Effects of Recombinant Human Granulocyte–Macrophage Colony-Stimulating Factor in Patients with Myelodysplastic Syndromes

The myelodysplastic syndromes are characterized by ineffective hematopoiesis and refractory cytopenias. In an attempt to improve hematopoiesis, we administered recombinant human granulocyte–macrophage colony-stimulating factor (GM-CSF) to eight patients with myelodysplastic syndrome, as part of a Phase I trial. The GM-CSF was given by continuous intravenous infusion daily for two weeks and then again after a two-week rest period. Over the entire dose range tested (30 to 500 μg per square meter of body-surface area), treatment was associated with marked increases in peripheral-blood leukocytes (5- to 70-fold), including granulocytes (5- to 373-fold), in all eight patients. The absolute number of monocytes, eosinophils, and lymphocytes increased in all patients. Three of eight patients also had 2- to 10-fold increases in platelet counts and improvement in erythropoiesis, with the result that two of three patients who had required red-cell and platelet transfusions no longer needed them (at 20 to 27 weeks of follow-up). Treatment was also associated with increased marrow cellularity and a decreased percentage of blasts in the bone marrow of patients with excess blasts, resulting in an increase in the ratio of differentiated myeloid cells to immature myeloid cells. We observed relatively few side effects, but bone pain was dose-limiting when it was associated with high white-cell counts. Our results showed that GM-CSF is a potent stimulator of hematopoiesis in vivo and may produce hematologic improvement in the short term (8 to 32 weeks of observation) in patients with myelodysplastic syndrome. More experience, with longer follow-up periods, will be necessary to assess the long-term safety and efficacy of this new treatment. (N Engl J Med 1987; 317:1545–52.) THE myelodysplastic syndromes are a group of stem-cell disorders characterized by maturation defects resulting in ineffective hematopoiesis, refractory cytopenias often leading to infection or hemorrhage, and an increased risk of leukemic transformation. 1 2 3 4 5 6 7 No currently available treatment has been shown to be consistently effective in producing sustained improvement in hematopoiesis or in delaying leukemic evolution. 8 9 10 11 Several agents, including retinoids, vitamin D analogues, and cytotoxic drugs such as low-dose cytarabine have been used to treat patients with myelodysplastic syndrome 9 10 11 12 13 14 15 16 17 18 ; this therapy has been based mainly on the agents' potential for inducing