Multiple drug resistance in acute myelocytic leukemia/acute lymphocyte leukemia patients and MDR evaluation

Background and objectivesDrug resistance is a common cause of treatment failure in malignant disorders especially hematological malignancies. Overexpression of P-glycoprotein (pgp) is the most common cause of drug resistance. Studies on the importance of pgp are controversial that is attributed to the lack of a standard method for pgp assay and the lack of consistency with clinical data. The aim of this study is Multiple drug resistance (MDR) evaluation according to pgp expression in leukemic cells at the beginning of treatment, and prediction of responses to treatment, relapse or death. Materials and MethodsBetween June 2001 and May 2006, we studied 185 leukemic patients. Diagnosis was performed on each case via morphology, based on immunotypes, and by cytogenetic method; pgp expression was also evaluated by flowcytometry. For pgp evaluation, we collected peripheral blood or bone marrow samples in EDTA. Then, patients went under treatment by standard protocols and their responses to treatment were observed. Patient follow ups for response to treatment, complete remission, resistance to induction, relapse or death were conducted. Finally, clinical data were compared with laboratory results. Mann-Whitney, kruscal-valis, kaplan-meier, and chi-square tests were used for data analysis. ResultsFrom 185 patients with the median age of 28.5 years (within the age range of 11-76), 128 patients showed AML and 57 ALL. 62% were male and 38% female. Pgp expression showed no significant correlation with age, sex, type of leukemia, and white blood cells count. There was no significant association between pgp expression and AML subtype. Two-year Overall Survival (OS) and Disease Free Survival (DFS) were 63% and 42% respectively. DFS showed significant correlation with pgp in ALL and non-M3 subtype of AML (P=0.024). Conclusionsexpression of pgp would be a prognostic factor for relapse prediction and might be important in treatment planning.