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. 2025 Oct;104(10):5379-5387.
doi: 10.1007/s00277-025-06662-x. Epub 2025 Oct 20.

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

Eva A S Koster  1 , Peter A von dem Borne  2 , Joost G K van der Hem  2 , Peter van Balen  2 , Erik W A Marijt  2 , Jennifer M L Tjon  2 , Tjeerd J F Snijders  3 , Daniëlle van Lammeren  4 , Hendrik Veelken  2 , J H Frederik Falkenburg  2 , Liesbeth C de Wreede  5 , Constantijn J M Halkes  2
Affiliations

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

Eva A S Koster et al. Ann Hematol. 2025 Oct.

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.

Keywords: Acute leukemia; Allogeneic stem cell transplantation; Chimerism; Donor lymphocyte infusion; Graft-versus-Host-Disease; Graft-versus-Leukemia effect.

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Conflict of interest statement

Declarations. Ethics approval: The study was approved by the Medical Ethics Committee Leiden The Hague Delft (RP 22.002) and performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Consent to participate: Informed consent was obtained from all individual participants included in the study. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Probability of cGRFS, current use of tIS for GvHD, relapse and non-relapse mortality for all patients receiving DLI (n = 83). Outcome of the multi-state model over time since first DLI. The ‘relapse’ and ‘non-relapse mortality’ states are absorbing: these curves represent cumulative incidences. The structure of the model is shown in Supplemental Figure 2
Fig. 2
Fig. 2
BM chimerism response after DLI for the patients with mixed chimerism at the time of first DLI (n = 28).The best BM chimerism response achieved at different time points after the first DLI (complete response: conversion to full-donor chimerism, partial response: decreasing mixed chimerism, no response: stable/increasing mixed chimerism). Two patients relapsed before the first chimerism measurement after DLI (relapse at 0.8 and 1.4 months after low-dose 4-month DLI) and two patients relapsed before reaching a complete response (relapse at 4.8 and 6.4 months after low-dose 4-month DLI, both also received the 6-month DLI before relapse). One other patient converted to full-donor chimerism after start of interferon. Events after reaching a complete response are not shown
See this image and copyright information in PMC

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