异基因造血干细胞移植治疗18例阵发性睡眠性血红蛋白尿症疗效分析

Outcomes of allogeneic hematopoietic stem cell transplantation for 18 patients with paroxysmal nocturnal haemoglobinuria

目的评价异基因造血干细胞移植（allo—HSCT）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2007年12月至2015年2月间接受allo-HSCT治疗的18例PNH患者临床资料，其中原发PNH4例，再生障碍性贫血-PNH综合征（AA—PNH）14例。9例为单倍体相同供者移植（其中1例为双份脐血植入失败后行挽救性单倍体相同供者移植），7例为HLA相合同胞供者移植，2例为HLA相合无关供者移植。13例患者接受改良白消安／环磷酰胺方案为主的清髓性预处理，5例接受非清髓性预处理（氟达拉滨＋抗胸腺细胞球蛋白＋环磷酰胺或白消安方案）。移植物抗宿主病（GVHD）预防：同胞供者移植为环孢素联合短程甲氨蝶呤，单倍体相同供者及无关供者移植为环孢素或他克莫司、霉酚酸酯联合短程甲氨蝶呤。结果所有患者均获造血重建（其中1例患者脐血植入失败后行单倍体相同供者移植）。中性粒细胞绝对计数≥0．5×10^9/L的中位时间为移植后11（10～26）d，PLT恢复至≥20×10^9/L的中位时间为移植后15（11～120）d。3例（17．6％）患者发生急性GVHD（aGVHD），其中Ⅱ度2例，Ⅳ度1例。2例（12．5％）发生局限型慢性GVHD（cGVHD）。中位随访14．6（2．0～86．7）个月，18例患者中死亡3例（17．6％），死因分别为重度aGVHD、肺部重症感染、肺部感染合并移植相关血栓性微血管病。预期5年无病生存率为（80．5±10．2）％。无复发病例。结论allo—HSCT治疗PNH疗效确切，预后良好，在抗补体C5单抗尚未广泛应用的情况下，可作为有价值的治疗手段。

Objective To evaluate the outcomes of allogeneic hematopoietic stem cell transplantation （allo-HSCT） for paroxysmal nocturnal haemoglobinuria （PNH） and aplastic anemia （AA）- PNH syndrome. Methods The clinical data of 18 PNH or AA-PNH patients, including 4 classic PNH and 14 AA-PNH, received allo-HSCT from Dec 2007 to Feb 2015 were analyzed retrospectively. Nine patients received HLA-haploidentical donor HSCT （1 patient received salvage HLA-haploidentical donor HSCT after the graft failure of double cord blood transplantation）, 7 patients received HLA-identical sibling donor HSCT, and 2 HLA-identical unrelated donor HSCT. The conditioning regimens were as follow： 13 patients received modified BU/CY-based regimens, 5 non-myeloablative regimens [fludarabine （Flu） ＋ antithymocyte globulin （ATG） ＋ cyclophosphamide （CY） or busulfan （BU） ]. Prophylaxis for graft-versushost disease （GVHD）： the patients with HLA-identical sibling donor received cyclosporine （CsA） plus short-term methotrexate （MTX）, the patients with HLA-haploidentical donor or HLA-identical unrelated donor received CsA or taerolimus （FK506）＋ mycophenolate mofetil （MMF）＋ short-term methotrexate （MTX）. Results All patients were engrafted successfully （1 patient engrafted by haploidentical donor after the graft failure of double cord blood transplantation）. The median days of neutrophils （ANC） above 0.5 × 10^9/L and platelets （PLT） more than 20 × 10^9/L were 11 （10-26） days and 15 （11- 120） days, respectively. Three patients （ 17.6% ） developed acute GVHD （aGVHD）, 2 for grade Ⅱ aGVHD, 1 for grade IV aGVHD. Of 16 patients, 2 occurred limited chronic GVHD （cGVHD）. After a median follow-up of 14.6 （2.0-86.7）months, 3 patients （17.6%） died, out of which one died of severe aGVHD, one died of severe pulmonary infection, one pulmonary infection with transplantassociated thrombotic microangiopathy. The 5-year estimated disease free survival was （80.5 ± 10.2）%. No patient relapsed. Conclusion Allo-HSCT is an effective and curable therapy for PNH or AA-PNH with improved prognosis, and offers a valid therapeutic option for these patients before humanized monoclonal antibody against C5 are widely used clinically.