儿童异基因造血干细胞移植相关性血栓性微血管病9例病例分析并文献复习

Allogeneic hematopoietic stem cell transplantation - associated thrombotic microangiopathy： 9 cases report of children and literature review

目的总结分析儿童异基因造血干细胞移植（allo－HSCT）相关血栓性微血管病（TA－TMA）的临床特征、疗效及转归。方法回顾性分析2008年1月至2017年11月于首都医科大学附属北京儿童医院血液肿瘤中心接受allo－HSCT后发生TA－TMA的9例患儿临床资料、治疗及预后特点。结果纳入研究的283例行allo－HSCT患儿，9例（3.2%）发生TA－TMA。9例患儿中，男5例，女4例，中位年龄94个月（39-129个月），中位发病时间为移植后63 d（6-342 d），血小板中位数为44×10^9/L[（7-75）×10^9/L]，血红蛋白中位数为76 g/L（40-105 g/L），乳酸脱氢酶（LDH）中位水平为594 U/L（445-1 386 U/L）。所有患儿中5例出现神经系统症状，4例出现肾脏受累，6例出现胃肠道受累表现。TA－TMA确诊后的主要治疗措施为减停钙调磷酸酶体抑制剂，血浆置换，利妥昔单抗及去纤苷。4例经治疗后病情得到控制，治疗有效，5例患儿治疗无效死亡。结论TA－TMA是allo－HSCT后的致死性并发症，可导致全身多器官、系统功能损害，累及〉2个系统提示预后不良，联合治疗效果优于单药治疗，选择个体化的治疗方案对减缓TA－TMA病情进展及改善预后至关重要。

ObjectiveTo analyze the clinical characteristics, treatment and prognosis of allogeneic hemato-poietic stem cell transplantation（allo-HSCT）-associated thrombotic microangiopathy （TA-TMA） in children.MethodsThe clinical information, treatment and prognosis of 9 cases with TA-TMA hospitalized following allo-HSCT from January 2008 to November 2017 in Hematology Oncology Center, Beijing Children′s Hospital, Capital Medical University were retrospectively analyzed.ResultsOf all the 283 allo-HSCT recipients, 9 patients （3.2%） were diagnosed as TA-TMA.Among them, there were 5 male and 4 female, with a median age of 94 months （39-129 months）. The median time to of diagnosis was 63 days （6-342 days） after HSCT.Additionally, the median platelet counts, hemoglobin and lactate dehydrogenase（LDH） levels were 44×10^9/L[（7-75）×10^9/L], 76 g/L（40-105 g/L） and 594 U/L（445-1 386 U/L）. Neurological symptoms were found in 5 of the patients, 4 had kidney involvement, and 6 had gastrointestinal involvement.The major treatment of TA-TMA was plasma exchange, Rituximab and defibrotide instead of the use of calcineurin inhibitors.Finally, 4 patients achieved response after treatment, 5 children died of ineffective treatment.ConclusionTA-TMA is a fatal complication after allo-HSCT.It can lead to multi-organ and multi-systems dysfunction.If there are more than 2 systems involved in TA-TMA, it suggests poor prognosis.The combined therapy is better than monotherapy, and the selective individual treatment of TA-TMA is essential.