HBsAg阳性患者异基因造血干细胞移植后的临床研究

A clinical study of allo-hematopoietic stem cell transplantation in HBsAg positive leukemia

目的探讨HBsAg阳性患者接受异基因造血干细胞移植（allo—HSCT）后的肝脏不良事件的发生及影响该类患者长期生存的危险因素。方法回顾性分析本所2001年3月至2006年11月接受allo—HSCT治疗的26例HBsAg阳性患者的临床资料。造血干细胞来源：18例为HLA配型相合同胞，7例为HLA配型不合亲缘供者，1例为无关供者。所有患者移植前后均排除丙型肝炎病毒感染。2例移植前HBVDNA阳性，其余均表达阴性。结果26例患者急性移植物抗宿主病（aGVHD）累积发生率为50．0％。在可评估的20例中，5例发生了慢性GVHD，累积发生率25．0％。移植后出现肝功能异常共有15例（57．7％）。出现肝功能受损的病因主要为：乙型肝炎及肝脏GVHD。移植后乙型肝炎再燃5年累积发生率33．4％，发生中位时间为82（65—159）d。拉米夫定预防性应用13例，1例发生乙型肝炎事件；未给药组为11例，7例发生乙型肝炎事件，两者累积发生率差异有统计学意义（P=0．006）；预防用药组未发生一例肝衰竭，未预防用药组发生4例肝衰竭。死亡原因：5例肝衰竭，3例肺部感染，2例移植后疾病复发。26例患者中共有10例死亡，5年生存率（OS）为59．0％。多因素分析最终确定与OS发生相关的危险因素为肝衰竭（P=0．000）。结论HBsAg阳性患者接受allo—HSCT治疗后常出现肝功能异常表现，其首要病因为乙型肝炎，所导致的肝衰竭严重影响患者预后。而对HBsAg阳性患者预防性应用拉米夫定能够有效预防移植后乙型肝炎的复燃。

Objective To explore the incidence and risk factors of hepatic events and overall survival among HBsAg positive leukemia patients after allo-hematopoietic stem cell transplantation （ allo- HSCT）. Methods A retrospective clinical study was conducted at the bone marrow transplant unit in our hospital between March 2001 and November 2006. A total of 26 HBsAg positive leukemia patients were included in the study. 18 patients received HLA-identical sibling allo-HSCT, 7 patients received HLA- mismatched related and 1 patient received HLA-identical unrelated. All the patients were free from hepatitis C infection before and after allo-HSCT. HBV serologic markers, including HBsAg, HBeAg, HBsAb, HBeAb and HBcAb were tested. 2 patients were positive for HBV-DNA before allo-HSCT. Results The cumulative incidence for acute graft vs host disease （aGVHD） grades Ⅰ -Ⅳ was 50.0%. The cumulative incidence for chronic GVHD was 25.0%. 15 （57. 7% ） of all the patients had abnormalities of liver function after allo- HSCT. The types of hepatic disease were reactivation of HBV and hepatic GVHD. The cumulative incidence in 5 years for hepatitis B reactivation was 33.4% ,the median day of hepatitis B reactivation was 82th（65th- 159th） day. The virologic and clinical outcomes were compared between two groups; one received lamivudine as prophylactic （group 1 ） and the other did not receive lamivudine（ group 2）. After transplantation, 1 patient in group 1 and 7 patients in group 2 had hepatitis due to reactivation of HBV. The cumulative incidence for hepatitis B reactivation was statistically different between the two groups （ P = 0. 006）. None in group 1 but 4 in group 2 died of HBV-related hepatic failure. 10 of the 26 patients died after transplantation. The overall survival （OS） in 5 years was 59.0%. The causes of death included hepatic failure （5 cases）, lung infection （3 cases） and relapse of leukemia （2 cases ）. By multivariate Cox analysis, development of hepatic failure was a significant predictor of mortality （P = 0. 000）. Conclusion HBsAg positive leukemiapatients often suffered from hepatic injury after allo-HSCT. The principal cause of hepatic damage was the reactivation of HBV. Hepatic failure caused by HBV was the principal reason of death. Prophylaxis with lamivudine in HBsAg positive leukemia recipients can reduce the reactivation of HBV.