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HLA Evolutionary Divergence as a Prognostic Marker for AML Patients Undergoing Allogeneic Stem Cell Transplantation
- Source :
- Cancers, Vol 12, Iss 1835, p 1835 (2020), Cancers, Volume 12, Issue 7
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
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 (&lt<br />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<br />3.2) and 2.1 (95% CI 1.3&ndash<br />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 &lt<br />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<br />3.6) and event-free survival (EFS) was significantly reduced (5 year EFS 25.7% versus 54.4%, p &lt<br />0.001). We here introduce HED, a fundamental metric of immunopeptidome diversity, as a novel prognostic factor for AML patients undergoing allogeneic HSCT.
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 12
- Issue :
- 1835
- Database :
- OpenAIRE
- Journal :
- Cancers
- Accession number :
- edsair.dedup.wf.001..6145366a1168971485d47306b2c88386