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.