CAJ | 학술논문

目的探讨儿童获得性再生障碍性贫血(AAA)异基因造血干细胞移植(allo-HSCT)后淋巴组织增生性疾病(PTLD)的流行病学、临床特点、诊治及预后.方法选择2002年7月至2012年5月于本中心完成allo-HSCT的71例AAA患儿作为研究对象.患儿常规行氟达拉滨+环磷酰胺+兔-抗人T淋巴细胞球蛋白±全身放疗为基础的预处理,移植后主要采用环孢霉素和甲氨蝶呤预防移植物抗宿主病.对移植后外周血Epstein-Barr病毒(EBV)-DNA拷贝数持续升高的患儿,抢先予以利妥昔单抗治疗.确诊为PTLD后即予以免疫抑制剂减量或停药.结果 AAA患儿行allo-HSCT后PTLD的发生率为4.2％(3/71),临床均表现为抗感染治疗无效的反复发热伴扁桃体和淋巴结肿大.其中,2例患儿移植后予以监测外周血EBV-DNA拷贝数,在PTLD发生前均出现拷贝数的持续升高,且第1次予利妥昔单抗治疗后拷贝数仍持续上升.3例PTLD患儿中,2例治疗有效,随访至今仍无病生存；1例治疗效果不明显,于PTLD发生后34 d死亡.结论 PTLD是儿童AAA allo-HSCT后一种少见的并发症,病死率较高；动态监测患儿外周血EBV-DNA拷贝数对诊治有一定的指导作用；利妥昔单抗抢先治疗有利于降低PTLD的发生率及病死率.
목적 탐토인동획득성재생장애성빈혈(AAA)이기인조혈간세포이식(allo-HSCT)후림파조직증생성질병(PTLD)적류행병학、림상특점、진치급예후.방법 선택2002년7월지2012년5월우본중심완성allo-HSCT적71례AAA환인작위연구대상.환인상규행불체랍빈+배린선알+토-항인T림파세포구단백±전신방료위기출적예처리,이식후주요채용배포매소화갑안접령예방이식물항숙주병.대이식후외주혈Epstein-Barr병독(EBV)-DNA고패수지속승고적환인,창선여이리타석단항치료.학진위PTLD후즉여이면역억제제감량혹정약.결과 AAA환인행allo-HSCT후PTLD적발생솔위4.2％(3/71),림상균표현위항감염치료무효적반복발열반편도체화림파결종대.기중,2례환인이식후여이감측외주혈EBV-DNA고패수,재PTLD발생전균출현고패수적지속승고,차제1차여리타석단항치료후고패수잉지속상승.3례PTLD환인중,2례치료유효,수방지금잉무병생존；1례치료효과불명현,우PTLD발생후34 d사망.결론 PTLD시인동AAA allo-HSCT후일충소견적병발증,병사솔교고；동태감측환인외주혈EBV-DNA고패수대진치유일정적지도작용；리타석단항창선치료유리우강저PTLD적발생솔급병사솔.
Objective To explore the epidemiology,clinical characteristics,diagnosis,treatment and prognosis of post-transplantation lymphoproliferative diseases (PTLD) in children with acquired aplastic anemia (AAA) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods From July 2002 to May 2012,a total of 71 children who underwent allo-HSCT with AAA at the Institute of Shanghai Children's Medical Center were included in this study.All of these children's clinical data were analyzed.The conditioning regimen included fludarabine,cyclophosphamide and rabbit-antithymocyte globulin with or without total body radiotherapy,and graft-versus-host disease prophylaxis mainly consisted of cyclosporine and methotrexate.For these patients who were monitored by Epstein-Barr virus (EBV)-DNA copies in peripheral blood mononuclear cells after allo-HSCT,a preemptive treatment with anti-CD20 monoclonal antibody rituximab was given when EBV-DNA copies rose persistently.Once PTLD was diagnosed,reduction or withdrawal of immunosuppression was administered.Results The incidence of PTLD for children with AAA after allo-HSCT was 4.2％ (3/71).All the PTLD patients were presented with persistent fever with no reaction to any antibiotics,progressive antiadoncus and lymphadenectasis.Two cases of the PTLD patients were monitored by EBV-DNA copies after allo-HSCT,and both had persistent high level of EBV-DNA copies before the diagnosis of PTLD,also after the first course of rituximab.After therapies,two of the three PTLD patients were cured and alive till now; however,another one had no effect to the therapy and died 34 days after the diagnosis of PTLD.Conclusions PTLD is a rare and potentially fatal complication for children with AAA after allo-HSCT.Dynamic monitoring of EBV-DNA copies could have certain guiding on the early diagnosis and treatment for PTLD.The preemptive treatment with rituximab could reduce the incidence and mortality of PTLD.