亲缘单倍体造血干细胞移植治疗成人噬血细胞性淋巴组织细胞增生症临床特点分析

The clinical characteristics of adult hemophagocytic lymphohistiocytosis treated with haploidentical donor hematopoietic stem cell transplantation

目的探讨亲缘单倍体造血干细胞移植（HIDHSCT）治疗成人噬血细胞性淋巴组织细胞增生症（HLH）的临床特征。方法回顾性分析首都医科大学附属北京友谊医院2009年8月至2014年8月HIDHSCT治疗的20例成人HLH的疗效和预后。结果预处理方案包括全身照射／依托泊苷／环磷酰胺和马利兰／依托泊苷／环磷酰胺，抗人胸腺细胞球蛋白剂量为8mg／kg。干细胞来源均为外周血。中位白细胞植活时间13（9-27）d，中位血小板植活时间14（10～28）d。移植后出现混合嵌合状态4例，无病例植入失败。发生Ⅱ～Ⅳ度急性移植物抗宿主病8例，慢性移植物抗宿主病9例。EB病毒（EBV）复燃12例，复燃中位时间33（15～80）d，其中确诊移植后淋巴组织增殖性疾病（PTLD）2例，疑似PTLD7例，原发病复发3例。移植后中位随访20（0．5～108）个月，2年总生存率为（60．0±11．0）％。截至随访结束，存活12例，死亡8例，死于移植后100d内5例。移植前未获得缓解者5例，4例死亡，均死于移植后100d内。结论HIDHSCT治疗成人HLH在移植早期容易发生混合嵌合，EBV复燃发生显著，移植早期相关死亡表现突出。

Objective To analyze the clinical characteristics of adult patients with hemophagocytic lymphohistiocytosis （HLH） receiving haploidentical donor hematopoietic stem cell transplantation （HID HSCT）. Method We retrospectively reviewed 20 adult patients with HLH from August 2009 to August 2014. The clinical features and outcome were analyzed. Results Conditioning regimens consisted of total body irradiation/etoposide/cyclophosphamide （TBI/VP-16/CTX） and busulfan （Bu）/VP-16/CTX in HLH with anti-thymocyte globulin （ATG） 8 mg/kg. The stem cells were mobilized from donors＇ peripheral blood. Median time to white blood cell engraftment was 13 （9 -27） days. Median time to platelet engraftment was 14 （ 10 - 28 ） days. Mixed chimerism after transplantation developed in 4 patients and no patient presented graft failure. Eight patients developed grade 11 to III acute graft-versus-host disease （ GVHD）, while as chronic GVHD occurred in 9 patients. Among 12 patients with EB virus （ EBV ） reactivation, 2 patients developed post-transplant lymphoproliferative disorder （ PTLD）, 7 were suspected as PTLD and 3 were considered as relapse of primary disease. With a median follow-up of 20 months （range-0. 5 -108 months） after transplantation, the estimated 2-year overall survival （OS） rate was （60. 0 ± 11.0） % in all patients. During the follow-up, 12 patients survived, 8 died including 5 within 100 days after HSCT. Among 5 non-remission patients before HSCT, 4 patients died within 100 days after HCT. Conclusions HID HSCT is an effective treatment for adult patients with HLH to achieve remission and long-term survival. High proportion of mixed chimerism has been seen at early stage after transplantation. EBV reactivation and early transplant-related mortality are common.