论文部分内容阅读
目的探讨谷胱甘肽硫转移酶(GSTs)家族中GSTT1和GSTM1基因多态性与急性髓系白血病(AML)疗效,药物不良反应与预后的关系。方法AML患者180例,用多重PCR方法检测GSTT1和GSTM1基因型,比较不同基因型患者的诱导治疗完全缓解(CR)率,药物不良反应发生率,总体生存期,无复发生存期和复发率。结果(1)GSTT1和GSTM1基因双非缺失型(double-present型)患者一疗程CR率高于GSTT1,GSTM1任一基因缺失型(null型),二者差异有统计学意义(P=0.013),GSTT1/GSTM1的null基因型患者发生不CR的危险度是double-present型患者的8.736倍(95%CI1.146~66.574)。GSTT1present型一疗程CR率高于GSTT1null型,二者比较亦有统计学意义(P=0.021,OR=2.572,95%CI1.136~5.826);(2)GSTT1和GSTM1基因型分布与诱导治疗后中性粒细胞<0.5×109/L及PLT<20×109/L持续时间差异无统计学意义,GSTM1null型患者发生AST异常的危险度是GSTM1present型的2.593倍(P=0.016,95%CI1.176~5.717);(3)double-present型总体和无复发生存期较GSTT1/GSTM1的null型患者长(平均总体生存期为68.4、38.5个月,P=0.028;平均无复发生存期为73.5、34.9个月,P=0.014),GSTT1null型患者无复发生存期短于GSTT1present型患者(平均无复发生存期为26.7、64.3个月,P=0.038),但二者总体生存期无统计学意义(P=0.653)。double-present型患者复发率显著低于GSTT1/GSTM1的null型患者(13.3%、35.6%,P=0.019)。结论GSTT1,GSTM1基因型与AML患者治疗CR率、复发率、化疗的不良反应及预后均有显著相关性,GSTT1和GSTM1基因型有助于指导AML患者个体化治疗方案的制定。
Objective To investigate the relationship between GSTT1 and GSTM1 gene polymorphisms and acute myeloid leukemia (AML) efficacy, adverse drug reactions and prognosis in glutathione S-transferase (GSTs) family. Methods One hundred and eighty AML patients were recruited. The genotypes of GSTT1 and GSTM1 were detected by multiplex PCR. The complete remission (CR) rate, adverse drug reaction (ADR), overall survival, recurrence-free survival and relapse rate were compared among different genotypes. Results (1) The CR rate of one course of GSTT1 and GSTM1 gene double-present patients was higher than that of GSTT1 and GSTM1 null genes, the difference was statistically significant (P = 0.013) The risk of non-CR in patients with null genotype of GSTT1 / GSTM1 was 8.736 times (95% CI, 1.146 to 66.574) in double-present patients. The CR rate of GSTT1present type was higher than that of GSTT1null type (P = 0.021, OR = 2.572, 95% CI1.136-5.826). (2) The distribution of GSTT1 and GSTM1 genotypes was significantly higher than that of GSTT1null type There was no significant difference in the duration of neutrophils <0.5 × 109 / L and PLT <20 × 109 / L. The risk of AST abnormality in GSTM1 null patients was 2.593 times that of GSTM1 present type (P = 0.016, 95% CI1). 176 to 5.717). (3) The double-present overall and non-recurrences were longer than null patients with GSTT1 / GSTM1 (mean overall survival was 68.4 and 38.5 months, P = 0.028; mean recurrence-free survival was 73.5 , 34.9 months, P = 0.014). The patients with GSTT1null type had shorter relapse-free survival than GSTT1present type patients (mean recurrence-free survival was 26.7 and 64.3 months, P = 0.038), but their overall survival was not statistically significant (P = 0.653). The relapse rate of double-present patients was significantly lower than that of null patients with GSTT1 / GSTM1 (13.3%, 35.6%, P = 0.019). Conclusion The genotypes of GSTT1 and GSTM1 are significantly correlated with CR rates, relapse rates, adverse reactions and prognosis of AML patients. The genotypes of GSTT1 and GSTM1 are helpful to guide the individualized treatment of AML patients.