New Research Offers Hope for Safer and More Effective Blood Stem Cell Transplants

Study Title: Systematic identification of minor histocompatibility antigens informs outcomes after allogeneic stem cell transplantation
Publication: Nature Biotechnology
Dana-Farber Cancer Institute authors: Nicoletta Cieri, MD, PhD, Nidhi Hookeri, Kari Stromhaug, Julia Keating, Raphael Kfuri-Rubens, Yiren Shao, Kaila Powell, Helen Ji, Cleo Forman, David A. Braun, MD, PhD, Livius Penter, MD, Haesook T. Kim, PhD, Giacomo Oliveira, PhD, Shuqiang Li, PhD, Kenneth J. Livak, PhD, Derin B. Keskin, PhD, Vincent T. Ho, MD, Jerome Ritz, MD, Robert J. Soiffer, MD, Catherine J. Wu, MD

Summary: 
Dana-Farber researchers investigated the molecular mechanisms underlying T cell alloreactivity in allogeneic hematopoietic cell transplants (allo-HCT). By systematically identifying and characterizing minor histocompatibility antigens (mHAgs), researchers are uncovering their crucial roles in both Graft-versus-Leukemia (GvL) effects and Graft-versus-Host Disease (GvHD). A new analytical framework has been developed using whole-exome sequencing data from donor-recipient pairs to personalize the assessment of alloreactivity. This approach enables the prediction of disease relapse and immune-mediated complications such as acute and chronic GvHD. These findings could revolutionize post-transplant treatment, improving personalized therapeutic strategies and donor selection.

Significance: 
By systematically identifying and characterizing the molecular determinants of alloreactivity—especially mHAgs, which play a dual role in both beneficial and harmful immune responses—this research offers the possibility of significantly improving patient outcomes. Personalized assessments of alloreactivity can now help predict which patients are at higher risk for complications, enabling tailored treatment strategies, such as early immunosuppressive therapy or modified intensity regimens. This research has the potential to inform better donor selection processes and optimize the use of protective mHAgs to prevent relapse. The insights gained from mHAg analysis may help shape future post-transplant therapies and donor matching, ultimately reducing the incidence of GvHD while maintaining strong Graft-versus-Leukemia effects.

Funding: 
This research was supported by grants from the National Institutes of Health: NIH/NCI-P01 CA229092, NIH/NHLBI-P01 HL158505, NIH/NHLBI R01 HL157174, and from the Leukemia & Lymphoma Society: SCOR-22937-22.