-Author name in bold denotes the presenting author
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Clinically Relevant Abstract denotes an abstract that is clinically relevant.

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1735 How Many Patients Have Congenital Neutropenia? a Population-Based Estimation from the Nationwide French Severe Chronic Neutropenia RegistryClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 201. Granulocytes, Monocytes, and Macrophages: Poster II
Hematology Disease Topics & Pathways:
Adult, Diseases, Bone Marrow Failure, Genetic Disorders, Pediatric, Study Population
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Jean Donadieu, MD, PhD1, Blandine Beaupain, MsC2*, Hélène Lapillonne, MD, PhD3*, Odile Fenneteau, PharmD4*, Flore Sicre de Fontbrune5,6,7,8,9,10*, Yves Bertrand, M.D.11,12*, Nathalie Aladjidi, M.D.13,14*, Vincent Barlogis, M.D., Ph.D.15*, Wadih Abou Chahla, M.D.16*, Thierry Lamy, PhD, MD17,18,19, Aline Moignet Autrel, MD20*, Claire Fieschi, MD, PhD21*, Thierry Leblanc, M.D.22,23*, Despina Moshous, MD, PhD24,25*, Jean Soulier, MD, PhD26,27, Sarah cohen Beaussant28*, Francois Delhommeau, MD, PhD29*, Helene Cavé, PharmD, PhD30*, Catherine Paillard, MD, PhD31*, Elodie Gouache, MD32*, Fares bou Mitri28*, Damien Bonnet33*, Laurence Olivier Faivre34*, Philippe Labrune, MD, PhD35*, Marlène Pasquet, M.D., Ph.D.36*, Virginie Gandemer, MD, PhD37,38*, Nizar Mahlaoui, MD39*, Karl Balabanian40*, Francoise Bachelerie, PhD41* and Christine Bellanne-Chantelot, PhD, PharmD42,43*

1Service d'Hémato-Oncologie Pédiatrique, Hopital Trousseau, Paris, Cedex, France
2Registre des Neutropénies, Hopital Trousseau, AP-HP, Paris, France
3Pediatric Hematology and Oncology Department, Hôpital Armand Trousseau, Paris, France
4Laboratoire d’Hématologie, APHP, Hôpital Robert Debré,, Paris, France
5Hematology and transplantation unit, Saint-Louis Hospital, Paris, France
6Hématologie greffe, Hôpital Saint-Louis, Paris, France
7Centre de Référence Aplasie Médullaire, Service d’Hématologie Greffe, Assistance Publique des Hôpitaux de Paris, Hôpital Saint-Louis, Paris, France
8St-Louis Hospital, APHP, Bone Marrow Transplantation Unit, Paris, France
9Bone-marrow transplantation department, CHU Saint-Louis, Paris, France
10Transplantation Unit, Saint Louis Hospital, APHP, University Paris VII, Paris, France
11Institute of Pediatric Hematology and Oncology, Civil Hospital of Lyon, Claude Bernard University, Lyon, France
12Claude Bernard University, Lyon 1, Lyon, France
13Centre de Référence National des Cytopénies Auto-immunes de l'Enfant (CEREVANCE), Bordeaux, France
14Pediatric Oncology Hematology Unit, Plurithématique CIC (CICP), Centre d’Investigation Clinique (CIC) 1401, INSERM, Bordeaux University Hospital, Bordeaux, France
15Department of Pediatric Hematology, La Timone Hospital, AP-HM, Marseille, France
16Department of Pediatric Hematology, Jeanne de Flandre Hospital, CHRU de Lille, Lille, France
17UMR U1236, Rennes, France
18INSERM CIC 1414, Hospital Pontchaillou, Rennes, France
19Department of Hematology, Rennes University Hospital, Rennes, France
20Clinical Hematology Department, Rennes CHU, Rennes, France
21Service d’Immunologie clinique, Hôpital Saint-Louis, AP-HP, Paris, France
22Pediatric Hematology Unit, Robert-Debré Hospital, AP-HP, Paris, France
23French Reference Center for Aplastic Anemia, Paris, France
24Department of Pediatric Immunology, Hematology and Rheumatology, Necker Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
25INSERM UMR 1163, Laboratory of Genome Dynamics in the Immune System, Equipe Labellisée Ligue contre le Cancer, Paris, France
26INSERM U944, Institut Universitaire d'Hématologie, Hopital Saint-Louis, Paris, France
27Hematology Laboratory and INSERM U944, Hopital Saint-Louis Centre Hayem 2ETG, Paris, France
28Centre de référence des neutropénies chroniques Registre des neutropenies, Hopital Trousseau, Paris, France
29APHP, Hôpital Saint Antoine, Service d'hématologie Biologique, Paris, France
30UMRS 1131, Institut de Recherche Saint-Louis, Inserm, University of Paris, Paris, France
31Pediatric Hematology Department, Strasbourg University Hospital, Strasbourg, France
32Pediatric hematology department, Trousseau hospital, APHP, Paris, France
33Centre de Référence Malformations Cardiaques Congénitales Complexes - M3C, Necker Enfants Malades Université de Paris, Paris, FRA
34Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD, Hôpital d'Enfants, Dijon, France, CHU Dijon, DIJON, France
35Service de Pédiatrie Centre de référence des glycogénoses, APHP Hopital Beclere, CLAMART, France
36Pediatric Oncology Immunology Hematology Unit, Children’s hospital, CHU de Toulouse, Toulouse, France
37CHU Hopital Sud, Rennes, FRA
38CNRS UMR 6290 Institut de Génétique et Développement de Rennes, Rennes, France
39CEREDIH, Grp Hosp. Necker-Enfants Malades, Paris, France
40Université de Paris, Saint Louis Research Institute, EMiLy, Inserm U1160, Paris, FRA
41Immunologie 92296 Châtenay-Malabry, Université Paris Saclay Faculte de Pharmacie Inserm U996, Clamart, FRA
42Hopital Pitié Salpétriére APHP, Département de Génétique, AP-HP Hôpital Pitié- Salpêtrière, UPMC Univ Paris 06, Paris, France
43Département de Neurologie, Hôpital Pitié-Salpêtrière, Paris, France

