Results and follow-up of a phase III randomized study of recombinant human-granulocyte stimulating factor as support for immunosuppressive therapy in patients with severe aplastic anaemia


Professor E. Gluckman, Hôpital Saint-Louis, Department of Hematology and Bone Marrow Transplantation, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France. E-mail:


Summary. In patients with idiopathic severe aplastic anaemia who are treated with immunosuppressive agents to combat T lymphocyte-mediated destruction of haematopoietic progenitor cells, neutropenia is a major cause of infections and toxicity. Evidence from preliminary studies suggests that recombinant human glycosylated granulocyte colony-stimulating factor (lenograstim) increases the number and functionality of neutrophils in patients with severe aplastic anaemia. This randomized, parallel-group, multicentre study was conducted to evaluate the efficacy and safety of subcutaneous lenograstim during the first 12 weeks of standard immunosuppressive therapy in 102 patients with de novo severe aplastic anaemia. The addition of lenograstim to standard therapy resulted in an increase in the proportion of patients showing complete neutrophil response (83·0%vs 44·9%; P < 0·0001). This was seen even among patients with very severe aplastic anaemia (69·2%vs 31·6%; P = 0·012). In patients receiving lenograstim, median time to complete neutrophil response was shorter (6·3 vs 16·1 weeks; P = 0·0001) and mean duration of first neutrophil response was longer (P = 0·0248) than in the control group. At a median follow-up of 5 years, no difference was observed between the groups in term of survival, haematological response and occurrence of secondary leukaemia (one patient in each group). We conclude that lenograstim support of immunosuppressive therapy might be used for patients with severe aplastic anaemia as it significantly enhances neutrophil recovery but does not modify the overall response and survival.