Results of Therapy with Interferon Alpha and Cyclic Combination Chemotherapy in Patients with Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Early Chronic Phase

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Abstract
The objective of the study was to investigate the toxicity and efficacy of cyclic combination therapy offered to patients with Ph-positive CML having a sub-optimal response to IFN-α. Patients in early chronic phase CML were treated with IFN-α at 5MU/m2 daily. Patients who did not achieve cytogenetic response after 6 months of IFN-α therapy, or Ph-suppression to less than 35% Ph-positive cells (partial cytogenetic response) after 12 months of therapy were offered cyclic intensive chemotherapy every 6 months, with IFN-α maintenance between cycles. The initial 3 cycles included daunorubicin, vincristine, cytosine arabinoside (ara-C) and prednisone (DOAP). Later cycles were given with cyclophosphamide replacing daunorubicin (COAP). Of 74 patients treated, 61 (82%) achieved complete hematologic response (CHR): 51 (69%) had a cytogenetic response, which was major (Ph < 35%) in 31 (42%), and complete in 23 (31%). Fifty-five patients (74%) achieved CHR by 6 months of therapy, 38 (69%; 51% of total) with a cytogenetic response - 13 (24%) had a major cytogenetic response. Seventeen patients received at least 1 course of DOAP therapy. Median survival of the overall cohort of patients was 120 months. With a median follow-up of 145 months (103+ to 155+ months), 40 patients (54%) have died. The median duration of cytogenetic response was 35 months (range 3 to 149+ months) and the estimated 10-year cytogenetic response rate was 37%. A durable complete cytogenetic response was observed in 16 patients (20%) with a median duration of 139+ months (range 12+ to 149+ months), 11 of them (15%) are now off IFN-a therapy for a median of 57+ months (range 12+ to 128+ months). The projected 10-year survival was 50% for the study group versus 35% for 208 patients who received other IFN-α based regimens at the MD Anderson Cancer Center (p<.01). In conclusion, the addition of intensive chemotherapy may improve survival in patients with CML who have not obtained an adequate cytogenetic response on an IFN-α-based regimen.