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Thrombotic Events Are Unusual Toxicities of Chimeric Antigen Receptor T-Cell Therapies

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  • معلومة اضافية
    • Contributors:
      Medicine, School of Medicine
    • بيانات النشر:
      MDPI
    • الموضوع:
      2023
    • Collection:
      Indiana University - Purdue University Indianapolis: IUPUI Scholar Works
    • نبذة مختصرة :
      Chimeric antigen receptor (CAR) T-cell therapy has greatly transformed the treatment and prognosis of B-cell hematological malignancies. As CAR T-cell therapy continues to be more readily adopted and indications increase, the field’s recognition of emerging toxicities will continue to grow. Among the adverse events associated with CAR T-cell therapy, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are the most common toxicities, while thrombotic events represent an under-reported, life-endangering complication. To determine thrombosis incidence post CAR T-cell therapy, we performed a multi-center, retrospective study on CAR T-cell therapy adult patients (N = 140) from Indiana University Simon Cancer Center and the University of North Carolina Medical Center treated from 2017 to 2022 for relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL, N = 3), diffuse large B-cell lymphoma (DLBCL, N = 92), follicular lymphoma (FL, N = 9), mantle cell lymphoma (MCL, N = 2), and multiple myeloma (MM, N = 34). We report 10 (7.14%) thrombotic events related to CAR T-cell therapy (DLBCL: N = 8, FL: N = 1, MM: N = 1) including 9 primary venous events and 1 arterial event that occurred with median time of 23.5 days post CAR T-cell infusion. In search of parameters associated with such events, we performed multivariate analyses of coagulation parameters (i.e., PT, PTT, and D-Dimer), scoring for adverse events (Padua Score and ISTH DIC Score) and grading for CAR T-cell toxicity severity (CRS grade and ICANS grade) and found that D-Dimer peak elevation and ICANS grade were significantly associated with post-CAR T-cell infusion thrombosis. While the pathophysiology of CAR T-cell associated coagulopathy remains unknown, our study serves to develop awareness of these emerging and unusual complications.
    • File Description:
      application/pdf
    • Relation:
      International Journal of Molecular Sciences; Schorr C, Forindez J, Espinoza-Gutarra M, Mehta R, Grover N, Perna F. Thrombotic Events Are Unusual Toxicities of Chimeric Antigen Receptor T-Cell Therapies. Int J Mol Sci. 2023;24(9):8349. Published 2023 May 6. doi:10.3390/ijms24098349; https://hdl.handle.net/1805/37548
    • الدخول الالكتروني :
      https://hdl.handle.net/1805/37548
    • Rights:
      Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0/
    • الرقم المعرف:
      edsbas.BC1BDBBE