Abatacept Prevents Severe Acute Graft-Versus-Host Disease Without Increasing Graft Failure Risk in Pediatric Bone Marrow Failure Syndromes

IF 2.3 3区医学 Q2 HEMATOLOGY

Pediatric Blood & Cancer Pub Date : 2025-09-28 DOI:10.1002/pbc.32085

Zahra Hudda, Stella M. Davies, Adam Lane, Deborah E. Schiff, Eric J. Anderson, Parinda A. Mehta, Kasiani C. Myers, Nicholas J. Gloude

{"title":"Abatacept Prevents Severe Acute Graft-Versus-Host Disease Without Increasing Graft Failure Risk in Pediatric Bone Marrow Failure Syndromes","authors":"Zahra Hudda, Stella M. Davies, Adam Lane, Deborah E. Schiff, Eric J. Anderson, Parinda A. Mehta, Kasiani C. Myers, Nicholas J. Gloude","doi":"10.1002/pbc.32085","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Pediatric patients with inherited or acquired bone marrow failure syndromes (BMFS) often require an allogeneic hematopoietic stem cell transplant (HSCT) to cure the hematological manifestations. Amongst these, those without a matched sibling donor (MSD), are at increased risk for graft failure and are known to tolerate graft-versus-host disease (GVHD) poorly. Abatacept (ABA) is Food and Drug Administration (FDA)-approved for the prevention of acute GVHD.</p>\n </section>\n \n <section>\n \n <h3> Objectives</h3>\n \n <p>Our primary objective was to investigate the cumulative incidence (CI) of severe acute (Grade III–IV) GVHD in patients with BMFS undergoing a matched unrelated donor (MUD) or mismatched related or unrelated donor (MMRD/MMUD) HSCT with ABA added to standard GVHD prophylaxis of calcineurin inhibitor and methotrexate or mycophenolate mofetil, and evaluate the incidence of graft failure. Secondary outcomes included overall survival (OS) and acute and chronic GVHD-free graft failure-free overall survival (GFS) at 1 year.</p>\n </section>\n \n <section>\n \n <h3> Study Design</h3>\n \n <p>We compared the CI of severe acute GVHD and graft failure by Day 180 in patients who received ABA (<i>n</i> = 26), against a historical cohort of HSCT BMFS patients who did not receive ABA (<i>n</i> = 21) in a combined retrospective review from two centers.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>None of the patients in the ABA cohort experienced severe (Grade III–IV) acute GVHD compared to 14% in our historical cohort (CI 0% vs. 14%, <i>p</i> = 0.05). All patients in our ABA cohort successfully engrafted, with one patient experiencing poor graft function. In the historical cohort, one patient experienced primary graft failure. The rates of chronic GVHD were comparable between the historical and ABA groups, 28.6% versus 19.2% (<i>p</i> = 0.51). The OS (95.2% vs. 96.0%, <i>p</i> = 0.3) and GFS at 1 year (64.3% vs. 65.3%, <i>p</i> = 0.5) were similar in the ABA group compared to the historical group.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>ABA was well tolerated in patients with BMFS and prevented severe acute GVHD without increasing the incidence of graft failure. Rates of chronic GVHD and GFS at 1 year were similar, but analysis was limited due to sample size and variability in ABA dosing.</p>\n </section>\n </div>","PeriodicalId":19822,"journal":{"name":"Pediatric Blood & Cancer","volume":"72 12","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/pbc.32085","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Blood & Cancer","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/pbc.32085","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Pediatric patients with inherited or acquired bone marrow failure syndromes (BMFS) often require an allogeneic hematopoietic stem cell transplant (HSCT) to cure the hematological manifestations. Amongst these, those without a matched sibling donor (MSD), are at increased risk for graft failure and are known to tolerate graft-versus-host disease (GVHD) poorly. Abatacept (ABA) is Food and Drug Administration (FDA)-approved for the prevention of acute GVHD.

