西罗莫司和伊马替尼治疗激素难治性慢性移植物抗宿主病的临床观察: 一项单中心回顾性分析

何云地; 黄瑞昊; 洪涛; 王蔚浩; 杜雨軒; 王筱淇; 王峥; 张云芳; 张曦

doi:10.16016/j.1000-5404.202108067

您当前的位置：

首页 >

文章列表页 >

西罗莫司和伊马替尼治疗激素难治性慢性移植物抗宿主病的临床观察: 一项单中心回顾性分析

专题报道：造血干细胞移植并发症的基础与临床研究 | 更新时间：2026-02-13

- 西罗莫司和伊马替尼治疗激素难治性慢性移植物抗宿主病的临床观察: 一项单中心回顾性分析
- Sirolimus versus imatinib in patients with steroid-refractory chronic graft-versus-host disease: a retrospective analysis of a single-center
- 第三军医大学学报 2021年43卷第21期页码：2313-2320
- 作者机构：
  
  1.400037 重庆，陆军军医大学(第三军医大学)第二附属医院血液病医学中心，全军血液病中心，创伤、烧伤与复合伤国家重点实验室
  2.563099 贵州遵义，遵义医科大学第二附属医院检验科
- 作者简介：
  
  [张曦，E-mail: zhangxxi@sina.com ZHANG Xi, E-mail: zhangxxi@sina.com
- 基金信息：
  
  国家自然科学基金国际(地区)合作与交流项目(82020108004);国家血液系统疾病临床医学研究中心2020年度开放课题重点项目(2020ZKZC02);国家重点研究计划重点专项(2017YFA0105502)
- DOI：10.16016/j.1000-5404.202108067
  中图分类号： R617;R733.7;R976
- 收稿：2021-08-10，
  
  修回：2021-09-17，
  
  纸质出版：2021-11-15
- 稿件说明：
移动端阅览
何云地, 黄瑞昊, 洪涛, 等. 西罗莫司和伊马替尼治疗激素难治性慢性移植物抗宿主病的临床观察: 一项单中心回顾性分析[J]. 第三军医大学学报, 2021,43(21):2313-2320.

Yundi HE, Ruihao HUANG, Tao HONG, et al. Sirolimus versus imatinib in patients with steroid-refractory chronic graft-versus-host disease: a retrospective analysis of a single-center[J]. Journal of Third Military Medical University, 2021, 43(21): 2313-2320.
何云地, 黄瑞昊, 洪涛, 等. 西罗莫司和伊马替尼治疗激素难治性慢性移植物抗宿主病的临床观察: 一项单中心回顾性分析[J]. 第三军医大学学报, 2021,43(21):2313-2320. DOI： 10.16016/j.1000-5404.202108067.

Yundi HE, Ruihao HUANG, Tao HONG, et al. Sirolimus versus imatinib in patients with steroid-refractory chronic graft-versus-host disease: a retrospective analysis of a single-center[J]. Journal of Third Military Medical University, 2021, 43(21): 2313-2320. DOI： 10.16016/j.1000-5404.202108067.

摘要

目的

对比西罗莫司和伊马替尼作为二线药物，治疗异基因干细胞移植后激素难治性慢性移植物抗宿主病(steroid-refractory chronic graft-versus-host disease，SR-cGVHD)的疗效和预后。

方法

回顾性分析2017年9月至2020年12月于我中心确诊为异基因造血干细胞移植后SR-cGVHD的33例患者临床资料，接受伊马替尼治疗16例，接受西罗莫司治疗17例。比较两组患者二线治疗后6个月和1年的缓解率、2年总生存(overall survival，OS)、2年无病生存(disease free survival，DFS)、1年无失败生存(failure free survival，FFS)和药物相关毒性。

