An investigation of toxicities and survival in Hispanic children and adolescents with ALL: Results from the Dana-Farber Cancer Institute ALL Consortium protocol 05-001.

Abstract

This study compared the relative incidence of treatment-related toxicities and the event-free and overall survival between Hispanic and non-Hispanic children undergoing therapy for acute lymphoblastic leukemia (ALL) on Dana-Farber Cancer Institute ALL Consortium protocol 05-001. Secondary analysis of prospectively collected data from a phase III multicenter study in children and adolescents of 1-18 years with previously untreated ALL. Between 2005 and 2011, 794 eligible patients enrolled on DFCI 05-001, 730 of whom were included in this analysis (19% [N=150] Hispanic, 73% [N=580] non-Hispanic). Hispanic patients were more likely to be ≥10 years of age (32%vs. 24%, P=0.045) at diagnosis. Toxicity analyses revealed that Hispanic patients had significantly lower cumulative incidence of bone fracture (P<0.001) and osteonecrosis (ON; P=0.047). In multivariable risk regression, the risk of ON was significantly lower in Hispanic patients ≥10 years (HR 0.23; P=0.006). Hispanic patients had significantly lower 5-year event-free survival (EFS) (79.4%; 95% CI: 71.6-85.2) and overall survival (OS) (89.2%; 95% CI: 82.7-93.4) than non-Hispanic patients (EFS: 87.5%; 95% CI: 84.5-90.0, P=0.004; OS: 92.7%; 95% CI: 90.2-94.6, P=0.006). Exploratory analyses revealed differences between Hispanic and non-Hispanic patients in the frequency of common variants in genes related to toxicity or ALL outcome. Hispanic children treated for ALL on DFCI 05-001 had fewer bone-related toxicities and inferior survival than non-Hispanic patients. While disease biology is one explanatory variable for outcome disparities, these findings suggest that biologic and non-biologic mechanisms affecting drug delivery and exposure in this population may be important contributing factors as well.