• G-CSF;
  • congenital neutropenia;
  • cyclic neutropenia;
  • Kostmann's syndrome

Summary . Congenital neutropenias include a heterogenous group of diseases characterized by a decrease in circulating neutrophils. In phase I/II/III studies in patients with severe congenital and cyclic neutropenia, treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) resulted in a rise in the absolute neutrophil counts (ANC) and a reduction in infections. We report the effects of long-term safety of subcutaneous r-metHuG-CSF administration in 54 patients (congenital n= 44, cyclic n= 10) treated for 4–6 years. A sustained ANC response was seen in 40/44 severe congenital neutropenia patients and 10/10 cyclic neutropenia patients. Two patients required an increase of > 25% in dose to maintain a clinical response; one patient became refractory to therapy. A significant decrease in the incidence of severe infections and the need for intravenous antibiotics was noted. Significant adverse events noted which may or may not be related to therapy included: osteopenia (n= 15), splenomegaly (n= 12), hypersplenism (n= 1), vasculitis (n= 2), glomerulonephritis (n= 1), BM fibrosis (n= 2), MDS/leukaemia (n= 3), and transient inverted chromosome 5q with excess blasts (n= 1). R-metHuG-CSF has been well tolerated in the majority of patients and resulted in a longterm improvement in their clinical status.