Chronic Myelogenous Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Chronic-Phase Chronic Myelogenous Leukemia
Long-term follow-up of the interferon-treated patients from a randomized trial comparing interferon with chemotherapy showed that the median survival had not been reached at 10 years for patients who had complete or major cytogenetic responses to interferon. Seventy-four percent of patients with complete cytogenetic responses and 55% of patients with major cytogenetic responses were alive and had shown no disease progression at date of publication (median follow-up time was not provided). Using molecular methods of analysis, however, small numbers of Ph1-positive cells can still be detected in the majority of patients having long-term cytogenetic remissions, and longer follow-up will be required to ascertain whether the disease will recur.
Patients older than 60 years with chronic-phase CML have a hematologic and cytogenetic response rate and duration of cytogenetic response similar to that in younger patients; however, the incidence of complications is greater in elderly patients. Interferon alpha has significant toxic effects that can result in dosage modification or discontinuation of therapy in many cases. A randomized, prospective trial of 407 patients compared two doses of interferon, 5 million units/m² daily versus 3 million units/m² daily; at a median follow-up of 53 months, no difference was seen in OS, progression-free survival, or number of major cytogenetic responses.[Level of evidence: 1iiA] As evidenced in the CLB-9013 study, common side effects included influenza-like syndrome, nausea, anorexia, weight loss, and neuropsychiatric symptoms, all of which were completely reversible with cessation of therapy. (Refer to the PDQ summaries on Nausea and Vomiting and Nutrition for information on some of these side effects.) Immune-mediated complications, such as hyperthyroidism, hemolysis, and connective tissue diseases may occur rarely after long-term treatment. Interferon alpha is quite costly, and daily subcutaneous injections can be troublesome. Pegylated interferon alpha is administered weekly; a randomized, noninferiority trial of 344 newly diagnosed CML patients could not rule out the possibility that pegylated interferon alpha may be slightly inferior to daily interferon alpha.[Level of evidence: 1iiDiv]
Patients whose disease is in cytogenetic remission should continue therapy for at least 2 to 3 years beyond remission, and perhaps indefinitely, as suggested by some investigators. After 1 year, patients with only a partial cytogenetic response should consider alternative therapy with imatinib mesylate or allogeneic BMT or SCT (if eligible). The French Chronic Myeloid Leukemia Study Group randomly assigned 721 patients to interferon and cytarabine versus interferon alone.[Level of evidence: 1iiA] Patients who received the combination had significantly more major cytogenetic responses (41% vs. 24%, P < .001) and improved 3-year survival (86% vs. 80%). Another trial by the Italian Cooperative Study Group on CML did not show a survival benefit for interferon plus cytarabine versus interferon alone.[Level of evidence: 1iiA] Both studies showed increased toxic effects for the combination versus interferon alone.[52,53] Interferon alpha is also effective for patients who have relapsed after allogeneic BMT.[54,55]