Summers ,&nbsp;Julian Stolper ,&nbsp;Diane Hanna ,&nbsp;David Hughes ,&nbsp;Stacie Wang ,&nbsp;Claudia Toro ,&nbsp;Elizabeth Williams ,&nbsp;Roxanne Dyas ,&nbsp;Lori Chait Rubinek ,&nbsp;Kaitlyn Taylor ,&nbsp;Chris J. Selman ,&nbsp;Anneke Grobler ,&nbsp;Katherine J. Lee ,&nbsp;Tom Snelling ,&nbsp;Theresa Cole ,&nbsp;Amanda Gwee ,&nbsp;Rachel Conyers","doi":"10.1016/j.jtct.2025.01.894","DOIUrl":"10.1016/j.jtct.2025.01.894","url":null,"abstract":"<div><div>An adaptive platform trial (APT) offers the ability to incorporate several research questions in the same target population across multiple domains (interventions), with the ability to add new questions in a perpetual manner. An APT is particularly appealing for pediatric hematopoietic stem cell transplant (HCT); an area of high heterogeneity, limited trial availability, and high mortality. Ideally, all domains in an APT would have the same primary endpoint. Therefore, an ordinal endpoint with multiple categories that combines various clinical outcomes into a single outcome measure is particularly appealing for APTs. Unfortunately, there is no accepted ordinal endpoint for pediatric HCT trials. This article aims to describe the methodology used to co-design a novel primary ordinal endpoint for the pediatric HCT APT — BANDICOOT. BANDICOOT is a study that aims to <em>build an adaptive novel platform design — improving the complications, cost-effectiveness, outcomes, and overall survival from hematopoietic stem cell transplantation.</em>The results of this process identified two potential ordinal endpoints that could be used, one focusing on organ support and the other on a combination of organ support, viral reactivation, and immune reconstitution. We explored the data extraction required for these endpoints from electronic medical records that we will utilize to validate the endpoints and determine which will be used in the APT BANDICOOT. In an era in which APTs are becoming increasingly utilized to answer important questions in clinical care, this article describes a reproducible strategy for the design of high-quality and meaningful ordinal endpoints.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 5","pages":"Pages 321.e1-321.e12"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374705","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}