# Immunogenetics of Outcomes Disparities After Allogeneic HCT

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2024 · $424,151

## Abstract

Project Summary/Abstract
Nowhere are racial disparities in cancer survival rates as striking as in hematopoietic cell transplantation (HCT)
because both the patient and the donor contribute to survival outcomes. HLA genetic features are ancestry-
informative. When ancestry-specific features are accounted for, survival disparities are diminished but major
gaps still exist between African, Hispanic, Asian and Caucasian American transplant patients. Relapse of the
blood cancer remains the chief cause of transplant failure; however, the role for the NKG2 axis, the major anti-
tumor pathway, in relapse and survival after HCT is ill-defined. The unmet need is to identify the NKG2
ligand/receptor immunogenetic factors involved in relapse and which account for disparities in survival. If these
factors were known, then prospective risk-assessment of the patient’s germline and optimized donor selection
could diminish or even abolish survival disparities across US populations. We have elucidated the survival
disparities between HCT patients of African, Hispanic, Asian and Caucasian American ancestry, and have
identified key ancestry-informative NKG2 ligand and receptor variants that impact gene expression and
survival. We propose to identify ancestry-specific NKG2 ligand and receptor missense and regulatory variation
that account for survival in each race, and examine the impact of optimal features across races to minimize or
abolish survival disparities in HCT. The specific aims are to 1) identify mechanisms that underpin NKG2
ligand/receptor expression variation in diverse races; 2) define NKG2 ligand/receptor ancestry-informative
variation for survival in each race, and 3) define survivorship disparities with ancestry-specific “ideal”
immunogenetic characteristics. The goals will be achieved through systematic analysis of NKG2
ligand/receptor variation to identify functional variants, followed by large-scale genotyping of related donor,
unrelated donor and cord blood transplant patients and donors and identification of ideal features that inform
survival within each race. The extent to which survival disparities may be diminished or even abolished through
transplantation of patients and donors with ideal characteristics will be defined. The information from this
project will increase the success of transplantation for all patients in need of this life-saving therapy.

## Key facts

- **NIH application ID:** 10841508
- **Project number:** 5R01CA231838-08
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Effie W Petersdorf
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $424,151
- **Award type:** 5
- **Project period:** 2023-05-15 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10841508

## Citation

> US National Institutes of Health, RePORTER application 10841508, Immunogenetics of Outcomes Disparities After Allogeneic HCT (5R01CA231838-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10841508. Licensed CC0.

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