Efficacy and toxicity of IFN-alpha 2b combined with cytarabine in chronic myelogenous leukaemia

Newly diagnosed chronic myelogenous leukaemia (CML) patients (n=65) were tr eated with interferon (IFN)-alpha 2b (5x10(6) IU/d s.c,) combined with mont hly courses of cytarabine (20 mg/d s,c, for 14d). Median age of patients en rolled 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%, respe ctively. The rate of complete haematological response was 60%. Evaluation o f cytogenetic response was available in 29/65 patients. A complete cytogene tic response was seen in 3/29 patients (10%). W.H.O. toxicity grade 3-4 occ urred in only 22/523 evaluable treatment cycles. Since the study protocol r equired intermittent or definitive discontinuation of cytarabine in case of moderate leucopenia (white blood cells (WBC) <5 x 10(9)/l)), combined cyto penia (WBC < 5 x 10(9)/l, platelets <100x10(9)/l), and isolated moderate th rombocytopenia (<100 x 10(9)/l), the drug had to be discontinued temporaril y or definitively in 200 cycles and the dose of cytarabine had to be reduce d in 3 5 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 t reatment of CML with IFN might only be achieved by the administration of a higher cumulative dose of cytarabine, suggesting that lower leucocyte count s of 2-4 x 10(9)/l have to be tolerated.