Objectives

Our primary objective was to investigate the cumulative incidence (CI) of severe acute (Grade III–IV) GVHD in patients with BMFS undergoing a matched unrelated donor (MUD) or mismatched related or unrelated donor (MMRD/MMUD) HSCT with ABA added to standard GVHD prophylaxis of calcineurin inhibitor and methotrexate or mycophenolate mofetil, and evaluate the incidence of graft failure. Secondary outcomes included overall survival (OS) and acute and chronic GVHD-free graft failure-free overall survival (GFS) at 1 year.

Study Design

We compared the CI of severe acute GVHD and graft failure by Day 180 in patients who received ABA (n = 26), against a historical cohort of HSCT BMFS patients who did not receive ABA (n = 21) in a combined retrospective review from two centers.

Results

None of the patients in the ABA cohort experienced severe (Grade III–IV) acute GVHD compared to 14% in our historical cohort (CI 0% vs. 14%, p = 0.05). All patients in our ABA cohort successfully engrafted, with one patient experiencing poor graft function. In the historical cohort, one patient experienced primary graft failure. The rates of chronic GVHD were comparable between the historical and ABA groups, 28.6% versus 19.2% (p = 0.51). The OS (95.2% vs. 96.0%, p = 0.3) and GFS at 1 year (64.3% vs. 65.3%, p = 0.5) were similar in the ABA group compared to the historical group.

Conclusion

ABA was well tolerated in patients with BMFS and prevented severe acute GVHD without increasing the incidence of graft failure. Rates of chronic GVHD and GFS at 1 year were similar, but analysis was limited due to sample size and variability in ABA dosing.

Abstract Image

查看原文本刊更多论文

阿巴接受预防严重的急性移植物抗宿主病而不增加儿童骨髓衰竭综合征的移植物衰竭风险。

背景：患有遗传性或获得性骨髓衰竭综合征（BMFS）的儿童患者通常需要异体造血干细胞移植（HSCT）来治疗血液学表现。其中，那些没有匹配的兄弟姐妹供体（MSD）的人，移植物衰竭的风险增加，并且对移植物抗宿主病（GVHD）的耐受性较差。abataccept （ABA）是美国食品和药物管理局（FDA）批准用于预防急性GVHD的药物。目的：我们的主要目的是研究BMFS患者在接受匹配的非相关供体（MUD）或不匹配的相关或非相关供体（MMRD/MMUD） HSCT时，在钙调磷酸酶抑制剂和甲氨蝶呤或霉酚酸酯的标准GVHD预防措施中添加ABA的累积发生率（CI），并评估移植物衰竭的发生率。次要结局包括1年总生存期（OS）和急性和慢性无gvhd移植物无衰竭总生存期（GFS）。研究设计：在两个中心的联合回顾性评价中，我们比较了接受ABA治疗的患者（n = 26）与未接受ABA治疗的HSCT BMFS患者（n = 21）在180天内严重急性GVHD和移植物衰竭的CI。结果：ABA队列中没有患者发生严重（III-IV级）急性GVHD，而我们的历史队列中这一比例为14% （CI 0% vs. 14%, p = 0.05）。在我们的ABA队列中，所有患者都成功移植，只有1例患者出现移植物功能不良。在历史队列中，一名患者经历了原发性移植物衰竭。慢性GVHD的发生率在历史组和ABA组之间具有可比性，分别为28.6%和19.2% （p = 0.51）。ABA组1年OS （95.2% vs. 96.0%, p = 0.3）和GFS （64.3% vs. 65.3%, p = 0.5）与历史组相似。结论：ABA在BMFS患者中耐受性良好，可预防严重急性GVHD，且不增加移植物衰竭的发生率。慢性GVHD和GFS的1年发生率相似，但由于样本量和ABA剂量的可变性，分析受到限制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Pediatric Blood & Cancer 医学-小儿科

CiteScore

4.90

自引率

9.40%

发文量

546

审稿时长

1.5 months

期刊介绍： Pediatric Blood & Cancer publishes the highest quality manuscripts describing basic and clinical investigations of blood disorders and malignant diseases of childhood including diagnosis, treatment, epidemiology, etiology, biology, and molecular and clinical genetics of these diseases as they affect children, adolescents, and young adults. Pediatric Blood & Cancer will also include studies on such treatment options as hematopoietic stem cell transplantation, immunology, and gene therapy.