Idiopathic chronic
neutropenia (ICN) describes a heterogeneous group of
hematologic diseases characterized by low circulating neutrophil levels often associated with recurrent
fevers, chronic mucosal
inflammation, and severe systemic
infections. The severity and risk of complications, including serious
infections, are inversely proportional to the absolute neutrophil count (ANC), with the greatest problems occurring in patients with an ANC of less than 0.5 × 109/L. This case report describes a 64-year-old female with longstanding
rheumatoid arthritis who subsequently developed ICN with frequent episodes of
sepsis requiring hospitalization and prolonged courses of
antibiotics over a 4-year period. She was treated with granulocyte
colony stimulating factors (
G-CSF) but had a delayed, highly variable, and volatile response. She was enrolled in a clinical trial evaluating the oral investigational agent ezatiostat. Ezatiostat, a
glutathione S-transferase P1-1 inhibitor, activates Jun
kinase, promoting the growth and maturation of hematopoietic progenitor stem cells. She responded by the end of the first month of treatment with stabilization of her ANC (despite tapering and then stopping
G-CSF), clearing of
fever, and healing of areas of
infection. This ANC response to ezatiostat treatment has now been sustained for over 8 months and continues. These results suggest potential roles for ezatiostat in the treatment of patients with ICN who are not responsive to
G-CSF, as an oral
therapy alternative, or as an adjunct to
G-CSF, and further studies are warranted.