Expression of the multidrug resistance-associated P-glycoprotein (P-170) in 59 cases of de novo acute lymphoblastic leukemia: prognostic implications

Abstract

Immunocytochemical detection of the multidrug resistance (MDR)-associated membrane protein (P-170) was performed at time of diagnosis in a series of 36 children and 23 adults with acute lymphoblastic leukemia (ALL) using two monoclonal antibodies JSB1 and C219. Immunophenotypes were obtained in all cases and karyotypes were analyzed in 37 cases. Detection with JSB1 or with C219 led to similar results in terms of positive cells and cases, but the intensity of staining was higher with JSB1. In the populations studied, the rate of first complete remission differed between MDR-positive and MDR-negative in adult patients only (56% v 93%, respectively, P = .05). Of the 16 MDR-positive patients who had presented a first complete remission, 13 (81%) relapsed, compared with 13 of 35 (37%) MDR-negative (P = .008) patients. A higher rate of relapse among MDR-positive compared with MDR-negative patients was observed in adults and in children taken separately (adults 100% v 46%; children 73% v 32%, respectively). The survival rates (Kaplan-Meier method) were significantly higher in MDR-negative compared with MDR-positive populations as a whole (P = .002) and among children (P = .05) and adults (P = .03) taken separately. Event-free survival curves followed this trend. The percentage of second complete remission was very low in the MDR-positive group (15%) compared with 38% for the MDR-negative group. These results were shown by multivariate analysis to be independent of age, immunophenotypes, and karyotypes and clearly show the importance of MDR phenotype detection in ALL.