P-glycoprotein expression in refractory hematological neoplasms and circumvention of resistance with verapamil or cyclosporine A containing protocols.

Abstract

Either p-glycoprotein (pgp) or the encoding gene mdr1 expression has been reported to be correlated with multidrug resistance and poor treatment response. To investigate the incidence of pgp in refractory hematological neoplasms we analyzed malignant cells from 40 patients by an immunoperoxidase method using the monoclonal antibody C219. Pgp was positive in 75% of acute nonlymphoblastic leukemia (ANLL) and 50% of acute lymphoblastic leukemia (ALL). Pgp positivity was similarly distributed in both Tdt (-) and (+) ANLLs (64% versus 100%). Addition of Verapamil (VRP) (12 patients) or Cyclosporine A (CsA) (7 patients) to the previous chemotherapy protocol resulted in complete response in 7 (58%) and 3 (43%) of the patients respectively. Partial response was observed in one patient who received CsA. Both chemosensitizers were tolerated well with few reversible side effects. The preliminary results of this study have been presented in the 15th International Cancer Congress, August 1990 Hamburg, Germany.