异基因造血干细胞移植后早期EB病毒激活的监测和抢先治疗  

Monitoring of early Epstein-Barr virus reactivation and preemptive therapy after allogeneic hematopoietic stem cell transplantation

作　　者：卢岳[1] 吴彤[1] 曹星玉[1] 王静波[1] 孙媛[1] 赵艳丽[1] 达万明[1] 纪树荃[1] 童春容[2] 陆道培[1] 

机构地区：[1]北京市道培医院干细胞治疗科,100049 [2]北京市道培医院临床特检中心,100049

出　　处：《中华内科杂志》2011年第5期383-387,共5页Chinese Journal of Internal Medicine

摘　　要：目的 研究异基因造血干细胞移植（allo-HSCT）后早期EB病毒（EBV）激活的监测及其抢先治疗的结果和预后.方法 以2007年1月至2009年1月在我院行allo-HSCT并连续监测血浆EBV DNA的277例患者为研究对象,其中亲缘人类白细胞抗原（HLA）单倍型移植116例;非血缘移植75例,同胞相合移植86例.预处理主要采用马利兰（BU）＋环磷酰胺（CY）/氟达拉滨（Flu）或全身照射（TBI）/Flu方案,此外,亲缘单倍型和非血缘移植加用抗胸腺细胞球蛋白（ATG）.移植后最初的3个月内每周采用实时定量PCR（RQ-PCR）方法检测血浆EBV DNA,若＞5×102拷贝/ml而无临床症状时诊断为EBV血症.抢先治疗主要应用阿昔洛韦10 mg/kg静脉点滴,每8小时1次,同时在情况允许时减少免疫抑制剂.结果 移植后100 d（＋100 d）内33例（11.9%）患者发生EBV血症,中位时间为＋44（＋19～＋84）d;EBV血症的发生率在同胞相合、亲缘单倍型和非血缘移植中分别为0、15.5%和20.0%,在亲缘单倍型与非血缘移植中EBV血症的发生率差异无统计学意义（P=0.09）,但均较同胞相合移植高（P=0.001）.33例患者均首先采用减少免疫抑制剂剂量和阿昔洛韦抢先抗病毒治疗,其中20例患者病毒血症转为阴性,治疗有效率为60.6%,中位时间为治疗后11（4～56）d,抗病毒治疗疗程的中位时间为21（14～60）d.单因素及多因素分析均表明,亲缘单倍型移植、非血缘移植以及Ⅱ～Ⅳ度急性移植物抗宿主病（aGVHD）是EBV血症发生的高危因素.发生EBV血症患者（33例）比未发生EBV血症患者（244例）的2年预期生存率明显降低（54.2%比72.1%,P=0.006）.结论 allo-HSCT后用RQ-PCR监测血浆EBV DNA载量可以及时确定EBV血症并给予抢先抗病毒治疗,且大多数患者对抢先治疗有完全反应,这样有利于减少高危患者EBV相关疾病的发生率和病死率;亲缘单倍型移植、非血缘移植及Ⅱ～Ⅳ度aGVHD是EBV血症的Objective To investigate early Epstein-Barr virus （EBV） reactivation and the outcome of preemptive therapy after allogeneic hematopoietic stem cell transplantation （allo-HSCT）. Methods From January 2007 to January 2009, totally 277 patients after allo-HSCT were studied （haploidentical 116,unrelated 75, matched sibling 86）. Conditioning regimens were mainly busulfan （BU） ＋ cyclophosphamide （ CY）/fludarabine（Flu） or total body irradiation （TBI） ＋ CY/Flu. Antihuman thymocyte globulin （ATG）was added in haploidentical and unrelated transplants. Plasma EBV DNA was monitored once to twice weekly in the first 3 months after allo-HSCT with real time quantitative polymerase chain reaction （RQ-PCR）. EBV viremia was diagnosed when EBV DNA was more than 5 × 102 copies/ml but without symptoms. Acyclovir （10 mg/kg, intravenous drip, 8 h） was used for preemptive therapy and immnuo-suppressants were decreased if possible. Results Totally 33 patients （ 11.9% ） developed EBV viremia with a median time at day 44 （day 19 to day 84）. The incidences of EBV viremia in the transplants from matched sibling,haploidentical, unrelated donors were 0, 15.5%, 20. 0%, respectively. There was no significant difference between haploidentical and unrelated transplants （ P = 0. 09 ）, but much less EBV viremia was seen in matched sibling transplant （ P = 0. 001 ）. Twenty of 33 patients （ 60. 6% ） had complete response to preemptive therapy. The median time to reach EBV DNA negative in plasma was 11 （4-56） d. The median duration of preemptive therapy was 21 （14-60） d. Both univariate and multivariate analysis indicated that haploidentical and unrelated transplants, acute graft versus host disease （GVHD） were the risk factors for EBV viremia. Two-year overall survival in the patients with EBV viremia was significantly lower than that without EBV viremia （54. 2% vs 72. 1%, P = 0. 006 ）. Conclusions Our large clinical study has demonstrated that preemptive therapy with acycl

关 键 词：造血干细胞移植 治疗结果 EBV血症 抢先治疗 

分 类 号：R4[医药卫生—临床医学]