OBJECTIVES: HSCT is considered the gold standard treatment for infants with SCID. This study aimed to determine whether or not age at diagnosis and or HSCT may impact clinical outcomes.

METHODS: A systematic search of the literature was carried out up to 1 November 2021. Electronic searches were conducted, including forward and backward searches, supplemented with grey literature and hand-searching. The primary outcome, as outlined in the PICO, was survival, with secondary outcomes including immune reconstitution and morbidity post-transplant.

RESULTS: Fifteen publications were included, representing 13 unique cohorts. The description of early versus late diagnosis and or HSCT varied considerably across the included studies. Evidence which suggested that earlier diagnosis and or HSCT led to improved survival outcomes was noted in 12 of the 13 independent studies. Eight studies reported the effect of pre-HSCT infections on survival outcomes; all observed that the presence of infections prior to HSCT negatively impacted survival with evidence to suggest that age may be a proxy for infection status up to the point of HSCT. Eight studies conducted sub-cohort analyses to investigate whether time period influenced outcomes, five of these found that survival outcomes improved over time. Concerning secondary outcomes, lower rates of repeat HSCT were noted for those receiving HSCT earlier, results for immune reconstitution were inconsistent, and data for neurological and developmental outcomes were limited.

CONCLUSIONS: Identified studies were limited by their observational nature, primarily involved retrospective review across multiple international settings and several decades, and were not designed to identify a causal relationship for the question of interest. However, despite its limited nature, the evidence was relatively consistent in demonstrating that earlier diagnosis and or HSCT are associated with improved survival for children with SCID. The findings of this review may provide a potential rationale for newborn screening for SCID.