Long-term safety of treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) in patients with severe congenital neutropenias

Br J Haematol. 1994 Dec;88(4):723-30. doi: 10.1111/j.1365-2141.1994.tb05110.x.


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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Bone Diseases, Metabolic / etiology
  • Bone Marrow / pathology
  • Child
  • Chronic Disease
  • Female
  • Follow-Up Studies
  • Granulocyte Colony-Stimulating Factor / adverse effects*
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Infant
  • Infant, Newborn
  • Infection Control
  • Male
  • Neutropenia / blood
  • Neutropenia / congenital*
  • Neutropenia / therapy*
  • Neutrophils
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Splenomegaly / etiology


  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor