中华内科杂志
中華內科雜誌
중화내과잡지
CHINESE JOURNAL OF INTERNAL MEDICINE
2011年
5期
383-387
,共5页
卢岳%吴彤%曹星玉%王静波%孙媛%赵艳丽%达万明%纪树荃%童春容%陆道培
盧嶽%吳彤%曹星玉%王靜波%孫媛%趙豔麗%達萬明%紀樹荃%童春容%陸道培
로악%오동%조성옥%왕정파%손원%조염려%체만명%기수전%동춘용%륙도배
造血干细胞移植%治疗结果%EBV血症%抢先治疗
造血榦細胞移植%治療結果%EBV血癥%搶先治療
조혈간세포이식%치료결과%EBV혈증%창선치료
Hematopoietic stem cell transplantation%Treatment outcome%EBV viremia%Preemptive therapy
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血症的高危因素;EBV血症对allo-HSCT后患者的生存有负面影响.
目的 研究異基因造血榦細胞移植(allo-HSCT)後早期EB病毒(EBV)激活的鑑測及其搶先治療的結果和預後.方法 以2007年1月至2009年1月在我院行allo-HSCT併連續鑑測血漿EBV DNA的277例患者為研究對象,其中親緣人類白細胞抗原(HLA)單倍型移植116例;非血緣移植75例,同胞相閤移植86例.預處理主要採用馬利蘭(BU)+環燐酰胺(CY)/氟達拉濱(Flu)或全身照射(TBI)/Flu方案,此外,親緣單倍型和非血緣移植加用抗胸腺細胞毬蛋白(ATG).移植後最初的3箇月內每週採用實時定量PCR(RQ-PCR)方法檢測血漿EBV DNA,若＞5×102拷貝/ml而無臨床癥狀時診斷為EBV血癥.搶先治療主要應用阿昔洛韋10 mg/kg靜脈點滴,每8小時1次,同時在情況允許時減少免疫抑製劑.結果 移植後100 d(+100 d)內33例(11.9%)患者髮生EBV血癥,中位時間為+44(+19～+84)d;EBV血癥的髮生率在同胞相閤、親緣單倍型和非血緣移植中分彆為0、15.5%和20.0%,在親緣單倍型與非血緣移植中EBV血癥的髮生率差異無統計學意義(P=0.09),但均較同胞相閤移植高(P=0.001).33例患者均首先採用減少免疫抑製劑劑量和阿昔洛韋搶先抗病毒治療,其中20例患者病毒血癥轉為陰性,治療有效率為60.6%,中位時間為治療後11(4～56)d,抗病毒治療療程的中位時間為21(14～60)d.單因素及多因素分析均錶明,親緣單倍型移植、非血緣移植以及Ⅱ～Ⅳ度急性移植物抗宿主病(aGVHD)是EBV血癥髮生的高危因素.髮生EBV血癥患者(33例)比未髮生EBV血癥患者(244例)的2年預期生存率明顯降低(54.2%比72.1%,P=0.006).結論 allo-HSCT後用RQ-PCR鑑測血漿EBV DNA載量可以及時確定EBV血癥併給予搶先抗病毒治療,且大多數患者對搶先治療有完全反應,這樣有利于減少高危患者EBV相關疾病的髮生率和病死率;親緣單倍型移植、非血緣移植及Ⅱ～Ⅳ度aGVHD是EBV血癥的高危因素;EBV血癥對allo-HSCT後患者的生存有負麵影響.
목적 연구이기인조혈간세포이식(allo-HSCT)후조기EB병독(EBV)격활적감측급기창선치료적결과화예후.방법 이2007년1월지2009년1월재아원행allo-HSCT병련속감측혈장EBV DNA적277례환자위연구대상,기중친연인류백세포항원(HLA)단배형이식116례;비혈연이식75례,동포상합이식86례.예처리주요채용마리란(BU)+배린선알(CY)/불체랍빈(Flu)혹전신조사(TBI)/Flu방안,차외,친연단배형화비혈연이식가용항흉선세포구단백(ATG).이식후최초적3개월내매주채용실시정량PCR(RQ-PCR)방법검측혈장EBV DNA,약＞5×102고패/ml이무림상증상시진단위EBV혈증.창선치료주요응용아석락위10 mg/kg정맥점적,매8소시1차,동시재정황윤허시감소면역억제제.결과 이식후100 d(+100 d)내33례(11.9%)환자발생EBV혈증,중위시간위+44(+19～+84)d;EBV혈증적발생솔재동포상합、친연단배형화비혈연이식중분별위0、15.5%화20.0%,재친연단배형여비혈연이식중EBV혈증적발생솔차이무통계학의의(P=0.09),단균교동포상합이식고(P=0.001).33례환자균수선채용감소면역억제제제량화아석락위창선항병독치료,기중20례환자병독혈증전위음성,치료유효솔위60.6%,중위시간위치료후11(4～56)d,항병독치료료정적중위시간위21(14～60)d.단인소급다인소분석균표명,친연단배형이식、비혈연이식이급Ⅱ～Ⅳ도급성이식물항숙주병(aGVHD)시EBV혈증발생적고위인소.발생EBV혈증환자(33례)비미발생EBV혈증환자(244례)적2년예기생존솔명현강저(54.2%비72.1%,P=0.006).결론 allo-HSCT후용RQ-PCR감측혈장EBV DNA재량가이급시학정EBV혈증병급여창선항병독치료,차대다수환자대창선치료유완전반응,저양유리우감소고위환자EBV상관질병적발생솔화병사솔;친연단배형이식、비혈연이식급Ⅱ～Ⅳ도aGVHD시EBV혈증적고위인소;EBV혈증대allo-HSCT후환자적생존유부면영향.
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 acyclovir that is guided by EBV viremia is effective in majority of the patients with high-risk for EBV reactivation after allo-HSCT, which may further decrease the risk for developing life-threatening EBV disease or post-transplantation lymphoproliferative disorder. Haploidentical and unrelated transplants, acute GVHD are the risk factors for EBV viremia which has negative impact on survival.
