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Vol. 43. Issue 8.
Pages 480-488 (November 2019)
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Vol. 43. Issue 8.
Pages 480-488 (November 2019)
Review
DOI: 10.1016/j.medin.2019.01.009
Cytokine release syndrome. Reviewing a new entity in the intensive care unit
Síndrome de liberación de citocinas. Revisando una nueva enfermedad en la unidad de cuidados intensivos
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Alejandra García Rochea, Cándido Díaz Lagaresb,
Corresponding author
c.diaz@vhebron.net

Corresponding author. Passeig de la Vall d́Hebron 119-129. Hospital Universitario Vall d́Hebron. 3ª planta. Servicio de Medicina Intensiva. CP 08035
, Elena Élezc, Ricard Ferrer Rocad
a Intensive Care Department. SODIR Research Group. Vall d́Hebron University Hospital, Barcelona, España
b Intensive Care Department. SODIR Research Group. Vall d́Hebron University Hospital, Barcelona, España
c Medical Oncology Department. VHIO. Vall d́Hebron University Hospital, Barcelona, España
d Intensive Care Department. SODIR Research Group. Vall d́Hebron University Hospital, Barcelona, España
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Table 1. Immunotherapy for cancer.
Table 2. CRS grading scales.
Table 3. Diagnostic criteria for sCRS.
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Abstract

Immunotherapy seeks to harness the power of the immune system to eradicate malignant tissues. Despite impressive therapeutic success, however, it can be accompanied by severe adverse effects such as cytokine release syndrome (CRS). These therapies cause the release of a great amount of cytokines, with IL-6 playing a central role, that can potentially lead to multiple organ dysfunction. The diagnosis is based on the presence of compatible clinical symptoms, elevated biomarkers and recent treatment with a biological agent. Mild cases can be managed through symptomatic treatment and fluids, while more severe episodes may need supportive therapy and specific care with the anti-IL-6 receptor monoclonal antibody tocilizumab. Although corticosteroids are also effective, they suppress T-cell activity, and so should only be considered as second line therapy or in cases of severe neurological involvement, since tocilizumab does not cross the blood-brain barrier. Cytokine release syndrome generally has a good prognosis, often being reversible and with a good response to specific treatment. Despite possible concerns about the admission of such patients (mainly with advanced oncological disease), we consider that the Intensive Care Unit should remain an option, since these individuals present a potentially reversible drug-related adverse event and are being treated with a new drug that could change the prognosis of the disorder. Intensive care medicine will become a key component in the management of the complications of modern cancer therapies, dealing with patients presenting an overactive immune system producing organ dysfunction while also trying to maintain treatment efficacy. This is the new paradigm.

Keywords:
Cytokine release syndrome
Cancer
Immunotherapy
Resumen

La inmunoterapia potencia el sistema inmunitario para erradicar las células malignas. A pesar de mostrar un importante éxito terapéutico, puede ir acompañada de efectos adversos graves, como el síndrome de liberación de citocinas. Dichas terapias pueden causar la liberación de importantes cantidades de citocinas, siendo IL-6 el mediador principal, e inducir un cuadro de disfunción multiorgánica. El diagnóstico se basa en la presencia de síntomas clínicos compatibles, elevación de biomarcadores y tratamiento reciente con un agente biológico. Los casos leves se pueden manejar con tratamiento sintomático y fluidoterapia, mientras que los episodios graves necesitarán tratamiento de soporte y específico con tocilizumab, un anticuerpo monoclonal anti-receptor de IL-6. Los corticoides, aunque efectivos, suprimen la actividad de las células T, por lo que su uso se considera de segunda línea o en afectación neurológica grave, ya que tocilizumab no cruza la barrera hematoencefálica. A pesar de que puedan existir dudas sobre el ingreso en unidades de críticos de estos pacientes, principalmente con enfermedad avanzada, consideramos que podrían beneficiarse del ingreso en las UCI, ya que se trata de pacientes con un evento adverso potencialmente reversible, recibiendo un nuevo fármaco que podría cambiar el pronóstico de su enfermedad. La medicina intensiva es clave en el manejo de las complicaciones de las nuevas terapias oncológicas, tratando pacientes con un sistema inmunitario excesivamente activado mientras se intenta preservar la eficacia del tratamiento. Este es el nuevo paradigma.

Palabras clave:
Síndrome de liberación de citocinas
Cáncer
Inmunoterapia

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