Clinical characteristics of primary hemophagocytic lymphohistiocytosis associated with perforin gene deficiency: a single-center retrospective study
10.3760/cma.j.issn.0253-2727.2023.07.009
- VernacularTitle:穿孔素基因缺陷原发性噬血细胞综合征的临床特征：单中心回顾性研究
- Author:
Mingzhu YU
1
;
Lin WU
;
Jia ZHANG
;
Jingshi WANG
;
Yini WANG
;
Zhao WANG
Author Information
1. 首都医科大学附属北京友谊医院血液科，北京 100050
- Keywords:
Perforin;
Mutation;
Epstein-Barr virus infections;
Lymphohistiocytosis, hemophagocytic
- From:
Chinese Journal of Hematology
2023;44(7):572-577
- CountryChina
- Language:Chinese
-
Abstract:
Objective:This study aimed to investigate the clinical characteristics of patients diagnosed with primary hemophagocytic lymphohistiocytosis (pHLH) associated with perforin gene deficiency.Methods:We retrospectively analyzed the clinical data of 16 pHLH patients associated with perforin gene deficiency at Beijing Friendship Hospital, Capital Medical University, from April 2014 to August 2021. The mutation sites, mutation types, family history, clinical characteristics, and prognosis of the patients were assessed.Results:A total of 16 patients, including ten males and six females, with a median onset age of 17.5 years (range: 4-42 years), were enrolled in this study. Sixteen different mutations were identified, consisting of 11 missense mutations, one nonsense mutation, two frameshift mutations, and two in-frame mutations. All patients harbored at least one deleterious missense mutation, with the most common mutation sites being c.1349C>T (p.T450M) and c.503G>A (p.S168N). Decreased natural killer (NK) cell activity was observed in 11 patients, reduced perforin protein expression in ten patients, concurrent Epstein-Barr virus (EBV) infection at onset in eight patients, a family history in two patients, and central nervous system involvement in four patients. Eleven cases underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), with eight cases surviving. The median survival time of non-transplanted patients was eight months (range: 4-18 months), while that of transplanted patients was reported as "not reached".Conclusions:Emphasizing the diagnosis of pHLH in adults with perforin gene deficiency. In addition, it should be noted that EBV infection can potentially act as a triggering factor in such disease, and allo-HSCT exerts a substantial effect on the prognosis of patients.
