Polymorphisms and the Incidence of Toxicities in Children with Acute Lymphoblastic Leukemia.

BACKGROUND

6-Mercaptopurine (6-MP), a thiopurine agent, is a essential medication for treating pediatric acute lymphoblastic leukemia (ALL). However, its side effects of neutropenia and hepatotoxicity might interrupt treatment, resulting in poor outcomes. Inosine triphosphate pyrophosphatase (), an enzyme in the thiopurine pathway, may prevent the accumulation of toxic thiopurine metabolites. Studies on and thiopurine-associated toxicities are scarce.

METHODS

This study retrospectively investigated 1- to 15-year-old children with ALL who received 6-MP during the maintenance phase of treatment between 2000 and 2020. Toxicity during the first year of maintenance therapy and the mean dose of 6-MP were analyzed.

RESULTS

The 209 patients had a median age of 4.8 (0.3-14.8) years. Of these, 124 patients (59.3%) had wild-type , 73 patients (34.9%) had heterozygous (het), and 12 patients (5.7%) had homozygous (hom), with an allele frequency of 0.23. The incidence of neutropenia among polymorphisms did not significantly differ ( = 0.813). In patients harboring hom, transaminitis was more frequent than other polymorphisms but without a significant difference ( = 0.063). The mean dose of 6-MP for patients with hom was significantly lower than that for patients with het or wild-type ( = 0.016).

CONCLUSIONS

Hom had a higher incidence of transaminitis and required a significantly larger dose reduction of 6-MP than wild-type . Further study is warranted to elucidate the effects of polymorphisms on toxicity in patients with ALL treated with 6-MP.