Stanford University Medical Center, California.
STUDY OBJECTIVE: To determine the hematopoietic effects and toxicity of recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with myelodysplastic syndromes. DESIGN: The G-CSF was administered by daily subcutaneous injection to outpatients in a phase I-II trial. Dose was escalated every 2 weeks between 0.1 to 3.0 micrograms/kg body weight.d over an 8-week treatment period. SETTING: Outpatient clinical research center at a university hospital. PATIENTS: Twelve consecutive patients with myelodysplastic syndromes: two refractory anemia, seven refractory anemia with excess of blasts, three refractory anemia with excess of blasts in transformation. MEASUREMENTS AND MAIN RESULTS: In 10 of 12 patients, elevations in blood leukocyte counts (2- to 10-fold) and absolute neutrophil counts (5- to 40-fold) were seen over the 8-week treatment period. Five of seven severely neutropenic patients (absolute neutrophil count, less than 0.5 x 10(9)/L) had a rise in count to 1.2 to 16.3 x 10(9)/L. Increased reticulocyte counts occurred in 5 patients, and were associated with decreased transfusion requirements in 2 of 9 erythrocyte transfusion-dependent patients. Treatment with G-CSF enhanced marrow myeloid cell maturation in 9 of 11 evaluable patients. Neutrophil chemotaxis and phagocytosis in vitro were improved or unchanged after treatment in 6 of 8 patients tested. In 11 of 12 patients, there were no substantial changes in platelet, lymphocyte, eosinophil, or monocyte counts. Three responding patients initially had abnormal cytogenetics that persisted after G-CSF therapy, suggesting induced differentiation of the abnormal clone. The therapy was associated with minimal toxicity. None of the patients' conditions converted to acute leukemia during treatment or in short-term follow-up. CONCLUSIONS: Treatment with G-CSF administered by subcutaneous injection is well tolerated and effective for improving the neutropenia, and less commonly the transfusion-dependent anemia, over 6 to 8 weeks in patients with myelodysplastic syndromes.