Racial and Ethnic Disparities in Outcomes following Hematopoietic Stem Cell Transplant (HCT) in Patients with Severe Combined Immunodeficiency (SCID)

Abstract

IntroductionBlack race and Hispanic ethnicity are associated with higher mortality among patients with SCID who undergo HCT. We hypothesized that Black and Hispanic patients have a higher incidence of infection pre-transplant and greater age at treatment, and that newborn screening (NBS) could substantially narrow these disparities. MethodsPatients with SCID who received HCT between 1982–2020 at one of 33 North American institutions in the Primary Immune Deficiency Treatment Consortium (PIDTC) were included. The probability of survival was estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used for multivariable analysis. The effect of NBS on disparities was evaluated by performing stratified analyses based on the trigger for diagnosis. Changes in racial/ethnic disparities were assessed over time. ResultsOf 925 patients included, 52% were non-Hispanic White, 22% were Hispanic, and 10% were Black. Genotypes varied by race and ethnicity as shown in Table 1. Overall survival (OS) among Black patients who received a transplant from donors other than matched siblings was significantly lower compared to non-Hispanic White patients (aHR 2.43, 95%CI 1.62, 3.65) after accounting for age, conditioning, donor, genotype, infection status, and year of HCT. OS among Hispanic patients was also lower (aHR 1.34, 95%CI 0.94, 1.90), but did not reach statistical significance (Figure 1). [Display omitted] Thirty-nine percent of both Black and Hispanic patients had an active infection at HCT compared to 34% of non-Hispanic White patients (p = 0.52). There were no racial/ethnic differences in age at treatment or baseline infection among those diagnosed by NBS, whereas disparities were noted among those diagnosed by family history (White: 57 days, Hispanic: 95 days, Black: 99 days; p = 0.02). When evaluated by treatment era, racial/ethnic disparities in age at treatment and baseline infection resolved in the modern era (after 2010).Table 1Frequency of SCID genotypes by Race and Ethnicity.GenotypeTotal N = 925NH White N = 477Hispanic N = 201Black N = 96Asian/PI N = 43Nat. American N = 42ADA55 (8.5)33 (10.0)9 (6.5)7 (10.6)0 (0.0)2 (6.9)CD3 delta10 (1.6)7 (2.1)0 (0.0)0 (0.0)0 (0.0)0 (0.0)DCLRE1C39 (6.1)11 (3.3)5 (3.6)0 (0.0)3 (8.6)16 (55.2)IL2RG274 (42.5)157 (47.4)41 (29.5)41 (62.1)21 (60.0)4 (13.8)IL7R67 (10.4)26 (7.9)31 (22.3)3 (4.5)1 (2.9)1 (3.4)JAK340 (6.2)19 (5.7)10 (7.2)8 (12.1)2 (5.7)0 (0.0)RAG180 (12.4)41 (12.4)17 (12.2)6 (9.1)3 (8.6)6 (20.7)RAG235 (5.4)10 (3.0)16 (11.5)0 (0.0)2 (5.7)0 (0.0)RMRP (CHH)13 (2.0)8 (2.4)2 (1.4)0 (0.0)1 (2.9)0 (0.0)Other/Unknown2811466230813 ConclusionBlack patients with SCID had a more than two-fold hazard of death compared to non-Hispanic White patients, even after accounting for age and infection status. Hispanic patients also demonstrated higher mortality, but this difference was not statistically significant. Disparities across all races and ethnicities in age at treatment and baseline infection were not noted among those diagnosed in the modern era.