Bloodstream infections exacerbate incidence and severity of symptomatic glucocorticoid-induced osteonecrosis.
Pediatr Blood Cancer
; 66(6): e27669, 2019 06.
Article
en En
| MEDLINE
| ID: mdl-30758124
ABSTRACT
BACKGROUND:
Osteonecrosis is a common toxicity associated with glucocorticoid (e.g., dexamethasone and prednisone) treatment of children with acute lymphoblastic leukemia (ALL), but risk factors are incompletely defined. Infections are also a common complication of ALL therapy. Lipopolysaccharide (LPS) is used experimentally to mimic infection-related systemic effects. To our knowledge, the contribution of systemic infections to the risk of glucocorticoid-induced osteonecrosis has not been investigated. PROCEDURE Patients with ALL on St. Jude Total Therapy XV (n = 365) were assessed for documented bacteremia prior to development of osteonecrosis, which was confirmed by MRI, and graded using the National Cancer Institute's Common Terminology for Adverse Events (version 3.0). In a preclinical model, Balb/cJ mice treated with dexamethasone plus or minus LPS were assessed for frequency and severity of osteonecrosis and arteriopathy.RESULTS:
We found that patients with ALL who experienced bacteremia had a higher frequency of symptomatic osteonecrosis (≥grade 2) than those who did not (OR 1.88; 95% CI, 1.03-3.41, P = 0.038). LPS exacerbated experimental dexamethasone-induced osteonecrosis. Mice treated with dexamethasone plus LPS had a higher incidence of osteonecrosis (P = 0.00086) and arteriopathy (P = 0.0047) than did those treated with dexamethasone alone, and the severity of osteonecrosis (P = 0.00045) and arteriopathy (P = 0.0048) was also more pronounced with the addition of LPS treatment. The increase in osteonecrosis was not explained by any alteration of dexamethasone pharmacokinetics by LPS.CONCLUSIONS:
These data identify systemic infection during ALL therapy as a novel risk factor in the development of glucocorticoid-induced osteonecrosis.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Osteonecrosis
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Índice de Severidad de la Enfermedad
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Dexametasona
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Bacteriemia
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Antineoplásicos Hormonales
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
Tipo de estudio:
Diagnostic_studies
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Animals
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Child
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Humans
/
Male
País/Región como asunto:
America do norte
Idioma:
En
Revista:
Pediatr Blood Cancer
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
/
PEDIATRIA
Año:
2019
Tipo del documento:
Article