BEAM-Campath同种异体干细胞移植治疗复发/难治性淋巴瘤:长期混合供体-受体嵌合的高发率和供体淋巴细胞输注的反应

Claire Burney , Karan Wadhera , Patricia Breslin , Rachel Pearce , Matthew Wells , Rajesh Alajangi , Rachel Protheroe , David I. Marks , James Griffin , Stephen Robinson
{"title":"BEAM-Campath同种异体干细胞移植治疗复发/难治性淋巴瘤:长期混合供体-受体嵌合的高发率和供体淋巴细胞输注的反应","authors":"Claire Burney ,&nbsp;Karan Wadhera ,&nbsp;Patricia Breslin ,&nbsp;Rachel Pearce ,&nbsp;Matthew Wells ,&nbsp;Rajesh Alajangi ,&nbsp;Rachel Protheroe ,&nbsp;David I. Marks ,&nbsp;James Griffin ,&nbsp;Stephen Robinson","doi":"10.1016/j.bbmt.2020.08.028","DOIUrl":null,"url":null,"abstract":"<div><p>BiCNU (carmustine), etoposide, Ara-C, melphalan (BEAM) and Campath conditioning was developed to reduce the high transplant-related mortality in patients with lymphoma while delivering intensive antilymphoma immunotherapy, as well as to some extent a platform for allogeneic stem cell engraftment. Significant numbers of patients appeared to have persistent recipient-derived hematopoiesis, and therefore we retrospectively analyzed patients with lymphoma undergoing BEAM-Campath conditioned allogeneic stem cell transplantation at our center (2003 to 2017) to characterize the patterns of chimerism and patient outcomes. Chimerism was analyzed with short tandem repeat PCR. Mixed donor-recipient chimerism (MDRC) was defined as 5% to 94.9% donor. Fifty-two patients (n = 30 male), with a median age of 45 years, were identified with histologic diagnoses of Hodgkin lymphoma (n = 13), diffuse large B cell lymphoma (n = 7), low-grade non-Hodgkin lymphoma (n = 16), mantle cell lymphoma (n = 10), and T cell lymphoma (n = 6). Pretransplant, 93% achieved complete response (52%) or partial response (41%) with a median of 3 prior therapies (n = 3 prior autologous stem cell transplantation). Donors were Matched sibling donors (MSD) (n = 21), matched unrelated donors (MUD) (n = 24), miss-matched unrelated donors (MMUD) (n = 6), and syngeneic (n = 1). Acute graft-versus host disease (GVHD) developed in 52% (81% grade I to II) and chronic GVHD (83% extensive) in 12%. MDRC of T cells (MDRCt) developed in 62% (n = 32), and 29% (n = 15) developed MDRC of myeloid cells (MDRCm) at a median onset of 100 days. Donor lymphocyte infusion (DLI) was given to 17 patients, with a median starting dose of 1 × 10<sup>6</sup>/kg. The first DLI was given at a median of 225 days post-transplant (range, 99 days to 5.3 years). Of these, 9 developed acute post-DLI GVHD and 2 limited chronic GVHD. Conversion to full donor occurred in 47<strong>%</strong> MDRCt and 50% MDRCm. Multivariate analysis identified sibling donor type as associated with increased MDRCt (<em>P</em> = .035; hazard ratio [HR], 0.17) and reduced total nucleated cell dose with increased MDRCm (<em>P</em> = .021; HR, 0.76). The median follow-up was 6 years, and 2-year NRM cumulative incidence was 16% (95% confidence interval [CI], 7% to 27%). Ten-year progression and extensive GVHD-free survival was 45% (95% CI, 28% to 61%), and overall survival was 66% (95% CI, 50% to 78%). One-year landmark analysis identified no increased GVHD or relapse risk with MDRCt or MDRCm but reduced nonrelapse mortality (NRM) risk with MDRCt (<em>P</em> = .001). BEAM-Campath allografts for high-risk lymphoma achieve long-term disease-free survival with low rates of GVHD and transplant-related mortality. The frequent development of myeloid MDRC demonstrates that BEAM-Campath is a nonmyeloablative conditioning regimen in almost a third of patients. MDRCt is associated with reduced NRM, but neither MDRCt or MDRCm is associated with increased GVHD or relapse.