环磷酰胺和环孢素预防移植物抗宿主病。

IF 96.2 1区 医学 Q1 MEDICINE, GENERAL & INTERNAL
David J Curtis, Sushrut S Patil, John Reynolds, Duncan Purtill, Clinton Lewis, David S Ritchie, David J Gottlieb, David T Yeung, Eric Wong, Siok-Keen Tey, Travis Perera, John Moore, Rachel M Koldej, Richard De Abreu Lourenco, John Stubbs, C Orla Morrissey, Nadia Munsef, Andrea Arenas, Geoffrey R Hill
{"title":"环磷酰胺和环孢素预防移植物抗宿主病。","authors":"David J Curtis, Sushrut S Patil, John Reynolds, Duncan Purtill, Clinton Lewis, David S Ritchie, David J Gottlieb, David T Yeung, Eric Wong, Siok-Keen Tey, Travis Perera, John Moore, Rachel M Koldej, Richard De Abreu Lourenco, John Stubbs, C Orla Morrissey, Nadia Munsef, Andrea Arenas, Geoffrey R Hill","doi":"10.1056/NEJMoa2503189","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Allogeneic peripheral-blood stem-cell transplantation (SCT) from a matched related donor after myeloablative conditioning is the preferred curative treatment for patients with high-risk blood cancers. The combination of a calcineurin inhibitor and an antimetabolite remains standard care for graft-versus-host disease (GVHD) prophylaxis in these patients. Data from two randomized trials have suggested that post-transplantation cyclophosphamide can reduce the risk of GVHD after SCT from a matched donor when it is added to or replaces the antimetabolite. However, the effects of post-transplantation cyclophosphamide specifically after SCT from a matched related donor remain uncertain, and effects in the context of myeloablative conditioning are unclear.</p><p><strong>Methods: </strong>We randomly assigned adults who were undergoing SCT from a matched related donor after myeloablative or reduced-intensity conditioning to receive either post-transplantation cyclophosphamide-cyclosporin (experimental prophylaxis) or cyclosporin-methotrexate (standard prophylaxis). The primary end point was GVHD-free, relapse-free survival.</p><p><strong>Results: </strong>Among 134 patients who underwent randomization, 66 were assigned to receive experimental prophylaxis and 68 to receive standard prophylaxis. GVHD-free, relapse-free survival was significantly longer with experimental prophylaxis (median, 26.2 months; 95% confidence interval [CI], 9.1 to not reached) than with standard prophylaxis (median, 6.4 months; 95% CI, 5.6 to 8.3; P<0.001 by a log-rank test). GVHD-free, relapse-free survival at 3 years was 49% (95% CI, 36 to 61) with experimental prophylaxis and 14% (95% CI, 6 to 25) with standard prophylaxis (hazard ratio for GVHD, relapse, or death, 0.42; 95% CI, 0.27 to 0.66). The cumulative incidence of grade III to IV acute GVHD at 3 months was 3% (95% CI, 1 to 10) in the experimental-prophylaxis group and 10% (95% CI, 4 to 19) in the standard-prophylaxis group. At 2 years, overall survival was 83% and 71%, respectively (hazard ratio for death, 0.59; 95% CI, 0.29 to 1.19). The incidence of serious adverse events was similar in the two groups in the first 100 days after SCT.</p><p><strong>Conclusions: </strong>The combination of post-transplantation cyclophosphamide and a calcineurin inhibitor led to longer GVHD-free, relapse-free survival than standard prophylaxis after transplantation from a matched related donor with either reduced-intensity or myeloablative conditioning in patients with blood cancers. (Funded by the Australian Government Medical Research Future Fund and others; ALLG BM12 CAST Australian-New Zealand Clinical Trials Registry number, ACTRN12618000505202.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2000,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Graft-versus-Host Disease Prophylaxis with Cyclophosphamide and Cyclosporin.