Patients with severe chronic neutropenia have blood neutrophil level <0.5 × 
10(9)/L, predisposing them to increased susceptibility to life-threatening 
bacterial infections. This chapter focuses on cyclic and congenital neutropenia, 
two very interesting and rare hematological conditions causing severe chronic 
neutropenia. Both disorders respond well to treatment with the myeloid growth 
factor, granulocyte colony-stimulating factor (G-CSF). This chapter describes 
the basic features of these diseases and addresses several current clinical 
issues regarding their diagnosis and management. Cyclic neutropenia is a rare, 
inherited autosomal dominant disorder due to mutations in the gene for 
neutrophil elastase (ELA-2 or ELANE). Usually these patients have regular 
oscillation of blood neutrophil counts with periods of severe neutropenia 
occurring every 21 days. During these periods, they have painful mouth ulcers, 
fevers, and bacterial infections. The most severe consequences are gangrene, 
bacteremia, and septic shock. Cyclic neutropenia patients respond well to 
treatment with granulocyte colony-stimulating factor (G-CSF) given by 
subcutaneous injections on a daily or alternate-day basis. Severe congenital 
neutropenia is also a rare hematological disease, but it is probably more common 
than cyclic neutropenia. Blood neutrophils are extremely low on a continuing 
basis; the levels may be <0.2 × 10(9)/L, and the risk of severe bacterial 
infections is even greater than in cyclic neutropenia. The majority of cases are 
due to autosomal dominant inheritance of mutations in the ELA-2 or ELANE gene. 
Less commonly, mutations in HAX-1, G6PC3, and other genes cause this disorder. 
Treatment with G-CSF is usually effective, but the dose of G-CSF required to 
normalize blood neutrophils varies greatly. Ten to thirty percent of severe 
congenital neutropenia patients evolve to develop acute myeloid leukemia, 
necessitating careful clinical monitoring.