Introduction: Congenital neutropenia (CN) is characterized by chronic neutropenia caused by a constitutional genetic defect and can be considered an orphan disease. Nationwide estimations of its incidence and prevalence are poorly documented but would provide key information to better follow-up of CN patients. Notably, orphan-drug status also is accorded based on such epidemiological parameters.

Methods: The French Severe Chronic Neutropenia Registry (FSCNR) has prospectively enrolled CN patients since 1993, with multiple source verifications in France of that information: pediatric and adult hemato-immunology units, diagnostic labs... We also actively collect all cases followed in France, regardless of the healthcare facility monitoring the patient. To calculate incidence at birth, we considered subjects born between 1/1/1995 and 12/31/2017, because information completeness has been validated for this 22-year period. Number of births per year was provided by the French National Institute of Statistics and Economic Studies (INSEE). We used American College of Medical Genetics class 4 and 5 variants for genetic classification and the overall CN classification developed elsewhere.1 To estimate expected prevalence, we assumed 50-year life expectancy for these patients and compared ongoing enrolment to the prevalence estimation and calculated FNSCR coverage. A Poisson distribution was assumed.

Results: On 15 July 2020, the FSCNR had identified 3205 patients. Reasons for non-enrolment of 2096 were, mainly: autoimmune neutropenia (n=501), foreign residency (n=214), other diagnosis (n=882) and diagnostic work-up not completed (n=249). Among the 1109 patients who fulfilled Chronic Neutropenia criteria, 242 had idiopathic neutropenia2 and 867 patients were considered to have CN1. Global results are presented in Table 1. In France, the CN incidence at birth (all subtypes combined) was 2.6×10–5 (95% CI: 2.04–2.8×10–5), which represents a mean of 23 new cases/year in a country with ~870,000 births/year.

For all CN combined, the expected prevalence, assuming 50-year life expectancy, would be 1131 cases in a country of 65×106 inhabitants while the FCSNR currently has 867 cases enrolled or an estimated 77% nationwide coverage. Based on our results and our assumptions for life expectancy, estimated prevalence of CN for 10 millions inhabitants is therefore 174 CN.

Genetic subtype representation is as follows: 20% SBDS, 17% ELANE (8% cyclic, 9% permanent), 9% GATA2, 7% SLC37A4, ~4–5% each of TAZ and CXCR4 and VPS13B, while the other subtypes are even rarer. At present, no cause has been identified for 25% of the cases.

Conclusion: The results of this analysis provide an estimation of the major CN-descriptive epidemiological parameters and the relative frequencies of several subtypes. Despite the FSCNR’s quite large registry, we estimate that about a quarter of the prevalent cases in France were missed, mainly those followed as adults.


1 Donadieu J, Beaupain B, Fenneteau O, Bellanne-Chantelot C. Congenital neutropenia in the era of genomics: classification, diagnosis, and natural history. Br.J.Haematol. 2017; 179(4): 557-574.

2 Sicre De Fontbrune F, Moignet A, Beaupain B et al. Severe chronic primary neutropenia in adults: report on a series of 108 patients. Blood 2015; 126(14): 1643-1650.

Acknowledgments: The French SCN registry is supported by grants from Amgen, Chugai, Prolong Pharma, X4 Pharma, Inserm, the Association 111 les Arts, the Association RMHE, the Association Sportive de Saint Quentin Fallavier. The authors thank the association IRIS and Mrs Grosjean and Mr Gonnot(ASSQF), the association Barth France for their support.

Disclosures: Sicre de Fontbrune: Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. cohen Beaussant: X4 Pharmaceuticals, Inc.: Current Employment.

*signifies non-member of ASH