\",\"authors\":\"David J Curtis, Sushrut S Patil, John Reynolds, Duncan Purtill, Clinton Lewis, David S Ritchie, David J Gottlieb, David T Yeung, Eric Wong, Siok-Keen Tey, Travis Perera, John Moore, Rachel M Koldej, Richard De Abreu Lourenco, John Stubbs, C Orla Morrissey, Nadia Munsef, Andrea Arenas, Geoffrey R Hill\",\"doi\":\"10.1056/NEJMoa2503189\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Allogeneic peripheral-blood stem-cell transplantation (SCT) from a matched related donor after myeloablative conditioning is the preferred curative treatment for patients with high-risk blood cancers. The combination of a calcineurin inhibitor and an antimetabolite remains standard care for graft-versus-host disease (GVHD) prophylaxis in these patients. Data from two randomized trials have suggested that post-transplantation cyclophosphamide can reduce the risk of GVHD after SCT from a matched donor when it is added to or replaces the antimetabolite. However, the effects of post-transplantation cyclophosphamide specifically after SCT from a matched related donor remain uncertain, and effects in the context of myeloablative conditioning are unclear.</p><p><strong>Methods: </strong>We randomly assigned adults who were undergoing SCT from a matched related donor after myeloablative or reduced-intensity conditioning to receive either post-transplantation cyclophosphamide-cyclosporin (experimental prophylaxis) or cyclosporin-methotrexate (standard prophylaxis). The primary end point was GVHD-free, relapse-free survival.</p><p><strong>Results: </strong>Among 134 patients who underwent randomization, 66 were assigned to receive experimental prophylaxis and 68 to receive standard prophylaxis. GVHD-free, relapse-free survival was significantly longer with experimental prophylaxis (median, 26.2 months; 95% confidence interval [CI], 9.1 to not reached) than with standard prophylaxis (median, 6.4 months; 95% CI, 5.6 to 8.3; P<0.001 by a log-rank test). GVHD-free, relapse-free survival at 3 years was 49% (95% CI, 36 to 61) with experimental prophylaxis and 14% (95% CI, 6 to 25) with standard prophylaxis (hazard ratio for GVHD, relapse, or death, 0.42; 95% CI, 0.27 to 0.66). The cumulative incidence of grade III to IV acute GVHD at 3 months was 3% (95% CI, 1 to 10) in the experimental-prophylaxis group and 10% (95% CI, 4 to 19) in the standard-prophylaxis group. At 2 years, overall survival was 83% and 71%, respectively (hazard ratio for death, 0.59; 95% CI, 0.29 to 1.19). The incidence of serious adverse events was similar in the two groups in the first 100 days after SCT.</p><p><strong>Conclusions: </strong>The combination of post-transplantation cyclophosphamide and a calcineurin inhibitor led to longer GVHD-free, relapse-free survival than standard prophylaxis after transplantation from a matched related donor with either reduced-intensity or myeloablative conditioning in patients with blood cancers. (Funded by the Australian Government Medical Research Future Fund and others; ALLG BM12 CAST Australian-New Zealand Clinical Trials Registry number, ACTRN12618000505202.).</p>\",\"PeriodicalId\":54725,\"journal\":{\"name\":\"New England Journal of Medicine\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":96.2000,\"publicationDate\":\"2025-06-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"New England Journal of Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1056/NEJMoa2503189\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"New England Journal of Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1056/NEJMoa2503189","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0

