Abstract
Objectives
PEG-Interferon alpha 2b (PEG-IFN) is a new formulation of Interferon with a prolonged half-life and can therefore be given once weekly. It has shown efficacy in patients refractory or intolerant to IFN. Within a German multicenter study (SHG CMLIIIA) PEG-IFN (PEG-Intron, Essex) was used in our centre for patients with CML in first chronic phase.
Methods:
17 patients with newly diagnosed bcr-abl positive CML in chronic phase were included in our centre as part of the CML IIIA study. Median age was 42 yrs (range 24 – 78 yrs). After initial cytoreduction with hydroxyurea patients received 3–6 μg/kg PEG-IFN subcutaneously once a week. One patient received additional cytarabine at a dose of 20 mg/m2 10 days per month.
Results:
After 3 months 13/17 patients had a complete hematological response, 3 had a partial hematological response, 1 patient had a hereditary thrombocytopenia and therefor did not fulfill hematological CR criteria. Cytogenetics/FISH after 6 months were available in 12 patients and showed 1 complete cytogenetic response, 3 partial cytogenetic responses, 5 minor cytogenetic reponses and no response in 3 patients. 9 patients remained on PEG-IFN for at least 12 months and showed 2 complete, 1 partial and 2 minor cytogenetic responses and no response in 4 patients. Thus the rate of major cytogenetic responses was 33% at 6 months and at 12 months. PEG-IFN treatment was stopped in 14 patients due IFN-intolerance (n=6), patient decision (n=1), blast crisis (n=2), accelerated phase (n=1) or cytogenetic non-response (n=4). Relevant toxicities included acute pancreatitis in 1 patient, a grand mal seizure in a patient with a history of subdural hematoma, exacerbation of supraventricular tachycardia in 1 patient, transient elevation of GPT in 1 patient and a local abscess at the injection site in 1 patient. All patients experienced fever and flu-like symptoms in the first 4 weeks which gradually improved.
Conclusion:
PEG-IFN at a dose of 3–6 μg/kg was effective in producing complete hematological remissions after 3 months in the majority of patients and showed major cytogenetic responses in one third of patients. However there was a considerable toxicity. Still 53% of patients were able to continue treatment for at least 12 months and 4 of these (44%) are in continuous partial or complete cytogenetic response. This response rate is comparable to the results for conventional IFN in combination with Ara-C from the recent IRIS study. However in the IRIS study only 10.8% remained on IFN compared to 53% in our cohort. For patients able to tolerate this treatment PEG-IFN appears to be a valid alternative to IFN+Ara-C or imatinib in chronic phase CML.
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