GVHD prophylaxis choice reshapes T cell recovery after transplant
- Post-transplant cyclophosphamide and tacrolimus/methotrexate prophylaxis were compared for T cell recovery in phase 3 trial patients using longitudinal T cell receptor sequencing.
- Cyclophosphamide depleted T cells broadly, so recovery restarted from fewer founder cells and left a narrower repertoire for a long period.
- Lower diversity tracked with less chronic GVHD, but early loss of pathogen-specific clones was linked to higher severe-infection risk.
💡 Points
The same depletion that seems to buy less chronic GVHD also strips early pathogen coverage, so a narrower repertoire reads as a trade-off, not a win. This is a human cohort readout: association, not mechanism. For anyone designing a prophylaxis combination, the prize is sparing protective clones while pruning alloreactive ones, and nothing here shows that separation can be achieved.