脐带血异基因造血干细胞移植后噬血细胞性淋巴组织细胞增生症1例临床分析

Clinical study on cytomegalovirus-associated haemophagocytic syndrome following allogeneic hemotoic stem cell transplantation

目的探讨异基因造血干细胞移植后噬血细胞性淋巴组织细胞增生症(HLH)的临床特征、诊断及治疗。方法回顾性分析1例急性髓系白血病非血缘相关脐带血造血干细胞移植(AML-URD-UCBT)患儿术后并发HLH的临床特点并复习相关文献。结果患儿移植术后第6天(+6 d,下同)出现皮肤、肝脏、肠道急性移植物抗宿主病(aGVHD),先后给予糖皮质激素、环孢素A(CsA)、赛尼哌、霉酚酸酯(MMF)、他克莫司(FK506)等免疫抑制治疗后,aGVHD症状好转,但+26 d后出现活动性巨细胞病毒(CMV)感染合并HLH,给予静脉注射用丙种球蛋白、无环鸟苷、更昔洛韦抗CMV治疗,输红细胞、血小板、血浆、纤维蛋白原等支持治疗,参照HLH-2004方案予依托泊苷、糖皮质激素及CsA治疗后,+61 d检测血CMV早期/晚期基质蛋白(CMV-PP65)转阴,+55、+63 d骨髓象未见噬血细胞,呈HLH完全缓解骨髓象,临床症状及血常规等实验室指标好转;+83 d检测血CMV-PP65及CMV脱氧核糖核酸(CMV-DNA)转阳,+86 d因严重肺部感染、肺出血、消化道出血及多器官功能衰竭而死亡。结论异基因造血干细胞移植后aGVHD及抗aGVHD的免疫抑制治疗,是引起移植后CMV感染相关HLH的危险因素;HLH-2004方案未考虑到异基因造血干细胞移植后HLH的特殊性,需进一步研究有针对性的治疗方案,以提高疗效。

Objective To study the clinical features, diagnosis and treatment of hematophagocyte lymphohistiocytosis （HLH） following allogeneic hemotoic stem cell transplantation （HSCT）. Methods One case of AML-M2a with HLH after unrelated donor umbilical cord blood transplantation （URD-UCBT） was reported and literature were reviewed. Results versus host disease （aGVHD） in the skin, liver and intestinal tract eorticosteroids, CsA, Zenapax, MMF and FK506 successively. The The patient until day ＋ 6. appeared acute He was treated symptoms were ever alleviated graft with , but cytomegalovirus-associated haemophagocytic syndrome occurred on day ＋ 26. According to HLH-2004 Therapeutic Guideline, he was treated with VP16, corticosteroids, CsA, antiviral agents, intravenous immunoglobulin and supportive therapy. He got improved after the therapy, but showed positive CMV-PP65 and CMV-DNA on day ＋ 83. He died of severe pulmonary infection, pulmonary hemorrhage, alimentary tract hemorrhage and multiple organ failure on day ＋ 86. Condusions aGVHD and immunosuppressive therapy were the risk factors for cytomegalovirus-assoeiated haemophagocytic syndrome following allogeneie HSCT. The specificity of HLH after HSCT was not considered in HLH-2004 Therapeutic Guideline. It is necessary to look for an appropriate treatment to improve the clinical outcome.