肾移植后晚发型淋巴组织增生性疾病的临床病理特点  

Clinicopathological characteristics of late-onset post-transplant lymphoproliferative disorders after renal transplantation

作　　者：于亚平[1] 王利平[1] 宋萍[1] 安志明[1] 周晓刚[1] 李峰[1] 唐玉梅[1] 翟勇平[1] 

机构地区：[1]南京军区南京总医院血液科,江苏南京210002

出　　处：《中华肿瘤防治杂志》2016年第12期816-822,共7页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的 移植后淋巴组织增生性疾病（post-transplant lymphoproliferative disorders,PTLD）是实体器官移植或造血干细胞移植后的一种严重并发症,主要与医源性免疫抑制和Epstein-Barr病毒（EBV）感染有关。由于发生率低,临床表现和病理形态多样,前瞻性临床研究少,目前对该病的认识还很不充分。本研究旨在探讨肾移植后晚发型PTLD的临床病理特点及治疗和预后。方法 2001-01-30-2013-12-30在南京军区南京总医院根据WHO造血与淋巴组织肿瘤分类标准共确诊4例肾移植后PTLD,回顾性分析该组患者的临床病理资料、EBV相关检查结果及治疗和预后,并对相关文献进行复习。结果 4例患者肾移植后均采用三联或四联免疫抑制治疗,肾移植至PTLD诊断时间为2.5-18年（中位9.5年）。4例的病理类型均为单形型,其中1例非特指型外周T细胞淋巴瘤（PTCL-NOS）和3例非生发中心型弥漫大B细胞淋巴瘤（DLBCL）。外周血EBV-DNA和病理组织原位杂交检测EBER均阴性。1例PTCL-NOS以皮肤病变起病,合并噬血细胞淋巴组织细胞增生症,3例DLBCL分别以颌下肿块、腰背痛和下肢无力起病。确诊后均予免疫抑制剂减量,同时行联合化疗或利妥昔单抗联合化疗。4例患者中,2例早期死亡,分别为疾病进展和化疗后并发感染性休克。另2例分别在完全缓解4个月和10个月后疾病复发,再次治疗未缓解。结论 肾移植后晚发型PTLD以单形型为主,DLBCL最常见,结外侵犯多见,与EBV感染无明显关系,化疗或免疫化疗效果差,预后不良。OBJECTIVE Post-transplant lymphoproliferative disorders （PTLD） are a serious complication after solid organ or allogeneic hematopoietic stem ceil transplantation. Iatrogenically impaired immune surveillance and Epstein- Barr virus （EBV） primary infection are key factors in the pathogenesis. Current knowledge on all aspects of PTLD is limited due to its rarity, clinical and morphologic heterogeneity, and the lack of prospective trials. This study is designed to investigate the clinicopathologic features and therapy of late-onset PTLD after renal transplantation. METHODS Four cases of PTLD following renal transplantation were diagnosed according to the 2008 WHO classification of tumors of hematopoietic and lymphoid tissues at our hospital between January 2001 and December 2013. The data of clinical, pathologic and immunohistochemistric features,treatment and prognosis were retrospectively analyzed. EBV associated assay, including in situ hybridization for EBV-encoded small RNAs （EBER）, serological EBV-specific antibodies and EBV-DNA of plasma were reported. RESULTS All 4 cases were male. The median age was 50.5 years （range from 24 to 57 years） at the time of PTLD diagnosis. The median interval between transplantation and late-onset PTLD diagnosis was 9.5 years （2.5 to 18 years）. One cases involved mainly lymph nodes and the remaining 3 cases involved skin, vertebral body and spinal cord,respectively. Histologic types of all four cases were monomorphic PTLD, 3 of which were diffuse large B cell lymphoma, non-germinal center type （DLBCL, non-GCB） and 1 was peripheral T cell lymphoma, non-specific （PTCL-NOS）. The proliferating index of Ki-67 was 60%-80%. EBV-DNA and EBER were all negative. Four patients received reduction of immunosuppression and chemotherapy（CHOP or EPOCH） or immunochemotherapy （R-CHOP）. Two patients died due to the associated HLH and CHOP-associated sepsis,respectively. Other two patients relapsed and was refractory to second-line therapy after complete response

关 键 词：肾移植 移植后淋巴组织增生疾病 EB病毒 化疗 

分 类 号：R699.2[医药卫生—泌尿科学] R551.2[医药卫生—外科学]