PMID- 37637234
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230829
IS  - 2590-017X (Electronic)
IS  - 2666-2345 (Print)
IS  - 2590-017X (Linking)
VI  - 6
IP  - 3
DP  - 2023 Aug
TI  - Autoimmune HLA Alleles and Neoepitope Presentation Predict Post-Allogenic 
      Transplant Relapse.
PG  - 127-132
LID - 10.36401/JIPO-22-19 [doi]
AB  - INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can 
      cure patients with high-risk myelodysplastic syndromes (MDS) and acute myeloid 
      leukemia (AML). However, many patients relapse or develop debilitating 
      graft-versus-host disease. Transplant restores T-cell reactivity against tumor 
      cells, implicating patient human leukocyte antigen (HLA)-dependent antigen 
      presentation via the major histocompatibility complex as a determinant of 
      response. We sought to identify characteristics of the HLA genotype that 
      influence response in allo-HSCT patients. METHODS: We collected HLA genotype and 
      panel-based somatic mutation profiles for 55 patients with AML and MDS and 
      available data treated at the University of California San Diego Moores Cancer 
      Center between May 2012 and January 2019. We evaluated characteristics of the HLA 
      genotype relative to relapse-free time and overall survival (OS) post-allo-HSCT 
      using univariable and multivariable regression. RESULTS: In multivariable 
      regression, the presence of an autoimmune allele was significantly associated 
      with relapse-free time (hazard ratio [HR], 0.25; p = 0.01) and OS (HR, 0.16; p < 
      0.005). The better potential of the donor HLA type to present peptides harboring 
      driver mutations trended toward better relapse-free survival (HR, 0.45; p = 0.07) 
      and significantly correlated with longer OS (HR, 0.33; p = 0.01) though only a 
      minority of cases had an HLA mismatch. CONCLUSION: In this single institution 
      retrospective study of patients receiving allo-HSCT for relapsed AML/MDS, 
      characteristics of an individual's HLA genotype (presence of an autoimmune allele 
      and potential of the donor HLA to better present peptides representing driver 
      mutations) were significantly associated with better outcomes. These findings 
      suggest that HLA type may guide the optimal application of allo-HSCT and merit 
      evaluation in larger cohorts. ClinicalTrials.gov Identifier: NCT02478931.
FAU - Castro, Andrea
AU  - Castro A
AUID- ORCID: 0000-0002-5873-2496
AD  - Bioinformatics and Systems Biology Program, University of California San Diego, 
      La Jolla, CA, USA.
AD  - Division of Medical Genetics, Department of Medicine, University of California 
      San Diego, La Jolla, CA, USA.
FAU - Goodman, Aaron M
AU  - Goodman AM
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, University 
      of California San Diego, La Jolla, CA, USA.
FAU - Rane, Zachary
AU  - Rane Z
AD  - School of Medicine, University of California San Diego, La Jolla, CA, USA.
FAU - Talwar, James V
AU  - Talwar JV
AD  - Bioinformatics and Systems Biology Program, University of California San Diego, 
      La Jolla, CA, USA.
AD  - Division of Medical Genetics, Department of Medicine, University of California 
      San Diego, La Jolla, CA, USA.
FAU - Frampton, Garrett M
AU  - Frampton GM
AD  - Foundation Medicine, Cambridge, MA, USA.
FAU - Morris, Gerald P
AU  - Morris GP
AD  - Department of Pathology, University of California San Diego, La Jolla, CA, USA.
FAU - Lippman, Scott M
AU  - Lippman SM
AD  - School of Medicine, University of California San Diego, La Jolla, CA, USA.
AD  - Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
FAU - Zhang, Xinlian
AU  - Zhang X
AD  - Division of Biostatistics and Bioinformatics, Herbert Wertheim School of Public 
      Health, University of California San Diego, La Jolla, CA, USA.
FAU - Kurzrock, Razelle
AU  - Kurzrock R
AD  - Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
FAU - Carter, Hannah
AU  - Carter H
AUID- ORCID: 0000-0002-1729-2463
AD  - Division of Medical Genetics, Department of Medicine, University of California 
      San Diego, La Jolla, CA, USA.
AD  - Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02478931
PT  - Journal Article
DEP - 20230515
PL  - United States
TA  - J Immunother Precis Oncol
JT  - Journal of immunotherapy and precision oncology
JID - 101768397
PMC - PMC10448732
OTO - NOTNLM
OT  - HLA genotype
OT  - acute myeloid leukemia
OT  - allo-HSCT
OT  - neoantigen
OT  - relapse
COIS- Conflict of Interest: Dr. Goodman is a consultant for Seattle Genetics. Garret 
      Frampton is an employee of Foundation Medicine and a shareholder of Roche. Dr. 
      Kurzrock has an equity interest in CureMatch Inc. and IDbyDNA; serves on the 
      Board of CureMatch and CureMetrix, and is a co-founder of CureMatch.
EDAT- 2023/08/28 06:43
MHDA- 2023/08/28 06:44
PMCR- 2023/05/15
CRDT- 2023/08/28 04:46
PHST- 2022/08/01 00:00 [received]
PHST- 2022/12/20 00:00 [revised]
PHST- 2023/03/20 00:00 [accepted]
PHST- 2023/08/28 06:44 [medline]
PHST- 2023/08/28 06:43 [pubmed]
PHST- 2023/08/28 04:46 [entrez]
PHST- 2023/05/15 00:00 [pmc-release]
AID - 10.36401/JIPO-22-19 [doi]
PST - epublish
SO  - J Immunother Precis Oncol. 2023 May 15;6(3):127-132. doi: 10.36401/JIPO-22-19. 
      eCollection 2023 Aug.