Treatment of Philadelphia chromosome-positive early chronic phase chronic myelogenous leukemia with daily doses of interferon alpha and low-dose cytarabine

Purpose: To evaluate the efficacy of the combination of interferon alpha (I FN-alpha) and daily low-dose cytarabine (ara-C) in the treatment of patient s with early chronic-phase chronic myelogenous leukemia (CML) (within 1 yea r af diagnosis). Improving the degree of hematologic and cytogenetic respon se in patients with Philadelphia chromosome (Ph)-positive CML may improve p rognosis. Both IFN-alpha and ara-C induce cytogenetic responses as single-a gent therapy in CML. Patients and Methods: One hundred forty patients with Ph-positive early chr onic-phase CML received subcutaneous injections of IFN-alpha 5 megaunits/m( 2) daily and ara-C 10 mg daily. Their median age was 46 years; 53% herd goo d-risk disease, 33% had intermediate-risk disease, and 14% had poor-risk di sease. Their results were compared with those of patients receiving IFN-alp ha with or without intermittent ara-C (7 days/mo). Results: A complete hematologic response (CHR) was achieved in 92% of patie nts. A cytogenetic response was seen in 74%: it was major in 50% (Ph-positi ve < 35%) and complete in 31% (Ph-positive 0%). With a median follow-up of 42 months, the 4-year estimated survival rate was 70% (95% confidence inter val, 61% to 79%). Significant side effects included fatigue (43%; grade 3/4 , 11%), weight loss (19%; grade 3/4, 11%), muscle and bone aches (20%; grad e 3/4, 7%), oral ulcers (4%), diarrhea (6%), and neurologic changes (27%, g rade 3/4, 6%), The median dole of IFN-alpha was 3.7 megaunits/m2 daily, mai nly because of reductions for myelosuppression (70% of cases); the median a ra-C dose was 7.5 mg daily. Prognostic risk groups were predictive for resp onse to the IFN-alpha plus ara-C combination. The incidence of CHR was high er with IFN-alpha plus daily ara-C compared with IFN-alpha plus intermitten t ara-C and IFN-alpha alone (no ara-C) (92% v 84% v 80%, P = .01), as were the incidences of cytogenetic response (74% v 73% v 58%; P = .003) and majo r cytogenetic response (50% v 38% v 38%; P = .06). The median rime to achie vement of major cytogenetic response war significantly shorter than that fo r previous IFN-alpha regimens (7 v 10 v 12 months; P < .01). However, with the present follow-up, the survival and time to blastic transformation were similar. Conclusion: The combination of IFN-alpha plus dairy low-dose ara-C seems to be promising for the treatment of CML. High rates of CHR and cytogenetic r esponse were observed with acceptable toxicity and a lower daily dole of IF N-alpha compared with our previous studies. J Clin Oncol 17:284-292, (C) 1999 by American Society of Clinical Oncology.