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@ARTICLE{Pabst:182099,
      author       = {C. Pabst and N. Schreck$^*$ and A. Benner$^*$ and U.
                      Hegenbart and S. Schönland and A. Radujkovic and M. Schmitt
                      and C. Müller-Tidow and L. Orsatti and P. Dreger and T.
                      Luft},
      title        = {{S}tatin-based endothelial prophylaxis and outcome after
                      allogeneic stem cell transplantation.},
      journal      = {European journal of clinical investigation},
      volume       = {53},
      number       = {2},
      issn         = {0014-2972},
      address      = {Oxford [u.a.]},
      publisher    = {Wiley-Blackwell},
      reportid     = {DKFZ-2022-02417},
      pages        = {e13883},
      year         = {2023},
      note         = {2023 Feb;53(2):e13883},
      abstract     = {Allogeneic haematopoietic stem cell transplantation
                      (alloSCT) often remains the only curative therapy for
                      hematologic malignancies. Although the management of
                      transplant-associated adverse events considerably improved
                      over the last decades, nonrelapse mortality (NRM) remains a
                      challenge, and endothelial dysfunction was identified as a
                      major contributor to NRM.Statin-based endothelial
                      prophylaxis (SEP) has been implemented in the standard of
                      care in our transplant centre to reduce NRM caused by
                      endothelial injury. Here, we retrospectively analysed the
                      impact of SEP on clinical outcome in a cohort of 347 alloSCT
                      patients.SEP (n = 209) was associated with significantly
                      reduced NRM (hazard ratio 0.61, $95\%$ CI 0.38-0.96) and
                      better overall survival (OS) after acute graft-versus-host
                      disease (HR 0.59, $95\%$ CI 0.37-0.93). Subgroup analyses
                      showed that the NRM benefit was mainly found in patients
                      with an intermediate endothelial activation and stress index
                      (EASIX), while relapse risk was not affected. On day 100
                      post-alloSCT, patients receiving SEP had significantly
                      higher levels of the rate-limiting enzyme of tryptophan
                      metabolism, indoleamine 2,3-dioxygenase (IDO), higher
                      kynurenine to tryptophan ratios as a proxy of IDO activity
                      and tended to have lower levels of the endothelial injury
                      marker ST2 (p = .055). No significant differences in
                      interferon-gamma or IL18 levels were observed. These
                      biomarker signatures suggest that the beneficial effects of
                      SEP might be mediated by both endothelial protection and
                      immunomodulation.Together, these data suggest that SEP
                      improves NRM and OS post-alloSCT in particular in patients
                      with intermediate endothelial risk and provide first
                      mechanistic clues about its potential mode of action.},
      keywords     = {allogeneic stem cell transplantation (Other) / endothelial
                      damage (Other) / endothelial protection (Other) /
                      immunosuppression (Other) / statin (Other) / thrombotic
                      microangiopathy (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:36199203},
      doi          = {10.1111/eci.13883},
      url          = {https://inrepo02.dkfz.de/record/182099},
}