Long-term safety of treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) in patients with severe congenital neutropenias.
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.
Bonilla
M A
MA
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York.
Dale
D
D
Zeidler
C
C
Last
L
L
Reiter
A
A
Ruggeiro
M
M
Davis
M
M
Koci
B
B
Hammond
W
W
Gillio
A
A
Welte
Karl
K
D000293:Adolescent; D000328:Adult; D001851:Bone Diseases, Metabolic / Q000209:etiology; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017053:Infection Control; D008297:Male; D009503:Neutropenia / Q000097:blood / Q000151:congenital* / Q000628:therapy*; D009504:Neutrophils; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013163:Splenomegaly / Q000209:etiology
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor