A GRIN3A polymorphism may be associated with glucocorticoid-induced symptomatic osteonecrosis in children with acute lymphoblastic leukemia

Abstract

Aim: To evaluate the association between candidate genetic polymorphisms and glucocorticoid-induced osteonecrosis in Arab children treated for acute lymphoblastic leukemia. Methods: A total of 189 children treated for acute lymphoblastic leukemia were genotyped for four SNPs with allele discrimination assays. The incidence and timing of radiologically confirmed symptomatic grade 4 osteonecrosis were classified based on the Ponte di Legno toxicity working group consensus definition. Results: Thirteen children developed grade 4 osteonecrosis (6.8%), of whom 12 received the intermediate/high-risk treatment protocol. GRIN3A variant allele carriers had to stop dexamethasone therapy earlier resulting in significantly shorter duration of dexamethasone treatment (mean [95% CI]: 75.17 [64.28–86.06] vs 85.90 [81.22–90.58] weeks; p = 0.054) and lower cumulative dose (mean [95% CI]: 1118.11 [954.94–1281.29] vs 1341.14 [1264.17–1418.11] mg/m2; p = 0.011). Conclusion: This is the first pharmacogenomics evaluation of the association between GRIN3A variants and glucocorticoid-induced osteonecrosis in Arab children.