亲缘单倍体供者与非血缘相合供者造血干细胞移植的临床疗效研究

Study on clinical outcomes of hematopoietic stem cell transplantation from HLAhaploidentical donors and unrelated donors

目的对比非血缘相合及血缘单倍体相合供者来源异基因造血干细胞移植（allo-HSCT）的疗效及安全性。方法分析2009年12月至2013年8月期间在解放军第三○九医院接受非血缘相合供者来源造血干细胞移植（uD-HSCT）31例与血缘单倍体相合供者来源造血干细胞移植（Hi—HSCT）28例高危或难治性急性白血病患者临床资料。移植预处理方案采用改良白舒非加环磷酰胺（BUCY）或环磷酰胺／全身放疗（CY／TBI）；移植物抗宿主病（GVHD）预防采用抗胸腺细胞球蛋白（ATG）、环孢菌素、甲氨蝶呤及霉酚酸酯联合方案；肝静脉闭塞病（VOD）采用前列腺素E联合低分子肝素、复方甘草酸苷预防。两组患者GVHD发生率比较用χ^2检验，造血恢复时间比较用t检验，两组患者生存及移植相关死亡采用Kaplan-Meier生存曲线分析，Log-rank检验进行组间生存比较。结果所有患者均获造血重建，UD-HSCT与Hi-HSCT两组中性粒细胞中位重建时间分别为10．8（9～18）d及10．6（9～16）d（P〉0．05），3年无病生存率（DFs）分别为48．3％及50．5％（P〉0．05），两组总生存率（OS）分别为54．8％和57．1％（户〉0．05）。UD—HSCT与Hi-HSCTⅢ～Ⅳ度GVHD发生率分别为（7例）22．5％和（5例）17．8％（P〉0．05），UD—HSCT组1例发生重度VOD死亡,两组移植相关死亡（TRM）分别为14例（45％）与12例（43％）（P〉0．05），因复发死亡病例分别为8例（57．1％）与6例（50％）（P〉0．05）。结论UD-HSCT与Hi-HSCT治疗高危成难治急性白血病患者可取得相似的疗效，两者均可作为无同胞相合供者高危难治白血病的有效选择方案。

Objective To compare the efficacy and adverse events of unrelated donor hematopoietic stem cell transplantation （UD-HSCT）and related HLA-haploidentical donor HSCT （Hi-HSCT）. Methods Clinical data of 31 high-risk or refractory leukemia patients receiving UD-HSCT and 28 high-risk or refractory leukemia patients receiving Hi-HSCT were compared in our hospital between December 2009 and August 2013. The conditioning regimen consisted of modified BUCY （Busulfex plus Cyclophosphamide） or modified total body irradiation （TBI） plus CY. Acute graft-versus-host disease （aGVHD） prophylaxis consisted of antithymocyte globulin （ATG）, cyclosporine （Csg）, methotrexate （MTX） and mycophenolate mofetil （MMF）. Veno-occlusive disease （VOD） prophylaxis consisted of prostaglandin E, low-dose unfractionated heparin and Gansu oxalic acid compound. Results Bone marrow engrafted successfully in all 59 patients. The median recovery time of neutrophilic granulocyte and platelets were 10.8（9-18） days and 10.6（9-16） days respectively （P 〉 0.05）. The 3-year probabilities of disease-free survival （DFS） in UD-HSCT and in Hi-HSCT groups were 48.3 % and 50.5 % respectively, and the overall survival （OS） were 54.8 % and 57.1% respectively. Grade III-IV aGVHD occurred in 7 patients （22.5 %） in the UD-HSCT group and 5 patients （17.8 %） in the Hi-HSCT group （P 〉 0.05）. One patient died of severe VOD in the UD-HSCT group. 14 patients （45 %） died of transplantation-related mortality （TRM） in the UD-HSCT group and 12 patients （43 % ） died of TRM in the Hi-HSCT group （P 〉 0.05）. Death from relapse occurred in 8 patients （57.1%） in the UD-HSCT group and 6 patients （50%） in the Hi-HSCT group （P 〉 0.05）, respectively. Conclusions There is no apparent difference in the efficacy and adverse between UD-HIST and Hi-HSCT, both would be effective treatment for high-risk and refractory leukemia.