Analysis of risk factors for myelodysplasias, leukemias and death from infection among patients with congenital neutropenia. Experience of the French Severe Chronic Neutropenia Study Group.
OBJECTIVE
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.


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.


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.
Donadieu
Jean
J
Service d'Hémato-Oncologie Pédiatrique, Hôpital Trousseau, Paris, France. jean.donadieu@trs.ap-hop-paris.fr
Leblanc
Thierry
T
Bader Meunier
Brigitte
B
Barkaoui
Mohamed
M
Fenneteau
Odile
O
Bertrand
Yves
Y
Maier-Redelsperger
Micheline
M
Micheau
Marguerite
M
Stephan
Jean Louis
JL
Phillipe
Noel
N
Bordigoni
Pierre
P
Babin-Boilletot
Annie
A
Bensaid
Philippe
P
Manel
Anne Marie
AM
Vilmer
Etienne
E
Thuret
Isabelle
I
Blanche
Stephane
S
Gluckman
Eliane
E
Fischer
Alain
A
Mechinaud
Françoise
F
Joly
Bertrand
B
Lamy
Thierry
T
Hermine
Olivier
O
Cassinat
Bruno
B
Bellanné-Chantelot
Christine
C
Chomienne
Christine
C
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007938:Leukemia / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D009190:Myelodysplastic Syndromes / Q000453:epidemiology* / Q000235:genetics; D009503:Neutropenia / Q000151:congenital* / Q000175:diagnosis / Q000188:drug therapy; D011446:Prospective Studies; D012307:Risk Factors; D018805:Sepsis / Q000401:mortality* / Q000517:prevention & control
D016179:Granulocyte Colony-Stimulating Factor