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 long-term improvement in their clinical status.