The Impact of Structural Inequity and Adverse Social Determinants of Health on Hematopoietic Cell Transplant Access in Pediatric Patients with Hematologic Malignancies and Myelodysplastic Syndromes

Introduction: Without prompt hematopoietic cell transplantation (HCT) in eligible patients, disease-free and overall survival rates remain low. Despite this, many studies conducted primarily in adults have shown significant disparities in HCT access and rates of post-transplant morbidity and mortality based on sociodemographic factors including neighborhood poverty. While studies have looked at the impact of social determinants of health (SDOH) on access to, and outcomes following, HCT in adult populations, there are limited data on the impact of structural inequities on receipt of transplant following referral in children. We hypothesize that children facing higher rates of structural inequity and adverse SDOH receive HCT at lower rates than their peers that face less structural inequity.

Methods: We performed a retrospective cohort study of children aged 0-21 who were referred to our center for consideration of first allogeneic transplant between January 1, 2015 and June 31, 2023 with a diagnosis of hematologic malignancy or myelodysplastic syndrome (MDS). Additional inclusion criteria included HCT eligibility based on disease status or cytogenetics. Data were abstracted from the electronic health record and address at time of referral was linked to three validated indices of SDOH – the Social Vulnerability Index (SVI), Area Deprivation Index (ADI), and Childhood Opportunity Index (COI). Univariable and multivariable cox proportional hazard models were used to determine the association between SDOH indices and transplant receipt. SAS 9.4 (Cary, NC) was used for analysis.

Results: Of 230 patients referred for HCT, the median age at referral was 9.5 years (IQR 5.6, 13.4) and 101 (43.9%) were female. One hundred (43.5%) were referred for acute lymphoblastic leukemia (ALL), 85 (34.8%) for acute myeloid leukemia (AML), and 27 (11.7%) for MDS. The patients represented a diverse cohort as 62 (27.1%) identified as Black, 60 (26.4%) identified as Hispanic, and 38 (16.6%) had a primary language other than English. One hundred twenty four patients (54.2%) had Medicaid as their primary insurance. One hundred eleven patients (48.7%) resided in low to very low childhood opportunity areas and 67 (29.4%) resided in areas with high to very high social vulnerability. Of those referred, 61 (61%) with ALL, 62 (78%) with AML, and 18 (66.7%) with MDS received a HCT. Of those who did not proceed to transplant, 27 with ALL (69%) received alternative therapies including CAR-T, while 15 (83%) with AML died from disease progression or complications prior to HCT. There were no significant differences in age, sex, insurance type, COI, or ADI scores between those who received a transplant and those who did not. Univariable factors associated with HCT receipt included female sex (HR 1.35, CI 1.12-2.08), primary diagnosis of AML (HR 2.10, CI 1.43-3.07) or infant leukemia (HR 2.44, CI 1.23-4.84) compared to B-ALL, and high social vulnerability at both the national (HR 1.57, 95% CI 1.04-2.37) and state level (HR 1.66, 95% CI 1.11-2.48) compared to low social vulnerability. After adjusting for all significant variables, a diagnosis of AML (HR 1.93, CI 1.29-2.87) and high social vulnerability at the national (HR 1.60, CI 1.06-2.43) and state level (HR 1.68, CI 1.12-2.52) remained factors associated with increased transplant receipt.

Conclusions: In this large, single-center retrospective cohort study of pediatric patients with hematologic malignancies and MDS, we surprisingly found that higher vulnerability, as proxied by the national and state SVI, is associated with increased odds of HCT receipt. These findings are in stark contrast to findings in adult populations, in which patients living in communities facing higher disparity and vulnerability receive HCT at disparately lower rates. We hypothesize that pediatric patients may receive more comprehensive, wrap around services and social supports especially when identified as facing excess barriers to care, accounting for the higher levels of transplant in at risk populations. Alternatively, patients from more vulnerable cohorts may present with higher risk features and cytogenetics that necessitate transplant over alternative therapies. To better understand these associations, multi-center prospective studies are needed. These will allow investigators to assess SDOH in real time while implementing programs to ensure equitable access to HCT for all children.