# Transplantation strategy affects the risk of GvHD after prophylactic and preemptive donor lymphocyte infusion

## TL;DR

This study shows that the risk of GvHD after donor lymphocyte infusion depends on factors like mixed chimerism and lymphopenia, which are influenced by the transplantation strategy.

## Contribution

The study identifies transplantation strategy as a key factor influencing DLI alloreactivity and suggests adjusting DLI doses based on patient conditions.

## Key findings

- Low 2-year cumulative incidence of GvHD requiring systemic treatment (7%) in patients receiving DLI.
- Most patients with mixed chimerism converted to full-donor chimerism without relapse, indicating effective GvL.
- DLI alloreactivity is influenced by conditions at the time of infusion, which are shaped by the transplantation strategy.

## Abstract

Donor lymphocyte infusion (DLI) after allogeneic stem cell transplantation (alloSCT) can boost Graft-versus-Leukaemia (GvL) reactivity but may induce Graft-versus-Host-Disease (GvHD). It is essential to understand which factors besides timing, donor type, and dose influence DLI alloreactivity. We previously identified viral infections, ≥ 5% patient cells in bone marrow chimerism, and lymphopenia at the time of DLI as relevant factors for GvHD after DLI following alemtuzumab-based T-cell depletion. Here, we investigated these factors and the alloreactivity after DLI following alloSCT with posttransplant cyclophosphamide in 83 patients with acute leukaemia/myelodysplastic syndrome receiving a prophylactic or preemptive DLI. 5% had viral infections close to DLI, 6% had ≥ 5% mixed chimerism, and 17% had lymphopenia. 2-year cumulative incidence of GvHD requiring systemic treatment was low: 7% (95%-confidence interval 1–14%). 22 of the 28 patients with ≥ 1% mixed chimerism at the time of DLI (79%) converted to full-donor chimerism. None of these responders relapsed, indicating achievement of GvL despite the low incidence of GvHD. Our data show that DLI alloreactivity is determined by the conditions at the time of DLI which are influenced by the transplantation strategy. Adjusting the DLI dose based on these conditions may improve the balance between GvHD and GvL.

The online version contains supplementary material available at 10.1007/s00277-025-06662-x.