After allogeneic hematopoietic stem cell transplantation (allo-HSCT), monitoring for relapse remains essential in guiding patient management and therapeutic decisions. One immune escape mechanism that has gained increasing attention is HLA loss relapse. HLA loss occurs when leukemic cells lose the mismatched HLA genes or complete haplotypes that were originally recognized by donor T cells. As a result, these malignant cells can evade the graft-versus-leukemia (GvL) effect and escape immune surveillance.
Why detecting HLA loss matters
Distinguishing between classical relapse and relapse with HLA loss is clinically important because the therapeutic strategies may differ significantly. In classical relapse, leukemic cells still express the mismatched HLA molecules, meaning donor lymphocyte infusion (DLI) or adjustment of immunosuppression may remain effective treatment options. In contrast, relapse with HLA loss may require alternative approaches, such as a second transplantation from a different donor, since the leukemic cells are no longer recognized by the original donor immune system. Accurate detection of HLA loss can therefore support more informed clinical decision-making and improve post-transplant monitoring strategies.
Advancements in molecular detection methods
GenDx has previously introduced a suite of qPCR assays targeting individual HLA markers. While effective, these approaches may be limited in multiplexing capabilities and informativity. Next-generation sequencing (NGS)-based approaches offer new opportunities for more comprehensive analysis. By combining chimerism monitoring with targeted HLA-region analysis, laboratories may benefit from:
- High marker informativity
- Multiplexed analysis in a single assay
- Integration with existing NGS workflows
- Streamlined data analysis
- Sensitive post-transplant monitoring
At GenDx, we are currently developing an NGS-based solution designed to support the detection of HLA loss alongside chimerism analysis. The assay is currently available as prototype.
In development: NGStrack HLA loss*
Our upcoming solution, NGStrack HLA loss, is being developed as an add-on assay for the NGStrack workflow. The prototype assay uses multiplexed STR markers located in the chromosome 6p21 HLA region to help detect the presence or loss of HLA genes in post-transplant samples.
The assay is intended to integrate with existing laboratory workflows and analysis through TRKengine software.
Learn more about our upcoming HLA loss solution: NGStrack HLA loss
