HEMATOPOIETIC GROWTH-FACTORS FOR THE TREATMENT OF MYELODYSPLASTIC SYNDROMES

Administration of recombinant human granulocyte colony-stimulating fac tor (rhG-CSF), rh granulocyte-macrophage colony-stimulating factor (rh GM-CSF) or rh interleukin-3 (rhIL-3) effectively stimulate and expand marrow myelopoiesis resulting in a dose-dependent increment of periphe ral blood neutrophils in most patients with myelodysplasias (MDS). Cli nical outcome with fewer infections have been reported in a few studie s using rhG-CSF or rhGM-CSF, including a large randomized, controlled trial with rhGM-CSF. Clinical effective stimulation of megakaryopoiesi s and erythropoiesis are however infrequent. Recently, rh erythropoiet in (rhEpo) has been used to overcome the ineffective erythropoiesis in MDS to reduce transfusions needed. However, the efficiency has been l ow in most studies with marked differences in response rates. The most impressive clinical results were obtained in patients with milder for ms of MDS combined with low prestudy endogenous S-Epo levels. The poss ible synergistic effect of combining rhEpo with rhG-CSF or rhGM-CSF ha s been studied with erythropoietic response rates of about 40%. The sa fety of the cytokine administration seems acceptable with no significa nt stimulation of leukemic myelopoiesis and subsequent progression int o overt acute myeloid leukemia. in conclusion, combinations of hematop oietic growth factors may be of clinical benefit in some patients with MDS. However, due to the cost and inpredictable clinical outcome ther e is a need for extended laboratory research to understand the functio nal defects of MDS stem cells and progenitors.