Quinine improves the results of intensive chemotherapy in myelodysplastic syndromes expressing P glycoprotein: results of a randomized study

Intensive chemotherapy produces a lower complete remission (CR) rate in the myelodysplastic syndromes (MDS) than in de novo acute myeloid leukaemia (AML), possibly due in part to a higher incidence of P glycoprotein (PGP) expression in MDS blast cells. We designed a randomized trial of intensive chemotherapy with or without quinine, an agent capable of reverting the multidrug resistance (mdr) phenotype, in patients aged ⩽ 65 years with high‐risk MDS. Patients were randomized to receive mitoxantrone 12 mg/m2/d days 2–5 + AraC 1 g/m2/12 h days 1–5, with (Q+) or without (Q−) quinine (30 mg/kg/d). 131 patients were included. PGP expression analysis was successful in 91 patients. In the 42 PGP‐positive cases, 13/25 (52%) patients in the Q+ group achieved CR, compared to 3/17 (18%) patients in the Q− group (P = 0.02) and median Kaplan‐Meier survival was 13 months in the Q+ group, and 8 months in the Q− group (P = 0.01). No life‐threatening toxicity was observed with quinine. In conclusion, the results of this randomized study show that quinine increases the CR rate and survival in PGP‐positive MDS cases treated with intensive chemotherapy.