MAINTENANCE TREATMENT OF THE ANEMIA OF MYELODYSPLASTIC SYNDROMES WITHRECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR AND ERYTHROPOIETIN - EVIDENCE FOR IN-VIVO SYNERGY

Patients with myelodysplastic syndromes (MDS) have refractory cytopeni as leading to transfusion requirements and infectious complications. I n vitro marrow culture data have indicated that granulocyte colony sti mulating factor (G-CSF) synergizes with erythropoeitin (EPO) for the p roduction of erythroid precursors. In an effort to treat the anemia an d neutropenia in this disorder, MDS patients were treated with a combi nation of recombinant human EPO and recombinant human G-CSF. Fifty-fiv e patients were enrolled in the study of which 53 (96%) had a neutroph il response. Forty-four patients were evaluable for an erythroid respo nse of which 21 (48%) responded, An erythroid response was significant ly more likely in those patients with relatively low serum EPO levels, higher absolute basal reticuloctye counts and normal cytogenetics at study entry. Seventeen (81%) of the patients who responded to combined G-CSF plus EPO therapy continued to respond during an 8-week maintena nce phase. G-CSF was then discontinued and all patients' neutrophil re sponses were diminished, whereas 8 continued to have an erythroid resp onse to EPO alone. In 7 of the remaining 9 patients, resumption of G-C SF was required for recurrent erythroid responses. The median duration of erythroid responses to these cytokines was 11 months, with 6 patie nts having relatively prolonged and durable responses for 15 to 36 mon ths. Our results also indicate that approximately one half of respondi ng patients require both G-CSF and EPO to maintain an effective erythr oid response, suggesting that synergy between G-CSF and EPO exists in vivo for the production of red blood cells in MDS. (C) 1996 by The Ame rican Society of Hematology.