The Severe Chronic Neutropenia International Registry: 10-Year Follow-up Report.

Background: The Severe Chronic Neutropenia International Registry (SCNIR) was organized 10 years ago to improve understanding and treatment of the group of rare hematologic disorders causing blood neutrophil counts to be < 500/muL for months or years.

Patients And Methods: Patients now enrolled include those with severe congenital neutropenia (n = 526), cyclic neutropenia (n = 205), idiopathic neutropenia (n = 349), autoimmune neutropenia (n = 68), and other (n = 15). More than 90% (1053 of 1163) of patients in the SCNIR have been treated with granulocyte colony-stimulating factor (G-CSF), median dose 3.33 mug/kg per day.

Results: Granulocyte colony-stimulating factor has reduced the occurrence of infection, hospitalization, and antibiotics and improved patients' quality of life. Most patients have noted few adverse effects with G-CSF treatment. Osteoporosis/osteopenia has been reported in 14% of all patients, and myelodysplastic syndrome and acute myelocytic leukemia have occurred in 57 patients, including severe congenital neutropenia (11.8%; 50 of 422), Shwachman-Diamond syndrome (8.1%; 3 of 37), and 4 others. The SCNIR is an important resource for studies on the genetic and molecular basis for the disorders causing chronic neutropenia.

Conclusion: The findings of mutations in the gene for neutrophil elastase as causing cyclic and congenital neutropenia, the role of mutations in the gene for the G-CSF receptor in the evolution of severe congenital neutropenia to acute myelocytic leukemia, and the importance of apoptosis as the cellular mechanism for several diseases causing severe chronic neutropenia have come from studies on these patients.