使用阿仑妥珠单抗治疗重型 B 型地中海贫血的造血干细胞移植。

IF 1.2 4区 医学 Q4 HEMATOLOGY
Pediatric Hematology and Oncology Pub Date : 2024-05-01 Epub Date: 2023-12-22 DOI:10.1080/08880018.2023.2296933
Luisanna M Sánchez, Anil George, Brian D Friend, Saleh Bhar, Ghadir Sasa, Erin E Doherty, John Craddock, David Steffin, Baheyeldin Salem, Khaled Yassine, Bilal Omer, Caridad Martinez, Kathryn Leung, Robert A Krance, Tami D John
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引用次数: 0

摘要

虽然配型相关供体(MRD)异基因造血干细胞移植(HSCT)是治疗输血依赖型β地中海贫血(TDT)的一种选择,但替代来源的使用越来越多,因此人们开始探索新型移植调节方案,以减少移植物抗宿主病(GVHD)和移植物失败(GF)对移植相关发病率和死亡率的影响。阿来珠单抗是一种 CD52 单克隆抗体,已成功应用于治疗其他血液病的髓鞘消融调理方案中,但在造血干细胞移植中使用阿来珠单抗治疗 TDT 的研究还很有限。本研究的目的是评估在接受标准丁螺环素治疗的同时接受阿仑妥珠单抗治疗的TDT患者的移植、GVHD发生率以及移植相关的发病率和死亡率。主要终点是无严重GVHD、无事件生存期(GEFS)。我们的队列包括24名患者,中位年龄为6.8岁(1.5-14.9岁)。11名患者接受了10/10 MRD造血干细胞移植,11名患者接受了10/10非血缘关系供体(UD),2名患者接受了不匹配的UD。所有患者都实现了初次移植。所有患者的5年GEFS为77.4%,5年总生存率(OS)为91%。在没有供体嵌合体丧失的情况下,GF(归因于移植物功能不佳)的5年累积发生率为13.8%(95% CI:4.5, 35.3)。我们的报告显示,II-IV级急性GVHD(12.5%)和慢性GVHD(4.4%)的发生率较低。年轻和MRD与GEFS、OS和EFS的显著改善有关。我们的研究结果表明,使用阿仑妥珠单抗可促进稳定的移植,降低严重GVHD的发生率,并可获得可接受的GEFS、OS和EFS。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Hematopoietic stem cell transplantation for B-thalassemia major with alemtuzumab.

While matched related donor (MRD) allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for transfusion-dependent beta-thalassemia (TDT), the use of alternative sources has increased, resulting in the exploration of novel transplant-conditioning regimens to reduce the contribution of graft-versus-host disease (GVHD) and graft failure (GF) to transplant-related morbidity and mortality. Alemtuzumab is a CD52 monoclonal antibody that has been successfully incorporated into myeloablative conditioning regimens for other hematologic conditions, yet there have been limited studies regarding the use of alemtuzumab in HSCT for TDT. The purpose of this study was to evaluate engraftment, incidence of GVHD, and transplant related morbidity and mortality in patients with TDT who received alemtuzumab in addition to standard busulfan-based conditioning. The primary endpoint was severe GVHD-free, event-free survival (GEFS). Our cohort included 24 patients with a median age of 6.8 years (range 1.5-14.9). Eleven patients received a 10/10 MRD HSCT, eleven 10/10 unrelated donor (UD), and two mismatched UD. All patients achieved primary engraftment. For all patients, 5-year GEFS was 77.4% and 5-year overall survival (OS) was 91%. The 5-year cumulative incidence of GF (attributed to poor graft function) without loss of donor chimerism was 13.8% (95% CI: 4.5, 35.3). We report low rates of significant acute GVHD grade II-IV (12.5%) and chronic GVHD (4.4%). Younger age and MRD were associated with significantly improved GEFS, OS and EFS. Our results show that the use of alemtuzumab promotes stable engraftment, may reduce rates of severe GVHD, and results in acceptable GEFS, OS, and EFS.

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来源期刊
CiteScore
2.60
自引率
5.90%
发文量
71
审稿时长
6-12 weeks
期刊介绍: PHO: Pediatric Hematology and Oncology covers all aspects of research and patient management within the area of blood disorders and malignant diseases of childhood. Our goal is to make PHO: Pediatric Hematology and Oncology the premier journal for the international community of clinicians and scientists who together aim to define optimal therapeutic strategies for children and young adults with cancer and blood disorders. The journal supports articles that address research in diverse clinical settings, exceptional case studies/series that add novel insights into pathogenesis and/or clinical care, and reviews highlighting discoveries and challenges emerging from consortia and conferences. Clinical studies as well as basic and translational research reports regarding cancer pathogenesis, genetics, molecular diagnostics, pharmacology, stem cells, molecular targeting, cellular and immune therapies and transplantation are of interest. Papers with a focus on supportive care, late effects and on related ethical, legal, psychological, social, cultural, or historical aspects of these fields are also appreciated. Reviews on important developments in the field are welcome. Articles from scientists and clinicians across the international community of Pediatric Hematology and Oncology are considered for publication. The journal is not dependent on or connected with any organization or society. All submissions undergo rigorous peer review prior to publication. Our Editorial Board includes experts in Pediatric Hematology and Oncology representing a wide range of academic and geographic diversity.
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