Bone marrow biopsy and aspirate evaluation in 90 patients with Essential Thrombocythemia treated with PEG interferon alpha-2b. Preliminary results

Ninety patients with Essential Thrombocythemia (ET) where object of a phase II prospective multicentre study designed to evaluate efficacy, safety and tolerability of a two years treatment with PEG Interferon -2b (PEG Intron, Schering Plough). The patients, 30 M and 60 F, 18–72 years old (median 45), observed in 16 Hematological Institutions of the Gruppo Italiano Malattie Mieloproliferative Croniche (GIMMC), received the ET diagnosis according to the PVSG criteria. At PEG Intron treatment start the patients showed: previous cytoreduction 97% (IFN 31%), platelet count >1000 x 109/L 81%, splenomegaly 22%. At the end of the first year The PEG Intron starting dose of 25 µg/week resulted increased to a mean value of 55 µg/week and the Hematological Response (HR = Plts <500x109/L) was registered in 79% of the patients still on treatment. At the end of second year 65 patient still receiving PEG Intron (mean dose 31 µg/week) showed a maintenance of the HR (66%), a Partial Response (17%) and a Minor Response (17%). By utilizing the data included in the study CRFs we preliminarily evaluated the bone marrow biopsy and aspirate both performed at baseline, after 1 and 2 years in 89 and 86, 79 and 67, 57 and 50 patients, respectively. Data concerning the bone marrow biopsies after 1 year of treatment are reported: BONE MARROW BIOPSY BASELINE % 1 YR % 2 YRS % -------------------------------------------------------------------------------- Cellularity increased 56 51 48 -------------------------------------------------------------------------------- Granulopoiesis increased 51 54 39 -------------------------------------------------------------------------------- Erytropoiesis increased 29 24 23 -------------------------------------------------------------------------------- MK number increased 99 90 84 -------------------------------------------------------------------------------- MK size increased 78 69 62 -------------------------------------------------------------------------------- MK ploidy 54 51 42 -------------------------------------------------------------------------------- MK dystrophy 52 56 59 -------------------------------------------------------------------------------- Fibrosis mild 40 37 46 -------------------------------------------------------------------------------- Fibrosis moderate 7 25 26 The increase of bone marrow fibrosis registered after one year (representative also of second year data) resulted not related to patient gender, age >45 years, platelet count >1000 x109/L, Hb <12 g/dL, splenomegaly, previous IFN treatment, PEG Intron dose >50 µg/week. In conclusion, the present study shows that in ET patients a two years PEG Intron treatment, able to induce and to maintain the Hematological Response in the majority of cases, is associated to a decrease of bone marrow cellularity, granulopoiesis, erytropoiesis, MK number, size and ploidy and, moreover, with an increase of MK dystrophy and of bone marrow fibrosis. These preliminary data on bone biopsy and aspirate will be object of a planned centralized reevaluation by a Panel of Pathologists and Clinicians.