Abstract • 56

Severe chronic neutropenia (SCN) is a heterogenous group of hematological disorders characterized by severe neutropenia with absolute neutrophil counts of less than 500/µl, including congenital neutropenias (CN), cyclic neutropenia (CyN) and idiopathic neutropenia (IN). Since 1987 r-metHuG-CSF (Filgrastim; G-CSF) has been used for the treatment of these patients leading to a benefit for more than ninety percent of SCN patients due to increase in absolute neutrophil counts. By the end of 1998, the Severe Chronic Neutropenia International Registry (SCNIR) had collected data on clinical course, response to and long term safety of G-CSF treatment in 646 SCN patients (CN 310, CyN 131, IN 205) with a maximum follow up of more than 10 years. Data document a different clinical course and treatment response depending on the SCN subtype: There is a refined risk of leukemia for the SCN subtype of congenital neutropenia. All cases (n=30) of MDS/AML have been limited to patients with CN. No cases of MDS/AML have occurred among patients with cyclic or idiopathic neutropenia. In leukemogenesis mutations of the G-CSF receptor seem to play an important role: All patients tested so far (n=9) demonstrated a G-CSF-receptor mutation. Other genetic abnormalities in leukemic cells included monosomy 7 (52%), trisomy 21 (26%) and ras mutations (44%).