Drug resistance factors in acute myeloid leukemia: a comparative analysis

To compare the clinical relevance of drug resistance factors in de novo acu te myeloid leukemia (AML), we determined their relationship to both respons e to induction chemotherapy and survival of the patients in univariate as w ell as multivariate analyses. The drug resistance factors immunocytochemica lly studied in 111 patients at the time of diagnosis included the lung resi stance protein (LRP), P-glycoprotein (P-gp), multidrug resistance protein ( MRP1) and bcl-2. In the univariate analyses, age (P = 0.005), karyotype (P = 0.03), LRP (P = 0.003), P-gp (P = 0.02) and bcl-2 (P = 0.03) predicted fo r response to induction chemotherapy, whereas MRP1 had no predictive value. Age (P = 0,05), karyotype (P = 0.05) and LRP (P = 0.03) retained their pre dictive value in the multivariate logistic regression analyses. With regard to overall survival, age (P = 0.008), karyotype (P = 0.006), LRP (P = 0.00 1) and P-gp (P = 0.01) were of prognostic value in the univariate Cox regre ssion analyses but only age (P = 0.01), karyotype (P = 0.02) and LRP (P = 0 .01) retained their prognostic significance in the multivariate analyses. A risk score based on the number of independent prognostic factors allowed d ivision of patients into four groups with different outcome. In these group s, the complete remission rates were 93%, 75%, 47% and 33%, respectively, a nd median overall survival was 2.4, 1.2, 0.6 and 0.2 years, respectively. T hus, several drug resistance factors did predict outcome in the univariate analyses but LRP was the only drug resistance factor with independent predi ctive and prognostic significance. The proposed risk score might be useful for risk-adapted treatment in the future.