The Role of Hemopoietic Cytokines in the Myelodysplastic Syndromes
Hemopoietic cytokines have been used to attempt to improve the cytopenias and to modulate the pathogenetic mechanisms in myelodysplastic syndromes (MDS). Neutropenia has generally been alleviated in 80–90% of MDS patients with G-CSF and GM-CSF therapy in numerous short-term and several long-term trials. A recent multi-institutional Phase III randomized trial of G-CSF vs. observation in RAEB/RAEB-T subtypes of MDS demonstrated that G-CSF caused no alteration in the incidence or rate of evolution to AML. Survival in RAEB-T patients was the same in both groups; however, RAEB patients receiving G-CSF had decreased survival. This effect was apparent only in the increased number of “high-risk” patients in the G-CSF group. Several trials utilizing the combination of GM-CSF plus low dose AraC have demonstrated either good responses, stable disease or disease progression in approximately equal thirds of the patients, with a high degree of treatment-related toxicity. No increased survival was shown compared to prior studies using either agent alone. These data indicate that other approaches are needed to attempt to alter the natural history of MDS. Cytopenias have been modestly improved with IL-3 as have thrombocytopenias in a minor proportion of patients with IL-6 treatment, although substantial toxicity was noted at high doses. Erythropoietin (Epo) in relatively high doses has improved the anemias in only approximately 20–25% of MDS patients. Epo combined with G-CSF has demonstrated erythropoietic synergistic activity and has led to an approximate 40–45% erythroid response rate in MDS. The biologic effects of the hemopoietic cytokines provide a basis for planning current clinical trials in this problematic disease.
This paper will focus on recent advances in attempts to modulate the cytopenias and pathogenetic mechanisms of myelodysplastic syndromes (MDS) by treatment with hemopoietic cytokines. Therapeutic results will be placed in the context of newer clinical and biological approaches for stratifying MDS.
KeywordsAcute Myeloid Leukemia Myelodysplastic Syndrome Recombinant Human Erythropoietin Restriction Fragment Length Polymorphism Erythroid Response
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