乙型肝炎病毒感染患者进行异基因造血干细胞移植的安全性评价

The safety evaluation of allogenetic hematopoietic stem cell transplantation in patients with hepatitis B virus

目的:对伴有乙型肝炎病毒(HBV)感染的恶性血液病患者抗病毒治疗后进行异基因造血干细胞移植(allo-HSCT)的安全性进行评价。方法:allo-HSCT患者45例,均为HBV感染的恶性血液病患者,移植前感染HBV的患者和供者均给予拉米夫定和(或)阿德福韦/恩替卡韦抗病毒治疗;移植前对HBV-DNA的拷贝数进行评估,移植后定期随访HBV-DNA含量,供者细胞的植入时间以及急、慢性移植物抗宿主病(GVHD)、肝静脉闭塞病(HVOD)的发生情况;移植后受者继续服用拉米夫定和(或)阿德福韦/恩替卡韦。结果:①HBV感染对造血干细胞的植入无明显影响,移植后16例发生了急性GVHD(aGVHD),累积发生率为(37.5±7.5)%,可评估的42例患者中,17例发生了慢性GVHD(cGVHD),累积发生率为(41.6±7.8)%,仅有1例患者发生HVOD;②移植后有28例患者发生肝功能异常,9例为乙肝再激活,15例为急性或慢性GVHD,其中有3例患者两者均有,乙肝再激活的累积发生率为(31±8.9)%,7例为药物性肝损害;③移植后随访中位时间为30(1～74)个月,共有13例死亡,3年生存率(OS)为(64.3±8.4)%。死亡原因:4例死于移植后肝功能衰竭,3例死于复发,3例死于肺部感染,2例死于多脏器功能衰竭,1例死于弥漫性肺泡出血。结论:移植前进行有效抗病毒治疗以及造血重建后服用拉米夫定和(或)阿德福韦/恩替卡韦的恶性血液病患者,进行allo-HSCT是安全的,不影响造血重建,未增加HVOD的发病率,亦不导致急、慢性GVHD发病率的上升,因而受者或供者HBV感染并非allo-HSCT的禁忌证。

Objective：Hepatitis B virus（HBV）infection is common in Asians,particularly in Chinese population,and may increase allogenetic hematopoietic stem cell transplantation（allo-HSCT）associated risk.If allo-HSCT is considered as an indicative therapy for the patients with hematological malignancies accompanied by active HBV infection,the transplantation has been suggested to delay until antiviral therapy is evaluated effective.Here we retrospectively analyzed impact of HBV infection on allo-HSCT safety.Method：Totally 45 patients were diagnosed as active HBV infection prior to transplantation out of all allo-HSCT performed.All those patients had hematological malignancies.HBV infection was assessed with HBV-DNA copy number.Both the patients and donors with HBV infection were treated with Lamivudine or Adefovir alone or combined prior to transplantation.Antiviral treatment was continued after transplantation,and meanwhile HBV-DNA copy number was detected regularly.The correlation of HBV infection with the time of donor cell engraftment,incidence of acute or chronic graft-versus-host disease and hepatic veno-occlusive disease（HVOD）were analyzed.Result：①The hematopoietic stem cell transplantation was not significantly affected by HBV infection following effective antiviral treatment.After transplantation 16 patients had acute graft-versus-host disease（aGVHD）,with the cumulative incidence rate（37.5±7.5）%;In the 42 evaluable patients,17 patients had chronic graft-versus-host disease（cGVHD）with the cumulative incidence rate（41.6±7.8）%;Only one patient had HVOD.②Twenty-eight patients had abnormal liver function after transplantation,9 patients had HBV reactivation,and 15 patients had aGVHD or cGVHD,including 3 patients with aGVHD and cGVHD,with the cumulative incidence rate HBV reactivation（31±8.9）%,and 7 patients had drug-induced liver injury.③The median time of follow-up was 30 months after transplantation（1-74 months）,there were 13 cases of death,the survival rate was（64.3±8.4）% over 3 years.The causes of death included liver failure after transplantation（4 cases）,recurrence（3 cases）,lung infection（3 cases）,multiple organ failure（2 cases）and diffuse alveolar hemorrhage（1 case）.Conclusion：Effective antiviral treatment may decrease or counteract the HBV infection associated risk in allo-HSCT settings.