Etoposide Therapy of Cytokine Storm Syndromes.
Adv Exp Med Biol
; 1448: 525-551, 2024.
Article
en En
| MEDLINE
| ID: mdl-39117837
ABSTRACT
Etoposide has revolutionized the treatment of primary as well as secondary hemophagocytic lymphohistiocytosis (HLH), and it is, together with corticosteroids, the most widely used therapy for HLH. In the early 1980s, long-term survival in primary HLH was <5% but with the etoposide-/dexamethasone-based protocols HLH-94 and HLH-2004, in combination with stem cell transplantation, 5-year survival increased dramatically to around 60% in primary HLH, and based on analyses from the HLH-2004 study, there is likely room for further improvement. Biologically, etoposide administration results in potent selective deletion of activated T cells as well as efficient suppression of inflammatory cytokine production. Moreover, etoposide has also been reported to promote programmed cell death (apoptosis) rather than proinflammatory lytic cell death (pyroptosis), conceivably ameliorating subsequent systemic inflammation, i.e., a treatment very suitable for cytokine storm syndromes (CSS). The combination of etoposide and corticosteroids may also be beneficial in cases of severe or refractory secondary HLH (sHLH) with imminent organ failure, such as infection-associated HLH caused by Epstein-Barr virus (EBV) or malignancy-triggered HLH. In CSS associated with rheumatic diseases (macrophage activation syndrome, MAS or MAS-HLH), etoposide is currently used as second- or third-line therapy. Recent studies suggest that etoposide perhaps should be part of an aggressive therapeutic intervention for patients with severe refractory or relapsing MAS, in particular if there is CNS involvement. Importantly, awareness of sHLH must be further increased since treatment of sHLH is often delayed, thereby missing the window of opportunity for a timely, effective, and potentially life-saving HLH-directed treatment.
Palabras clave
Critically ill; Cyclosporine A; Cytokine storm syndrome; Dexamethasone; Epstein-Barr virus; Etoposide; Familial hemophagocytic lymphohistiocytosis; Hypercytokinemia; Infection-associated HLH; Macrophage activation syndrome; Malignancy-associated HLH; Multiple organ failure; Rheuma-associated HLH; Secondary hemophagocytic lymphohistiocytosis; Sepsis; Systemic inflammatory response syndrome; Transplant-associated HLH; Treatment
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfohistiocitosis Hemofagocítica
/
Etopósido
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Síndrome de Liberación de Citoquinas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Adv Exp Med Biol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Suecia
Pais de publicación:
Estados Unidos