title: Efficacy of fludarabine, intermittent sequential high-dose cytosine arabinoside, and mitoxantrone (FIS-HAM) salvage therapy in highly resistant acute leukemias.
abstract: Patients with refractory acute leukemias after intensive induction and salvage 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/m2 q 12 h (days 1, 2, 8, and 9), cytosine arabinoside as a 45-min infusion every 3 h at 750 mg/m2 per single application (days 1, 2, 8, and 9), and mitoxantrone 10 mg/m2 (days 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 10 patients with ALL, 5 achieved a CR, 1 a PR, 1 was a nonresponder, and 3 died early. Overall, the CR rate was 38%. The median disease-free survival time was 50 days and median survival 90 days. Two patients underwent allogeneic bone marrow transplantation and are alive after 27 and 28 months. Neutropenia amounted to a median of 46 days. Toxicity WHO III/IV included infection (61%), diarrhea (48%), nausea/vomiting (43%), impairment of heart function (30%), and mucositis (26%). The current data indicate a significant activity of FIS-HAM chemotherapy in advanced acute leukemias. However, due to its pronounced toxicity, this regimen should be restricted to third-line therapy for patients expecting a suitable donor for allogeneic transplantation, and supportive treatment should be optimized.
authors.affiliation: University Hospital Grosshadern, Department of Medicine III, Ludwig-Maximilians-University, Munich, Germany. wolfgang.kern@med3.med.uni-muenchen.de
authors.forename: W
authors.initials: W
authors.lastname: Kern
authors.forename: E
authors.initials: E
authors.lastname: Schleyer
authors.forename: J
authors.initials: J
authors.lastname: Braess
authors.forename: E
authors.initials: E
authors.lastname: Wittmer
authors.forename: J
authors.initials: J
authors.lastname: Ohnesorge
authors.forename: M
authors.initials: M
authors.lastname: Unterhalt
authors.forename: B
authors.initials: B
authors.lastname: Wörmann
authors.forename: T
authors.initials: T
authors.lastname: Büchner
authors.forename: W
authors.initials: W
authors.lastname: Hiddemann
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D003561:Cytarabine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004351:Drug Resistance; D006801:Humans; D007938:Leukemia / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D007951:Leukemia, Myeloid / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000633:toxicity; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D016879:Salvage Therapy; D013810:Therapeutic Equivalency; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity
chemical_list: D003561:Cytarabine; D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine