Interferon-alpha-2C and LD ara-C for the treatment of patients with CML: Results of the austrian multicenter phase II study

Abstract

Small pilot studies of patients with CML have reported on encouraging response rates after treatment with interferon-alpha (IFNα) in combination with low-dose cytosine arabinoside (LD ara-C). We therefore initiated a multi-center phase II trial in order to investigate the efficacy and tolerability of this combination in newly diagnosed patients with Ph-positive chronic myelogenous leukemia (CML). Eighty-four patients were treated with IFN-α-2c at daily subcutaneous doses of 3.5 MU and LD ara-C added subcutaneously for 10 days every month at a dose of 10 mg/m 2, following an initial reduction of WBC to less than 20 × 10 9/l with hydroxyurea (HU). Within a median observation period of 28 (5–59) months the patients received a median of 7 (1–35) IFNα and LD ara-C cycles. Treatment was stopped due to side effects in 16 cases (19%) and to primary or secondary treatment failure in 38 cases (45%). In 45 patients (54%) complete hematological response (CHR) was achieved; in 39 patients (46%) cytogenetic responses including 15 (18%) complete cytogenetic responses (CHR) were observed. Median duration of cytogenetic responses was 15 months. Relapses were seen in 8 15 patients (53%) with complete cytogenetic remission (CCR), in 3 6 patients (50%) with partial cytogenetic response and in 9 18 patients (50%) with minor cytogenetic response. In conclusion, the combination of IFNα and LD ara-C resulted in encouraging rates of hematological and cytogenetic responses in patients with CML with low to moderate toxicity.