摘要

背景:来自匹配的相关供者的同种异体外周血干细胞移植(SCT)是高危血癌患者的首选治疗方法。钙调磷酸酶抑制剂和抗代谢物的联合使用仍然是这些患者预防移植物抗宿主病(GVHD)的标准治疗。来自两项随机试验的数据表明,当将环磷酰胺加入或替代抗代谢物时,移植后环磷酰胺可以降低匹配供体SCT后GVHD的风险。然而,移植后环磷酰胺在匹配相关供体SCT后的作用仍然不确定,在清髓条件下的作用也不清楚。方法:我们随机分配来自匹配的相关供体的成人,在清髓或降低强度后接受SCT,接受移植后环磷酰胺-环孢素(实验性预防)或环孢素-甲氨蝶呤(标准预防)。主要终点为无gvhd、无复发生存期。结果:在接受随机分组的134例患者中,66例接受实验性预防,68例接受标准预防。试验性预防的无gvhd、无复发生存期显著延长(中位26.2个月;95%可信区间[CI], 9.1至未达到)比标准预防(中位数,6.4个月;95% CI, 5.6 - 8.3;结论:血癌患者移植后环磷酰胺和钙调磷酸酶抑制剂联合使用,在低强度或清髓条件下,比从匹配的相关供体移植后的标准预防治疗,可使患者无gvhd和无复发生存期更长。(由澳大利亚政府医学研究未来基金和其他基金资助;澳大利亚-新西兰临床试验注册号(ACTRN12618000505202)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Graft-versus-Host Disease Prophylaxis with Cyclophosphamide and Cyclosporin.

Background: Allogeneic peripheral-blood stem-cell transplantation (SCT) from a matched related donor after myeloablative conditioning is the preferred curative treatment for patients with high-risk blood cancers. The combination of a calcineurin inhibitor and an antimetabolite remains standard care for graft-versus-host disease (GVHD) prophylaxis in these patients. Data from two randomized trials have suggested that post-transplantation cyclophosphamide can reduce the risk of GVHD after SCT from a matched donor when it is added to or replaces the antimetabolite. However, the effects of post-transplantation cyclophosphamide specifically after SCT from a matched related donor remain uncertain, and effects in the context of myeloablative conditioning are unclear.

Methods: We randomly assigned adults who were undergoing SCT from a matched related donor after myeloablative or reduced-intensity conditioning to receive either post-transplantation cyclophosphamide-cyclosporin (experimental prophylaxis) or cyclosporin-methotrexate (standard prophylaxis). The primary end point was GVHD-free, relapse-free survival.

Results: Among 134 patients who underwent randomization, 66 were assigned to receive experimental prophylaxis and 68 to receive standard prophylaxis. GVHD-free, relapse-free survival was significantly longer with experimental prophylaxis (median, 26.2 months; 95% confidence interval [CI], 9.1 to not reached) than with standard prophylaxis (median, 6.4 months; 95% CI, 5.6 to 8.3; P<0.001 by a log-rank test). GVHD-free, relapse-free survival at 3 years was 49% (95% CI, 36 to 61) with experimental prophylaxis and 14% (95% CI, 6 to 25) with standard prophylaxis (hazard ratio for GVHD, relapse, or death, 0.42; 95% CI, 0.27 to 0.66). The cumulative incidence of grade III to IV acute GVHD at 3 months was 3% (95% CI, 1 to 10) in the experimental-prophylaxis group and 10% (95% CI, 4 to 19) in the standard-prophylaxis group. At 2 years, overall survival was 83% and 71%, respectively (hazard ratio for death, 0.59; 95% CI, 0.29 to 1.19). The incidence of serious adverse events was similar in the two groups in the first 100 days after SCT.

Conclusions: The combination of post-transplantation cyclophosphamide and a calcineurin inhibitor led to longer GVHD-free, relapse-free survival than standard prophylaxis after transplantation from a matched related donor with either reduced-intensity or myeloablative conditioning in patients with blood cancers. (Funded by the Australian Government Medical Research Future Fund and others; ALLG BM12 CAST Australian-New Zealand Clinical Trials Registry number, ACTRN12618000505202.).

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
New England Journal of Medicine
New England Journal of Medicine 医学-医学:内科
CiteScore
145.40
自引率
0.60%
发文量
1839
审稿时长
1 months
期刊介绍: The New England Journal of Medicine (NEJM) stands as the foremost medical journal and website worldwide. With an impressive history spanning over two centuries, NEJM boasts a consistent publication of superb, peer-reviewed research and engaging clinical content. Our primary objective revolves around delivering high-caliber information and findings at the juncture of biomedical science and clinical practice. We strive to present this knowledge in formats that are not only comprehensible but also hold practical value, effectively influencing healthcare practices and ultimately enhancing patient outcomes.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信