含克拉屈滨的预处理方案造血干细胞移植治疗儿童重型地中海贫血疗效和安全性  

Efficacy and security of a new cladribine-based conditioning regimen for allogeneic hematopoietic stem cell transplantation in children with major thalassemia

作　　者：陆婧媛[1] 洪秀理[1] 庄燕红[1] 颜秀珍[1] 石洁 陈亚玫[1] 胡嘉升[1] 鹿全意[1] Lu Jingyuan;Hong Xiuli;Zhuang Yanhong;Yan Xiuzhen;Shi Jie;Chen Yamei;Hu Jiasheng;Lu Quanyi(Department of Hematology,Affiliated Zhongshan Hospital,Xiamen University,Xiamen 361004,China)

机构地区：[1]厦门大学附属中山医院血液科,361004

出　　处：《中华器官移植杂志》2019年第10期628-632,共5页Chinese Journal of Organ Transplantation

摘　　要：目的探讨含克拉屈滨的预处理方案在异基因造血干细胞移植(allo-HSCT)治疗儿童重型地中海贫血中的疗效和安全性。方法分析2017年3月至2018年7月在厦门大学附属中山医院完成的12例重型地中海贫血受者异基因干细胞移植的临床资料。受者中位年龄5岁(2~13岁),其中HLA全相合无关供者8例,HLA位点8/10相合无关供者1例,亲缘HLA全相合同胞供者2例,亲缘HLA半相合单倍体供者1例。所有受者均采用环磷酰胺+克拉屈滨+白消安+抗人胸腺细胞球蛋白的预处理方案。移植时输注单个核细胞中位数为10.97×10^8/kg(5.72~12.49×10^8/kg),CD34^+细胞中位数为12.2×10^6/kg(6.7~22×106/kg)。移植后采用环孢素A+短疗程甲氨蝶呤+吗替麦考酚酯预防移植物抗宿主病(GVHD)。结果移植后11例受者获得造血重建,1例植入失败。11例受者中性粒细胞植入的中位时间为11 d(8~17 d),血小板植入的中位时间为13 d(8~37 d)。移植后6例发生Ⅱ度以下急性GVHD,1例移植后35 d发生Ⅳ度肠道GVHD,后因合并严重感染于移植后70 d死于多器官衰竭,慢性GVHD 2例。巨细胞病毒血症发生率为25%,未出现巨细胞病毒病、肝静脉闭塞症、败血症等严重移植相关并发症。中位随访时间15个月(8~18个月),死亡1例,失败1例,10例受者健康生存并脱离输血。结论克拉屈滨为基础的预处理方案在儿童重型地中海贫血的干细胞移植中是安全有效的,但由于强烈的免疫抑制有可能导致移植后感染和病毒激活的风险增高。Objective To observe the efficacy and safety of intensive cladribine-based conditioning regimen for allogeneic hematopoietic stem cell transplantation(allo-HSCT)in children with major thalassemia.Methods Retrospective analysis was performed for the clinical data of 12 children with major thalassemia undergoing allo-HSCT from March 2017 to July 2018.All of them were diagnosed definitely and the median age at transplantation was 5 years(range:2-13 years),including HSCT from HLA-matched unrelated donor(n=8),HLA8/10-matched unrelated donor(n=1),HLA-matched sibing donor(n=2)and haploidentical donor(n=1).They received a new intensive conditioning regimen of cyclophosphamide(CTX),cladribine,busulfan(Bu)and antithymocytic globulin.The median doses of mononuclear cell(MNC)and CD34 positive cell were 10.97×10^8/kg(range:5.72-12.49×10^8/kg)and 12.2×10^6/kg(range:6.7-22×10^6/kg).Graft-versus-host disease(GVHD)was prevented by cyclosporine A(CSA),methotrexate(MTX)and mycophenolate mofetil(MMF).Results Engraftment succeeded(n=11)and failed(n=1).The median time of neutrophil and platelet engraftment was 11 days(range:8-17 days)and 13 days(range:8-37 days)respectively.There were grade II acute GVHD(n=6)and grade IV intestinal acute GVHD(n=1)at 35 days post-transplantation.The latter one finally died of severe infection at 70 days post-transplantation.Two recipients of DLI developed limited chronic GVHD.Three cases(25%)developed cytomegaloviremia.None suffered from severe transplantation-related complications,such as cytomegalovirus diseases,hepatic veno-occlusive disease(HVOD),hemorrhagic cystitis or septicemia,etc.The median follow-up time was 15(8-18)months.Among 11 survivors,ten became transfusion-independent.Conclusions Cladribine-based conditioning regimen is both safe and effective for allo-HSCT in children with major thalassemia.However,vigorous immunosuppression may increase the risks of infection and viral activation after transplantation.

关 键 词：造血干细胞移植 地中海贫血 预处理 

分 类 号：R73[医药卫生—肿瘤]