The heterozygous NUDT15 variant is not associated with the severity of 6-mercaptopurine-related side effects in early intensification therapy for childhood acute lymphoblastic leukemia

Abstract

Background: In the treatment of childhood acute lymphoblastic leukemia (ALL), 6-mercaptopurine (6-MP) is essential for early intensification and maintenance of therapy. Recently, an association between genetic variants of nudix hydrolase 15 (NUDT15) rs116855232 and 6-MP-induced severe myelotoxicity was reported. Given that the NUDT15 variant is relatively common in East Asian and Hispanic populations, it is important to evaluate its impact on 6-MP treatment and determine the dose for an effective therapy and avoid side effects in those populations. Since all the previous reports have focused on maintenance therapy, we studied the clinical impact of the NUDT15 variants in the early intensification therapy for the first time. Methods: Thirty patients with ALL who received early intensification therapy were retrospectively registered in this study. Clinical and laboratory data were collected from their clinical records, and genetic analysis of the NUDT15 variant was performed. Results: Twenty-four patients had CC (wild-type), six patients had CT (heterozygous variant), and none had TT (homozygous variant) of NUDT15 rs116855232. All patients showed myelotoxicity and hepatotoxicity but a correlation between these side effects and the NUDT15 haplotype was not observed. Conclusion: The heterozygous NUDT15 variant was not associated with 6-MP toxicity during early intensification therapy and a dose modification of 6-MP may not be recommended in children with the heterozygous variant of NUDT15.

Keywords

• Leukemia
• Children
• NUDT15
• Mercaptopurine
• Side effects