Haploidentical Stem Cell Transplantation for Severe Combined Immunodeficiency (SCID): Experience from Latin America

Introduction Severe combined immunodeficiencies (SCIDs) lead to early death from overwhelming infection, usually in the first year of life. Haploidentical transplantation should be considered when there are no matched related donors for its immediate donor availability and when any delays may lead to catastrophic results. Method Retrospective study including patients with SCID receiving their first hematopoietic cell transplantation (HCT) using a haploidentical donor in 6 Latin American transplant centers. Results At a median age of 9.3 months, 52 SCID patients were transplanted between 04/2011 and 06/2024. Bone marrow was the stem cell source in 86% and the father was the donor in 76% of all transplants. A total of 49 patients received a conditioning regimen, the majority being busulfan-based (81%). The 1-year and 2-year overall survival (OS) were 70% and 64.2%, respectively. At 100 days, cumulative incidence (CI) of acute graft versus host disease (GVHD) was 19.2% and, at 2 years, CI of chronic GVHD was 8.3%. The CI of CMV reactivation was 35.4% at a median of 25 days after transplant. Severe hepatic sinusoidal obstruction syndrome (SOS) was observed in one quarter of the cases (27%), all in the busulfan group. Twenty-one patients died, with 8 very early deaths (before day +28), seven due to infection and one due to SOS. In the conditioned group, there were 4 graft failures (1 primary and 3 secondary), 2 successfully rescued with a second procedure, and 2 deaths related to CMV infection. Mixed chimerism was frequent (46%) and led to an inability to stay off intravenous immunoglobulin (IGIV) after transplant in 30% of patients. One patient was later found to be FOXN1 mutated, currently expecting a thymus transplantation. Conclusions Haploidentical transplants are feasible and, considering the late diagnosis and active infection on admission, our OS was good. Earlier diagnosis through newborn screening and intensive infection prevention/treatment may allow for better outcomes in the future.