1. Endothelial activation predicts disseminated intravascular coagulopathy, cytokine release syndrome and prognosis in patients treated with anti-CD19 CAR-T cells
- Author
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Galli, Eugenio, Sora', Federica, Hohaus, Stefan, Fresa, Alberto, Pansini, Ilaria, Autore, Francesco, Metafuni, Elisabetta, Innocenti, Idanna, Limongiello, Maria Assunta, Giammarco, Sabrina, Laurenti, Luca, Bacigalupo, Andrea, Chiusolo, Patrizia, De Stefano, Valerio, Sica, Simona, Eugenio, Galli, Federica, Sora (ORCID:0000-0002-9607-5298), Stefan, Hohaus (ORCID:0000-0002-5534-7197), Alberto, Fresa, Ilaria, Pansini, Francesco, Autore, Elisabetta, Metafuni, Idanna, Innocenti, Luca, Laurenti (ORCID:0000-0002-8327-1396), Andrea, Bacigalupo (ORCID:0000-0002-9119-567X), Patrizia, Chiusolo (ORCID:0000-0002-1355-1587), Valerio, De Stefano (ORCID:0000-0002-5178-5827), Simona, Sica (ORCID:0000-0003-2426-3465), Galli, Eugenio, Sora', Federica, Hohaus, Stefan, Fresa, Alberto, Pansini, Ilaria, Autore, Francesco, Metafuni, Elisabetta, Innocenti, Idanna, Limongiello, Maria Assunta, Giammarco, Sabrina, Laurenti, Luca, Bacigalupo, Andrea, Chiusolo, Patrizia, De Stefano, Valerio, Sica, Simona, Eugenio, Galli, Federica, Sora (ORCID:0000-0002-9607-5298), Stefan, Hohaus (ORCID:0000-0002-5534-7197), Alberto, Fresa, Ilaria, Pansini, Francesco, Autore, Elisabetta, Metafuni, Idanna, Innocenti, Luca, Laurenti (ORCID:0000-0002-8327-1396), Andrea, Bacigalupo (ORCID:0000-0002-9119-567X), Patrizia, Chiusolo (ORCID:0000-0002-1355-1587), Valerio, De Stefano (ORCID:0000-0002-5178-5827), and Simona, Sica (ORCID:0000-0003-2426-3465)
- Abstract
Cytokine release syndrome (CRS) and consumptive coagulopathy can complicate the treatment with chimeric antigen receptor T (CAR-T) cells. The modified version of the Endothelial Activation and Stress Index (mEASIX), a score derived from haematopoietic stem cell transplantation, combines platelets, C-reactive protein (CRP), and lactate dehydrogenase (LDH) and has been correlated with CRS and endothelial biomarkers. In 38 consecutive patients with aggressive lymphoproliferative disease we measured a coagulative laboratory panel at baseline and early after infusion of anti-CD19 CAR-T. The panel was investigated also in the presence of CRS graded 2 or higher, or immune effector cell-associated neurotoxicity syndrome (ICANS). Moreover, we examined the relationship between mEASIX, coagulation biomarkers, and toxicities of CAR-T cells. During CRS grade 2 or higher, we found increased prothrombin time (PT) and activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, factor VIII (FVIII), and von Willebrand factor (vWF) antigen levels, and decreased platelet count and antithrombin levels. The occurrence of immune effector cell-associated neurotoxicity syndrome was associated with higher PT values, D-dimer, FVIII, and vWF levels, and decreased fibrinogen levels and platelet count. A higher mEASIX score correlated with increased aPTT values, fibrinogen, D-dimer, FVIII and vWF levels, and decreased antithrombin levels. Baseline mEASIX was predictive for consumptive coagulopathy and CRS graded 2 or higher, and for progression-free survival and overall survival.
- Published
- 2023