肾移植术后淋巴增殖性疾病的诊治体会

Diagnosis and treatment of lymphoproliferative diseases after renal transplantation

目的探讨肾移植术后淋巴细胞增殖性疾病(PTLD)的发病原因、临床特点、诊治方法及预后。方法回顾性分析2000年1月至2019年1月海军军医大学长征医院2844例肾移植受者中术后并发PTLD的13例受者的临床资料,收集受者性别、年龄、血肌酐、药物浓度、糖尿病、肾移植术后有无移植肾功能延迟恢复、急性排斥反应和免疫抑制剂方案的使用等相关资料。13例PTLD受者中,男11例,女2例,确诊时年龄为55岁(31~78岁)。结果PTLD病变位置分布在肺部1例,胃肠道8例,区域淋巴结2例,皮肤1例,颅内1例,均病理诊断为弥漫性大B淋巴细胞淋巴瘤,距肾移植手术中位时间为86个月(12~204个月)。76.9%受者病理组织EB病毒检测呈阳性。确诊后给予免疫抑制剂减量为主的综合治疗,无法耐受利妥昔单抗+CHOP(R-CHOP)方案化学药物治疗的受者切换为利妥昔单抗+来那度胺(R2)方案,2例受者肺部感染死亡,完全缓解10例,部分缓解1例,病情进展1例,总有效率91.6%。结论肾移植术后淋巴细胞增殖性疾病进展迅速,病死率高,与EB病毒感染密切相关,减少免疫抑制剂用量是综合治疗的核心,根据受者耐受性选择合理的化学药物治疗方案,R2方案为无法耐受一线R-CHOP方案的受者更多选择。

Objective To explore the causes,clinical characteristics,diagnoses and outcomes of post-lymphoproliferative disease(PTLD)after renal transplantation.Methods Retrospective reviews were conducted for a total of 2844 adult kidney recipients between January 2000 and January 2019.And 13 of them developed PTLD.Their clinical features and outcomes were analyzed.There were 11 males and 2 females with a median age of 55(31~78)years.All were diagnosed as diffuse large B-cell lymphoma at a median time of 86(12~204)months post-transplantation.Results The locations of PTLD were diverse,including lung,stomach,colon,skin and central nervous system.Biopsy immunohistochemical EBV positivity was detected in 76.9%of cases.After a tapering of immunosuppression intensity,6 cases were operated.Patients not tolerating R-CHOP regimen(rituximab+CHOP)were switched to R2 regimen(rituximab+nalidomide).The total effective rate was 91.6%,including complete remission(10 cases),partial remission(1 cases),progressive disease(1 case)and death(2 cases).Conclusions As a rare but serious complication after renal transplantation,PTLD is closely correlated with EBV infection.Reducing the dose of immunosuppressive drugs is a core of comprehensive treatment.Switching to R2 regimen is an effective alternative in the treatment of PTLD after renal transplantation.