PATHOPHYSIOLOGY AND TREATMENT OF SEVERE CHRONIC NEUTROPENIA

Severe chronic neutropenia (SCN) include a heterogeneous group of dise ases characterized by blood neutrophil counts chronically less than 0. 5 x 10(9)/L. In phase I-III studies in SCN patients, treatment with re combinant human granulocyte colony stimulating factor (r-metHuG-CSF; F ilgrastim) resulted in a rise in the absolute neutrophil counts (ANC) to above 1.0 x 10(9)/L associated with a reduction in bacterial infect ions, Long-term treatment with filgrastim up to 8 years demonstrate a sustained ANC response, a significant reduction of the need for intrav enous antibiotics and a dramatic improvement in the quality of life. I n 1994 an international registry for severe chronic neutropenia (SCNIR ) was established to improve care for chronic neutropenia and for furt her understanding the pathophysiology of this rare disease. Three-hund red and ten patients have been enrolled to this registry so far. World wide phase I-III studies with filgrastim and SCNIR provide information on 424 patients with severe chronic neutropenia, Adverse events inclu de the development of acute myeloid leukemia in approximately 7% of th e patients within the cohort of patients with congenital neutropenia ( Kostmann's syndrome) suggesting that congenital neutropenia is a prele ukemic syndrome. None of the patients with cyclic of idiopathic neutro penia developed leukemia suggesting that filgrastim is not involved in the development of leukemia.