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Vol. 154. Issue 3.
Pages 101-107 (February 2020)
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Vol. 154. Issue 3.
Pages 101-107 (February 2020)
Review
Risk of infection associated with new therapies for lymphoproliferative syndromes
Riesgo de infección asociada a nuevas terapias para el tratamiento de los síndromes linfoproliferativos
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Ibai Los-Arcosa,b, Juan Aguilar-Companya,c,
Corresponding author
juanaguilarcompany@gmail.com

Corresponding author.
, Isabel Ruiz-Campsa,b
a Servicio de Enfermedades Infecciosas, Hospital Universitari Vall d’Hebron, Barcelona, Spain
b Red Española de Investigación en Patologías Infecciosas (REIPI), Instituto de Salud Carlos III, Madrid, Spain
c Servicio de Oncología Médica, Hospital Universitari Vall d’Hebron, Barcelona, Spain
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Table 1. Main drugs of recent introduction in the treatment of lymphoproliferative diseases.
Table 2. Screening of imported infectious diseases prior to the start of a haematology-oncology treatment.
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Abstract

Over the last decade, there have been important developments in the treatment of lymphoproliferative disorders. Apart from conventional chemotherapy, a wide array of therapies have been developed, with different indications. The aim of this review is to evaluate the risk of infection associated with these therapies, as well as establishing prevention recommendations. In all cases, the patient’s underlying disease as well as concomitant or previous therapies have an impact in the risk of infection. Anti-CD20 antibodies (rituximab, ofatumumab and obinutuzumab) have been associated to a higher risk of bacterial and viral infection, as well as reactivation of latent infections and opportunistic infections. Alemtuzumab is associated to severe, protracted immunosuppression. Ibrutinib and acalabrutinib have been linked to bacterial infections (especially respiratory infections), invasive fungal infections and opportunistic infections. Idelalisib carries a higher risk of Pneumocystis jirovecii and infection and cytomegalovirus reactivation. Venetoclax is associated with respiratory infections and neutropenia. Immune checkpoint inhibitors are not directly associated with a higher risk of infection; nevertheless, the use of corticosteroids and immunosuppressants to control immune-related adverse events results in an increase of the risk of infection. Brentuximab, lenalidomide and HDAC inhibitors do not seem to be associated to a higher risk of infections. Although data are scarce, a higher number of infections have been observed with cellular therapies, mostly in patients with more than 3 previous antineoplastic treatments or those receiving tocilizumab or corticosteroids for managing the cytokine release syndrome.

In all patients, we recommend appropriate vaccination, screening for latent infections, and individualized prophylaxis recommendations.

Keywords:
Ibrutinib
Idelalisib
Immune checkpoint inhibitors
Vaccination
Rituximab
Alemtuzumab
Resumen

En la última década se han experimentado grandes cambios en los tratamientos de los síndromes linfoproliferativos. A la quimioterapia convencional se suman ahora un amplio abanico de terapias dirigidas con diferentes indicaciones. El objetivo de esta revisión es evaluar el riesgo de infección asociado a estas terapias, así como tratar de establecer unas recomendaciones de prevención. En todos los casos, la enfermedad de base del paciente, así como los tratamientos concomitantes o los recibidos previamente impactan en el riesgo de infección. Los anticuerpos anti CD20 (rituximab, ofatumumab y obinutuzumab) se asocian a un mayor riesgo de infección bacteriana, vírica y de reactivación de infecciones latentes, así como a infecciones oportunistas. Alemtuzumab se asocia a inmunosupresión grave y mantenida. Ibrutinib y acalabrutinib se asocian a infecciones bacterianas, especialmente respiratorias, infección fúngica invasora e infecciones oportunistas. Idelalisib se asocia a un aumento de la incidencia de neumonía por Pneumocystis jirovecii y reactivación de citomegalovirus (CMV). Venetoclax se asocia a infecciones respiratorias y neutropenia. Los inhibidores de checkpoint inmune parecen no incrementar, por sí mismos, el riesgo de infección; sin embargo, el uso de glucocorticoides e inmunosupresores para controlar efectos adversos inmunorelacionados sí conlleva un aumento del número de infecciones, incluyendo infecciones oportunistas. Brentuximab, lenalidomida y los inhibidores de HDAC no parecen asociarse a un mayor riesgo de infección. Aunque existe poca experiencia en el uso de terapias celulares, se ha observado un mayor número de infecciones en pacientes que han recibido más de 3 tratamientos antineoplásicos previamente, o en aquellos que han requerido tocilizumab o glucocorticoides para el manejo del síndrome de liberación de citocinas.

En todos los pacientes se recomienda una actualización del calendario vacunal, despistaje de infecciones latentes y profilaxis individualizada.

Palabras clave:
Ibrutinib
Idelalisib
Inhibidores del checkpoint inmune
Vacunación
Rituximab
Alemtuzumab

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