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@ARTICLE{Korell:179663,
      author       = {F. Korell and O. Penack and M. Mattie and N. Schreck$^*$
                      and A. Benner$^*$ and J. Krzykalla$^*$ and Z. Wang and M.
                      Schmitt and L. Bullinger and C. Müller-Tidow and P. Dreger
                      and T. Luft},
      title        = {{EASIX} and {S}evere {E}ndothelial {C}omplications {A}fter
                      {CD}19-{D}irected {CAR}-{T} {C}ell {T}herapy-{A} {C}ohort
                      {S}tudy.},
      journal      = {Frontiers in immunology},
      volume       = {13},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2022-00835},
      pages        = {877477},
      year         = {2022},
      abstract     = {Endothelial dysfunction is associated with two main
                      complications of chimeric antigen receptor T (CAR-T) cell
                      therapy, cytokine release syndrome (CRS) and immune effector
                      cell-associated neurotoxicity syndrome (ICANS). This study
                      evaluates the Endothelial Activation and Stress Index
                      (EASIX) as a prognostic marker for high-grade CRS and ICANS
                      in patients treated with CD19-directed CAR-T cells.In this
                      retrospective study, a training cohort of 93 patients from
                      the ZUMA-1 trial and a validation cohort of 121 patients
                      from two independent centers (University Hospital
                      Heidelberg, Charité University Medicine Berlin) were
                      investigated. The primary objective was to assess the
                      predictive capacity of EASIX measured immediately before the
                      start of lymphodepletion (EASIX-pre) for the occurrence of
                      grade ≥3 CRS and/or ICANS. To explore a possible
                      endothelial link, serum levels of endothelial stress markers
                      (angiopoietin-2, suppressor of tumorigenicity-2, soluble
                      thrombomodulin, and interleukin-8) were determined before
                      lymphodepletion and on day 7 after CART infusion in the
                      validation cohort (n = 47).The prognostic effect of
                      EASIX-pre on grade ≥3 CRS and/or ICANS was significant in
                      the training cohort [OR 2-fold increase 1.72 (1.26-2.46)]
                      and validated in the independent cohort. An EASIX-pre cutoff
                      >4.67 derived from the training cohort associated with a
                      4.3-fold increased odds ratio of severe CRS/ICANS in the
                      independent cohort. Serum endothelial distress markers
                      measured on day+7 correlated with EASIX-pre and associated
                      with severe complications.EASIX-pre is a powerful predictor
                      of severe CRS/ICANS after CD19-directed CART therapy and
                      might be used as a basis for risk-adapted prevention
                      strategies.},
      keywords     = {CAR-T cell (Other) / CRS (Other) / EASIX (Other) / ICANS
                      (Other) / prognostic biomarker (Other)},
      cin          = {C060},
      ddc          = {610},
      cid          = {I:(DE-He78)C060-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35464403},
      pmc          = {pmc:PMC9033201},
      doi          = {10.3389/fimmu.2022.877477},
      url          = {https://inrepo02.dkfz.de/record/179663},
}