RELATIONSHIP BETWEEN EXPRESSION OF P-GLYCOPROTEIN AND USE OF NONCYTOTOXIC DRUGS BEFORE CHEMOTHERAPY IN ACUTE-LEUKEMIA

Background - This study was designed to evaluate whether the expressio n of the P-glycoprotein responsible for multidrug resistance was influ enced by noncytotoxic drugs given for benign chronic disorders before primary chemotherapy for acute leukemia. Methods - Using flow cytometr y with the monoclonal antibody MRK16, we investigated the expression o f P-glycoprotein by peripheral blood leukemic blasts of 20 patients wi th acute nonlymphoblastic leukemia and 6 patients with acute lymphobla stic leukemia. MRK16-positive cells were confirmed histochemically by immunoglucose oxidase staining. Results - Ten of 26 patients had recei ved long-term medication: a non-steroid antiinflammatory drug, an anti ulcer agent, an antitubercular agent, a herb medicine, a new quinolone , a hemorrhoidal suppository, a laxative, a progestogen, a coronary va sodilator, prednisolone, or a protease inhibitor. The MRK-16- positive rates among the blasts was significantly higher in patients who recei ved the medication before chemotherapy (10/10, 100%) than in patients who received no drug (8/16, 50%) (p<0.01). The complete remission rati o at 2 to 3 months after primary chemotherapy tended to be higher in u nmedicated patients than in medicated patients. Conclusions - Drug tre atment for benign chronic disorders increased the expression of P-glyc oprotein before intensive chemotherapy in patients with acute leukemia and this increased expression was associated with a poorer remission rate.