In Essential Thrombocythemia (ET) patients the optimised pharmacokinetics of the weekly administered pegilated Interferons a (IFN) may increase the compliance to a long-lasting IFN treatment. This phase II study has been designed to evaluate in ET patients efficacy, safety and tolerability of a treatment with Peg Interferon a- 2b (Peg Intron, Schering-Plough). The major objective was to measure the Hematological Response rate (HR = PLTs < 500 x 109/L) after one year of treatment with Peg Intron. Since December 2000, in 16 Hematological Institutions of the Gruppo Italiano Malattie Mieloproliferative Croniche (GIMMC) the Peg Intron treatment has been started in 90 ET patients, 30 Males and 60 Females, median age 45 years (18-72), pretreated with alkylating agents (8%), Hydroxyurea (47%), IFN alpha (30%), Anagrelide (7%) and antiaggregating drugs (93%). At baseline the patients showed: age over 60 (17%), previous thrombosis (7%), platelet count > 1000 x 109/L (81%), peripheral granulocyte precursors (9%), splenomegaly (22%), mean platelet count 1112 x 109/L, mean Hb level 13.4 g/dl, mean WBC count 9.2 x109/L. The median treatment duration was 45 weeks. The initial very low dose of 25 mg/week was scheduled to be increased to 50, 75 and 100 mg/week if the HR was not reached at weeks 13, 26 and 39 respectively . At weeks 13, 26, 39 and 52 the mean platelet count was decreased to 59%, 48%, 44% and 43% of the baseline respectively, the Hematological Response was obtained in 17%, 50%, 72% and 67% of cases as Intention to treat (ITT), while in the patients really receiving Peg Intron the response was reached in 15/88 pts (17%), 45/84 pts (54%), 57/72 pts (79%) and 43/56 pts (77%) respectively. The increase of Peg Intron dose has been performed at weeks 13, 26 and 39 in 83%, 46% and 29% of patients respectively. Dose reduction and transitory interruption of Peg Intron was registered in 7 (8%) and 10 (11%) pts respectively. A drug withdrawal occurred in 8 patients (1 blastic transformation, 2 patient refusal, 2 neurotoxicity, 1 protocol violation, 1 hypertransaminasemia, 1 thyroid cancer ). The toxicity of Peg Intron was WHO grade III (1 case of leukopenia and 1 case of hypertransaminasemia), WHO grade II (mainly represented by leukopenia (9%) and flu-like syndrome (5%)), WHO grade I (mainly as injection syte inflammmation (44%), flu-like syndrome (31%), leukopenia (28%), hypertransaminasemia (14%) and anemia (9%)). Eight patients showed significant alteration of the laboratory thyroid parameters, in 3 cases requiring Peg Intron dose reduction. These preliminary data show that Peg Intron at low dose (median 50 mg/week) is able to induce the Hematological Response in the majority of ET patients, with acceptable safety and toxicity
