Evidence map›Paper›PMID 39798802›Full record

ArticleTransplantation and cellular therapy2025

The Association of HLA-E Ligand and NKG2 Receptor Variation With Relapse and Mortality After Haploidentical Related Donor Transplantation.

Effie W Petersdorf, Caroline McKallor, Mari Malkki, Katherine Hsu, Meilun He, Stephen R Spellman, Theodore Gooley, Philip Stevenson

Abstract read
In one paragraph

Article in Transplantation and cellular therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

8 authors.

Effie W PetersdorfDivision of Translational Science and Therapeutics, Fred Hutchinson Cancer Center, Seattle, Washington; University of Washington School of Medicine, Seattle, Washington. Electronic address: epetersd@fredhutch.org.
Caroline McKallorDivision of Translational Science and Therapeutics, Fred Hutchinson Cancer Center, Seattle, Washington.
Mari MalkkiDivision of Translational Science and Therapeutics, Fred Hutchinson Cancer Center, Seattle, Washington.
Katherine HsuDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Meilun HeCenter for International Blood and Marrow Transplant Research, National Marrow Donor Program/Be The Match, Minneapolis, Minnesota.
Stephen R SpellmanCenter for International Blood and Marrow Transplant Research, National Marrow Donor Program/Be The Match, Minneapolis, Minnesota.
Theodore GooleyDivision of Clinical Research, Fred Hutchinson Cancer Center, Seattle, Washington.
Philip StevensonDivision of Clinical Research, Fred Hutchinson Cancer Center, Seattle, Washington.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Data Resource for Analyzing Blood &Marrow TransplantsU24CA076518 · NCI · MEDICAL COLLEGE OF WISCONSIN · PI Amy M Moskop, Bronwen Shaw · 1998 to 2026
$105.2M
PB vs. BMU01HL069294 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI HOROWITZ, MARY MARESCA · 2001 to 2010
$63.3M
Easy-to-read Informed Consent for HCT Clinical TrialsU10HL069294 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI HOROWITZ, MARY MARESCA · 2011 to 2016
$43.8M
Hematopopietic Stem Cell TransplantationU01AI069197 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Effie W Petersdorf · 2005 to 2026
$18.9M
Stem Cell and Transplantation BiologyU54DK106829 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI DEREK L STIREWALT · 2015 to 2026
$9.1M
Clinical Significance of MHC Haplotypes in Hematopoietic Cell TransplantationR01CA100019 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETERSDORF, EFFIE W · 2003 to 2025
$9.1M
Immuno and Epigenetics of Hematopoietic Cell TransplantationR01CA218285 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Effie W Petersdorf · 2017 to 2026
$5.6M
Immunogenetics of Outcomes Disparities After Allogeneic HCTR01CA231838 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Effie W Petersdorf · 2018 to 2026
$3.7M
NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA100019NCI NIH HHS R01 CA218285NCI NIH HHS R01 CA231838NCI NIH HHS U24 CA076518NHLBI NIH HHS U01 HL069294NHLBI NIH HHS U10 HL069294NIAID NIH HHS U01 AI069197NIDDK NIH HHS U54 DK106829
6 · The paper itself

Abstract

backgroundRecurrence of blood malignancy is the major cause of mortality after hematopoietic cell transplantation. NKG2 receptor/HLA-E ligand complexes play a fundamental role in the surveillance and elimination of transformed cells but their role in the control of leukemia in transplantation is unknown.

objectiveWe tested the hypothesis that gene variation of patient and/or donor HLA-E ligand and donor NKG2C-NKG2A receptors are associated with the risks of relapse and mortality (primary endpoints) and GVHD and non-relapse mortality (secondary endpoints) after haploidentical transplantation. STUDY

designWe retrospectively defined donor NKG2 receptor haplotypes and patient HLA-E ligands in 1629 haploidentical related transplantations. HLA-E residue 107 was genotyped in patients and donors. Single nucleotide polymorphisms descriptive of NKG2C and NKG2A haplotypes were characterized in donors. Overall mortality, relapse, nonrelapse mortality and chronic GVHD were studied using Cox regression models. Acute GVHD was studied by logistic regression.

resultsThe hazard of relapse for patients transplanted from NKG2C-del/del donors was 51% lower than that from wt/wt donors (hazard ratio, HR, .49 [95% CI, .26 to .89) contributing to a HR for mortality of .62 (95% CI, .38 to 1.02). The HR of mortality among patients transplanted from a donor with 2 vs. 0 copies of the NKG2A rs35909400-rs2734440-rs12824474 CCC haplotype was HR 2.28 (95% CI, 1.34 to 3.86). The HRs of mortality for ArgArg and ArgGly patients compared to GlyGly patients were 1.42 (95% CI, 1.11 to 1.82) and 1.43 (95% CI, 1.13 to 1.81), respectively. Hazard ratios for nonrelapse mortality for patients with ArgGly or ArgArg genotypes compared to patients with GlyGly genotype were HR 1.60 (95% CI, 1.06 to 2.41) and HR 1.79 (95% CI, 1.21 to 2.66), respectively. Assessment of donor receptor/patient ligand pairings showed that among Arg-positive patients, the HR of mortality from donors with any wt-CCC/CCC haplotype was HR 2.52 (95% CI, 1.45 to 4.38) relative to donors with any wt-non CCC/CCC haplotype.

conclusionsThe success of haploidentical transplantation may be defined by the cumulative effects of donor NKG2 receptor and patient HLA-E ligand polymorphisms. Patient HLA-E ligand and donor NKG2C-NKG2A receptor haplotypes shed new light on their role in the control of malignancy.

Indexed as

Hematopoietic Stem Cell TransplantationHistocompatibility Antigens Class INK Cell Lectin-Like Receptor Subfamily CTransplantation, HaploidenticalAdolescentAdultAgedChildFemaleGenotypeGraft vs Host DiseaseHaplotypesHLA-E AntigensHumansLigandsMaleHistocompatibility Antigens Class IHLA-E AntigensLigandsNK Cell Lectin-Like Receptor Subfamily CHaploidentical transplantationHaplotypesHLA-E ligandNKG2 receptorRelapseSurvival

Identifiers

PMID39798802
PMCPMC11875940

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.