 visitante ::
identificación
|
|||||||||||||||
|
Buscar | Enviar | Ayuda | Servicio de Bibliotecas | Sobre el DDD | Català English Español | |||||||||
| Página principal > Artículos > Artículos publicados > Characterization of the endotheliopathy, innate-immune activation and hemostatic imbalance underlying CAR-T cell toxicities : |
(Hospital Clínic i Provincial de Barcelona) (Hospital Clínic i Provincial de Barcelona) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Hospital Clínic i Provincial de Barcelona) (Hospital Clínic i Provincial de Barcelona) (Charité Universitätsmedizin Berlin, Germany) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Hospital Clínic i Provincial de Barcelona) (Hospital Clínic i Provincial de Barcelona)
| Fecha: | 2023 |
| Resumen: | Background Chimeric antigen receptor (CAR)-T cell-based immunotherapy constitutes a revolutionary advance for treatment of relapsed/refractory hematological malignancies. Nevertheless, cytokine release and immune effector cell-associated neurotoxicity syndromes are life-threatening toxicities in which the endothelium could be a pathophysiological substrate. Furthermore, differential diagnosis from sepsis, highly incident in these patients, is challenging. Suitable laboratory tools could be determinant for their appropriate management. Methods Sixty-two patients treated with CAR-T cell immunotherapy for hematological malignancies (n=46 with CD19-positive diseases, n=16 with multiple myeloma) were included. Plasma samples were obtained: before CAR-T cell infusion (baseline); after 24-48 hours; at suspicion of any toxicity onset and 24-48 hours after immunomodulatory treatment. Biomarkers of endothelial dysfunction (soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble TNF receptor 1 (sTNFRI), thrombomodulin (TM), soluble suppression of tumorigenesis-2 factor (ST2), angiopoietin-2 (Ang-2)), innate immunity activation (neutrophil extracellular traps (NETs), soluble C5b-9 (sC5b-9)) and hemostasis/fibrinolysis (von Willebrand Factor antigen (VWF:Ag), ADAMTS-13 (A13), α2-antiplasmin (α2-AP), plasminogen activator inhibitor-1 antigen (PAI-1 Ag)) were measured and compared with those in cohorts of patients with sepsis and healthy donors. Results Patients who developed CAR-T cell toxicities presented increased levels of sVCAM-1, sTNFRI and ST2 at the clinical onset versus postinfusion values. Twenty-four hours after infusion, ST2 levels were good predictors of any CAR-T cell toxicity, and combination of ST2, Ang-2 and NETs differentiated patients requiring intensive care unit admission from those with milder clinical presentations. Association of Ang-2, NETs, sC5b-9, VWF:Ag and PAI-1 Ag showed excellent discrimination between severe CAR-T cell toxicities and sepsis. Conclusions This study provides relevant contributions to the current knowledge of the CAR-T cell toxicities pathophysiology. Markers of endotheliopathy, innate immunity activation and hemostatic imbalance appear as potential laboratory tools for their prediction, severity and differential diagnosis. |
| Ayudas: | Instituto de Salud Carlos III PI19/00669 Instituto de Salud Carlos III ICI19/00025 Instituto de Salud Carlos III PI22/00367 "la Caixa" Foundation CP042702 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021-SGR-01118 |
| Nota: | Altres ajuts: Fundació Clínic, Barcelona (HCB/2020/0401); Jazz Pharmaceuticals (IST-16-10355) |
| Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.  |
| Lengua: | Anglès |
| Documento: | Article ; recerca ; Versió publicada |
| Publicado en: | Journal for immunotherapy of cancer, Vol. 11 Núm. 4 (april 2023) , ISSN 2051-1426 |
