重型再生障碍性贫血患者造血干细胞移植治疗后淋巴组织增殖性疾病的临床分析

Clinical Analysis of Post⁃Transplant Lymphoproliferative Disorder after Hematopoietic Stem Cell Transplantation in Severe Aplastic Anemia Patients

目的:分析重型再生障碍性贫血(SAA)患者造血干细胞移植(HSCT)后淋巴组织增殖性疾病(PTLD)的临床特征,以提高对PTLD的诊疗水平。方法:回顾分析2010年9月至2017年9月在单中心行HSCT的192例SAA患者的临床资料,分析PTLD的有效预警和治疗方法。本组患者预处理方案中均含有ATG并接受间充质干细胞(MSC)输注。结果:192例SAA患者HSCT移植后有14例并发了EBV+PTLD,总体发生率为7.29%,其中临床诊断5例,病理诊断9例,移植后PTLD发生中位时间72(35-168)d,所有PTLD均发生了EBV感染,且EBV高载量大于1×104 copies/ml(P<0.01)。年龄≤12岁和>12岁患者分别有11.11%和2.38%发生PTLD(P<0.01)。单因素及多因素分析结果显示,EBV感染、≤12岁患者、非血缘HSCT中HLA配型不相合供者移植及发生II度以上aGVHD均为PTLD高危因素(P<0.05)。监测发现EBV>104 copies/ml时,减停免疫抑制剂(RIS)和利妥昔单抗(RTX)抢先治疗有效,疗效不佳者及时联合化疗及EBV⁃CTL治疗后所有患者PTLD得到控制,治疗有效率100%。随访中位时间为65(62-115)个月,除1例患者在PTLD控制后7个月时死于脑出血外,余下患者均长期生存,总体生存率为92.85%。结论:SAA患者接受预处理含有ATG和MSC的HSCT后PTLD发生与EBV高拷贝密切相关,年龄≤12岁儿童、非血缘HSCT中供者为HLA不全相合的移植及合并有II度以上aGVHD者移植后PTLD高发;RIS/RTX抢先治疗有效,疗效不佳患者及时应用CTL及联合化疗是控制病情有效及重要方法。

Objective:To analyze the clinical characteristics of SAA patients with post⁃transplantation lymphoproliferative disease(PTLD)after allogeneic hematopoietic stem cell transplantation,and to improve diagnosis and treatment of PTLD.Methods:The clinical data of 192 patients with SAA patients who underwent HSCT in a single center from September 2010 to September 2017 were analyzed retrospectively.All patients were received antithymocyte globulin(ATG)conditioning regimen and mesenchymal stem cell(MSC)infusion.Results:Among 192 cases,PTLD occurred in 14 cases,the incidence was 7.29%,9 of them were diagnosed by pathology,and 5 were diagnosed clinically.EBV infection occurred with a median time of 72(35-168)days,Viral load higher than 1×104 copies/ml occured in all PTLD patients.The incidence of probable PTLD in patients≤12 years old and>12 years old was 11.11%,2.38%,respectively(P<0.01).Univariate and multivariate analysis that the EBV infection,patients age≤12 years old,HLA⁃mismatch in URD⁃HSCT,grade II to IV aGVHD were the independent risk factors for PTLD.All PTLD patients were treated with rituximab(RTX)when EBV⁃DNA load higher than 1×104 copies/ml,or reducted the use of immunosuppression(RIS),patients with poor therapeutic effect were treated combined with EBV⁃specific CTLs(EBV⁃CTL)and chemotherapy.All patients were treated effectively,and the total effective rate was 100%.The median follow⁃up time was 65(62-115)months,and the overall survival rate was 92.85%.One patients died of cere⁃bral hemorrhage,7 months after PTLD curred.Conclusion:The incidence of PTLD after HSCT with SAA who used ATG and MSC in conditioning regimen closely relates to EBV infection,age of patients≤12 years,HLA⁃mismatch in URD⁃HSCT,grade II to IV GVHD.Rituximab combined with RIS may reduce the incidence of PTLD,combined EBV⁃CTL and chemotherapy may be the useful and most important treatment for PTLD.