结果

伊马替尼和西罗莫司治疗6个月整体缓解率分别是62.5%和41.2%(

=0.303)，1年整体缓解率分别是73.3%和43.8%(

=0.149)，6个月完全缓解率分别是12.5%和23.5%(

=0.656)，1年完全缓解率分别是20.0%和31.3%(

=0.685)，差异无统计学意义；伊马替尼2年OS和2年DFS均优于西罗莫司(

=0.041，

=0.043)；伊马替尼和西罗莫司的药物相关毒性率差异无统计学意义。

结论

伊马替尼和西罗莫司治疗SR-cGVHD缓解率疗效相当，伊马替尼在短期生存和无病生存方面优于西罗莫司。

Abstract

Objective

To compare the efficacy and prognosis of imatinib and sirolimus as second-line treatment for steroid-refractory chronic graft-versus-host disease (SR-cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods

Clinical data of 33 patients diagnosed as SR-cGVHD after allo-HSCT in the Medical Center of Hematology of Army Medical University from September 2017 to December 2020 were collected and analyzed retrospectively. Among them

16 patients were treated with imatinib and 17 with sirolimus. The response rate at the time points of 6 months and 1 year after initiation of second-line treatment

2-year overall survival (OS)

2-year disease free survival (DFS)

1-year failure free survival and drug-related toxicity were compared between the 2 groups.

Results

For the imatinib and sirolimus patients

their 6-month overall response rate (ORR) was 62.5% and 41.2% (

=0.303)

while 1-year ORR was 73.3% and 43.8% (

=0.149)

6-month complete response (CR) rate was 12.5% and 23.5% (

=0.656)

while 1-year CR rate was 20.0% and 31.3% (

=0.685)

respectively

and no statistical significance was observed between the 2 groups. The patients with imatinib treatment achieved better outcomes than those treated with sirolimus in terms of 2-year OS and 2-year DFS (

=0.041

=0.043). There was no significant difference in the occurrence of drug-related toxicity between the 2 groups.

Conclusion

Imatinib and sirolimus shows similar response rate to SR-cGVHD after allo-HSCT

but the former is superior to the latter in terms of short-term OS and DFS.

关键词

Keywords

references

FERRARA J L M, LEVINE J E, REDDY P, et al . Graft-versus-host disease[J ] . Lancet, 2009, 373(9674): 1550-1561. DOI: 10.1016/S0140-6736(09)60237-3.

JURADO M, VALLEJO C, PÉREZ-SIMÓN J A, et al . Sirolimus as part of immunosuppressive therapy for refractory chronic graft-versus-host disease[J ] . Biol Blood Marrow Transplant, 2007, 13(6): 701-706. DOI: 10.1016/j.bbmt.2007.02.003.

PARRA SALINAS I, BERMUDEZ A, LÓPEZ CORRAL L, et al . Treatment of steroid-refractory chronic graft-versus-host disease with imatinib: Real-life experience of the spanish group of hematopoietic transplantation (GETH)[J ] . Clin Transplant, 2021, 35(5): e14255. DOI: 10.1111/ctr.14255.

MARTIN P J, LEE S J, PRZEPIORKA D, et al . National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: Ⅵ. the 2014 clinical trial design working group report[J ] . Biol Blood Marrow Transplant, 2015, 21(8): 1343-1359. DOI: 10.1016/j.bbmt.2015.05.004.

JAGASIA M H, GREINIX H T, ARORA M, et al . National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: Ⅰ. the 2014 diagnosis and staging working group report[J ] . Biol Blood Marrow Transplant, 2015, 21(3): 389-401. DOI: 10.1016/j.bbmt.2014.12.001.

LEE S J, WOLFF D, KITKO C, et al . Measuring therapeutic response in chronic graft-versus-host disease. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: Ⅳ. The 2014 response criteria working group report[J ] . Biol Blood Marrow Transplant, 2015, 21(6): 984-999. DOI: 10.1016/j.bbmt.2015.02.025.

ZENG Y J, WANG S B, WANG J S, et al . Optimal donor for severe aplastic anemia patient requiring allogeneic hematopoietic stem cell transplantation: a large-sample study from China[J ] . Sci Rep, 2018, 8(1): 2479. DOI: 10.1038/s41598-018-20853-9.

