P-glycoprotein and terminal transferase expression identify prognostic subsets within cytogenetic risk classes in acute myeloid leukemia

Clinical and biological features were assessed in 204 consecutive de novo a dult acute myeloid leukemia (AML) patients who received intensive chemother apy regimens. Multiparameter flow cytometric assays both of the multidrug r esistance (MDR-1)-associated P-glycoprotein (PGP) using the UIC2 monoclonal antibody (MoAb), and of terminal transferase (TdT) were performed. Cytogen etic findings were obtained from 196 patients with high resolution banding. At onset, UIC2 and TdT positivities were detected in 58.5% and 24% of case s, respectively. There were strict correlations either between UIC2 negativ ity and FAB M3 or between TdT and FAB MO-Mi (P = 0.001 and < 0.0001, respec tively). On the other hand, age was significantly associated with cytogenet ic risk classes (P < 0.0001). CD34 positivity was highly correlated with Td T expression (P < 0.0001). Moreover, CD7 and CD11b were significantly repre sented in UIC2+ subset (P < 0.0001). Rhodamine 123 (Rh 123) efflux was sign ificantly higher in 75 UIC2 positive patients compared to 65 UIC2 negative ones (P < 0.001). As regards to cytogenetics, TdT positivity was strongly r elated either to t(9;22) or single/associated anomalies of chromosome 7; on the other hand, most or all cases with t(8;21) or t(15;17) were UIC2 or Td T negative, respectively. The rate of first complete remission (CR) differe d both between UIC2 + and UIC2 - cases and between TdT + and TdT - ones (40 % versus 72%, P < 0.001; and 36% versus 61%, P = 0.001, respectively). The survival rates (Kaplan-Meier method) were significantly shorter either in U IC2 + or in TdT + patients (P = 0.005 and = 0.011, respectively). UIC2 and TdT negative cases showed longer remission duration (P = 0.03 and = 0.22, r espectively). The additional effect of UIC2 and TdT on prognosis allowed us to identify two subsets of patients, the first [UIC2 - TdT - ] at better a nd the second [UIC2 + TdT + ] at worse clinical outcome compared to single UIC2 and TdT cases, concerning CR (P < 0.001), survival (P<0.0001) and CR d uration (P=0.007). The combinations [UIC2 + TdT -] and [UIC2 - TdT - ] show ed an intermediate clinical course. A strong difference was found between p oor risk and intermediate/favorable risk cytogenetic classes with regard to CR rate (P < 0.0001), overall survival and CR duration (P < 0.001). Nevert heless, within the poor risk class, UIC2 positivity was able to identify pa tients at worst prognosis with regard to CR (P = 0.005), survival (P = 0.02 ) and CR duration (P = 0.015). On the other hand, UIC2 and TdT negativity a llowed us to distinguish patients with longer survival (P = 0.012 and = 0.0 4, respectively) and CR duration (P = 0.04 and = 0.025, respectively) withi n the intermediate/favorable risk class. The independent prognostic value o f UIC2, TdT and cytogenetic risk classes was confirmed in multivariate anal ysis. These results suggest that PGP and TdT expressions, together with cyt ogenetic findings, may represent a basic predictor of chemotherapeutic fail ure in AML. (C) 1999 Elsevier Science Ltd. All rights reserved.