Long-term follow-Up of the italian trial of interferon-alpha versus conventional chemotherapy in chronic myeloid leukemia. The Italian Cooperative Study Group on Chronic Myeloid Leukemia.

Several prospective randomized studies have shown that the treatment of chronic myeloid leukemia with interferon-alpha (IFN-alpha) prolongs the survival by comparison with conventional chemotherapy. However, although IFN-alpha can induce cytogenetic responses, true complete remissions are rarely achieved and information on the long-term effects of IFN-alpha treatment is limited. For that purpose, we updated and analyzed a prospective comparative trial of IFN-alpha and conventional chemotherapy that was initiated in 1986. The first analysis of the trial was already published, and showed a survival advantage for IFN-alpha (N Engl J Med 12:820, 1994). The observation period of living patients now ranges between 95 and 129 months and we examined the long-term effects of IFN-alpha treatment, always by comparison with conventional chemotherapy and according to the intention-to-treat principle. The patients who were submitted to allogeneic bone marrow transplantation (BMT) in chronic phase (38 of 322 or 12%) were censored at the date of BMT. Seventy-three of the original 284 nontransplanted patients were alive, 56 (30%) in the IFN-alpha arm and 17 (18%) in the chemotherapy arm. Forty-one patients overall (14%) were still receiving IFN-alpha. In the IFN-alpha arm 9 patients were in continuous complete cytogenetic remission and 11 were in major or minor cytogenetic remission. Median and 10-year survival of low-risk patients were 104 months (95% CI, 85 to 127 months) and 47% (95% CI, 36% to 59%) in IFN-alpha arm versus 64 months (95% CI, 49 to 98 months) and 30% (95% CI, 16% to 44%) in chemotherapy arm (P = .03). Median and ten-year survival of non-low-risk patients were 69 months (95% CI, 56 to 76 months) and 16% (95% CI, 8% to 24%) in IFN-alpha arm versus 46 months (95% CI, 39 to 61 months) and 5% (95% CI, 0% to 11%) in chemotherapy arm (P = .006). A low Sokal's risk, hematologic response, and cytogenetic response were associated with a longer survival. No major or unusual side effects were recorded after the 5th year of IFN-alpha treatment. Fourteen patients died in chronic phase, 9 (4%) in IFN-alpha arm and 5 (5%) in chemotherapy arm, mainly of cardiovascular accidents (6 cases) and of other cancers (5 cases). We conclude that a policy of chronic treatment with IFN-alpha maintained a significant survival advantage over conventional chemotherapy on a long-term basis and irrespective of the risk. However, the great majority of the long-term survivors were in the low-risk group. The question of treatment discontinuation was not addressed in this study. Copyright 1998 by The American Society of Hematology.

RCT Entities:   Population Interventions Outcomes