MULTIDRUG-RESISTANT ACUTE-LEUKEMIA CELLS ARE RESPONSIVE TO PROLONGED EXPOSURE OF DAUNORUBICIN - IMPLICATIONS FOR LIPOSOME-ENCAPSULATED DAUNORUBICIN

We examined the cytotoxic effects of free daunorubicin (DNR) and lipos ome-encapsulated DNR on multidrug-resistant (MDR1) leukemia cells of p atients with acute leukemias who had failed primary induction treatmen t that included DNR. This was analyzed ex-vivo with DNR concentrations and exposure times that normally can be achieved in-vivo for both dru gs with induction treatment. The leukemic blasts of patients both with drug-resistant AML and drug-resistant ALL were, ex-vivo, very sensiti ve to DNR concentrations and exposure times that can be achieved in-vi vo by liposome-encapsulated DNR, However, under identical conditions, free DNR and liposome-encapsulated DNR had a similar cytotoxic profile , arguing against a unique mechanism of cytotoxicity by the liposomal constructure. These data suggest that liposome-encapsulated DNR may be preferable to free DNR for the treatment of acute leukemias. (C) 1998 Elsevier Science Ltd. All rights reserved.