GAO L, ZHANG C, GAO L, et al . Favorable outco me of haploidentical hematopoietic stem cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia: a multicenter study in Southwest China[J ] . J Hematol Oncol, 2015, 8: 90. DOI: 10.1186/s13045-015-0186-5.

肖函, 王欣, 罗小华, 等. 非高危急性髓系白血病患者首次完全缓解后行自体与异基因外周血造血干细胞移植的疗效对比[J]. 第三军医大学学报, 2020, 42(17): 1717-1723. DOI: 10.16016/j.1000-5404.202005132.

XIAO H, WANG X, LUO X H, et al . Efficacy of autologous versus allogeneic peripheral blood hematopoietic stem cell transplantation in non-high-risk acute myeloid leukemia patients in first complete remission[J ] . J Third Mil Med Univ, 2020, 42(17): 1717-1723. DOI: 10.16016/j.1000-5404.202005132.

蔺诗佳, 刘雨青, 姚浛, 等. EVI1基因阳性的急性髓系白血病患者临床特点及其造血干细胞移植的疗效观察[J]. 第三军医大学学报, 2020, 42(17): 1699-1705. DOI: 10.16016/j.1000-5404.202006024.

LIN S J, LIU Y Q, YAO H, et al . Clinical characteristics of EVI1 + AML and clinical observation of hematopoietic stem cell transplantation on these patients[J ] . J Third Mil Med Univ, 2020, 42(17): 1699-1705. DOI: 10.16016/j.1000-5404.202006024..

蔺诗佳, 赵伟, 陈婷, 等. 二次移植治疗异基因造血干细胞移植后复发急性髓系白血病5例临床观察[J]. 第三军医大学学报, 2019, 41(23): 2301-2306. DOI: 10.16016/j.1000-5404.201908017.

LIN S J, ZHAO W, CHEN T, et al . Second allogeneic hematopoietic stem cell transplantation in tre atment of relapsed acute myeloid leukemia: clinical report of 5 cases[J ] . J Third Mil Med Univ, 2019, 41(23): 2301-2306. DOI: 10.16016/j.1000-5404.201908017.

PARK H, GARRIDO-LAGUNA I, NAING A, et al . Phase I dose-escalation study of the mTOR inhibitor sirolimus and the HDAC inhibitor vorinostat in patients with advanced malignancy[J ] . Oncotarget, 2016, 7(41): 67521-67531. DOI: 10.18632/oncotarget.11750.

赵菲, 王佳丽, 施圆圆, 等. 芦可替尼挽救性治疗激素难治性移植物抗宿主病: 一项单中心回顾性分析[J]. 临床血液学杂志, 2020, 33(1): 18-24. DOI: 10.13201/j.issn.1004-2806.2020.01.005.

ZHAO F, WANG J L, SHI Y Y, et al . The utility of ruxolitinib in patients with steroid-refractory graft-versus-host disease: retrospective analysis of a single center[J ] . J Clin Hematol, 2020, 33(1): 18-24. DOI: 10.13201/j.issn.1004-2806.2020.01.005.

中华医学会血液学分会造血干细胞应用学组, 中国抗癌协会血液病转化委员会. 慢性移植物抗宿主病(cGVHD)诊断与治疗中国专家共识(2021年版)[J]. 中华血液学杂志, 2021, 42(4): 265-275. DOI: 10.3760/cma.j.issn.0253-2727.2021.04.001.

Applied Hematopoietic Stem Cell Group of Hematology Branch of Chinese Medical Association, Hematological Disease Transformation Committee of Chinese Anti-Cancer Association. Chinese consensus on the diagnosis and management of chronic graft-versus-host disease (2021)[J]. Chin J Hematol, 2021, 42(4): 265-275. DOI: 10.3760/cma.j.issn.0253-2727.2021.04.001.

