Effect of genetic mutations on outcomes of stem cell transplantation in children with hemophagocytic lymphohistiocytosis

Abstract

Primary hemophagocytic lymphohistiocytosis (p-HLH) can be cured with allogeneic haematopoietic stem cell transplantation (allo-HSCT). It remains unclear whether HSCT outcomes are affected by the presence of different genetic mutations. We used data obtained from children who underwent allo-HSCT for HLH to examine the effects of genetic mutations on HSCT outcomes. Data from 153 paediatric patients in 18 paediatric stem cell centres were retrospectively evaluated. Patients were divided into four groups: 1) with PRF1 mutation (n = 46), 2) with UNC13D mutation (n = 38), 3) with STX11/STXBP2 mutation (n = 25) and 4) with Griscelli syndrome type 2/ Chediak-Higashi syndrome (GS2/CHS) diagnosis (n = 44). Statistical analysis showed no difference between the subgroups in terms of engraftment, VOD, acute GVHD, chronic GVHD, TRM, OS and EFS rates. The most important factor affecting OS and EFS in all genetic subgroups was remission status before HSCT. The 5-year EFS values for children with mutations in PRF1, UNC13D, STX11/STXBP2 and GS2/CHS were 71%, 66.6%, 74% and 66.7, respectively (log-rank >0.05). However, with prospective studies covering more patients, and creating different genetic subgroups by performing more detailed genetic analyses, special approaches for different genetic subgroups can be revealed in the future.

Fig. 1. Kaplan–Meier estimates of overall survival (OS) after HSCT in different genetic subgroups.

OS was calculated from the time of HSCT to the last follow-up time or death or second HSCT. For children with mutations in PRF1, UNC13D, STX11/STXBP2 and GS2/CHS, 5-year OS post-HSCT values were 72% (95% CI, 63–81), 77.6% (95% CI, 70–85), 74% (95% CI, 65–83) and 72.7% (95% CI, 66–79), respectively (log-rank >0.05). PRF1 perforin1, STX11 syntaxin 11, STXBP2 syntaxin binding protein 2, GS2 Gricelli syndrome type 2, CHS Chediak–Higashi syndrome, HSCT Hematopoietic stem cell transplantation.

Fig. 2. Kaplan–Meier estimates of event free survival after HSCT in different genetic subgroups.

Death, relapse or graft failure were defined as events. Five-year EFS values for children with mutations in PRF1, UNC13D, STX11/STXBP2 and GS2/CHS were 71% (95% CI, 63–80), 66.6% (95% CI, 58–75), 74% (95% CI, 65–83) and 66.7% (95% CI, 60–75), respectively (log-rank >0.05). EFS Event free survival, PRF1 perforin1, STX11 syntaxin 11, STXBP2 syntaxin binding protein 2, GS2 Gricelli syndrome type 2, CHS Chediak–Higashi syndrome, HSCT Hematopoietic stem cell transplantation.