BACKGROUND AND OBJECTIVES: The two main complications of severe chronic 
neutropenia are fatal sepsis and myelodysplasia/acute leukemia (MDS/AL). 
Granulocyte colony-stimulating factor (G-CSF) therapy has significantly reduced 
the frequency and severity of infections, but its possible influence on the risk 
of malignancy is not known.
DESIGN AND METHODS: The French Severe Chronic Neutropenia (SCN) Registry has 
prospectively collected data since 1994 on 231 patients with various forms of 
SCN, namely severe congenital neutropenia (n=101), cyclic neutropenia (n=60), 
glycogen storage disease type Ib (GSDIb) (n=15) and Shwachman-Diamond syndrome 
(SDS)(n=55). The median overall follow-up is 11.1 years. Parameters of exposure 
to G-CSF therapy, such as the time averaged dose, follow up after first use of 
G-CSF, and the cumulative dose, have been recorded.
RESULTS: Eight septic deaths occurred, of which 6 among patients with severe 
congenital neutropenia and 2 in patients with cyclic neutropenia; none of these 
8 patients was receiving G-CSF therapy. No septic deaths occurred during G-CSF 
therapy. Thirteen cases of MDS/AL were recorded. The cumulative incidence of 
MDS/AL was 2.7% (SD 1.3%) at 10 years and 8.1% (SD 2.7%) at 20 years.
INTERPRETATION AND CONCLUSIONS: Risk factors for MDS/AL were the diagnostic 
category, the severity of neutropenia, younger age at diagnosis, and strong 
exposure to G-CSF. MDS/AL only occurred in patients with severe congenital 
neutropenia and SDS. Owing to their particular susceptibility to infections, 
patients with severe congenital neutropenia had the strongest exposure to G-CSF; 
the risk of leukemia increased with the degree of G-CSF exposure in this 
subgroup.