Severe chronic primary neutropenia in adults: report on a series of 108 patients
Flore Sicre de Fontbrune
(1)
,
Aline Moignet
(2, 3)
,
Blandine Beaupain
(4)
,
Felipe Suarez
(5)
,
Lionel Galicier
(6)
,
Gérard Socie
(7)
,
Bruno Varet
(8)
,
Paul Coppo
(9, 10, 11)
,
Marc Michel
(12)
,
Cécile Pautas
(13)
,
Eric Oksenhendler
(14)
,
Etienne Lengline
(1)
,
Louis Terriou
,
Philippe Moreau
(15)
,
Sylvain Chantepie
,
Nicole Casadevall
(16, 17)
,
Jean Marie Michot
,
Martine Gardembas
,
Mauricette Michallet
(18)
,
Laure Croisille
,
Marie Audrain
(19)
,
Christine Bellanne-Chantelot
(20)
,
Jean Donadieu
(21, 4)
,
Thierry Lamy
(3)
1
Hôpital Saint-Louis
2 CHU Pontchaillou [Rennes]
3 CIC - Centre d'Investigation Clinique [Rennes]
4 CHU Trousseau [APHP]
5 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
6 Service d'Immunopathologie [Hôpital Saint-Louis, Paris]
7 Service d'hématologie greffe [Saint-Louis]
8 CHU Necker - Enfants Malades [AP-HP]
9 UPMC - Université Pierre et Marie Curie - Paris 6
10 Cnr-mat - Centre de référence des microangiopathies thrombotiques [CHU Saint-Antoine]
11 CHU Saint-Antoine [AP-HP]
12 Service de médecine interne [Mondor]
13 Service d'hématologie clinique
14 Département d'Immunologie Clinique
15 CHU Nantes - Centre hospitalier universitaire de Nantes
16 Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine]
17 Hématopoïèse normale et pathologique
18 Service d'hématologie [Hôpital Edouard Herriot - HCL]
19 Laboratoire d'Immunologie
20 Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière]
21 Registre français des neutropénies chroniques sévères
2 CHU Pontchaillou [Rennes]
3 CIC - Centre d'Investigation Clinique [Rennes]
4 CHU Trousseau [APHP]
5 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
6 Service d'Immunopathologie [Hôpital Saint-Louis, Paris]
7 Service d'hématologie greffe [Saint-Louis]
8 CHU Necker - Enfants Malades [AP-HP]
9 UPMC - Université Pierre et Marie Curie - Paris 6
10 Cnr-mat - Centre de référence des microangiopathies thrombotiques [CHU Saint-Antoine]
11 CHU Saint-Antoine [AP-HP]
12 Service de médecine interne [Mondor]
13 Service d'hématologie clinique
14 Département d'Immunologie Clinique
15 CHU Nantes - Centre hospitalier universitaire de Nantes
16 Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine]
17 Hématopoïèse normale et pathologique
18 Service d'hématologie [Hôpital Edouard Herriot - HCL]
19 Laboratoire d'Immunologie
20 Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière]
21 Registre français des neutropénies chroniques sévères
Flore Sicre de Fontbrune
- Function : Author
- PersonId : 776419
- ORCID : 0000-0003-2000-1556
Felipe Suarez
- Function : Author
- PersonId : 758757
- ORCID : 0000-0002-3537-9052
Lionel Galicier
- Function : Author
- PersonId : 762207
- ORCID : 0000-0002-0360-7620
Eric Oksenhendler
- Function : Author
- PersonId : 761987
- ORCID : 0000-0001-8588-7138
Louis Terriou
- Function : Author
Philippe Moreau
- Function : Author
- PersonId : 759214
- ORCID : 0000-0003-1780-8746
Sylvain Chantepie
- Function : Author
- PersonId : 776420
- ORCID : 0000-0003-0457-2252
Jean Marie Michot
- Function : Author
Martine Gardembas
- Function : Author
Laure Croisille
- Function : Author
Abstract
Severe chronic primary neutropenia (CPN) is a rare entity, and long-term outcome and risk factors for infections in severe CPN adults have not been described to date. We report the characteristics and outcomes of 108 severe adult CPN patients enrolled in a multi-institutional observational study. Severe CPN adults were mostly female (78%), and median age at diagnosis was 28.3 years. Diagnosis was fortuitous in 62% of cases. The median absolute neutrophil count (ANC) at diagnosis was 0.4 × 109/L, and median ANC without granulocyte colony-stimulating factor (G-CSF) during follow-up was 0.5 × 109/L. Twenty-three of 66 (34.8%) evaluable patients had neutrophil autoantibodies, and 6 of 47 (12.8%) a T-cell clone. The presence of neutrophil autoantibodies or T-cell clone was not associated with any specific clinical or biological characteristics. No death or hematologic malignancies occurred, and 44 severe bacterial infections were reported in 27 patients with a median follow-up of 8.3 years. Fifty patients received G-CSF either sporadically (n = 24) or continuously (n = 26) and responded (96%). Nineteen patients received immunosuppressive therapies: overall response (OR) was 41%, and median duration of response was 3 months. At diagnosis, the only predictive factor for the occurrence of severe bacterial infections was an ANC count below 0.2 × 109/L (OR, 0.76). Severe CPN in adults is characterized by a female predominance and a benign outcome with a low rate of severe bacterial infections and no secondary malignancies. G-CSF is efficient and well tolerated but is not required in a majority of patients