Results of therapy with interferon alpha and cyclic combination chemotherapy in patients with Philadelphia chromosome positive chronic myelogenous leukemia in early chronic phase

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-alpha. Patients in early chronic phase CML we re treated with IFN-alpha at 5MU/m(2) daily. Patients who did not achieve c ytogenetic response after 6 months of IFN-alpha 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-alpha maintenance between cycles. The initial 3 cycles included daunorubicin, vincristine, cytosine arabinoside (ara-C) and prednisone (DOA P). Later cycles were given with cyclophosphamide replacing daunorubicin (C OAP). Of 74 patients treated, 61 (82%) achieved complete hematologic response (CH R): 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 lea st 1 course of DOAP therapy. Median survival of the overall cohort of patie nts was 120 months. With a median follow-up of 145 months(103+ to 155+ mont hs). 40 patients (54%) have died. The median duration of cytogenetic respon se was 35 months (range 3 to 149+ months) and the estimated 10-year cytogen etic response rate was 37%. A durable complete cytogenetic response was obs erved in 16 patients (20%) with a median duration of 139+ months (range 12 to 149+ months), ii of them (15%) are now off IFN-alpha, therapy for a med ian of 57+ months (range 12+ to 128+ months). The projected 10-year surviva l was 50% fur the study group versus 35% for 208 patients who received othe r IFN-alpha based regimens at the MD Anderson Cancer Center (p < .01). In c onclusion, the addition of intensive chemotherapy may improve survival in p atients with CML who have not obtained an adequate cytogenetic response on an IFN-alpha -based regimen.