Reduction of CFU-GM and circulating hematopoietic progenitors in a subgroup of children with chronic neutropenia associated with severe infections and delayed recovery.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2019
Historique:
received: 17 08 2018
accepted: 01 03 2019
entrez: 15 3 2019
pubmed: 15 3 2019
medline: 18 12 2019
Statut: epublish

Résumé

Myelopoiesis was evaluated in 66 pediatric patients with chronic neutropenia who were positive for anti-neutrophil antibodies (median age at diagnosis: 11 months, median neutrophil count at diagnosis: 419/μl). Other causes of neutropenia were excluded. Bone marrow morphology, clonogenic tests and/or the peripheral blood CD 34+ cell count, and apoptotic rate were evaluated in 61 patients with neutropenia lasting > 12 months or severe infections. The peripheral blood CD 34+ cell count and apoptotic rate were evaluated in five patients with shorter neutropenia. The median follow-up time was 29 months (range 7-180 months). Forty-seven patients (71.2%) had a spontaneous recovery after 7-180 months (median 29 months). The group of patients younger than 24 months at diagnosis (n = 50) had a higher probability of recovery (40/50 vs. 7/16 χ2 p<0.01) with a shorter period of neutropenia (median 26 versus 47 months, Kaplan-Meier analysis p = 0.001). The colony-forming units-granulocyte-macrophage (CFU-GM) were significantly decreased in 26/35 patients (74%) evaluated for clonogenic tests. All patients with normal CFU-GM recovered (9/9 patients); whereas, neutropenia persisted in 12/26 patients with reduced CFU-GM (46%, Pearson χ2 p = 0.02). In 36/55 (65%) patients evaluated by flow cytometry we observed reduced circulating CD34+ cells compared with controls of the same age. An increase in the circulating CD34+ cell apoptotic rate was observed in 28/55 patients (51%). Infections requiring hospitalization were observed in 9/18 (50%; Pearson χ2, p = 0.03) patients with both decreased circulating CD34+ cells and increased CD34+ apoptotic rates. In the group aged < 24 months, we observed a significant correlation between the persistence of neutropenia and decreased circulating CD34+ cells (Pearson χ2 p = 0.008). In conclusion, reduced CFU-GM and circulating hematopoietic progenitors were observed in a subgroup of children with chronic neutropenia who were positive for anti-neutrophil antibodies and had a higher incidence of severe infections and delayed spontaneous remission.

Identifiants

pubmed: 30870474
doi: 10.1371/journal.pone.0213782
pii: PONE-D-18-24311
pmc: PMC6417780
doi:

Substances chimiques

Antigens, CD34 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0213782

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Fabio Timeus (F)

Pediatric Onco-Hematology, Regina Margherita Children Hospital, Turin, Italy.

Nicoletta Crescenzio (N)

Pediatric Hematology, Regina Margherita Children Hospital, University of Turin, Turin, Italy.

Luiselda Foglia (L)

Pediatric Hematology, Regina Margherita Children Hospital, University of Turin, Turin, Italy.

Alessandra Doria (A)

Pediatric Hematology, Regina Margherita Children Hospital, University of Turin, Turin, Italy.

Maria Giuseppina Stillitano (MG)

Pediatric Hematology, Regina Margherita Children Hospital, University of Turin, Turin, Italy.

Emanuela Garelli (E)

Pediatric Hematology, Regina Margherita Children Hospital, University of Turin, Turin, Italy.

Raffaela Mazzone (R)

Biochemistry Laboratory, Regina Margherita Children Hospital, Turin, Italy.

Laura Vivalda (L)

Pediatric Hematology, Regina Margherita Children Hospital, University of Turin, Turin, Italy.

Stefano Vallero (S)

Pediatric Onco-Hematology, Regina Margherita Children Hospital, Turin, Italy.

Ugo Ramenghi (U)

Pediatric Hematology, Regina Margherita Children Hospital, University of Turin, Turin, Italy.

Paola Saracco (P)

Pediatric Hematology, Regina Margherita Children Hospital, University of Turin, Turin, Italy.

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Classifications MeSH