Glutathione S-transferase polymorphisms and outcome of chemotherapy in childhood acute myeloid leukemia

Purpose: Glutathione 5-transferase theta (GSTT1) and mu (GSTM1) genes are p olymorphic, the genes being absent in approximately 15% and 50% of the popu lation, respectively. Because glutathione S-transferases may be involved in the metabolism of chemotherapy drugs, we hypothesized that presence or abs ence of the genes may influence the outcome of treatment for childhood acut e myeloid leukemia (AML). Patients and Methods: We genotyped GSTT1 and GSTM1 in 306 children with AML receiving chemotherapy on Children's Cancer Group therapeutic studies. Out comes were compared in those with and without GSTT1 and GSTM1 genes. Results: patients with the GSTT1-negative genotype had reduced survival com pared with those with at least one GSTT1 allele (GSTT1 positive) (52% v 40% at 5 years; log-rank P = .05). A multivariate model of survival adjusted f or age group, sex, WBC count, chloroma, CNS involvement, and French-America n-British group confirmed the increased risk of death in the GSTT1-null cas es (relative risk,AQ 1.6; P = .02). The frequency of death in remission was increased in GSTT1-negative cases compared with GSST1-positive cases (24% v 12%, log-rank P = .05). The frequency of relapse from end of induction wa s similar in GSTT1-negative and GSTT1-positive cases (38% v 35%, log-rank P = .5). Conclusion: Children who lacked GSTT1 had greater toxicity and reduced surv ival after chemotherapy for AML compared with children with at least one GS TT1 allele. If confirmed in further studies, GSTT1 genotype might be useful in selecting appropriate chemotherapy regimens for children with AML. J Cl in Oncol 19:1279-1287. (C) 2001 by American Society of Clinical Oncology.