中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (19): 3503-3506.doi: 10.3969/j.issn.1673-8225.2010.19.017

• 干细胞移植 stem cell transplantation • 上一篇    下一篇

异基因造血干细胞移植肝炎病毒再激活的预防

刘忠文,雷平冲,陈玉清,张  茵   

  1. 河南省人民医院血液科,河南省郑州市  450003
  • 出版日期:2010-05-07 发布日期:2010-05-07
  • 作者简介:刘忠文,男,1968年生,河南省郑州市人,汉族,2000年华中科技大学同济医学院毕业,博士,副主任医师,主要从事造血干细胞移植基础与临床应用方面的研究。 liuzhongwen@126.com

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

Liu Zhong-wen, Lei Ping-chong, Chen Yu-qing, Zhang Yin   

  1. Department of Hematology, Hennan Provincial People’s Hospital, Zhengzhou  450003, Henan Province, China
  • Online:2010-05-07 Published:2010-05-07
  • About author:Liu Zhong-wen, Doctor, Associate chief physician, Department of Hematology, Hennan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China liuzhongewen@126.com

摘要:

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1.02×103 U/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<1.0×103 U/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<1.0×103 U/mL,巩固化疗结束后移植。例4于CR1期移植,干细胞输入前1 d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1.0×103 U/mL。例5丙型肝炎病毒RNA持续<1.0×103 U/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。

关键词: 乙型肝炎病毒, 再激活, 预防, 细胞移植, 造血干细胞

Abstract:

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.

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