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首页|HLA匹配同胞供者异基因造血干细胞移植治疗重型再生障碍性贫血41例疗效分析

HLA匹配同胞供者异基因造血干细胞移植治疗重型再生障碍性贫血41例疗效分析

Outcome of allogeneic hematopoietic cell transplantation (allo-HSCT) with HLA-matched sibling donors for 41 severe aplastic anemia

中文摘要英文摘要

目的 评价人组织相容性抗原(HLA)匹配同胞供者异基因造血干细胞移植(MSD allo-HSCT)治疗重型再生障碍性贫血(SAA)患者的疗效。方法 回顾性分析我院2003年5月-2011年8月31日接受MSD allo-HSCT治疗的41例SAA患者临床资料,其中SAA-I型患者28例,SAA-II型患者9例,肝炎后再障患者4例,中位年龄23(5-41)岁,异基因骨髓移植(allo-BMT)17例,异基因外周血干细胞移植(allo-PBSCT)24例,预处理方案为环磷酰胺(CY)+抗人胸腺细胞球蛋白(ATG)+氟达拉滨(Flu) 20例,应用CY+ATG+ Flu+阿糖胞苷(Ara-C)±白消安(Bu)或马法兰(Mel)21例,移植物抗宿主病(GVHD)预防方案采用环孢素(CsA)加短疗程甲氨蝶呤(MTX)患者25例,他克莫司(FK506) 加短疗程甲氨蝶呤(MTX)患者16例,allo-BMT组患者回输CD34+细胞中位数3.48(2.39 -4.8)×106/kg;allo-PBSCT组患者回输CD34+细胞中位数2.95(1.27-5.98)×106/kg。结果 41例患者移植后均获得造血重建(100%),中性粒细胞(ANC)恢复至≥0.5×109 /L中位时间 14(10-23)天,血小板(PLT) 恢复至≥20×109 /L中位时间 19(8-38)天。12例患者发生急性移植物抗宿主病(aGVHD)(29.3%±7.1%),其中I-II度aGVHD 11例, IV度aGVHD 1例,2例患者发生慢性移植物抗宿主病(cGVHD),其中局限型与广泛型cGVHD各 1例。4例患者出现移植物排斥(GR)(11.8%±5.7%),进行供者外周血干细胞输注后均恢复造血并存活。41例患者中死亡5例(18.9% ±9.0%),其中1例患者死于广泛型cGVHD,4例患者死于侵袭性真菌感染(IFIs)。中位随访23(3-79)个月,36例患者生存,预期5年生存率(OS)81.1% ±9.0%。单因素分析结果显示,移植后OS率较低与选用PBSCT、发生aGVHD、回输CD34+数量≤2.5×106/kg、移植前输注红细胞>30u、移植后发生IFIs显著相关(P值分别为0.034、0.001、0.006、0.000和0.001);移植后发生aGVHD与供受者ABO血型不同、移植前输注PLT>100u、输注红细胞>30u、回输CD34+数量≤2.5×106/kg显著相关(P值分别为0.019、0.038、0.005和0.005);GR的发生与移植前输注PLT>100u显著相关(P=0.038)。结论 MSD allo-HSCT治疗SAA疗效显著,有效减少移植前输血量、采用骨髓移植、适当增加回输CD34+数量、有效防治aGVHD及移植后IFIs对于提高MSD allo-HSCT疗效至关重要。

Objegtive To evaluate the eficacy of allogeneic hematopoietic stem cell transplantation from HLA- matched siblings(MSD allo-HSCT) for severe aplastic anemia (SAA).Methods Retrospective analysis the clinical data of forty-one SAA patients received MSD allo-HSCT from 2003.5 to 2011.8.31,twenty-eight patients suffered from SAA-I,nine patients suffered from SAA-II, four patients suffered from aplastic anemia post-hepatitis,median age is 23(5-43)years old,seventeen patients conducted allogeneic bone marrow transplantation(allo-BMT), twenty-four patients conducted allogeneic peripheral blood stem cell transplantation(allo-PBSCT),20 patients'conditioning regimen was CY+ATG+Flu, 21 patients'conditioning regimen was CY+ATG+Flu±Bu/Mel, 25 paitents'GVHD preventing regimen was CSA+MTX,16 paitents' GVHD preventing regimen was FK506+MTX,the median reinfusion quantity of CD34+ was 3.48(2.39 -4.8)×106/kg in allo-BMT and 2.95(1.27-5.98)×106/kg in allo-PBSCT. Resuits Hematopoiesis reconstitution was achieved in all 41 patients(100% ).The median time of neutrophils reached to 0.5×l09/L and platelets reached to 20×109/L were 14(10-23)days and 19(8-38)days,respectively.12 patients developed acute graft-versus-host diseaes(aGVHD),all out of them, 11 patients developed grade I-II aGVHD,one patients developed grade IV aGVHD,two patients occurred chronic GVHD( cGVHD),one with local cGVHD and the other one with widely cGVHD. Graft rejection(GR) was occurred in 4 patients, all 4 patients recovery haemopoietic and survival with donor peripheral blood stem cell infusion.5 patients died(18.9% ±9.0%),oen patients died of widely cGVHD,4 patients died of invasive fungal infections. Median follow-up time was 23(3-79) months. 36 patients survive,and prospective OS is 81.1% ±9.0%.Univariate analysis showed that five factors can reduce OS, including conducted PBSCT,occurrence of aGVHD, infusion quantity of CD34+ cells no more than 2.5×106/kg ,the number of blood transfusion befor transplantation more than 30u and occurrence of invasive fungal infections after transplantation(P=0.034,0.001,0.006,0.000, 0.001) ;four factors were related with occurrence of aGVHD, including the difference of donor and recipient's ABO blood group, the number of platelet transfusion befor transplantation more than 100u, the number of blood transfusion befor transplantation more than 30u ,infusion quantity of CD34+ no more than 2.5×106/kg(P=0.019, 0.038,0.005,0.005);the number of platelet transfusion befor transplantation more than 100u was related with occurrance of GR(P=0.038). Conclusion MSD allo-HSCT is an effective therapy for patients with SAA. Reducing the number of blood transfusion befor transplantation, using bone marrow transplantation,increasing infusion quantity of CD34+ cells,effective prevention and treatment of aGVHD and invasive fungal infections after transplantation may improve the eficacy of MSD allo-HSCT for SAA.

韩明哲、杨栋林、陈欣、冯四洲

临床医学内科学

重型再生障碍性贫血异基因造血干细胞移植同胞供者

severe aplastic anemiaallogeneic hematopoietic stem cell transplantationsibling donor

韩明哲,杨栋林,陈欣,冯四洲.HLA匹配同胞供者异基因造血干细胞移植治疗重型再生障碍性贫血41例疗效分析[EB/OL].(2012-02-27)[2025-08-02].http://www.paper.edu.cn/releasepaper/content/201202-1035.点此复制

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