A prospective comparison of alpha-IFN and conventional chemotherapy in Ph+ chronic myeloid leukemia. Clinical and cytogenetic results at 2 years in 322 patients. The Italian Cooperative Study Group on Chronic Myeloid Leukemia.
BACKGROUND
Standard or conventional treatment of chronic myeloid leukemia (CML) had little effect on the course and the duration of the disease. Treatment with human natural and recombinant alpha-interferon (IFN) was shown to induce hematologic responses, together with partial or complete repopulation of the marrow with Ph negative cells (karyotypic response). These findings prompted a prospective comparison of IFN and conventional treatment in CML.


METHODS
A multicenter prospective controlled study in previously untreated or minimally treated chronic phase Ph+ CML was employed: 322 patients were recruited between 1986 and 1988 and assigned to treatment with human recombinant alpha-IFN (Roferon-A) or hydroxyurea, with a randomization ratio of 2:1. The results of the first 2 years of treatment were analyzed and compared, based on the intention-to-treat policy.


RESULTS
From 8 mo of treatment on, hematologic and karyotypic responses (KR) were more frequent and better in the IFN arm than in the CHT arm. Overall, a major KR (Ph neg greater than 66%) was achieved at least once in 35/218 (16%) IFN-treated patients vs 1/104 CHT-treated ones (P less than 0.0001). None of these 36 patients has progressed from chronic to blastic phase as yet. After 2 years of treatment, 21 of 218 IFN patients (10%) had a major KR vs 1 of 104 CHT patients (P = 0.003), and the cumulative proportion of blastic metamorphosis was 19% in the IFN arm vs 27% in the CHT arm (P = 0.17). Side effects were more frequent in the IFN arm, but compliance with the treatment policy was identical in both arms. The treatment cost was about 11 US dollars per patient per month in the CHT arm, and 200 times higher in the IFN arm.


CONCLUSIONS
During the first 2 years of treatment, IFN was more expensive, had more side effects, but was more effective than CHT in terms of hematologic and karyotypic responses.
D000328:Adult; D000368:Aged; D001752:Blast Crisis; D002066:Busulfan / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000648:ultrastructure; D011446:Prospective Studies; D011994:Recombinant Proteins; D012074:Remission Induction
D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002066:Busulfan; D006918:Hydroxyurea