Mitoxantrone and high-dose cytosine arabinoside for the treatment of refractory acute lymphocytic leukemia

Abstract

Twenty-five adult patients with refractory acute lymphocytic leukemia received salvage therapy with mitoxantrone 5 mg/m² intravenously over 1 hour daily for 5 days and cytosine arabinoside 3 g/m² intravenously over 2 hours every 12 hours for six doses. Overall, nine patients (36%) achieved complete remission, eight (32%) died during induction, and eight (32%) had resistant disease. No significant associations were found between pretreatment patient characteristics and remission. Remission durations were short with a median of 9 weeks; the overall median survival was 10 weeks. The major dose-limiting toxic effects were related to myelosuppression. Febrile episodes requiring hospitalization occurred in 23 patients (92%), including five episodes of fever of unknown origin (20%) and 18 episodes of documented infections (72%). The authors conclude that the combination of mitoxantrone and high-dose cytosine arabinoside has significant activity in adults with refractory acute lymphocytic leukemia. The addition of colony-stimulating growth factors to the intensive chemotherapy, and the use of the combination regimen as part of front-line maintenance intensification therapy may further improve the prognosis in these patients.