Low Nonrelapse Mortality after HLA-Matched Related 2-Step Hematopoietic Stem Cell Transplantation Using Cyclophosphamide for Graft-versus-Host Disease Prophylaxis and the Potential Impact of Non- Cyclophosphamide-Exposed T Cells on Outcomes

Dolores Grosso , Matthew Carabasi , Joanne Filicko-O'Hara , John L. Wagner , William O'Hara , Michael Sun , Beth Colombe , W. Shi , Maria Werner-Wasik , Shannon Rudolph , Onder Alpdogan , Adam Binder , Margaret Kasner , Thomas Klumpp , Ubaldo Martinez-Outschoorn , Neil Palmisiano , Lindsay Wilde , Pierluigi Porcu , Usama Gergis , Neal Flomenberg
{"title":"Low Nonrelapse Mortality after HLA-Matched Related 2-Step Hematopoietic Stem Cell Transplantation Using Cyclophosphamide for Graft-versus-Host Disease Prophylaxis and the Potential Impact of Non- Cyclophosphamide-Exposed T Cells on Outcomes","authors":"Dolores Grosso ,&nbsp;Matthew Carabasi ,&nbsp;Joanne Filicko-O'Hara ,&nbsp;John L. Wagner ,&nbsp;William O'Hara ,&nbsp;Michael Sun ,&nbsp;Beth Colombe ,&nbsp;W. Shi ,&nbsp;Maria Werner-Wasik ,&nbsp;Shannon Rudolph ,&nbsp;Onder Alpdogan ,&nbsp;Adam Binder ,&nbsp;Margaret Kasner ,&nbsp;Thomas Klumpp ,&nbsp;Ubaldo Martinez-Outschoorn ,&nbsp;Neil Palmisiano ,&nbsp;Lindsay Wilde ,&nbsp;Pierluigi Porcu ,&nbsp;Usama Gergis ,&nbsp;Neal Flomenberg","doi":"10.1016/j.bbmt.2020.06.021","DOIUrl":null,"url":null,"abstract":"<div><p>The use of cyclophosphamide (CY) for bidirectional tolerization of recipient and donor T cells is associated with reduced rates of graft-versus-host disease (GVHD) and nonrelapse mortality (NRM) after HLA-matched hematopoietic stem cell transplantation (HSCT). However, recurrent disease remains the primary barrier to long-term survival. We extended our 2-step approach to HLA-matched related HSCT using a radiation-based myeloablative conditioning regimen combined with a high dose of T cells in an attempt to reduce relapse rates while maintaining the beneficial effects of CY tolerization. After conditioning, patients received their grafts in 2 components: (1) a fixed dose of 2 × 10<sup>8</sup>/kg T cells, followed 2 days later by CY, and (2) a CD34-selected graft containing a small residual amount of non-CY-exposed T cells, at a median dose of 2.98 × 10<sup>3</sup>/kg. Forty-six patients with hematologic malignancies were treated. Despite the myeloablative conditioning regimen and use of high T cell doses, the cumulative incidences of grade II-IV acute GVHD, chronic GVHD, and NRM at 1 year and 5 years were very low, at 13%, 9%, and 4.3%, respectively. This contributed to a high overall survival of 89.1% at 1 year and 65.8% at 5 years. Relapse was the primary cause of mortality, with a cumulative incidence of 23.9% at 1 year and 45.7% at 5 years. In a post hoc analysis, relapse rates were significantly lower in patients receiving greater than versus those receiving less than the group median of non-CY-exposed residual T cells in the CD34 product (19.3% versus 58.1%; <em>P</em> = .009), without a concomitant increase in NRM. In its current form, this 2-step regimen was highly tolerable, but strategies to reduce relapse, potentially the addition of T cells not exposed to CY, are needed.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.06.021","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biology of Blood and Marrow Transplantation","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1083879120303967","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 1

