Pediatric Age at Hematopoietic Stem Cell Transplant: Associations with Non-Malignant Genetic Disease and Race

Introduction: Increasingly, hematopoietic stem cell transplant (HSCT) is used in pediatrics to treat both malignant and nonmalignant conditions. Many of the nonmalignant disorders for which HSCT is curative are genetic, and it has long been recognized that the diagnostic odyssey for patients with genetic disorders is frequently quite long. Notably, the diagnostic odyssey is longer for non-white patients with genetic diseases than for white patients with genetic diseases. We hypothesized that this disparity would also manifest as older age at time of HSCT, which could be associated with greater co-morbidities and worse outcomes. While previous studies have analyzed the association between race and pediatric HSCT access and survival, (PMID:32497418; 35071585; 34900869)we sought to determine if the diagnostic odyssey is longer for racial minorities compared to Caucasians.

Methods: To test this hypothesis, we utilized the 2019 version of the Kids’ Inpatient Database (KID), developed by the Healthcare Cost and Utilization Project (HCUP), sponsored by the Agency for Healthcare Research and Quality (AHRQ).

The HSCT sample was identified using ICD-10-PCS Procedure Codes for transfusion of hematopoietic/cord blood stem cells: Allogenic: 30243X3, 30243Y3, 30243X4, 30233X4, 30243Y2; Autologous: 30243Y0.

A variable for pediatric genetic disease (PGD) was generated using 348 ICD-10-CM diagnostic codes corresponding to 283 pediatric genetic diseases for which the carrier frequency is greater than 1 in 500 in the general population or in an at-risk subpopulation (e.g., sickle cell anemia in AA). We controlled for malignant disease leading to HSCT using ICD-10-CM diagnostic codes to identify lymphomas, leukemias, myelodysplastic syndrome, myeloproliferative neoplasms, neuroblastomas, and brain tumors.

Multiple linear regression was used to test if age of HSCT procedure was significantly associated with race, known non-malignant PGD, malignant disease, payer status, and location (rural vs. urban).

Results: We identified 1,178 pediatric aged patients (age 20 and younger) who received HSCT in 2019 (Allogenic N=618; autologous N=560). The clinical characteristics of these patients are described in Table 1. The average age for Caucasian pediatric patients treated with HSCT is 6.8 years (82 months). Comparing PGD vs. all other diagnoses related to HSCT, patients with known PGD are transplanted on average 1.9 years (22 months) earlier than matched controls (P<0.001). This difference persists after controlling for race, disease severity, transplant type, Medicaid status, and rural health system location.

African American and Asian pediatric patients are treated with HSCT on average 1.6 years (18 months) older than matched Caucasian controls (P=0.003 and 0.032, respectively). The effect of race persists even after controlling for thalassemias and sickle cell disease, associated with non-European ancestry.

Conclusions: Age at transplant may be a useful surrogate for ongoing health disparities and to inform real-world research. African American and Asian ancestries are associated with HSCT at an older age, suggesting a prolonged diagnostic or therapeutic odyssey. This effect persists after controlling for factors such as non-malignant and malignant conditions, payer status, rural location, and genetic diseases that are over-represented in racial groups. More work is required to determine if this delay in treatment is due to differences in the spectrum of genetic diseases treated by HSCT in children of different ancestries, and if these delays in therapy may be associated with increased comorbidities and worse HSCT outcomes.

Higashi:Sema4: Current Employment, Current equity holder in publicly-traded company. Kruszka:Sema4: Current Employment, Current equity holder in publicly-traded company. Francis:Sema4: Current Employment, Current equity holder in publicly-traded company. Parsons:Sema4: Current Employment, Current equity holder in publicly-traded company. Oh:GSK, Janssen, Merck, Pfizer: Consultancy; Sema4: Current Employment, Current equity holder in publicly-traded company. Onel:Sema4: Current Employment, Current equity holder in publicly-traded company.