In vivo administration of granulocyte‐macrophage colony stimulating factor enhances neutrophil function in patients with myelodysplastic syndromes

Abstract

We studied the long-term in vivo effects of recombinant granulocyte-macrophage colony stimulating factor (rhGM-CSF) on granulocyte functions in nine patients with myelodysplastic syndrome (MDS). The treatment schedule consisted of a 14 d course of rhGM-CSF (250 micrograms/m2/d s.c.) for patients with refractory anaemia (RA) and refractory anaemia with ringed sideroblasts (RARS), while patients with refractory anaemia with excess of blasts (RAEB) and refractory anaemia with excess blasts in transformation (RAEBt) received a 14 d combination course of rhGM-CSF (250 micrograms/m2 s.c.) and low dose cytosine arabinoside (20 mg/m2 s.c.). rhGM-CSF increased the mean neutrophil count from 3.9 x 10(9)/l to 44 x 10(9)/l. Significant increases of myeloperoxidase content in granulocytes occurred during treatment (P = 0.003). Phagocytosis and killing of Staph. aureus by granulocytes was markedly enhanced during treatment. Microbicidal capacity normalized in four out of six patients during GM-CSF therapy. However, chemotaxis in response to zymosan-activated serum (ZAS) and f-Met-Leu-Phe (f-MLP), was further impaired on the last day of treatment, which was associated with a marked increase in the expression of the granulocyte adhesion receptors CD11a (P = 0.01), CD11b (P = 0.002), CD11c (P = 0.00015) and CD18 (P = 0.0014). GM-CSF therapy did not cause significant changes in hexose monophosphate (HMP)-shunt activity, chemiluminescence, nor superoxide production. The present results show that in vivo administration of GM-CSF is able to repair at least in part the neutrophil anomalies in patients with myelodysplastic syndrome (MDS), which might be useful in modulating host response to infections. However, increased adherence and impaired chemotaxis may explain some toxicities observed during treatment with GM-CSF.