ORIGINAL ARTICLE
Open Access

Genomic Predictors of Engraftment and Graft-Versus-Host Disease After Allogeneic Stem Cell Transplantation

Mikkel Søndergaard Larsen1, Anne-Kristine Holm Nielsen2, Jonas Erik FrederiksenORCID 3

1Department of Hematology, Rigshospitalet, Copenhagen University Hospital Copenhagen, Denmark.
2Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.
3Department of Hematology and Stem Cell Transplantation, Odense University Hospital, University of Southern Denmark, Odense, Denmark
DOI: 10.18081/ajbm.2025.4.399

Publication History: Received 29 September 2025, Revised 30 October 2025, Accepted 19 November 2025, Available online 16 December 2025
Copyright: © 2025 Frederiksen, et al. This is an open-access article under a Creative Commons license (CC BY 4.0).
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ABSTRACT

Background

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for a wide range of hematologic disorders; however, graft failure and graft-versus-host disease (GVHD) remain major determinants of transplant-related morbidity and mortality. While donor–recipient HLA matching is central to transplant success, the contribution of non-HLA genomic factors to engraftment and GVHD risk is not fully defined.

Methods

We conducted a retrospective, population-based cohort study including 312 adult patients who underwent first allo-HSCT at Danish transplantation centers between 2010 and 2023. Donor and recipient genomic data were analyzed using targeted next-generation sequencing focusing on immune regulatory and stem cell homing–related genes. Primary outcomes were neutrophil engraftment and acute GVHD, with overall survival as a secondary endpoint. Associations between genomic variants and transplant outcomes were evaluated using Kaplan–Meier analysis, competing-risk models, and multivariable Cox regression.

Results

Neutrophil engraftment was achieved in 95.2% of patients at a median of 17 days. Polymorphisms in the CXCL12 pathway were associated with delayed engraftment (median 20 vs 16 days; P = 0.004) and increased graft failure. Acute GVHD of grade II–IV occurred in 27.9% of patients and was significantly associated with variants in IL6, TNF, and NOD2/CARD15. Patients harboring ≥2 high-risk genomic variants exhibited inferior 3-year overall survival (44.1% vs 66.4%; log-rank P < 0.001). Genomic risk remained independently associated with GVHD and survival after adjustment for clinical and transplant-related factors.

Conclusion

Non-HLA genomic variation significantly influences engraftment kinetics, GVHD development, and survival following allo-HSCT in a Danish cohort. Incorporation of targeted genomic profiling into pre-transplant risk assessment may enhance personalized transplant strategies and improve clinical outcomes.

Keywords: Allogeneic stem cell transplantation; Genomics; Graft-versus-host disease; Engraftment; Precision medicine

Recommended Citation

Mikkel Søndergaard Larsen MS, Nielsen AH, Frederiksen JE. Genomic Predictors of Engraftment and Graft-Versus-Host Disease After Allogeneic Stem Cell Transplantation. Advanced Journal of Biomedicine & Medicine. 2025;13(4):399-415. doi:10.18081/ajbm.2025.4.399

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Larsen MS, Nielsen AH, Frederiksen JE (2025). Genomic Predictors of Engraftment and Graft-Versus-Host Disease After Allogeneic Stem Cell Transplantation<br /> . Advanced Journal of Biomedicine & Medicine, 13(4), 399-415. https://doi.org/10.18081/ajbm.2025.4.399
Larsen MS, Nielsen AH, Frederiksen JE. "Genomic Predictors of Engraftment and Graft-Versus-Host Disease After Allogeneic Stem Cell Transplantation<br /> ." Advanced Journal of Biomedicine & Medicine, vol. 13, no. 4, 2025, pp. 399-415. DOI: 10.18081/ajbm.2025.4.399.
Larsen MS, Nielsen AH, Frederiksen JE. Genomic Predictors of Engraftment and Graft-Versus-Host Disease After Allogeneic Stem Cell Transplantation<br /> . AJBM. 2025;13(4):399-415. DOI: 10.18081/ajbm.2025.4.399. PMID: .
Larsen MS, Nielsen AH, Frederiksen JE 2025, "Genomic Predictors of Engraftment and Graft-Versus-Host Disease After Allogeneic Stem Cell Transplantation<br /> ", Advanced Journal of Biomedicine & Medicine, vol. 13, no. 4, pp. 399-415.
@article{larsen2025, title={Genomic Predictors of Engraftment and Graft-Versus-Host Disease After Allogeneic Stem Cell Transplantation<br /> }, author={Larsen MS, Nielsen AH, Frederiksen JE}, journal={Advanced Journal of Biomedicine & Medicine}, volume={13}, number={4}, pages={399-415}, year={2025}, doi={10.18081/ajbm.2025.4.399} }
TY - JOUR AU - Larsen MS, Nielsen AH, Frederiksen JE TI - Genomic Predictors of Engraftment and Graft-Versus-Host Disease After Allogeneic Stem Cell Transplantation<br /> JO - American Journal of Biomedicine VL - 13 IS - 4 SP - 399-415 PY - 2025 DO - 10.18081/ajbm.2025.4.399 ER -
%0 Journal Article %A Larsen MS, Nielsen AH, Frederiksen JE %T Genomic Predictors of Engraftment and Graft-Versus-Host Disease After Allogeneic Stem Cell Transplantation<br /> %J American Journal of Biomedicine %V 13 %N 4 %P 399-415 %D 2025 %R 10.18081/ajbm.2025.4.399 %M
Larsen MS, Nielsen AH, Frederiksen JE (2025). Genomic Predictors of Engraftment and Graft-Versus-Host Disease After Allogeneic Stem Cell Transplantation<br /> . Advanced Journal of Biomedicine & Medicine, 13(4), 399-415. https://doi.org/10.18081/ajbm.2025.4.399

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