Treatment of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor. A phase I-II trial.

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.