Recurrent bacterial infections, but not fungal infections, characterise patients with ELANE-related neutropenia: a French Severe Chronic Neutropenia Registry study

Gioacchino A Rotulo (1, 2, 2) , Geneviève Plat (3) , Blandine Beaupain (2, 2) , Stéphane Blanche (4) , Despina Moushous (4) , Flore Sicre de Fontbrune , Thierry Leblanc (5) , Cécile Renard , Vincent Barlogis (6) , Marie-Gabrielle Vigue , Claire Freycon (7) , Christophe Piguet , Marlène Pasquet (3) , Claire Fieschi , Wadih Abou-Chahla , Virginie Gandemer (8, 9) , Fanny Rialland (10) , Frédéric Millot (11) , Aude Marie-Cardine (12) , Catherine Paillard (13) , Pacifique Levy , Nathalie Aladjidi (14) , Martin Biosse-Duplan (15) , Christine Bellanné-Chantelot , Jean Donadieu (2)

1 Therapeia Rehabilitation Center
2 CHU Trousseau [APHP]
3 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
4 Hôpital Necker - Enfants Malades [AP-HP]
5 Hôpital Robert Debré
6 APHM - Assistance Publique - Hôpitaux de Marseille
7 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
8 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
9 IGDR - Institut de Génétique et Développement de Rennes
10 CHU Nantes - Centre Hospitalier Universitaire de Nantes
11 CHU de Poitiers - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
12 CHU Rouen
13 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
14 CHU Bordeaux
15 Hôpital Bretonneau

Among 143 patients with elastase, neutrophil-expressed (ELANE)-related neutropenia enrolled in the French Severe Chronic Neutropenia Registry, 94 were classified as having severe chronic neutropenia (SCN) and 49 with cyclic neutropenia (CyN). Their infectious episodes were classified as severe, mild or oral, and analysed according to their natural occurrence without granulocyte-colony stimulating factor (G-CSF), on G-CSF, after myelodysplasia/acute leukaemia or after haematopoietic stem-cell transplantation. During the disease’s natural history period (without G-CSF; 1913 person-years), 302, 957 and 754 severe, mild and oral infectious events, respectively, occurred. Among severe infections, cellulitis (48%) and pneumonia (38%) were the most common. Only 38% of episodes were microbiologically documented. The most frequent pathogens were Staphylococcus aureus (37·4%), Escherichia coli (20%) and Pseudomonas aeruginosa (16%), while fungal infections accounted for 1%. Profound neutropenia (<200/mm(3) ), high lymphocyte count (>3000/mm(3) ) and neutropenia subtype were associated with high risk of infection. Only the p.Gly214Arg variant (5% of the patients) was associated with infections but not the overall genotype. The first year of life was associated with the highest infection risk throughout life. G-CSF therapy achieved lower ratios of serious or oral infectious event numbers per period but was less protective for patients requiring >10 µg/kg/day. Infections had permanent consequences in 33% of patients, most frequently edentulism.

Mots clés: *ELANE-related neutropenia; *opportunistic infections; *severe congenital neutropenia

Domaines: Sciences du Vivant [q-bio]

Gioacchino A Rotulo, Geneviève Plat, Blandine Beaupain, Stéphane Blanche, Despina Moushous, et al.. Recurrent bacterial infections, but not fungal infections, characterise patients with ELANE-related neutropenia: a French Severe Chronic Neutropenia Registry study. British Journal of Haematology, 2021, 194 (5), pp.908-920. ⟨10.1111/bjh.17695⟩. ⟨hal-03477300⟩