旁系造血干细胞移植治疗急性白血病的临床分析

张维婕; 张书芹; 费新红; 程昊钰; 殷宇明; 王静波

doi:10.13201/j.issn.1004-2806.2020.11.004

旁系造血干细胞移植治疗急性白血病的临床分析

- 航天中心医院血液科(北京, 100049)
基金项目:
首都临床特色应用研究与成果推广(北京市科技计划项目)(No:Z171100001017103)

详细信息

通讯作者: 王静波,E-mail:dpwangjingbo@vip.sina.com

中图分类号: R733.71

收稿日期: 2020-08-12

Clinical analysis of hematopoietic stem cell transplantation from collateral related donors in the treatment of acute leukemia

- Department of Hematology, Aerospace Center Hospital, Beijing, 100049, China

More Information

Corresponding author: WANG Jing-bo, E-mail: dpwangjingbo@vip.sina.com

Received Date: 12 August 2020

摘要

摘要: 目的:评估旁系异基因造血干细胞移植（allo-HSCT）治疗急性白血病的疗效。方法:回顾性分析2012-07-01—2019-12-31接受旁系allo-HSCT的28例急性白血病患者的临床资料,其中男女各14例,中位年龄30（12～47）岁;急性髓系白血病19例,急性淋巴细胞白血病4例,急性混合细胞白血病2例,慢性髓系白血病急变期3例;表亲供者20例,堂亲供者8例;采用TBI联合CLAG预处理方案13例,采用CLAG联合改良BUCY预处理方案15例。结果:1例患者因感染性休克死于细胞未植活期,其余27例患者中性粒细胞、血小板中位植活时间分别为16（10～28）d、18（11～80）d。急性移植物抗宿主病累计发生率为（42.9±2.5）%,慢性移植物抗宿主病累计发生率为（21.3±10.5）%。其中17例发生CMV血症,4例发生EBV血症,8例发生出血性膀胱炎。中位随访时间11.5（1～95）个月,存活11例,移植后2年总生存（OS）率、无白血病生存（LFS）率分别为（37.8±9.5）%、（68.6±11.1）%,其中表亲为供者移植后2年OS率及LFS率分别为（28.6±10.6）%、（59.5±14.8）%,堂亲为供者移植后2年OS率及LFS率分别为（60.0±18.2）%、（85.7±13.2）%。2组生存分析采用Log-rank检验发现,OS率及LFS率比较差异均无统计学意义（P=0.150、0.403）。Cox多因素分析提示,移植前疾病状态、HLA相合程度为影响患者OS[HR=6.268（95%CI 4.636～11.346）,P=0.012;HR=5.668（95%CI 1.410～22.776）,P=0.015]及LFS[HR=8.054（95%CI 0.987～65.688）,P=0.051;HR=4.340（95%CI 1.183～15.926）,P=0.027]的独立预后不良因素。结论:旁系供者可以作为急性白血病allo-HSCT供者,移植前疾病状态及HLA相合程度是旁系移植的独立预后不良因素。
- 旁系供者 /
- 异基因造血干细胞移植 /
- 急性白血病
Abstract: Objective:To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation（allo-HSCT）from collateral related donors in the treatment of acute leukemia.Method:To conduct a retrospective analysis on the clinical data from 28 cases of acute leukemia,with equal gender ratio and a median age of 30（from 12 to 47）,and receiving treatment of allo-HSCT from collateral related donors.The patients included 14 cases of acute myeloma leukemia,4 cases of acute lymphoblastic leukemia,2 cases of biphenotypic acute leukemia and the rest 3 of acute phase of chronic myeloid leukemia.Twenty of the donors were patients' cousins on mother's side and 8 donors were patients' cousins on father's side.Thirteen cases received the conditioning regiments consisting of TBI and CLAG,while the other 15 cases received the conditioning regiments consisting of CLAG and the modified BUCY.Result:One patient died of septic shock prior to the cell engraftment stage.For the rest 27 patients,the median time of neutrophils engraftment was 16（10 to 28）days,whereas platelet engraftment was 18（11 to 80）days.The cumulative incidence of patients that experienced acute graft versus host disease was（42.9±2.5）%;and the cumulative incidence of patients that experienced chronic graft versus host disease was（21.3±10.5）%,among whom 17 cases developed CMV,4 cases developed EBV and 8 cases developed hemorrhagic cystitis.The median follow-up time was 11.5（1 to 95）months,and 11 patients were still alive.Two years after transplantation,the overall survival（OS）rate and the leukemia free survival（LFS）rate were（37.8±9.5）% and（68.6±11.1）%,respectively,among which,the OS and LFS of patients donated by cousins on mother's side were（28.6±10.6）% and（59.5±14.8）%,and the OS and LFS of patients donated by cousins on father's side were（60.0±18.2）% and（85.7±13.2）%,respectively.There was no statistical significance in OS（P=0.150）and LFS（P=0.403）comparison between the two groups by means of survival analysis with Log-rank test.The Cox multi factor analysis indicated that pretransplant disease status as well as HLA consistency were independent unfavorable prognostic factors that affected the OS[HR=6.268（95%CI 4.636 to 11.346）,P=0.012;HR=5.668（95%CI 1.410 to 22.776）,P=0.015]and LFS[HR=8.054（95%CI 0.987 to 65.688）,P=0.051;HR=4.340（95%CI 1.183 to 15.926）,P=0.027].Conclusion:Collateral relatives can be donors of allo-HSCT in the treatment of acute leukemia,and pretransplant disease status as well as HLA consistency is an independent unfavorable prognostic factor of transplantation from collateral related donors.
- collateral related donors /
- allogeneic hematopoietic stem cell transplantation /
- acute leukemia