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.08.028","citationCount":"2","resultStr":"{\"title\":\"BEAM-Campath Allogeneic Stem Cell Transplant for Patients with Relapsed/Refractory Lymphoma: High Incidence of Long-Term Mixed Donor-Recipient Chimerism and the Response to Donor Lymphocyte Infusions\",\"authors\":\"Claire Burney ,&nbsp;Karan Wadhera ,&nbsp;Patricia Breslin ,&nbsp;Rachel Pearce ,&nbsp;Matthew Wells ,&nbsp;Rajesh Alajangi ,&nbsp;Rachel Protheroe ,&nbsp;David I. Marks ,&nbsp;James Griffin ,&nbsp;Stephen Robinson\",\"doi\":\"10.1016/j.bbmt.2020.08.028\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>BiCNU (carmustine), etoposide, Ara-C, melphalan (BEAM) and Campath conditioning was developed to reduce the high transplant-related mortality in patients with lymphoma while delivering intensive antilymphoma immunotherapy, as well as to some extent a platform for allogeneic stem cell engraftment. Significant numbers of patients appeared to have persistent recipient-derived hematopoiesis, and therefore we retrospectively analyzed patients with lymphoma undergoing BEAM-Campath conditioned allogeneic stem cell transplantation at our center (2003 to 2017) to characterize the patterns of chimerism and patient outcomes. Chimerism was analyzed with short tandem repeat PCR. Mixed donor-recipient chimerism (MDRC) was defined as 5% to 94.9% donor. Fifty-two patients (n = 30 male), with a median age of 45 years, were identified with histologic diagnoses of Hodgkin lymphoma (n = 13), diffuse large B cell lymphoma (n = 7), low-grade non-Hodgkin lymphoma (n = 16), mantle cell lymphoma (n = 10), and T cell lymphoma (n = 6). Pretransplant, 93% achieved complete response (52%) or partial response (41%) with a median of 3 prior therapies (n = 3 prior autologous stem cell transplantation). Donors were Matched sibling donors (MSD) (n = 21), matched unrelated donors (MUD) (n = 24), miss-matched unrelated donors (MMUD) (n = 6), and syngeneic (n = 1). Acute graft-versus host disease (GVHD) developed in 52% (81% grade I to II) and chronic GVHD (83% extensive) in 12%. MDRC of T cells (MDRCt) developed in 62% (n = 32), and 29% (n = 15) developed MDRC of myeloid cells (MDRCm) at a median onset of 100 days. Donor lymphocyte infusion (DLI) was given to 17 patients, with a median starting dose of 1 × 10<sup>6</sup>/kg. The first DLI was given at a median of 225 days post-transplant (range, 99 days to 5.3 years). Of these, 9 developed acute post-DLI GVHD and 2 limited chronic GVHD. Conversion to full donor occurred in 47<strong>%</strong> MDRCt and 50% MDRCm. Multivariate analysis identified sibling donor type as associated with increased MDRCt (<em>P</em> = .035; hazard ratio [HR], 0.17) and reduced total nucleated cell dose with increased MDRCm (<em>P</em> = .021; HR, 0.76). The median follow-up was 6 years, and 2-year NRM cumulative incidence was 16% (95% confidence interval [CI], 7% to 27%). Ten-year progression and extensive GVHD-free survival was 45% (95% CI, 28% to 61%), and overall survival was 66% (95% CI, 50% to 78%). One-year landmark analysis identified no increased GVHD or relapse risk with MDRCt or MDRCm but reduced nonrelapse mortality (NRM) risk with MDRCt (<em>P</em> = .001). BEAM-Campath allografts for high-risk lymphoma achieve long-term disease-free survival with low rates of GVHD and transplant-related mortality. The frequent development of myeloid MDRC demonstrates that BEAM-Campath is a nonmyeloablative conditioning regimen in almost a third of patients. MDRCt is associated with reduced NRM, but neither MDRCt or MDRCm is associated with increased GVHD or relapse.</p></div>\",\"PeriodicalId\":9165,\"journal\":{\"name\":\"Biology of Blood and Marrow Transplantation\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2020-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.08.028\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biology of Blood and Marrow Transplantation\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1083879120305437\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biology of Blood and Marrow Transplantation","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1083879120305437","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: 2

摘要

