Recombinant human GM-CSF: present clinical results and potential use in oncologic and hematologic disorders.

The human recombinant GM-CSF (hrGM-CSF) is a glycosylated hematopoietic growth factor, derived from CHO cells (Schering Plough/Sandoz) used in these studies. The hrGM-CSF can be given intravenously (i.v.) in 4- to 24-h infusions or subcutaneously (scx) once or twice a day. Many patients (more than a thousand) have been treated with the hrGM-CSF in various pathologies, in association with anti-cancer chemotherapy, after bone marrow transplants or for myelodysplasias, refractory anemias, some neutropenias and infections. The reversion of neutropenia is dose-dependent with either a sc or i.v. administration. Recommended doses are from 5.0 to 10.0 micrograms/kg/per day. When the product is given sc the effect is delayed by one day but is more prolonged than with the i.v. route. The treatment duration has been investigated in different studies: a minimal duration of 5 days seems appropriate. When given in association with high doses of cytotoxic chemotherapeutic agents 10 to 14 days are required. In bone marrow transplants (autologous or allogenic with T-cell depletion), the hrGM-CSF has been shown to significantly reduce the time necessary for engraftment. Contrary to some fears, it was not shown that hrGM-CSF increased the risk of blastic transformation in myelodysplastic syndromes. In association with cytosine-arabinoside a certain number of partial and complete responses have been obtained. The toxic effects of the product are also dose-dependent. At doses greater than 11 micrograms/kg per day, there is a risk of stimulating inflammatory phenomena whereas at lower doses, more moderate side effects (myalgia, fever, injection site reaction) occur in only 30% of the cases. The GM-CSF will certainly be important in the future in haematology, oncology and for the treatment of infectious diseases.