Fine particulate matter and minimal residual disease in childhood acute lymphoblastic leukemia from the REDIAL consortium
Thanh T Hoang, Amy E Hughes, Pagna Sok, Omar Rosales, Kathleen F Ludwig, Laura J Klesse, Van Huynh, Kenneth M Heym, Rodrigo Erana, Juan Carlos Bernini, Dimarys Sanchez, Sandi L Pruitt, Austin L Brown, Olga A Taylor, M Monica Gramatges, Mark Zobeck, Karen R Rabin, Philip J Lupo, Michael E Scheurer,Abstract
Background
In acute lymphoblastic leukemia (ALL), minimal residual disease (MRD) is an established biomarker of treatment response and strongly associated with poor outcomes. Among children with ALL, air pollution has been associated with lower survival but has not been evaluated with prognostic biomarkers like end of induction (EOI) MRD.
Methods
Using the Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium, we analyzed 2,125 pediatric patients with ALL. Daily fine particulate matter (PM2.5) estimates were obtained from the Centers for Disease Control and Prevention and linked to patients’ residential and treatment center census tracts. Mean daily PM2.5 during induction was calculated using two definitions: 1) based solely on patients’ residential address, and 2) Days 1-7 based on the treatment center and Days 8 to EOI on patients’ residence. Patients were categorized in quartiles based on mean daily PM2.5. EOI MRD ≥0.1% or ≥ 0.01% was considered positive. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated using logistic regression.
Results
In B-ALL, mean daily residential PM2.5 during induction was associated with positive EOI MRD in quartiles 2 (aOR: 1.56, 95% CI: 1.08, 2.24) and 3 (aOR: 1.51, 95% CI: 1.05, 2.17) but not quartile 4 (aOR: 1.19). The association across all three quartiles strengthened when restricted to NCI high-risk B-ALL (aOR range: 1.73-2.28).
Conclusions
Residential PM2.5 was associated with positive EOI MRD in patients with NCI high-risk B-ALL. Our findings contribute to a growing body of evidence that environmental exposures are associated with inferior outcomes among children diagnosed with ALL.