A European phase II study of recombinant human granulocyte colony-stimulating factor (lenograstim) in the treatment of severe chronic neutropenia in children. Lenograstim Study Group.
We conducted a multicentre, open-label prospective study to evaluate the efficacy and tolerability of lenograstim (human-identical glycosylated rHuG-CSF) in the prevention of infectious episodes of severe chronic neutropenia in 19 patients. The median follow up period was 54.6 months. Lenograstim was administered subcutaneously at a starting dosage of 5 microg/kg per day. Neutrophil recovery was achieved in all patients at induction dosages of 5 (n = 15), 10 (n = 2), 15 (n = 1) or 20 microg/kg per day (n = 1) and occurred at a median 7 days after therapy initiation. Alternate-day administration of double-dose lenograstim was feasible in 7 of 17 patients. Lenograstim treatment significantly (P = 0.012) reduced the incidence of treated infections and hospitalization for infection compared with the pre study period and significantly (P < 0.001) improved perceived health and disease-related symptoms. One patient discontinued treatment because of adverse events (pustulosis) initially related to lenograstim therapy but not confirmed. One patient withdrew by personal choice and was therefore only treated occasionally. One patient committed suicide after 45 months because of social difficulties. One patient was lost during follow up, and three patients presented with a spontaneous neutrophil recovery after 9, 15 and 27 months, respectively. Moderate and transient side-effects related to lenograstim were observed (thrombocytopenia, n = 2; splenomegaly, n = 2; moderate anaemia (without transfusion requirement), n = 5; bone pain, n = 2; increased of alkaline phosphatase, n = 5).


CONCLUSIONS
Lenograstim produced a sustained neutrophil recovery in patients with severe chronic neutropenia, reduced the incidence and severity of infection, and improved quality of life.
Donadieu
J
J
Département de Pédiatrie, Centre Hospitalier d'Orléans, France.
Boutard
P
P
Bernatowska
E
E
Tchernia
G
G
Couillaud
G
G
Philippe
N
N
Le Gall
E
E
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006410:Hematopoiesis / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007223:Infant; D000078224:Lenograstim; D008297:Male; D009503:Neutropenia / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D009894:Opportunistic Infections / Q000276:immunology / Q000517:prevention & control; D011446:Prospective Studies; D011788:Quality of Life; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim