异基因造血干细胞移植肝炎病毒再激活的预防

Prevention of hepatitis virus reactivation in patients undergoing allogeneic hematopoietic stem cell transplantation

背景：感染肝炎病毒的血液病患者进行造血干细胞移植,存在拉米夫定等核苷类似物的耐药、药物持续时间、丙型肝炎病毒的靶向治疗等问题。目的：探讨异基因造血干细胞移植患者肝炎病毒再激活的预防措施。方法：河南省人民医院2005-01/2008-07收治的5例感染乙型或丙型肝炎病毒的白血病患者,均经锁骨下静脉行外周血造血干细胞移植,回输的单个核细胞数量为（8.6~19.3）×108/kg,CD34＋细胞数量为（5.1~15.4）×106/kg。例1于初次诱导缓解化疗时开始应用拉米夫定,7个月后加用恩替卡韦,3个月后乙型肝炎病毒DNA降至1.02×103U/mL,此间白血病复发,再次缓解后进行移植。例2于诊断明确后给予格列卫＋拉米夫定,2个月后乙型肝炎病毒DNA降至〈1.0×103U/mL进行移植。例3于诱导缓解化疗开始应用拉米夫定,10周后乙型肝炎病毒DNA降至〈1.0×103U/mL,巩固化疗结束后移植。例4于CR1期移植,干细胞输入前1d给予拉米夫定。例5于CR1期移植。检测5例患者的病毒复制及肝功能状态。结果与结论：5例患者均完成9个月随访,全部获造血功能重建,均未发生肝静脉阻塞综合征,均未出现病毒复制增加或肝功能损害。例1在移植后单用恩替卡韦6个月后停药,例2于移植后8个月停用拉米夫定,例3、例4于移植后6个月停药,移植后4例患者乙型肝炎病毒DNA均持续小于1.0×103U/mL。例5丙型肝炎病毒RNA持续〈1.0×103U/mL。拉米夫定可以预防异基因造血干细胞移植患者乙型肝炎病毒再激活,在拉米夫定效果不理想的情况下,恩替卡韦可以实现有效预防。

BACKGROUND：Hematopathy patients carrying hepatitis virus would present problems such as hepatitis virus resistance to nucleoside analogue drugs or targeted therapy of hepatitis C virus when undergoing allogeneic hematopoietic stem cell transplantation（Allo-HSCT）.OBJECTIVE：To investigate the prophylaxis of hepatitis virus reactivation in patients undergoing Allo-HSCT.METHODS：Five leukemia patients with HBV or HCV infection undergoing Allo-HSCT at the Hennan Provincial People＇s Hospital from January 2005 to July 2008 were collected.The infused number of mononuclear cells was（8.6-19.3） ×108/kg,with（5.1-15.4） ×106/kg CD34＋ cells.Case 1 received lamivudine treatment at the beginning of remission induction chemotherapy,and entecavir was added after 7 months.When the number of hepatitis B DNA copies was reduced to 1.02×103 U/mL at 3 months after operation,and received a second transplantation due to leukemia relapse.Case 2 was treated by imatinib mesylate＋lamivudine,transplanted when the number of hepatitis B DNA copies was under 1.0×103 U/mL after 2 months.Case 3 was treated by lamivudine at the beginning of remission induction chemotherapy,followed by consolidation chemotherapy and transplantation when the number of hepatitis B DNA copies was under 1.0×103 U/mL after 10 weeks.Case 4 was transplanted at the CR1 phase,and the lamivudine was applied at 1 day before transplantation.Case 5 were transplanted at the CR1 phase.The virus replication and hepatic functional status were detected in all patients.RESULTS AND CONCLUSION：All cases were followed-up for 9 months.All patients rebuilt hematopoietic function,no venous occlusive disease,virus replication,or hepatic function damage occurred.The medication was stopped after 6 months in case 1,at 8 months in case 2,and at 6 months in case 3 and case 4.The number of hepatitis B DNA copies was persistently under 1.0×103 U/mL in case 4,and the number of hepatitis C DNA copies was persistently under 1.0×103 U/mL in case 5.Lamivudine could prevent hepatitis B reactivation in patients undergoing Allo-HSCT,and entecavir is still valid if the result is unsatisfactory.