Impact of the homozygous mutation in Nudix hydrolase 15 on myelosuppression with 6-mercaptopurine in a European girl with acute lymphoblastic leukemia: a case report

Abstract

Abstract A 6-year-old girl diagnosed with intermediate-risk acute lymphoblastic leukemia (ALL) presented with severe myelotoxicity and multiple infections during phase IB induction treatment with 6-mercaptopurine (6-MP). In the subsequent treatment phases, which included 6-MP, the patient continued to show bone marrow aplasia and neutropenia, necessitating numerous dose adjustments and interruptions. The recommended dose was eventually reduced to 5 %. A pharmacogenetic analysis, conducted in induction phase IB, detected three single-nucleotide polymorphisms (SNPs) of the thiopurine S-methyltransferase (TPMT) gene, and the phenotype of a normal metabolizer was observed. As a result of a second pharmacogenetic analysis, pathological polymorphisms were revealed in Nudix hydrolase 15 (NUDT15), which may explain the patient’s myelotoxicity. Hence, a pharmacogenetic analysis performed in advance would have been able to prevent her from suffering severe toxicity and/or treatment failure.

Keywords

• pharmacogenetics
• 6-mercaptopurine
• acute lymphoblastic leukemia