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. 2023 Apr;201(1):86-94.
doi: 10.1111/bjh.18596. Epub 2022 Dec 11.

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

Eugenio Galli  1   2 , Federica Sorà  1   2 , Stefan Hohaus  1   2 , Alberto Fresa  1   2 , Ilaria Pansini  1 , Francesco Autore  2 , Elisabetta Metafuni  2 , Idanna Innocenti  2 , Maria Assunta Limongiello  2 , Sabrina Giammarco  2 , Luca Laurenti  1   2 , Andrea Bacigalupo  1   2 , Patrizia Chiusolo  1   2 , Valerio De Stefano  1   2 , Simona Sica  1   2
Affiliations

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

Eugenio Galli et al. Br J Haematol. 2023 Apr.

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.

Keywords: CAR-T cells; cytokine release syndrome; disseminated intravascular coagulation; endothelium activation; immune neurotoxicity syndrome; non-Hodgkin lymphoma.

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References

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