1. HLA Evolutionary Divergence as a Prognostic Marker for AML Patients Undergoing Allogeneic Stem Cell Transplantation
- Author
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Roerden, Malte, Nelde, Annika, Heitmann, Jonas S., Klein, Reinhild, Rammensee, Hans-Georg, Bethge, Wolfgang A., and Walz, Juliane S.
- Subjects
AML ,allogeneic stem cell transplantation ,hemic and lymphatic diseases ,graft-versus-leukemia effect ,acute myeloid leukemia ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,HLA evolutionary divergence ,lcsh:RC254-282 - Abstract
The diversity of human leukocyte antigens (HLAs) enables the presentation of immense repertoires of peptides, including tumor-associated antigens (TAAs). As a surrogate for immunopeptidome diversity, the HLA evolutionary divergence (HED) between individual HLA alleles might directly define the ability to present TAAs, a prerequisite for graft-versus-leukemia effects. We therefore analyzed the impact of HED on survival within a cohort of 171 acute myeloid leukemia (AML) patients after matched donor allogeneic hematopoietic stem cell transplantation (HSCT). Low HED (<, 25th percentile) of HLA class I (HEDclass I) or HLA-DR antigens (HEDDR) was a strong determinant for adverse overall survival after allogeneic HSCT (OS), with a hazard ratio for death of 1.9 (95% CI 1.2&ndash, 3.2) and 2.1 (95% CI 1.3&ndash, 3.4), respectively. Defining a cutoff value for the combined HEDtotal (HEDclass I and HEDDR), the respective 5 year OS was 29.7% and 64.9% in patients with low and high HEDtotal (p <, 0.001), respectively. Furthermore, the risk of relapse was significantly higher in patients with low HEDtotal (hazard ratio (HR) 2.2, 95% CI 1.3&ndash, 3.6) and event-free survival (EFS) was significantly reduced (5 year EFS 25.7% versus 54.4%, p <, 0.001). We here introduce HED, a fundamental metric of immunopeptidome diversity, as a novel prognostic factor for AML patients undergoing allogeneic HSCT.
- Published
- 2020