异基因造血干细胞移植治疗原发性噬血细胞综合征合并中枢神经系统病变一例报告及文献复习

目的 探讨原发性噬血细胞综合征（HLH）合并中枢神经系统病变诊断要点以及异基因造血干细胞移植（Allo-HSCT）治疗情况。 方法：对1例根据HLH-2004诊断标准确诊的原发性HLH合并中枢神经系统病变的病例临床特点进行分析，完善基因测序、免疫学指标检测和家系调查，进行Allo-HSCT。 结果：确诊11岁男性病例1例，表现为反复发热、全血细胞减少，脾大、骨髓中可见噬血现象，NK细胞活性下降（10.39%）。基因检测和家系调查显示患者携带分别来自父系和母系的PRF1基因的复杂杂合改变，两位胞姐各自携带不同突变位点；全家成员穿孔素蛋白表达量均有不同程度下降。病程中出现癫痫，头颅核磁共振提 示多发病变。确诊原发性HLH合并中枢神经系统病变。给予HLH-2004方案治疗后，接受胞姐HLA 5/10相合Allo-HSCT。目前移植后14个月，一般情况良好。 结论 对于合并中枢神经系统病变的原发性HLH，尽早进行Allo-HSCT是获得长期生存及治愈的唯一方法。

A case report of allogeneic hematopoietic stem cell transplantation in primary hemophagocytic lymphohistiocytosis with central nervous system involvement and literature review

Objective To investigate the essentials of diagnosis and the treatment of allogeneic hematopoietic stem cell transplantation (allo-HSCT ) in primary hemophagocytic lymphohistiocytosis (HLH) with central nervous system (CNS) involvement. Methods One case with PRF1 gene mutations were conducted pedigree investigation, including family genetic screening and detection of immunological parameters to diagnose primary HLH with CNS involvement according to HLH-2004 and accepted allo-HSCT. Results A 11-year-old man presented recurrent fever, pancytopenia and splenomegaly. His laboratory test revealed bone marrow hemophagocytosis and reduced level of NK cell activity (10.39%). The DNA mutations of patient includes missense mutation c.T172C (p.S58P) from father and non-frameshift deletions c.1083_1094del (p.361_365del) from mother in PRF1 gene. Two sisters respectively carried one mutation. The perforin protein expression levels of all the family members were decreased in different degrees. The patient developed seizure during the episode and brain MRI showed multifocal lesions. Based on the HLH-2004 diagnostic criteria, the patient was diagnosed as primary HLH with CNS involvement. Following with HLH-2004 treatment protocol, the patient accepted HLA haplo-identical allo-HSCT. Conclusion Allo-HSCT is an effective treatment for primary HLH with CNS involvement to achieve cure and long-term survival.