title: Results of therapy with interferon alpha and cyclic combination chemotherapy in patients with philadelphia chromosome positive chronic myelogenous leukemia in early chronic phase.
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-alpha. Patients in early chronic phase CML were treated with IFN-alpha at 5MU/m(2) daily. Patients who did not achieve cytogenetic 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 (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-alpha 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-alpha 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-alpha-based regimen.
authors.affiliation: Department of Leukemia; University of Texas MD Anderson Cancer Center Houston, Texas 77030, USA.
authors.forename: F J
authors.initials: FJ
authors.lastname: Giles
authors.forename: H
authors.initials: H
authors.lastname: Kantarjian
authors.forename: S
authors.initials: S
authors.lastname: O'Brien
authors.forename: M B
authors.initials: MB
authors.lastname: Rios
authors.forename: J
authors.initials: J
authors.lastname: Cortes
authors.forename: M
authors.initials: M
authors.lastname: Beran
authors.forename: C
authors.initials: C
authors.lastname: Koller
authors.forename: M
authors.initials: M
authors.lastname: Keating
authors.forename: M
authors.initials: M
authors.lastname: Talpaz
mesh_terms: D000206:Actuarial Analysis; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000633:toxicity; D003561:Cytarabine / Q000008:administration & dosage / Q000633:toxicity; D020732:Cytogenetic Analysis; D003630:Daunorubicin / Q000008:administration & dosage / Q000633:toxicity; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000633:toxicity; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D015466:Leukemia, Myeloid, Chronic-Phase / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage / Q000633:toxicity; D011241:Prednisone / Q000008:administration & dosage / Q000633:toxicity; D012307:Risk Factors; D015996:Survival Rate; D013810:Therapeutic Equivalency; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D016898:Interferon-alpha; D003561:Cytarabine; D014750:Vincristine; D003520:Cyclophosphamide; D011239:Prednisolone; D011241:Prednisone; D003630:Daunorubicin