Does TCR profiling predict graft-versus-host disease in stem cell transplant patients?

T-cell receptor (TCR) profiling is a technique that analyzes the diversity and composition of T-cell receptors in the blood. In stem cell transplant patients, doctors want to know if changes in the TCR repertoire can predict graft-versus-host disease (GVHD) before symptoms appear. Research suggests that TCR profiling can indeed predict GVHD, as well as other complications like viral reactivation, by detecting immune system changes early after transplant.

What the research says

A 2025 study of 108 allogeneic hematopoietic stem cell transplant recipients performed longitudinal TCR beta repertoire profiling at baseline and three early post-transplant time points ². The study found that reduced baseline TCR diversity was linked to Epstein-Barr virus reactivation, while cytomegalovirus reactivation was associated with post-transplant clonal expansion and reduced donor-recipient repertoire similarity ². Most importantly, sequence-based predictive models achieved an area under the curve (AUC) of 0.834 for GVHD, indicating good predictive ability ². The study also identified complication-specific predictive windows, suggesting that immune perturbations precede these events ².

Another study from 2026 used next-generation sequencing to profile TCR alpha and beta chains in HSCT recipients with and without acute GVHD ⁵. It found that TCR repertoires showed significantly increased diversity in patients with active aGVHD compared to those without, and this elevated diversity decreased as GVHD symptoms improved ⁵. The study also identified common TCR repertoire signatures among different patients who developed aGVHD, suggesting shared antigen-driven T-cell responses ⁵.

A 2021 mouse study examined donor T-cell repertoire in recipient lymphoid and GVHD target organs after bone marrow transplantation ⁶. It found that TCR diversity narrowed in lymphoid organs, with reduced unique clones and increased dominant clones in allogeneic T cells ⁶. The top clones in peripheral blood, gut, liver, and lungs were highly shared, indicating that blood TCR profiling can predict dominant clones in GVHD target organs ⁶.

What to ask your doctor

• Is TCR profiling available at our center for predicting GVHD after my stem cell transplant?
• How often would TCR monitoring be done, and at what time points after transplant?
• What would the results mean for my GVHD risk and how might it change my treatment plan?
• Are there any other tests or biomarkers that should be used alongside TCR profiling?
• What are the limitations of TCR profiling, and how accurate is it for predicting GVHD?