INDUCING REMISSION IN DRUG-RESISTANT ACUTE MYELOID-LEUKEMIA WITH CYCLOSPORINE-A

Recent research suggests that over expression of P-glycoprotein is inv olved in the resistance of some malignancies to structurally unrelated cytotoxic agents (Pastan & Gottesman, 1987; Kaye & Kerr 1991). It is postulated that P-glycoprotein decreases intracellular concentrations of cytotoxic agents by promoting their active efflux across the cell m embrane (Musto et al. 1991). Modulating agents such as cyclosporin A a nd its analogues, (Sonneveld & Nooter 1990), verapamil, quinidine, the newer cephalosporines and torenifene have been put forward to inhibit resistance, by inhibiting active drug efflux. We report a case of acu te myeloid leukaemia which was resistant to standard induction therapy . In vitro tests showed cyclosporin A to increase the sensitivity of t he patient's myeloblasts to daunorubicin by threefold. Remission was s uccessfully induced when cyclosporin A was combined with daunorubicin, cytosine, arabinoside and etoposide.