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

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.

• Authors: Jean Donadieu, Thierry Leblanc, Brigitte Bader Meunier, Mohamed Barkaoui, Odile Fenneteau, Yves Bertrand, Micheline Maier-Redelsperger, Marguerite Micheau, Jean Louis Stephan, Noel Phillipe, Pierre Bordigoni, Annie Babin-Boilletot, Philippe Bensaid, Anne Marie Manel, Etienne Vilmer, Isabelle Thuret, Stephane Blanche, Eliane Gluckman, Alain Fischer, Françoise Mechinaud, Bertrand Joly, Thierry Lamy, Olivier Hermine, Bruno Cassinat, Christine Bellanné-Chantelot, Christine Chomienne, French Severe Chronic Neutropenia Study Group
• Journal: Haematologica (Haematologica) Vol. 90 Issue 1 Pg. 45-53 (Jan 2005) ISSN: 1592-8721 [Electronic] Italy
• PMID: 15642668 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Granulocyte Colony-Stimulating Factor

Topics

• Acute Disease
• Adolescent
• Adult
• Child
• Child, Preschool
• Female
• Granulocyte Colony-Stimulating Factor (therapeutic use)
• Humans
• Infant
• Infant, Newborn
• Leukemia (epidemiology, genetics)
• Male
• Myelodysplastic Syndromes (epidemiology, genetics)
• Neutropenia (congenital, diagnosis, drug therapy)
• Prospective Studies
• Risk Factors
• Sepsis (mortality, prevention & control)