A EUROPEAN PHASE-II STUDY OF RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR (LENOGRASTIM) IN THE TREATMENT OF SEVERE CHRONIC NEUTROPENIA IN CHILDREN

We conducted a multicentre, open-label prospective study to evaluate t he efficacy and tolerability of lenograstim (human-identical glycosyla ted rHuG-CSF) in the prevention of infectious episodes of severe chron ic neutropenia in 19 patients. The median follow up period was 54.6 mo nths. Lenograstim was administered subcutaneously at a starting dosage of 5 mu g/kg per day. Neutrophil recovery was achieved in all patient s at induction dosages of 5 (n = 15), 10 (rr = 2), 15 (n = 1) or 20 mu g/kg per day (it = 1) and occurred at a median 7 days after therapy i nitiation. 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 hospitalizati on for infection compared with the pre study period and significantly (P < 0.001) improved perceived health and disease-related symptoms. On e patient discontinued treatment because of adverse events (pustulosis ) initially related to lenograstim therapy but not confirmed. One pati ent withdrew by personal choice and was therefore only treated occasio nally. One patient committed suicide after 45 months because of social difficulties. One patient was lost during follow up, and three patien ts 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 pai n, n = 2; increased of alkaline phosphatase, n = 5). Conclusion Lenogr astim produced a sustained neutrophil recovery in patients with severe chronic neutropenia, reduced the incidence and severity of infection, and improved quality of life.