Effect of granulocyte macrophage colony-stimulating factor in a patient with benign systemic mastocytosis

We report the in vitro and in vivo effects of granulocyte macrophage colony stimulating factor (GMCSF), a known inhibitor of in vitro mast cell differ entiation, in a patient with benign, adult-onset systemic mastocytosis. In vitro effects of GM-CSF on bone marrow cultures before the start of treatme nt showed a marked inhibition of mast cell marker expression [tryptase, Kit , and high-affinity IgE receptor (Fc epsilon RI alpha)] at both protein and mRNA levels. Therefore, the patient was treated with daily injections of G M-CSF for 10 weeks. After an initial improvement, increasing worsening of c linical symptoms was noted. and the patient refused further treatment. Lesi onal skin biopsies showed an increase of toluidine blue-positive mast cells , compared with uninvolved skin, with further significant increase after tr eatment. Similar results were obtained on staining for mast cell-specific t ryptase and Kit, as well as for CD1a and Fc epsilon RI alpha. These finding s show that GM-CSF inhibits human bone marrow mast cell differentiation in vitro, and also in mastocytosis. However, GM-CSF apparently enhances recrui tment of mast cell as well as dendritic cell precursors into the tissue dur ing systemic treatment. These findings and the observed adverse clinical ef fects in the present patient male it unlikely that GM-CSF monotherapy will be beneficial for the treatment of mastocytosis.