Background:
The objectives of the study were to evaluate the antileukemic efficacy and toxicity profiles of the combination of fludarabine and intermediate-dose cytosine arabinoside (ara-c) in refractory or relapsed adult acute lymphocytic leukemia (all). patients and methods. thirty adults with refractory or relapsed all were treated. their median age was 45 years, 60% were in second or subsequent relapse, and 37% had philadelphia chromosome-positive disease. treatment consisted of ara-c 1 g/m2 during a period of 2 hours daily for 6 days, and fludarabine 30 mg/m2 during a period of 30 minutes daily for 5 days on days 2-6. fludarabine was given 4 hours before ara-c to increase the rate of ara-c 5'-triphosphate (ara-ctp) accumulation in leukemic cells. courses were repeated every 3 weeks or longer, depending on patient response and side effects.
Results:
Nine (30%) patients achieved a complete remission (cr), 8 (27%) died during remission induction, and 13 (43%) had resistant disease. the median cr duration was 22 weeks, and the median survival was 12 weeks for all patients, and 34 weeks for those who had a response to treatment. except for low platelet counts, which predicted shorter survival time, no other prognostic factors were demonstrated, considering the small number of patients treated. myelosuppression-associated febrile episodes were the most common side effects, occurring in 28 (93%) patients. neurotoxicity was noted in two (7%) patients.
Conclusions:
Fludarabine and ara-c are an active and relatively safe antileukemic combination in refractory or relapsed all. future studies will incorporate other anti-all agents, such as topoisomerase ii-reactive drugs, to improve the overall efficacy, and growth factors, to reduce myelosuppression-related complications.