Failure of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in a patient with Kostmann syndrome

We present a seven-month-old boy referred to our hospital with a history of recurrent suppurative infections starting in his neonatal period. Anemia, absolute neutropenia absolute neutrophil count (ANC: 500 cells/mu l), pneumonia, purulent otitis media and maturational arrest of granulocytes at promyelocyte-myelocyte level in bone marrow were detected on his admission. He was diagnosed as Kostmann syndrome and recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy was started at a dose of 10 mu g/kg/d, gradually increasing up to 120 mu g/kg/d in sequential seven-day courses. As there was no response, rhG-CSF was stopped and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was started subcutaneously with 2.5 mu g/kg/d and was escalated by doubling the dose every seven days to 20 mg/kg/d, By this therapy absolute neutrophil count (ANC) transiently reached above 500 cells/mu l, but eosinophilia developed with a total white cell count of 88.200 cells/mu l, and a differential count showing 86 percent eosinophils. Since eosinophilia of this magnitude has deleterious effects, and neutrophil production did not significantly increase, we tried combined therapy with rhG-CSF and rhGM-CSF at doses of 10-20 mu g/kg/d and 5-10 mu g/kg/d, respectively, without any effect on absolute neutrophil count. The patient succumbed from sepsis eight months after the diagnosis.