Outcome of hematopoietic stem cell transplantation for severe combined immunodeficiency and impact of newborn screening on overall survival: A single referral center study

Abstract

Background: Hematopoietic stem cell transplantation (HSCT) is a curative treatment for infants with severe combined immunodeficiency (SCID). Different factors determine HSCT success and overall survival (OS). Specifically, prompt diagnosis of SCID, preferably through newborn screening (NBS), is critical.

Objective: We explored variable factors including the impact of NBS that are associated with HSCT outcomes and OS in a multiethnic SCID cohort.

Methods: One hundred patients with SCID diagnosed and treated with HSCT at Sheba Medical Center in Israel between 1996 and 2024 were studied.

Results: We distinguished 3 groups: Palestinians (62%), Israeli Jews (16%), and Israeli non-Jews (22%). The OS rate was 68%, increasing to 84% when excluding mortality in the first month after transplantation. Better outcomes were significantly associated with the use of bone marrow (BM) as a stem cell source (P = .003), the availability of matched related donors (P = .045), and the use of conditioning (P = .0006). As a result of delayed diagnosis, Palestinian patients had more infections, more events of early post-HSCT death, and inferior OS rates compared to other patients. SCID cases identified by NBS demonstrated superior OS (93%) compared to cases identified by clinical presentation (P = .04). Improvement in OS was most significant after the implementation of the NBS program for SCID in Israel (P = .03).

Conclusion: Our study delineates and reinforces specific factors that influence OS after undergoing HSCT for SCID. Importantly, it raises the value of early diagnosis and treatment of affected infants, highlighting the benefit of NBS for SCID in determining the clinical outcome.

Keywords: HSCT; SCID; Severe combined immunodeficiency; TREC; clinical outcome; hematopoietic stem cell transplantation; newborn screening; overall survival.