YALNIZ F F, MURAD M H, LEE S J, et al . Steroid refractory chronic graft-versus-host disease: cost-effectiveness analysis[J ] . Biol Blood Marrow Transplant, 2018, 24(9): 1920-1927. DOI: 10.1016/j.bbmt.2018.03.008.

DISTLER J H, JVNGEL A, HUBER L C, et al . Imatinib mesylate reduces production of extracellular matrix and prevents development of experimental dermal fibrosis[J ] . Arthritis Rheum, 2007, 56(1): 311-322. DOI: 10.1002/art.22314.

PÉREZ-SIMÓN J A, SÁNCHEZ-ABARCA I, DÍEZ-CAMPELO M, et al . Chronic graft-versus-host disease: Pathogenesis and clinical management[J ] . Drugs, 2006, 66(8): 1041-1057. DOI: 10.2165/00003495-200666080-00002.

CHEN G L, ARAI S, FLOWERS M E, et al . A phase 1 study of imatinib for corticosteroid-dependent/refractory chronic graft-versus-host disease: response does not correlate with anti-PDGFRA antibodies[J ] . Blood, 2011, 118(15): 4070-4078. DOI: 10.1182/blood-2011-03-341693.

OLIVIERI A, LOCATELLI F, ZECCA M, et al . Imatinib for refractory chronic graft-versus-host disease with fibrotic features[J ] . Blood, 2009, 114(3): 709-718. DOI: 10.1182/blood-2009-02 -204156.

OLIVIERI A, CIMMINIELLO M, CORRADINI P, et al . Long-term outcome and prospective validation of NIH response criteria in 39 patients receiving imatinib for steroid-refractory chronic GVHD[J ] . Blood, 2013, 122(25): 4111-4118. DOI: 10.1182/blood-2013-05-494278.

FENG Y M, CHEN X L, CASSADY K, et al . The role of mTOR inhibitors in hematologic disease: from bench to bedside[J ] . Front Oncol, 2020, 10: 611690. DOI: 10.3389/fonc.2020.611690.

KIRKEN R A, WANG Y L. Molecular actions of sirolimus: sirolimus and mTor[J]. Transplant Proc, 2003, 35(3 Suppl): 227S-230S. DOI: 10.1016/s0041-1345(03)00230-6.

PANWALKAR A, VERSTOVSEK S, GILES F J. Mammalian target of rapamycin inhibition as therapy for hematologic malignancies[J]. Cancer, 2004, 100(4): 657-666. DOI: 10.1002/cncr.20026.

ALYEA E P, LI S L, KIM H T, et al . Sirolimus, tacrolimus, and low-dose methotrexate as graft-versus-host disease prophylaxis in related and unrelated donor reduced-intensity conditioning allogeneic peripheral blood stem cell transplantation[J ] . Biol Blood Marrow Transplant, 2008, 14(8): 920-926 . DOI: 10.1016/j.bbmt.2008.05.024.

朱雯, 冯一梅, 陈婷, 等. 西罗莫司联合钙调磷酸酶抑制剂治疗糖皮质激素耐药/依赖广泛型慢性移植物抗宿主病临床观察[J]. 中华血液学杂志, 2020, 41(9): 716-722. DOI: 10.3760/cma.j.issn.0253-2727.2020.09.003.

ZHU W, FENG Y M, CHEN T, et al . The clinical observation of sirolimus combined with calcineurin inhibitors for steroid-resistant/steroid-dependent extensive cGVHD[J ] . Chin J Hematol, 2020, 41(9): 716-722. DOI:10.3760/cma.j.issn.0253-2727.2020.09.003.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

慢性移植物抗宿主病患者免疫细胞亚群分选的表面标志组合策略

新药时代下如何为异基因造血干细胞移植赋能

祛铁治疗改善恶性血液病患者造血干细胞移植后造血功能的临床分析

皮肤优势型慢性移植物抗宿主病小鼠模型的构建

泊沙康唑在异基因造血干细胞移植期间预防侵袭性真菌病的效果和安全性: 单中心回顾性分析