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@ARTICLE{Crivello:212409,
      author       = {P. Crivello and E. Arrieta-Bolaños$^*$ and M. He and T.
                      Wang and S. Fingerson and S. M. Gadalla and S. Paczesny and
                      S. G. E. Marsh and S. J. Lee and S. R. Spellman and Y.-T.
                      Bolon and K. Fleischhauer$^*$},
      title        = {{I}mpact of the {HLA} {I}mmunopeptidome on {S}urvival of
                      {L}eukemia {P}atients {A}fter {U}nrelated {D}onor
                      {T}ransplantation.},
      journal      = {Journal of clinical oncology},
      volume       = {41},
      number       = {13},
      issn         = {0732-183X},
      address      = {Alexandria, Va.},
      publisher    = {American Society of Clinical Oncology},
      reportid     = {DKFZ-2023-00128},
      pages        = {2416-2427},
      year         = {2023},
      note         = {2023 May 1;41(13):2416-2427},
      abstract     = {Immunopeptidome divergence between mismatched HLA-DP is a
                      determinant of T-cell alloreactivity and clinical
                      tolerability after fully HLA-A, -B, -C, -DRB1, -DQB1 matched
                      unrelated donor hematopoietic cell transplantation (UD-HCT).
                      Here, we tested this concept in HLA-A, -B, and -C
                      disparities after single class I HLA-mismatched UD-HCT.We
                      studied 2,391 single class I HLA-mismatched and 14,426 fully
                      HLA-matched UD-HCT performed between 2008 and 2018 for acute
                      leukemia or myelodysplastic syndromes. Hierarchical
                      clustering of experimentally determined peptide-binding
                      motifs (PBM) was used as a proxy for immunopeptidome
                      divergence of HLA-A, -B, or -C disparities, allowing us to
                      classify 1,629/2,391 $(68.1\%)$ of the HLA-mismatched UD-HCT
                      as PBM-matched or PBM-mismatched. Risks associated with
                      PBM-matching status were assessed by Cox proportional
                      hazards models, with overall survival (OS) as the primary
                      end point.Relative to full matches, bidirectional or
                      unidirectional PBM mismatches in graft-versus-host (GVH)
                      direction (PBM-GVH mismatches, $60.7\%)$ were associated
                      with significantly lower OS (hazard ratio [HR], 1.48; P <
                      .0001), while unidirectional PBM mismatches in
                      host-versus-graft direction or PBM matches (PBM-GVH matches,
                      $39.3\%)$ were not (HR, 1.13; P = .1017). PBM-GVH mismatches
                      also had significantly lower OS than PBM-GVH matches in
                      direct comparison (HR, 1.32; P = .0036). The hazards for
                      transplant-related mortality and acute and chronic
                      graft-versus-host disease but not relapse increased stepwise
                      from full HLA matches to single PBM-GVH matches, and single
                      PBM-GVH mismatches. A webtool for PBM-matching of single
                      class I HLA-mismatched donor-recipient pairs was
                      developed.PBM-GVH mismatches inform mortality risks after
                      single class I HLA-mismatched UD-HCT, suggesting that
                      prospective consideration of directional PBM-matching status
                      might improve outcome. These findings highlight
                      immunopeptidome divergence between mismatched HLA as a
                      driver of clinical tolerability in UD-HCT.},
      cin          = {ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36669145},
      doi          = {10.1200/JCO.22.01229},
      url          = {https://inrepo02.dkfz.de/record/212409},
}