Primary hemophagocytic lymphohistiocytosis in adults: the utility of family surveys in a single-center study from China

Zhili Jin,Jingshi Wang,Zhao Wang,Wenyuan Lai,Zhuo Gao,Yini Wang,Jia Zhang,Lin Wu

doi:10.1186/s13023-017-0753-7

Abstract

BackgroundThis study investigated the clinical characteristics of primary hemophagocytic lymphohistiocytosis (HLH) in adults, including immunological markers, pedigree findings, and conditions of allogeneic hematopoietic stem cell transplantation (Allo-HSCT).MethodsThe study included clinical data of 18 adult patients with primary HLH treated in our center from June 2010 to January 2017.ResultsOf these 18 cases, pathogenic variants were found in the following genes: PRF1 (n = 11), UNC13D (n = 5), SH2D1A (n = 2), RAB27a (n = 1), and LYST (n = 2). One patient had pathogenic variants in both PRF1 and UNC13D genes, one patient had pathogenic variants in both LYST and UNC13D genes and another patient had pathogenic variants in both PRF1 and SH2D1A genes. Additionally, 3 of the 18 cases involved homozygous pathogenic variants, while 2 cases involved hemizygous pathogenic variants. The remaining 13 cases involved compound heterozygous pathogenic variants. The natural killer (NK) cell activity test was conducted in all 18 cases where 14(77.8%)patients showed reduction in NK cell activity. Furthermore, this article presents 3 representative results of the pedigree findings from 12 patients who underwent family surveys. The 8 patients who underwent Allo-HSCT had a median survival of 27.2 months, as compared with the median survival of 7 months for the10 patients who did not undergo Allo-HSCT, a significant difference between the two groups of patients (p = 0.006).ConclusionPRF1 was one of the most commonly mutated gene in adult patients with primary HLH. Family surveys and immunological markers were important for the HLH diagnosis and the selection of an appropriate donor. Allo-HSCT was an effective therapy for adult primary HLH.

Highlights

This study investigated the clinical characteristics of primary hemophagocytic lymphohistiocytosis (HLH) in adults, including immunological markers, pedigree findings, and conditions of allogeneic hematopoietic stem cell transplantation (Allo-HSCT)
General conditions of adult patients with primary Hemophagocytic lymphohistiocytosis (HLH) Of the 18 adult HLH patients, there were 10 males(55.6%)and 8 females(44.4%), with the median age of onset at 25.5 years (18, 54). Of these 18 cases, pathogenic variants were found in the following genes: PRF1 (n = 11), UNC13D (n = 5), SH2D1A (n = 2), RAB27a (n = 1), and LYST (n = 2)
A study by Ueda et al [11] analyzed the gene pathogenic variants in pediatric HLH patients and showed that nonsense and frameshift pathogenic variants that occurred in infants mostly happened in the classical onset of HLH while missense pathogenic variants occurred in the later onset of the disease at older ages

Summary

Introduction

This study investigated the clinical characteristics of primary hemophagocytic lymphohistiocytosis (HLH) in adults, including immunological markers, pedigree findings, and conditions of allogeneic hematopoietic stem cell transplantation (Allo-HSCT). Diagnosis of patients with primary HLH was based on a disease onset at an early age and a positive family history. Immunological markers are important for the early diagnosis of primary HLH. Janka et al [3] showed that NK cell activity was reduced in almost all patients at the early stage of primary HLH. Timely detection of NK cell activity is important for the early diagnosis of the disease. Detection of the immunological markers has been considered to be significantly better than genetic testing and has been used as an effective and rapid screening for primary HLH in the diagnostic processes of international studies [4, 5]

Methods

Results

Discussion

Conclusion