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.

Galli, E., Sorà, F., Hohaus, S., Fresa, A., Pansini, I., Autore, F., Metafuni, E., Innocenti, I., Limongiello, M., Giammarco, S., Laurenti, L., Bacigalupo, A., Chiusolo, P., De Stefano, V., Sica, S., Endothelial activation predicts disseminated intravascular coagulopathy, cytokine release syndrome and prognosis in patients treated with anti-CD19 CAR-T, <<BRITISH JOURNAL OF HAEMATOLOGY>>, 2023; Apr;201(1) (na): 86-94. [doi:10.1111/bjh.18596] [https://hdl.handle.net/10807/232448]

Endothelial activation predicts disseminated intravascular coagulopathy, cytokine release syndrome and prognosis in patients treated with anti-CD19 CAR-T

Galli, Eugenio;Sorà, F;Hohaus, Stefan;Fresa, Alberto;Pansini, Ilaria;Autore, Francesco;Metafuni, Elisabetta;Innocenti, Idanna;Laurenti, Luca;Bacigalupo, Andrea;Chiusolo, Patrizia;De Stefano, Valerio;Sica, Simona
2022

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.
2022
Inglese
Galli, E., Sorà, F., Hohaus, S., Fresa, A., Pansini, I., Autore, F., Metafuni, E., Innocenti, I., Limongiello, M., Giammarco, S., Laurenti, L., Bacigalupo, A., Chiusolo, P., De Stefano, V., Sica, S., Endothelial activation predicts disseminated intravascular coagulopathy, cytokine release syndrome and prognosis in patients treated with anti-CD19 CAR-T, <<BRITISH JOURNAL OF HAEMATOLOGY>>, 2023; Apr;201(1) (na): 86-94. [doi:10.1111/bjh.18596] [https://hdl.handle.net/10807/232448]
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