# Immuno and Epigenetics of Hematopoietic Cell Transplantation

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2024 · $616,280

## Abstract

PROJECT SUMMARY/ABSTRACT
Hematopoietic cell transplantation from related and unrelated donors can cure life-threatening blood disorders;
however, graft-versus-host disease (GVHD) and relapse remain the major obstacles. When matched donors
are not available, the properties of that govern (un)favorable HLA mismatches are not well-defined. These
deficiencies have important implications for a large fraction of patients who lack HLA-matched donors, and for
all patients at risk for disease relapse. The advent of improved GVHD prevention regimens has increased the
safety and efficacy of haploidentical transplantation and it is anticipated that its use in multi-locus mismatched
unrelated transplantation will substantially increase options for patients. The unmet needs are to understand
the mechanisms through which HLA-DR and -DQ genes modulate transplant risks, and a means to apply the
research findings to clinical care. We have recently identified important features of HLA-DQ molecules and
HLA-DR expression that describe (un)favorable mismatches, and they represent an entirely new paradigm for
the HLA class II region. We propose to define the underlying mechanisms through which matched and
mismatched HLA-DR and -DQ function in transplantation. The specific aims are to: determine the role of HLA-
DQ structure and expression in outcome; determine the role of HLA-DRβ molecules in outcome; determine the
impact of HLA-DR-DQ haplotype variation on clinical outcome after HLA-matched and -mismatched allogeneic
transplantation, and design tools to translate class II features into clinical practice. The goals will be achieved
through systemic analysis of HLA-DR and -DQ variation, peptide repertoire and expression in large ethnically
diverse transplant populations with complete clinical data. This proposal will fill the knowledge gap in the
immunobiological basis of GVHD, relapse and survivorship in transplantation. The information will increase the
safety, efficacy and availability of transplantation for all patients in need of this life-saving therapy.

## Key facts

- **NIH application ID:** 10843133
- **Project number:** 5R01CA218285-08
- **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:** $616,280
- **Award type:** 5
- **Project period:** 2017-08-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10843133

## Citation

> US National Institutes of Health, RePORTER application 10843133, Immuno and Epigenetics of Hematopoietic Cell Transplantation (5R01CA218285-08). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10843133. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*