目的:探讨巨细胞病毒( CMV)和EB病毒( EBV)共激活对异基因造血干细胞移植患者预后的影响。方法连续纳入2011年12月至2013年8月苏州大学附属第一医院血液科330例异基因造血干细胞移植患者,通过定量PCR方法持续监测移植后患者CMV及EBV DNA拷贝数至移植后1年,采用χ2检验和Kaplan-Meier法回顾性分析CMV及EBV病毒血症的发生情况及临床随访资料。结果中位随访时间为16个月(7~25个月),共有113例(34.2%)患者发生单独CMV病毒血症(CMV+组),82例(24.8%)患者发生单独EBV病毒血症(EBV+组),32例(9.7%)患者出现CMV及EBV共激活,即合并存在CMV及EBV病毒血症( CMV/EBV+组)。基线比较发现CMV/EBV+组中HLA不全合的患者比例及发生急性移植物抗宿主病( aGVHD)的患者比例显著高于EBV+组或CMV+组患者[78.1%(25/32)比58.5%(48/82)、50.4%(57/113),P=0.047、0.008;56.3%(18/32)比32.9%(27/82)、34.5%(39/113),P=0.022、0.026]。此外,CMV/EBV+组中移植后淋巴细胞增殖性疾病(PTLD)发生率与EBV+组类似[12.5%(4/32)比11.0%(9/82),P=0.802],CMV病发病率与CMV+组类似[9.4%(3/32)比7.1%(8/113), P=0.665]。生存分析提示CMV+、EBV+、CMV/EBV+组患者2年总生存率分别为68.7%、61.5%和62.4%,差异无统计学意义( P=0.598、0.717);CMV+、EBV+、CMV/EBV +组患者6个月非复发死亡率( NRM)分别为8.9%、8.1%和18.7%,CMV/EBV+组显著高于其他两组(P=0.036、0.032)。结论 CMV及EBV共激活组中HLA不全相合移植及发生aGVHD患者多见。与单独CMV或EBV病毒血症患者相比,其PTLD或CMV病发生率及2年总生存率类似,但6个月NRM较高,提示CMV及EBV共激活可能是异基因造血干细胞移植后早期死亡的高危因素。
Objective To evaluate the impact of cytomegalovirus ( CMV) and Epstein-Barr virus ( EBV) co-activation on the prognosis of allogeneic hematopoietic stem cell transplantation ( allo-HSCT ) patients.Methods We retrospectively analyzed 330 consecutive allo-HSCT patients at First Affiliated Hospital of Soochow University from December 2011 to August 2013.CMV and EBV DNA were regularly monitored by quantitative polymerase chain reaction ( PCR) from the engraftment of granuloCyte within one year after transplantation.The incidences of viremia and clinical outcomes were analyzed by χ2 test and Kaplan-Meier analysis.Results After a median follow-up period of 16 ( 7 -25 ) months, a total of 113 (34.2%)patients were identified with CMV viremia (CMV+) alone, 82(24.8%)with EBV viremia (EBV+)alone and 32 ( 9.7%) with CMV and EBV co-activation ( CMV/EBV +) . The proportion of patients undergoing HLA mismatched transplantation and ones with acute graft-versus-host disease ( aGVHD ) in CMV/EBV+group was significantly higher than CMV +group or EBV +group ( 78.1%( 25/32 ) vs 58.5%(48/82) or 50.4%(57/113),P =0.047,0.008;56.3%(18/32) vs 32.9%(27/82) or 34.5%(39/113),P=0.022, 0.026).The incidence of post-transplant lymphoproliferative disorder (PTLD) was similar to EBV+group (12.5%(4/32) vs 11.0%(9/82), P=0.802) and so did the incidence of CMV disease when compared with CMV+group ( 9.4%( 3/32 ) vs 7.1%( 8/113 ) , P=0.665 ) .The 2-year overall survival ( OS ) of CMV +, EBV +and CMV/EBV +groups was 68.7%, 61.5% and 62.4%respectively.And no significant difference existed between CMV/EBV +and the other two groups ( P =0.598, 0.717).However, the 6-month non-relapse mortality (NRM) of CMV/EBV+group was significantly higher than that of CMV+or EBV+group (18.7%vs 8.9%, P=0.036;18.7%vs 8.1%, P=0.032). Conclusions HLA mismatch transplants and aGVHD are frequent in CMV and EBV co-activation group