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参考文献(12)

[1]	Huang XJ,Liu DH,Liu KY,et al.Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies[J].Bone Marrow Transplant,2006,38:291-297.
[2]	Passwen JR,Baldomero H,Bader P,et al.Is the use of unrelated donor transplantation leveling off in Europe?[J].Bone Marrow Transplant,2018,53:1139-1148. [3] Gordon MY,Blackett NM.Reconstruction of the hematopoietic system after stem cell transplantation[J].Cell Transplant,1998,7:339-344.
[4]	章忠明,赖永榕.急性移植物抗宿主病防治进展[J].临床血液学杂志,2017,30(9):665-668.
[5]	Xu LP,Wu DP,Han MZ,et al.A review of hematopoietic cell transplantation in China:data and trends during 2008-2016[J].Bone Marrow Transplant,2017,52:1512-1518.
[6]	Lv M,Chang YJ,Huang XJ.Update of the "Beijing Protocol" haplo-identical hematopoietic stem cell transplantation[J].Bone Marrow Transplant,2019,54:703-707.
[7]	Rocha V,Franco RF,Porcher R,et al.Host defense and inflammatory gene polymorphisms are associated with outcomes after HLA-identical sibling bone marrow transplantation[J].Blood,2002,100:3908-3918.
[8]	Shimazaki C,Ochiai N,Uchida R,et al.Non-T-cell-depleted HLA haploidentical stem cell transplantation in advanced hematologic malignancies based on the feto-maternal michrochimerism[J].Blood,2003,101:3334-3336.
[9]	Keen LJ,DeFor TE,Bidwell JL,et al.Interleukin-10 and tumor necrosis factor alpha region haplotypes predict transplant-related mortality after unrelated donor stem cell transplantation[J].Blood,2004,103:3599-3602.
[10]	Wang Y,Wu DP,Liu QF,et al.Donor and recipient age,gender and ABO incompatibility regardless of donor source:validated criteria for donor selection for haematopoietic transplants[J].Leukemia,2018,32:492-498.
[11]	Zhang YY,Liu DH,Liu KY,et al.HLA-haploidentical hematopoietic SCT from collateral related donors without in vitro T-cell depletion for hematological malignancies[J].Bone Marrow Transplant,2014,49:496-501.
[12]	Mo XD,Zhang YY,Zhang XH,et al.The role of collateral related donors in haploidentical hematopoietic stem cell transplantation[J].Science Bulletin,2018,63:1376-1382.
[13]	Wang Yu,Chang YJ,Xu LP,et al.Who is the best donor for a related HLA haplotype-mismatched transplant?[J].Blood,2014,124:843-850.