The results of allogenic hematopoietic stem cell transplantation in primary immunodeficiencies with hemophagocytic lymphohistiocytosis

Abstract

Hemophagocytic syndrome is the primary clinical manifestation in patients with familial hemophagocytic lymphohistiocytosis (HLH) and may also occur as a phenotypic manifestation of other primary immunodeficiencies (PIDs). Allogenic hematopoietic stem cell transplantation (HSCT) is a gold standard therapy for both. In our study, we analyzed the results of HSCT in patients with PIDs associated with HLH. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Out of 314 patients with various PIDs who had undergone HSCT at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology between 2012 and 2020, 44 patients diagnosed with HLH before HSCT were included in our study. They were divided into 2 groups: familial HLH group (patients with defined genetic abnormalities or with typical clinical presentation of familial HLH, n = 24) and Other HLH group (verified cases of other PIDs, n = 20). Pre-HSCT infections occurred in both groups, whilе inflammatory bowel disease, immune cytopenia, arthritis, and vasculitis were observed only in the Other HLH group. The median age at HSCT was 2 years in both groups. Conditioning regimens included one or two alkylators and serotherapy. Peripheral blood with TCRab+/ CD19+ graft depletion was used in 41 patients and native bone marrow in 3 patients. The median time of follow-up was 6.9 years in the familial HLH group and 4.3 years in the Other HLH group (p = 0.012). The rate of graft failure (non-engraftment or rejection) in the familial HLH group was 0.08 (95% confidence interval (CI) 0.02–0.31) vs 0.25 (95% CI 0.12–0.53) in the Other HLH group (p = 0.12). No significant differences in the rates of acute and chronic graft-versus-host-disease and viral reactivations were seen between the groups. The overall survival was 0.92 (95% CI 0.8–1.0) in the familial HLH group and 0.85 (95% CI 0.69–1.0) in the Other HLH group (p = 0.5). The event-free survival (where an event was defined as graft failure, lack of control of HLH in patients with mixed chimerism or death) was 0.83 (95% CI 0.68–0.98) and 0.65 (95% CI 0.44–0.85), respectively (p = 0.17). The patients with PID presenting with hemophagocytic syndrome had lower event-free survival rates and higher risks of graft failure and loss of disease control in mixed chimerism than the patients with familial HLH.