CAJ | 학술논문

目的总结探讨儿童肝移植术后淋巴细胞增生性疾病(PTLD)临床特点、诊断方法、综合治疗方案及预后.方法 2011年1月至2013年12月,在上海仁济医院肝移植中心接受器官移植患儿202例,回顾性分析其中并发PTLD的6例患儿的临床特点和诊断方法,探讨抗排异药物剂量调整、利妥昔单抗、抗病毒治疗以及手术综合治疗方案后的效果.结果 (1) PTLD发生率为2.9％(6/202)6例PTLD患儿中男3例,女3例,原发病均为先天性胆道闭锁,手术方法均为劈离式肝移植.(2)PTLD发生时间多为术后6个月内;临床表现非特异性,6例均有发热,5例累及胃肠道表现为腹泻、腹痛及腹胀,1例累及呼吸道表现为咳嗽、急促,3例累及外周淋巴结;病理结果显示多形性淋巴细胞增生2例,B淋巴细胞增生4例.(3)2例患儿未检测EB病毒(EBV)-DNA,死亡前经剖腹探查病理确诊为PTLD.存活4例患儿EBV-DNA检测高载量后,即病理活检确诊为PTLD.(4)2例患儿死亡,未采用综合治疗;存活的4例患儿均进行抗排异反应的免疫药物(他克莫司)剂量调整并应用利妥昔单抗,其中抗病毒(阿昔洛韦)治疗2例,因并发肠梗阻肠穿孔给予外科肿瘤切除和肠穿孔修补术1例,随访4个月～1年,肝功能正常,均无瘤生存.结论儿童肝移植术后EBV-DNA持续监测是提示和早期诊断PTLD重要依据;免疫药物剂量调整、利妥昔单抗以及手术等综合治疗可能有利于提高PTLD患儿存活率.
목적 총결탐토인동간이식술후림파세포증생성질병(PTLD)림상특점、진단방법、종합치료방안급예후.방법 2011년1월지2013년12월,재상해인제의원간이식중심접수기관이식환인202례,회고성분석기중병발PTLD적6례환인적림상특점화진단방법,탐토항배이약물제량조정、리타석단항、항병독치료이급수술종합치료방안후적효과.결과 (1) PTLD발생솔위2.9％(6/202)6례PTLD환인중남3례,녀3례,원발병균위선천성담도폐쇄,수술방법균위벽리식간이식.(2)PTLD발생시간다위술후6개월내;림상표현비특이성,6례균유발열,5례루급위장도표현위복사、복통급복창,1례루급호흡도표현위해수、급촉,3례루급외주림파결;병리결과현시다형성림파세포증생2례,B림파세포증생4례.(3)2례환인미검측EB병독(EBV)-DNA,사망전경부복탐사병리학진위PTLD.존활4례환인EBV-DNA검측고재량후,즉병리활검학진위PTLD.(4)2례환인사망,미채용종합치료;존활적4례환인균진행항배이반응적면역약물(타극막사)제량조정병응용리타석단항,기중항병독(아석락위)치료2례,인병발장경조장천공급여외과종류절제화장천공수보술1례,수방4개월～1년,간공능정상,균무류생존.결론 인동간이식술후EBV-DNA지속감측시제시화조기진단PTLD중요의거;면역약물제량조정、리타석단항이급수술등종합치료가능유리우제고PTLD환인존활솔.
Objective To summarize the clinical characteristics,early diagnosis,comprehensive treatment and prognosis of 6 cases of children with post-transplantation lymphoproliferative disorder (PTLD) after liver transplantation.Method Data of 6 cases with PTLD seen between January 2011 and December 2013 were retrospectively analyzed.The anti-rejection drug dose adjustments,the effect of rituximab,antiviral therapy and comprehensive treatment program after surgery were explored.Result (1)The diagnosis of PTLD was confirmed by histologic findings.Six cases of PTLD including 3 males and 3 females were diagnosed as congenital biliary atresia and underwent split liver transplantation.The occurrence rate of PTLD was 2.9％.(2) The median time to the development of PTLD was less than 6 months.The initial symptom of PTLD in all patients was fever and clinical manifestations of PTLD were non-specific,depending on the involving organs.Five cases of PTLD developed gastrointestinal symptoms,including diarrhea,abdominal pain,and abdominal distension.One case developed respiratory symptoms,including cough and tachypnea.Three cases had lymph node involvement.In 2 cases pathophysiology involved polymorphic lymphocyte proliferation and in 4 cases B lymphocyte proliferation.(3) Two cases died,in whom EBV DNA was not detected and were diagnosed as PTLD by surgical pathology before death.Four survived cases had high EBV-DNA load and then were diagnosed as PTLD by biopsy pathology.(4) Of the 6 cases of PTLD,2 cases died and 4 cases survived.The overall mortality was 33％.The dead cases were only treated with laparotomy because of intestinal obstruction or perforation and the survived cases were treated with tacrolimus at reduced doses or discontinuation and rituximab.In 2 cases antiviral therapy (acyclovir) was continued,including 1 cases of intestinal obstruction treated with surgical repair.All the survived patients were followed up for 4 months to 1 year and no evidence has been found.Conclusion EBV infection is the high risk factor for PTLD after liver transplantation.Close clinical surveillance of EBV DNA for pediatric liver transplantation was important for the early diagnosis of PTLD.Reducing doses of immunosuppressive agents and rituximab is the initial therapy for PTLD.A reduction in the dose of tacrolimus is suggested.Operation therapy can also play a role in the management of local complications.