Efficacy of fludarabine, intermittent sequential high-dose cytosine arabinoside, and mitoxantrone [FIS-HAM] salvage therapy in highly resistant acuteleukemias

Patients with refractory acute leukemias after intensive induction and salv age attempts have a particularly poor prognosis and therapeutic options are limited. In the current study, the pharmacologically based FIS-HAM regimen was applied, which included fludarabine 15 mg/m(2) q 12 h (days 1, 2, 8, a nd 9), cytosine arabinoside as a 45-min infusion every 3 h at 750 mg/m(2) p er single application (days 1, 2, 8, and 9), and mitoxantrone 10 mg/m(2) (d ays 3, 4, 10, 11). Twenty-six intensively pretreated patients [median age: 38 years; range: 22-65; 16 cases of acute myeloid leukemia (AML) and 10 of acute lymphoblastic leukemia (ALL)] were included. Of 16 patients with AML, 5 achieved a complete remission (CR, 31%), 1 a partial remission (PR, 6%), 2 were nonresponders (13%), and 8 succumbed to early death (ED, 50%). Of 1 0 patients with ALL, 5 achieved a CR, I a PR, 1 was a nonresponder, and 3 d ied early. Overall, the CR rate was 38%. The median disease-free survival r ime was 50 days and median survival 90 days. Two patients underwent allogen eic bone marrow transplantation and are alive after 27 and 28 months. Neutr openia amounted to a median of 46 days. Toxicity WHO III/IV included infect ion (61%), diarrhea (48%), nausea/vomiting (43%), impairment of heart funct ion (30%), and mucositis (26%). The current data indicate a significant act ivity of FIS-HAM chemotherapy in advanced acute leukemias. However, due to its pronounced toxicity, this regimen should be restricted to third-line th erapy for patients expecting a suitable donor for allogeneic transplantatio n, and supportive treatment should be optimized.