Hematopoietic Stem Cell Transplantation for Patients with Autosomal Recessive Complete INF-2 Receptor 2 Deficiency: Experience in Oman

Autosomal recessive complete INF-gamma receptor-2 (IFN-gamma R2) deficiency is a rare, potentially fatal primary immune deficiency that predisposes to disseminated mycobacterial disease. Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment. Few patients have been reported so far. Here we report the outcomes of HSCT in 7 patients with IFN gamma-R2 deficiency from 3 Omani families who underwent HSCT at Sultan Qaboos University Hospital in Oman. All patients were homozygous for the same mutation (c.-175_+102de1) of INFGR2. Four patients underwent HLA-matched related donor (MRD) HSCT (3 siblings and 1 parent), and the other 3 underwent T cell-depleted (TCD) haploidentical HSCT from a family donor. The stem cell source was peripheral blood stem cells in 5 patients and bone marrow in 2 patients. Five patients received myeloablative conditioning, and 2 had reduced-intensity conditioning. The overall survival rate was 85.7%, and the event-free survival was 71.4%. One of the 7 patients died on day +31 with gram-negative sepsis, and the other 6 patients were cured from their original disease (median follow-up of 78.5 months). One patient had primary graft failure following a TCDhaploidentical transplantation and underwent successful retransplantation from another haploidentical relative. Three patients received a donor lymphocyte infusion for mixed chimerism. Our findings indicate that HSCT is curative for complete IFN-gamma R2 deficiency. In this cohort from Oman, 85.7% of the patients were cured with either an MRD or a TCD haploidentical transplantation. Genetic analysis at birth in children of high-risk couples permits early diagnosis, prevents the morbidity of BCG vaccination, and can enable safer and more successful transplantation outcomes. (C) 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Automated summary

Autosomal recessive complete IFN-gamma receptor-2 deficiency is a rare primary immune deficiency with potential fatal consequences due to mycobacterial diseases. Hematopoietic stem cell transplantation has shown to be curative with a survival rate of 85.7%. Early genetic analysis in high-risk couples' children can aid in early diagnosis and improve transplantation outcomes.