Treatment of advanced stages of Philadelphia chromosome-positive chronic myelogenous leukemia with interferon-alpha and low-dose cytarabine

Abstract

Purpose: To evaluate the efficacy of interferon-alpha (IFN-A) and low-dose cytarabine (ara-C) combination chemotherapy in patients with chronic myelogenous leukemia (CML).

Patients and methods: Sixty patients with advanced phases of Philadelphia chromosome (Ph)-positive CML received combination therapy with IFN-A 5 x 10(6) U/m2 daily, and low-dose ara-C 15 mg/m2 daily for 2 weeks every 4 weeks until remission, then for 1 week every month as maintenance. Forty patients were in late chronic-phase CML, and 20 were in accelerated-phase CML (16 with clonal evolution only, four with other criteria). Their outcome was compared with 58 patients (39 late chronic-phase CML and 19 accelerated-phase CML) who had been previously treated with IFN-A alone in the same dose schedule.

Results: In late chronic-phase CML, patients receiving IFN-A plus ara-C had a better complete hematologic response (CHR) rate compared with those treated with IFN-A alone (55% v 28%; P = .02), a trend for better Ph suppression (15% v 5%; P = .13), and a longer survival (3-year survival rate 75% v 48%; P less than .01). These differences do not seem to be caused by imbalances in prognostic factors between the two treatment groups. In accelerated-phase CML, the addition of ara-C to IFN-A did not improve the response rate of treated patients, and the difference in survival was accounted for by different patient characteristics. Suppression of clonal evolution was observed in five patients (25%). Patients with clonal evolution as the only criterion for disease acceleration had a longer survival than those with other or additional accelerated-phase criteria (3-year survival rate 67% v 22%; P less than .01).

Conclusion: The results with the combination of IFN-A plus ara-C in late chronic-phase CML are encouraging, and suggest the need for its evaluation in early chronic-phase CML.