title: Efficacy and toxicity of IFN-alpha2b combined with cytarabine in chronic myelogenous leukaemia.
abstract: Newly diagnosed chronic myelogenous leukaemia (CML) patients (n = 65) were treated with interferon (IFN)-alpha2b (5 x 106 IU/d s.c.) combined with monthly courses of cytarabine (20 mg/d s.c. for 14 d). Median age of patients enrolled was 45 years. The endpoints of the study were clinical efficacy and toxicity. The survival rates at 3 years and 5 years were 77% and 56%, respectively. The rate of complete haematological response was 60%. Evaluation of cytogenetic response was available in 29/65 patients. A complete cytogenetic response was seen in 3/29 patients (10%). W.H.O. toxicity grade 3-4 occurred in only 22/523 evaluable treatment cycles. Since the study protocol required intermittent or definitive discontinuation of cytarabine in case of moderate leucopenia (white blood cells (WBC) <5 x 109/l), combined cytopenia (WBC < 5 x 109/l, platelets <100 x 109/l), and isolated moderate thrombocytopenia (<100 x 109/l), the drug had to be discontinued temporarily or definitively in 200 cycles and the dose of cytarabine had to be reduced in 35 cycles. Thus, only 25% of the planned dose of cytarabine could be administered. At this dosage it would appear that cytarabine had no effect on survival and did not improve remission rates. We conclude that a clinical benefit for the addition of cytarabine to the treatment of CML with IFN might only be achieved by the administration of a higher cumulative dose of cytarabine, suggesting that lower leucocyte counts of 2-4 x 109/l have to be tolerated.
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum, Mainz, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Lindauer
authors.forename: D
authors.initials: D
authors.lastname: Domkin
authors.forename: H
authors.initials: H
authors.lastname: Döhner
authors.forename: H J
authors.initials: HJ
authors.lastname: Kolb
authors.forename: A
authors.initials: A
authors.lastname: Neubauer
authors.forename: D
authors.initials: D
authors.lastname: Huhn
authors.forename: H
authors.initials: H
authors.lastname: Kreiter
authors.forename: B
authors.initials: B
authors.lastname: Koch
authors.forename: C
authors.initials: C
authors.lastname: Huber
authors.forename: W
authors.initials: W
authors.lastname: Aulitzky
authors.forename: T
authors.initials: T
authors.lastname: Fischer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced; D011994:Recombinant Proteins; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D003561:Cytarabine