Glutathione S-Transferases (GSTT1 and GSTM1) Genes Polymorphisms and Response and Prognosis of Chinese Patients with De Novo Acute Myeloid Leukemia.

The GSTT1 and GSTM1 genes are polymorphic in humans, with the phenotypic absence of enzyme activity caused by a homozygous inherited deletion of the gene. A number of prior studies have reported on GST genotype and outcome of therapy for AML. In this study, we analyzed the prognostic significance of gene polymorphism of GSTT1, GSTM1 in Chinese patients with de novo AML other than M3. A total of 254 cases were entered. There are 157 males and 97 females, ranging in age from 15 to 75 years (median: 32 years). Patients were diagnosed following WHO criteria, 81 were AML with t(8;21) AML1/ETO, 54 were AML with inv(16) or t(16;16) CBF-β/MYH11, 4 were AML with 11q23 abnormalities (MLL), 1 was minimally differentiated, 3 were AML without maturation, 44 were AML with maturation, 17 were acute myelomonocytic leukemia, 42 were acute monocytic leukemia, and 8 were acute erythroid leukemia. All the patients were treated with HAD regimen (Homoharringtonine, HHT, 2.5mg/m² intravenously on days 1 to7; Ara-c, 150 mg/m²/d continuous infusion on days 1 to 7, and DNR,45 mg/m² intravenously on days1 to 3.) as induction therapy. Postremission therapy consisted of HA regimen (HHT and Ara-c)(course 1 and 4), DA regimen (DNR and Ara-c)(courses 2 and 5), and MA regimen (MTZ and Ara-c) or HAM (Ara-c 1g/m²,q12h, intravenously on days 1 to 4, combined with MTZ 8mg/m², intravenously on days 5 to 7(courses 3 and 6). The multiplex PCR method was used to simultaneously amplify and analyze GSTM1,GSTT1, and β-globin from patients. 21 patients died before marrow recovery or adequate assessment of response. 165 (68.5%) achieved a CR after the first course of chemotherapy and 194 (80.5%) achieved a CR after the second course of chemotherapy. Median follow-up was 36 months (11 to 111 months). 104 patients were last known to be alive after entering the study, the other 138 patients are now decease. Twelve patients lost to follow-up are censored at the date they were last known to be alive. Median OS and median RFS was 22 months and 19 months, respectively. OS rates at 3 years and 5 years were 38.9%±3.5% and 25.2%±6.5%, respectively. RFS rates at 3 years and 5 years were 32.8%±3.9% and 22.4%±5.2%, respectively. The rate of early death after the initiation of chemotherapy was similar between the GSTT1+/ GSTM1+ group and GSTT1− / GSTM1- group. The CR rates was higher in GSTM1+ group(71.9%) than GSTM1− group(60.8%) (OR=1.882; P =0.034) after the initiation of chemotherapy, and The CR rates was higher in GSTT1+ group(82.6%) than GSTT1− group (70.75)(OR=2.204; P =0.024) after the second course of chemotherapy. Overall survival and disease-free survival of patients who achieved complete remission (CR) in GSTT1 and GSTM1 double present group(50.1%±9.6% and 43.1%±9.6% at 5 years, respectively) was better than GSTT1- and/or GSTM1- group(27.2%±4.6% and 15.7%±6.3% at 5 years, respectively) (p=0.03 and p=0.022, respectively). For patients with AML with inv(16)(p13q22) or t(16;16)(p13;q22)(CBFβ/MYH11), Overall survival was better in GSTT1+ group than GSTT1− group(69.7%±10.5% v 27.5%±13.0% at 5 years)(p=0.013). Our data showed AML patients with deletions of GSTM1 or GSTT1 or both had a lower probability to achieve CR on induction therapy as compared to patients with intact GST genes and a shorter survival.