BiCNU (carmustine)、依托泊苷(etoposide)、Ara-C、melphalan (BEAM)和Campath调节剂的开发是为了降低淋巴瘤患者移植相关的高死亡率,同时提供强化抗淋巴瘤免疫治疗,并在一定程度上为异体干细胞移植提供平台。大量患者似乎具有持续的受体来源造血功能,因此我们回顾性分析了2003年至2017年在我们中心接受BEAM-Campath条件异体干细胞移植的淋巴瘤患者,以表征嵌合模式和患者结局。用短串联重复PCR分析嵌合现象。混合供受体嵌合(MDRC)定义为5%至94.9%的供体。52例患者(n = 30名男性),中位年龄45岁,组织学诊断为霍奇金淋巴瘤(n = 13),弥漫性大B细胞淋巴瘤(n = 7),低级别非霍奇金淋巴瘤(n = 16),套细胞淋巴瘤(n = 10)和T细胞淋巴瘤(n = 6)。移植前,93%的患者获得完全缓解(52%)或部分缓解(41%),中位既往治疗3次(n = 3次既往自体干细胞移植)。供体包括匹配的兄弟姐妹供体(MSD) (n = 21)、匹配的非亲属供体(MUD) (n = 24)、不匹配的非亲属供体(MMUD) (n = 6)和同基因供体(n = 1)。52%(81%为I至II级)发生急性移植物抗宿主病(GVHD), 12%发生慢性GVHD(83%为广泛)。62% (n = 32)的患者出现T细胞MDRC (MDRCt), 29% (n = 15)的患者出现髓样细胞MDRC (MDRCm),发病时间中位数为100天。17例患者给予供体淋巴细胞输注(DLI),起始中位剂量为1 × 106/kg。第一次DLI是在移植后225天(99天至5.3年)给予的。其中9例发展为急性GVHD, 2例发展为有限的慢性GVHD。47%的MDRCt和50%的MDRCm转为完全供者。多因素分析发现,兄弟姐妹供体类型与MDRCt增加有关(P = 0.035;风险比[HR], 0.17),随着MDRCm的增加,有核细胞总剂量降低(P = 0.021;人力资源,0.76)。中位随访时间为6年,2年NRM累计发生率为16%(95%可信区间[CI], 7%至27%)。十年进展和广泛无gvhd生存率为45% (95% CI, 28%至61%),总生存率为66% (95% CI, 50%至78%)。一年的里程碑式分析发现,MDRCt或MDRCm没有增加GVHD或复发风险,但MDRCt降低了非复发死亡率(NRM)风险(P = 0.001)。BEAM-Campath同种异体移植治疗高风险淋巴瘤可实现长期无病生存,GVHD发生率低,移植相关死亡率低。髓系MDRC的频繁发展表明BEAM-Campath在近三分之一的患者中是非清髓性调节方案。MDRCt与NRM降低相关,但MDRCt或MDRCm均与GVHD增加或复发无关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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
BEAM-Campath Allogeneic Stem Cell Transplant for Patients with Relapsed/Refractory Lymphoma: High Incidence of Long-Term Mixed Donor-Recipient Chimerism and the Response to Donor Lymphocyte Infusions

BiCNU (carmustine), etoposide, Ara-C, melphalan (BEAM) and Campath conditioning was developed to reduce the high transplant-related mortality in patients with lymphoma while delivering intensive antilymphoma immunotherapy, as well as to some extent a platform for allogeneic stem cell engraftment. Significant numbers of patients appeared to have persistent recipient-derived hematopoiesis, and therefore we retrospectively analyzed patients with lymphoma undergoing BEAM-Campath conditioned allogeneic stem cell transplantation at our center (2003 to 2017) to characterize the patterns of chimerism and patient outcomes. Chimerism was analyzed with short tandem repeat PCR. Mixed donor-recipient chimerism (MDRC) was defined as 5% to 94.9% donor. Fifty-two patients (n = 30 male), with a median age of 45 years, were identified with histologic diagnoses of Hodgkin lymphoma (n = 13), diffuse large B cell lymphoma (n = 7), low-grade non-Hodgkin lymphoma (n = 16), mantle cell lymphoma (n = 10), and T cell lymphoma (n = 6). Pretransplant, 93% achieved complete response (52%) or partial response (41%) with a median of 3 prior therapies (n = 3 prior autologous stem cell transplantation). Donors were Matched sibling donors (MSD) (n = 21), matched unrelated donors (MUD) (n = 24), miss-matched unrelated donors (MMUD) (n = 6), and syngeneic (n = 1). Acute graft-versus host disease (GVHD) developed in 52% (81% grade I to II) and chronic GVHD (83% extensive) in 12%. MDRC of T cells (MDRCt) developed in 62% (n = 32), and 29% (n = 15) developed MDRC of myeloid cells (MDRCm) at a median onset of 100 days. Donor lymphocyte infusion (DLI) was given to 17 patients, with a median starting dose of 1 × 106/kg. The first DLI was given at a median of 225 days post-transplant (range, 99 days to 5.3 years). Of these, 9 developed acute post-DLI GVHD and 2 limited chronic GVHD. Conversion to full donor occurred in 47% MDRCt and 50% MDRCm. Multivariate analysis identified sibling donor type as associated with increased MDRCt (P = .035; hazard ratio [HR], 0.17) and reduced total nucleated cell dose with increased MDRCm (P = .021; HR, 0.76). The median follow-up was 6 years, and 2-year NRM cumulative incidence was 16% (95% confidence interval [CI], 7% to 27%). Ten-year progression and extensive GVHD-free survival was 45% (95% CI, 28% to 61%), and overall survival was 66% (95% CI, 50% to 78%). One-year landmark analysis identified no increased GVHD or relapse risk with MDRCt or MDRCm but reduced nonrelapse mortality (NRM) risk with MDRCt (P = .001). BEAM-Campath allografts for high-risk lymphoma achieve long-term disease-free survival with low rates of GVHD and transplant-related mortality. The frequent development of myeloid MDRC demonstrates that BEAM-Campath is a nonmyeloablative conditioning regimen in almost a third of patients. MDRCt is associated with reduced NRM, but neither MDRCt or MDRCm is associated with increased GVHD or relapse.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 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