Fludarabine and cytarabine as a sequential infusion regimen for treatment of adults with recurrent, refractory or poor prognosis acute leukemia

We did a retrospective analysis on the safety and efficacy of sequential in fusion fludarabine and cytosine arabinoside (ara-C) in treating refractory. recurrent or poor prognosis acute leukemia in adult patients. Forty-five a dult patients with acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) received a total of 68 courses of sequential continuous infu sion of fludarabine for 2 days (total dose 71.5 mg/m(2)) followed by 3 days of ara-C (total dose 7590 mg/m(2)). Thirty-nine patients had refractory or recurrent disease. and six had other adverse prognostic features. Thirty-s ix patients had AML. seven had ALL. and two had CML in blastic phase. Compl ete remission was seen in 20 patients (44%), and partial remission in 5 pat ients (11%). giving a total response rate of 56%, similar for both AML and ALL. Duration of response to prior therapy did not affect the response rate . All 3 patients with Philadelphia chromosome positive ALL obtained complet e remission. Median remission duration was 4.7 months (range 0.6-36.6), and median overall survival was 5.0 months: (0.7-40+). Median overall survival was 10.1 months in responders. Pulmonary toxicity was seen in 8 patients. of whom 2 died from adult respiratory distress syndrome. No cardiac toxicit y was observed, but 3 patients had transient cerebellar toxicity. Profound myelosuppression was seen in all patients. We conclude that the sequential infusion of fludarabine and ara-C is an effective non-cardiotoxic regimen f or adults with refractory. recurrent or poor prognosis acute leukemia. may he particularly useful for resistant Philadelphia chromosome positive ALL. and may warrant further investigation in this subset. Pulmonary rather than neurological toxicity may be a unique side effect of the regimen.