单倍型造血干细胞移植治疗阵发性睡眠性血红蛋白尿症的临床观察

Clinical observation of HLA haploidentical donor hematopoietic stem cell transplantation for patients with paroxysmal nocturnal haemoglobinuria

目的 评价单倍型造血干细胞移植治疗阵发性睡眠性血红蛋白尿症（PNH）的疗效.方法 回顾性分析2010年10月至2014年10月接受单倍型移植治疗的9例PNH患者的临床资料,其中原发PNH1例,再生障碍性贫血-阵发性睡眠性血红蛋白尿症（AA-PNH）8例.9例中,8例以改良白消安＋环磷酰胺联合抗胸腺细胞球蛋白（ATG）进行清髓性预处理,1例二次移植受者（挽救性单倍型移植）采取减量全身照射＋环磷酰胺＋ ATG方案预处理.粒细胞集落刺激因子动员的供者骨髓联合外周血干细胞作为移植物来源.环胞素A或他克莫司＋吗替麦考酚酯＋短程甲氨蝶呤预防移植物抗宿主病（GVHD）.结果 所有患者均获完全植入及造血重建.中性粒细胞≥0.5×10^9/L的中位时间为移植后12 d（11～26 d）,血小板恢复至≥20×10^9/L的中位时间为移植后15 d（11～120 d）.2例受者（22.2％,2/9）发生急性GVHD,均为Ⅱ度,2例（22.2％,2/9）发生局限型慢性GVHD.受者中位随访时间为14.0个月（4.0～30.8个月）,期间死亡2例,死因分别为肺部重症感染、肺部感染合并移植相关的血栓性微血管病.受者预期2年无病存活率为（72.9±16.5）％.无复发病例.结论 单倍型造血干细胞移植治疗PNH疗效确切,对于缺少HLA相合供者的患者可作为替代的移植手段.

Objective To evaluate the outcome of HLA haploidentical donor hematopoietic stem cell transplantation （HSCT） for paroxysmal nocturnal haemoglobinuria （PNH）.Method The clinical data of 9 PNH patients receiving haploidentical donor HSCT from Oct.2010 to Oct.2014 were analyzed retrospectively.There was one case of PNH de novo, and 8 cases of aplastic anemia-PNH syndrome （AA-PNH）.The conditioning regimens were as follows： 8 patients received modified busulfan and cytoxan （BuCy）-based regimens combined with anti-thymocyte globulin （ATG）, and 1 patient who received salvage haploidentical donor HSCT after the graft failure of double cord blood transplantation was given reduced-intensity total body irradiation （TBI） ＋ cyclophosphomide ＋ ATG.Granulocyte colony stimulating factor-mobilized bone marrow and peripheral blood stem cells were transplanted as graft.Prophylaxis for graft-versus-host disease （GVHD） was ciclosporin A or tacrolimus ＋ mycophenolate mofetil （MMF） ＋ short-term methotrexate （MTX）.Result All patients were engrafted successfully.The median time of neutrophils to 0.5 ×^109/L and platelets to 20×10^9/L was 12 （11-26） days and 15 （11-120） days, respectively.Two patients （22.2%） developed grade Ⅱ acute GVHD, and 2 limited chronic GVHD.Median follow-up time was 14.0 （4.0-30.8） months.Of the two deaths, one died of severe pulmonary infection, and one pulmonary infection with transplant associated thrombotic microangiopathy.Two-year estimated disease-free survival was （72.9 ± 16.5） %.No patient relapsed.Conclusion HLA haploidentical donor HSCT is an effective and curable therapy for PNH, and offers a valid therapeutic option for patients without HLA matched donor.