Abstract

The use of cyclophosphamide (CY) for bidirectional tolerization of recipient and donor T cells is associated with reduced rates of graft-versus-host disease (GVHD) and nonrelapse mortality (NRM) after HLA-matched hematopoietic stem cell transplantation (HSCT). However, recurrent disease remains the primary barrier to long-term survival. We extended our 2-step approach to HLA-matched related HSCT using a radiation-based myeloablative conditioning regimen combined with a high dose of T cells in an attempt to reduce relapse rates while maintaining the beneficial effects of CY tolerization. After conditioning, patients received their grafts in 2 components: (1) a fixed dose of 2 × 108/kg T cells, followed 2 days later by CY, and (2) a CD34-selected graft containing a small residual amount of non-CY-exposed T cells, at a median dose of 2.98 × 103/kg. Forty-six patients with hematologic malignancies were treated. Despite the myeloablative conditioning regimen and use of high T cell doses, the cumulative incidences of grade II-IV acute GVHD, chronic GVHD, and NRM at 1 year and 5 years were very low, at 13%, 9%, and 4.3%, respectively. This contributed to a high overall survival of 89.1% at 1 year and 65.8% at 5 years. Relapse was the primary cause of mortality, with a cumulative incidence of 23.9% at 1 year and 45.7% at 5 years. In a post hoc analysis, relapse rates were significantly lower in patients receiving greater than versus those receiving less than the group median of non-CY-exposed residual T cells in the CD34 product (19.3% versus 58.1%; P = .009), without a concomitant increase in NRM. In its current form, this 2-step regimen was highly tolerable, but strategies to reduce relapse, potentially the addition of T cells not exposed to CY, are needed.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
使用环磷酰胺进行hla匹配相关2步造血干细胞移植预防移植物抗宿主病后的低非复发死亡率和非环磷酰胺暴露的T细胞对结果的潜在影响
环磷酰胺(CY)用于受体和供体T细胞的双向耐受与hla匹配的造血干细胞移植(HSCT)后移植物抗宿主病(GVHD)和非复发死亡率(NRM)的降低有关。然而,复发性疾病仍然是长期生存的主要障碍。我们将两步方法扩展到hla匹配的相关HSCT,使用基于放射的清髓调节方案结合高剂量T细胞,试图降低复发率,同时保持CY耐受性的有益效果。经调节后,患者接受2组移植物:(1)固定剂量2 × 108/kg T细胞,2天后接受CY, (2) cd34选择的移植物含有少量未CY暴露的T细胞,中位剂量为2.98 × 103/kg。对46例恶性血液病患者进行了治疗。尽管采用了清髓调节方案和使用高剂量的T细胞,但1年和5年II-IV级急性GVHD、慢性GVHD和NRM的累积发病率非常低,分别为13%、9%和4.3%。这使得1年和5年的总生存率分别达到89.1%和65.8%。复发是死亡的主要原因,1年和5年的累计发病率分别为23.9%和45.7%。在一项事后分析中,接受CD34产品中非cy暴露残余T细胞大于或小于组中位数的患者的复发率显著低于接受CD34产品中位数的患者(19.3%对58.1%;P = 0.009), NRM未同时升高。在目前的形式下,这种两步治疗方案是高度耐受的,但需要减少复发的策略,可能需要添加未暴露于CY的T细胞。
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 去求助
来源期刊
CiteScore
6.60
自引率
0.00%
发文量
1061
审稿时长
3-6 weeks
期刊介绍: Biology of Blood and Marrow Transplantation publishes original research reports, reviews, editorials, commentaries, letters to the editor, and hypotheses and is the official publication of the American Society for Transplantation and Cellular Therapy. The journal focuses on current technology and knowledge in the interdisciplinary field of hematopoetic stem cell transplantation.
期刊最新文献
Table of Contents Editorial Board Goal-Oriented Monitoring of Cyclosporine Is Effective for Graft-versus-Host Disease Prevention after Hematopoietic Stem Cell Transplantation in Sickle Cell Disease and Thalassemia Major Early Mixed Lymphoid Donor/Host Chimerism is Associated with Improved Transplant Outcome in Patients with Primary or Secondary Myelofibrosis Real-World Issues and Potential Solutions in Hematopoietic Cell Transplantation during the COVID-19 Pandemic: Perspectives from the Worldwide Network for Blood and Marrow Transplantation and Center for International Blood and Marrow Transplant Research Health Services and International Studies Committee
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1