儿童获得性再生障碍性贫血造血干细胞移植后淋巴组织增生性疾病的临床研究

摘要

Objective To study the clinical features of lymphoproliferative disease(PTLD) after hema-topoietic stem cell transplantation ( allo-HSCT) for children acquired aplastic anemia ( AAA) .Methods A total of 142 AAA children in No.187 Hospital of PLA from Jun.2010 to Jun.2013 were included in the stud,were routinely given fludarabine +cyclophosphamide +rabbit -anti-human T lymphocyte globulin +total body irradiation combined treatment methods,after allo-HSCT, the children were given methotrexate and cyclosporine to prevent the autonomic nerve anti-host disease.For children with rising Epstein-Barr virus (EBV)-DNA copy numbers in peripheral blood after transplantation,rituximab should be applied first for treatment.In case of diagnosed PTLD,the application of immunosuppressants should be reduced or termina-ted.Results PTLD probability of AAA children after allo-HSCT was 4.2%, with recurrent fever, lymph nodes and tonsil enlargement as clinical manifestations,but had no effect without positive anti-infection treat-ment.There were 4 cases of EBV-DNA copy number increase in peripheral blood after transplantation before PTLD,which continued to increase after first rituximab therapy.Among 6 cases of PTLD,there were 4 cases of effective treatment,which still live without any disease till now;therapeutic effect of 2 cases was not ideal, which died on the 34th d and 96th d since the occurrence of PTLD respectively.Conclusion PTLD is a rare complication of AAA Children after allo-HSCT,but the fatality rate is high;dynamic monitoring of EBV-DNA in peripheral blood is helpful to the diagnosis and treatment;advance use of rituximab treatment helps to reduce the incidence and mortality of PTLD in children.%目的：探讨儿童获得性再生障碍性贫血（ AAA）造血干细胞移植（ allo－HSCT）后淋巴组织增生性疾病（ PTLD）的临床特点。方法选择2010年6月至2013年6月解放军第第一八七中心医院诊治的142例儿童AAA患儿，所选患儿均常规应用氟达拉滨＋环磷酰胺＋兔－抗人 T淋巴细胞球蛋白＋全身放疗的组合治疗方法，经过allo－HSCT后，患儿应用甲氨蝶呤和环孢霉素来对植物抗宿主病进行预防。对于移植后外周血Epstein－Barr病毒（ EBV）－DNA拷贝数不断升高的患儿，首先应用利妥昔单进行治疗。当确诊为 PTLD 时减少或者停止应用免疫抑制剂。结果 AAA 患儿进行allo－HSCT 后PTLD发生率为4.2％，患儿临床上表现为反复发热，同时可见淋巴结及扁导体肿大，经过积极的抗感染治疗无效果。其中有4例患儿经过移植后对外周血 EBV－DNA拷贝数进行监测，在出现PTLD前均存在拷贝数持续升高的现象，同时进行第一次利妥昔单治疗后拷贝数仍然不断升高。6例 PTLD患儿中有4例治疗有效，到目前位置仍然无任何疾病；2例治疗效果不理想，在出现 PTLD的第34、96日死亡。结论 PTLD是AAA患儿进行 allo－HSCT 后很少见到的一种并发症，但一旦发病病死率较高；对患儿外周血EBV－DNA拷贝数进行动态监测，对诊治有一定的帮助；提前应用利妥昔单抗治疗有助于降低PTLD患儿的发生率及病死率。