CYTOGENETICS AND P-GLYCOPROTEIN (PGP) ARE INDEPENDENT PREDICTORS OF TREATMENT OUTCOME IN ACUTE MYELOID-LEUKEMIA (AML)

Clinical and biological features have recognized prognostic significan ce in acute myeloid leukemia (AML). To evaluate the interaction of the se variables and weighted effect on treatment outcome, prognostic vari ables from 96 previously untreated patients were analyzed for associat ion with expression of the MDR1 gene product P-glycoprotein (Pgp), and effect on response to induction chemotherapy, progression-free surviv al and overall survival. Multivariate relationships were analyzed usin g six prognostic variables, including age, cytogenetic pattern, gender , CD34(+) surface phenotype, AML type (de novo versus secondary) and P gp. Univariate comparisons indicate that Pgp (P=0.0001), cytogenetic p attern (P=0.0004) and a CD34(+) phenotype (P=0.0005) are predictive of primary treatment failure, whereas Pgp (P=0.0001) had the greatest pr edictive value in multivariate analysis. Only cytogenetic pattern reta ined prognostic significance (P=0.0143) for response to induction ther apy after adjustment for Pgp. Although all variables except gender wer e associated with Pgp, specimens harboring the favorable karyotypic ab normalities t(15;17), t(8;21) and inv(16) exclusively lacked Pgp expre ssion. In a multivariate model, both Pgp and cytogenetic pattern predi cted response and overall survival, whereas secondary AML and cytogene tic pattern influenced remission duration. These findings indicate tha t cytogenetic pattern has prognostic relevance that is independent of Pgp, and implies the presence of undefined biological mechanisms affec ting chemotherapy resistance.