A PHASE-II STUDY OF RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR (RHUG-CSF, LENOGRASTIM) IN THE TREATMENT OF AGRANULOCYTOSIS IN CHILDREN

The present study evaluated the clinical efficacity and tolerability o f the subcutaneous (SC) administration of lenograstim, a glycosylated form of rHuG-CSF identical to human G-CSF, in the treatment of congeni tal agranulocytosis, Assessment criteria included neutrophil response and response stability, incidence and severity of infection and gingiv ostomatitis and quality of life, Lenograstim, at induction dosages of 5 (n = 9), 10 (n = 2) or 20 (n = 1) mu g/kg/day SC, produced neutrophi l recovery in all of 12 children with congenital agranulocytosis, Ther e was a median delay of 7 days to recovery after establishement of the effective induction dose. Whereas this dosage maintained a stable neu trophil response in 7 patients, the remaining 5 required dosage increa ses and dose reduction during maintenance therapy was not possible in these 5 cases, Among 4 patients stabilised at a dosage of 5 mu g/kg/da y, in 2 cases a lower minimum effective dose of 2 mu g/kg/day was atta ined over the maintenance phase. Administration of twice the daily dos e of lenograstim on alternate days was feasible in 3 of 8 patients. Le nograstim therapy reduced the incidence of infection and hospitalisati on for infection relative to the prestudy period, while in 6 of 9 case s there was complete recovery from gingivostomatitis, Only one patient discontinued treatment on account of adverse events. Finally, perceiv ed health and disease related symptoms showed a significant (p < 0.001 ) amelioration in the course of the study. Thus, lenograstim produced sustained neutrophil recovery in patients with congenital agranulocyto sis, decreased the incidence and severity of infection and improved th e quality of life.