title: 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.
abstract: 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.
authors.affiliation: Service d'Hémato-Oncologie Pédiatrique, Hôpital Trousseau, Paris, France. jean.donadieu@trs.ap-hop-paris.fr
authors.forename: Jean
authors.initials: J
authors.lastname: Donadieu
authors.forename: Thierry
authors.initials: T
authors.lastname: Leblanc
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bader Meunier
authors.forename: Mohamed
authors.initials: M
authors.lastname: Barkaoui
authors.forename: Odile
authors.initials: O
authors.lastname: Fenneteau
authors.forename: Yves
authors.initials: Y
authors.lastname: Bertrand
authors.forename: Micheline
authors.initials: M
authors.lastname: Maier-Redelsperger
authors.forename: Marguerite
authors.initials: M
authors.lastname: Micheau
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Stephan
authors.forename: Noel
authors.initials: N
authors.lastname: Phillipe
authors.forename: Pierre
authors.initials: P
authors.lastname: Bordigoni
authors.forename: Annie
authors.initials: A
authors.lastname: Babin-Boilletot
authors.forename: Philippe
authors.initials: P
authors.lastname: Bensaid
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Manel
authors.forename: Etienne
authors.initials: E
authors.lastname: Vilmer
authors.forename: Isabelle
authors.initials: I
authors.lastname: Thuret
authors.forename: Stephane
authors.initials: S
authors.lastname: Blanche
authors.forename: Eliane
authors.initials: E
authors.lastname: Gluckman
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Françoise
authors.initials: F
authors.lastname: Mechinaud
authors.forename: Bertrand
authors.initials: B
authors.lastname: Joly
authors.forename: Thierry
authors.initials: T
authors.lastname: Lamy
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Bruno
authors.initials: B
authors.lastname: Cassinat
authors.forename: Christine
authors.initials: C
authors.lastname: Bellanné-Chantelot
authors.forename: Christine
authors.initials: C
authors.lastname: Chomienne
mesh_terms: 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
chemical_list: D016179:Granulocyte Colony-Stimulating Factor