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HLA Class I Genotyp...
HLA Class I Genotype Is Associated with Relapse Risk after Allogeneic Stem Cell Transplantation for NPM1-Mutated Acute Myeloid Leukemia
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- Narayan, Rupa (author)
- Massachusetts General Hospital
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- Niroula, Abhishek (author)
- Lund University,Lunds universitet,Hematogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Dana-Farber Cancer Institute,Broad Institute
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- Wang, Tao (author)
- Medical College of Wisconsin
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Kuxhausen, Michelle (author)
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He, Meilun (author)
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- Meyer, Everett (author)
- Stanford University
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- Chen, Yi Bin (author)
- Massachusetts General Hospital
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- Bhatt, Vijaya Raj (author)
- University of Nebraska Medical Center
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Beitinjaneh, Amer (author)
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- Nishihori, Taiga (author)
- H. Lee Moffitt Cancer Center & Research Institute
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- Sharma, Akshay (author)
- St Jude Children´s Research Hospital, Memphis
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- Brown, Valerie I. (author)
- Pennsylvania State University College of Medicine
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- Kamoun, Malek (author)
- University of Pennsylvania
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- Diaz, Miguel A. (author)
- Hospital Infantil Universitario Niño Jesús
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- Abid, Muhammad Bilal (author)
- Medical College of Wisconsin
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- Askar, Medhat (author)
- Baylor University Medical Centre,Memorial Sloan-Kettering Cancer Center
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- Kanakry, Christopher G. (author)
- National Cancer Institute, USA
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- Gragert, Loren (author)
- Tulane University School of Medicine
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Bolon, Yung Tsi (author)
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- Marsh, Steven G.E. (author)
- Anthony Nolan Research Institute,University College London
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- Gadalla, Shahinaz M. (author)
- National Cancer Institute, USA
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- Paczesny, Sophie (author)
- Medical University of South Carolina
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Spellman, Stephen (author)
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- Lee, Stephanie J. (author)
- Medical College of Wisconsin,Fred Hutchinson Cancer Research Center
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(creator_code:org_t)
- Elsevier BV, 2023
- 2023
- English.
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In: Transplantation and cellular therapy. - : Elsevier BV. - 2666-6367. ; 29:7, s. 1-452
- Related links:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Mutation-bearing peptide ligands from mutated nucleophosmin-1 (NPM1) protein have been empirically found to be presented by HLA class I in acute myeloid leukemia (AML). We hypothesized that HLA genotype may impact allogeneic hematopoietic stem cell transplantation (allo-HCT) outcomes in NPM1-mutated AML owing to differences in antigen presentation. We evaluated the effect of the variable of predicted strong binding to mutated NPM1 peptides using HLA class I genotypes from matched donor-recipient pairs on transplant recipients’ overall survival (OS) and disease-free survival (DFS) as part of the primary objectives and cumulative incidence of relapse and nonrelapse mortality (NRM) as part of secondary objectives. Baseline and outcome data reported to the Center for International Blood and Marrow Transplant Research from a study cohort of adult patients (n = 1020) with NPM1-mutated de novo AML in first (71%) or second (29%) complete remission undergoing 8/8 matched related (18%) or matched unrelated (82%) allo-HCT were analyzed retrospectively. Class I alleles from donor-recipient pairs were analyzed for predicted strong HLA binding to mutated NPM1 using netMHCpan 4.0. A total of 429 (42%) donor-recipient pairs were classified as having predicted strong-binding HLA alleles (SBHAs) to mutated NPM1. In multivariable analyses adjusting for clinical covariates, the presence of predicted SBHAs was associated with a lower risk of relapse (hazard ratio [HR],.72; 95% confidence interval [CI],.55 to.94; P =.015). OS (HR,.81; 95% CI,.67 to.98; P =.028) and DFS (HR,.84; 95% CI,.69 to 1.01; P =.070) showed a suggestion of better outcomes if predicted SBHAs were present but did not meet the prespecified P value of <.025. NRM did not differ (HR, 1.04; P =.740). These hypothesis-generating data support further exploration of HLA genotype-neoantigen interactions in the allo-HCT context.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Keyword
- Acute myeloid leukemia
- allogeneic transplant
- cellular therapy
- HLA genotype
- immunotherapy
- neoantigen
- NPM1
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Narayan, Rupa
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Niroula, Abhishe ...
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Wang, Tao
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Kuxhausen, Miche ...
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He, Meilun
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Meyer, Everett
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show more...
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Chen, Yi Bin
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Bhatt, Vijaya Ra ...
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Beitinjaneh, Ame ...
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Nishihori, Taiga
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Sharma, Akshay
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Brown, Valerie I ...
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Kamoun, Malek
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Diaz, Miguel A.
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Abid, Muhammad B ...
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Askar, Medhat
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Kanakry, Christo ...
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Gragert, Loren
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Bolon, Yung Tsi
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Marsh, Steven G. ...
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Gadalla, Shahina ...
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Paczesny, Sophie
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Spellman, Stephe ...
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Lee, Stephanie J ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
- Articles in the publication
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Transplantation ...
- By the university
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Lund University