儿童肾移植术后淋巴组织增生性疾病两例报告暨文献复习

Post-transplantation lymphoproliferative disorders of kidney in children: two cases report and literature review

目的报道2例儿童肾移植术后淋巴组织增生性疾病(post-transplantation lymphoproliferative disorders,PTLD)并复习文献,旨在提高对PTLD的认识。方法收集并分析复旦大学附属儿科医院收治的2例PTLD患儿的临床资料。检索从建库至2020年1月的PubMed、Embase、Web of Science、Scopus、Cochrane Library、万方、中国知网、维普数据库和中国生物医学文献服务系统等数据库,收集PTLD相关文献并行文献复习。多因素Logistic回归分析PTLD患儿预后的影响因素。结果两例PTLD患儿移植前EB病毒及巨细胞病毒血清学检查均为阴性,均接受过抗胸腺细胞免疫球蛋白诱导治疗。病例1和病例2分别于肾移植术后3个月、12个月诊断为PTLD,伴EB病毒及巨细胞病毒血清学反应阳性。病例1病理诊断为单形性PTLD,病例2临床考虑非霍奇金淋巴瘤,二者均予免疫抑制剂减量联合抗CD20单克隆抗体和化疗,PTLD缓解,移植肾功能正常。但例1患儿于肾移植后30个月死于颅内真菌感染。结合本中心2例及文献复习的54例儿童肾移植PTLD进行分析,移植至PTLD发生的中位时间为41.8个月,初发部位以消化道[17例(30.4%)]、呼吸系统[8例(14.3%)]、神经系统[7例(12.5%)]和咽淋巴环[7例(12.5%)]为主,病理类型以单形性PTLD为主[34例(60.8%)]。56例患儿诊断PTLD时EB病毒血清学反应均为阳性。治疗包括免疫抑制剂减量联合抗CD20单克隆抗体和化疗。PTLD缓解48例,其中8例移植物失功;11例死亡患者中3例死于感染,8例死于PTLD。多因素Logistic回归分析结果显示,单形性PTLD为患儿死亡的危险因素(OR=21.616,95%CI 1.007~464.107,P=0.049)。结论肾移植儿童PTLD大多与EB病毒感染有关,临床表现具有多样性。单形性PTLD预后不良,病死率较高。

Objective To report two cases of post-transplantation lymphoproliferative disorders(PTLD)after kidney transplantation in children and review the literature,and to improve clinicians'understanding of PTLD in children.Methods The clinical data of two children with PTLD admitted to the Children's Hospital of Fudan University were collected and analyzed.The PTLD-related literature of PubMed,Embase,Web of Science,Scopus,Cochrane Library,Wanfang,CNKI,Weipu Database and China Biomedical Literature Service System from the establishment of the database to January 2020 were collected for literature review.Multivariate logistic regression analysis method was used to analyze the influencing factors of prognostic in children with PTLD.Results Both of the patients had negative Epstein-Barr virus(EBV)and Cytomegalovirus(CMV)before transplantation and anti-thymocyte immunoglobulin(ATG)were induced during transplantation.PTLD in case 1 and case 2 was diagnosed at 3 and 12 months after transplantation,respectively,with positive EBV and CMV serological reaction.The pathological diagnosis was monomorphic PTLD in case 1 and the case 2 was clinically considered as non-hodgkin lymphoma.They all received thrapies of immunosuppressive reduction combined with anti-CD20 monoclonal antibody and chemotherapy.PTLD was relieved and graft function was normal in 2 cases,while case 1 died two and half years after transplantation due to intracranial fungal infection.According to the analysis of 56 children(including 2 cases in this study)with PTLD from the literature review,the median time of PTLD from transplantation was 41.8 months.The initial involved organs were digestive tract[17 cases(30.4%)],respiratory system[8 cases(14.3%)],nervous system[7 cases(12.5%)]and pharyngeal lymph ring[7 cases(12.5%)],respectively.The main pathologic type of PTLD was monomorphic[34 cases(60.8%)].Fifty-six cases were all positive in EBV serological reaction when PTLD was diagnosed.The treatment included immunosuppressive reduction combined with anti-CD20 monoclonal antibody and chemotherapy.Forty-eight cases of PTLD were relieved,while 8 cases lost graft function.Eleven cases died,including 3 cases due to infection and the other 8 cases due to PTLD.Multivariate logistic regression showed that monomorphic PTLD was a risk factor of death for PTLD children(OR=21.616,95%CI 1.007-464.107,P=0.049).Conclusions PTLD in children with kidney transplantation is mostly associated with EBV infection,and the clinical manifestations are diverse.Monomorphic PTLD has a poor prognosis and high mortality.