Prophylactic and pre-emptive donor lymphocyte infusion in patients with acute myeloid leukemia and myelodysplastic syndrome: validation of current recommendations and proposal of a modified outcome assessment

Prophylactic and pre-emptive donor lymphocyte infusion (pro/preDLI) is used to prevent hematologic relapse of acute myeloid leukemia and myelodysplastic syndromes after allogeneic stem cell transplantation. Given the lack of prospective trials, outcome reports, risk factor analyses and published recommendations on DLI administration have had to rely on information from registry studies, frequently limited by inconsistent reporting and missing data. We, therefore, performed an extensive review of the charts of recipients of pro/preDLI in two German centers to investigate the clinical applicability of current guidelines in a well-defined cohort. Furthermore, as the outcome after pro/preDLI is unsatisfactorily described by conventional parameters, we constructed a model for "treatment success", defined as leukemia-free survival without intensive immunosuppressive treatment for graft-versus-host disease (GvHD). Eighty-three patients had received DLI: proDLI (N=36), preDLI for incomplete chimerism (N=27) and preDLI for persisting minimal residual disease/molecular relapse (N=20). According to current guidelines concerning initial T-cell doses and timing of DLI, 42% of patients had received DLI as recommended (standard intensity), whereas 30% had received DLI at lower cell doses and/or at a later timepoint (low intensity) and 28% had received DLI at higher cell doses and/or at an earlier timepoint (high intensity). Two-year rates of overall survival, leukemia-free survival, relapse incidence and non-relapse mortality within the entire cohort were 80%, 67%, 27% and 8%, respectively. One-year rates of high-grade acute/chronic GvHD were 34% and 27%, respectively, among all patients and 53% and 33% after high-intensity DLI. One-year treatment success rates were 72% and 69% after low- and standard-intensity DLI, respectively, in contrast to 34% after high-intensity DLI. Apart from advanced disease at the time of allogeneic stem cell transplantation, high-intensity DLI was the major risk factor for lower overall survival (hazard ratio [HR]=6.12), lower leukemia-free survival (HR=5.43), higher acute GvHD (HR=2.51), and lower treatment success (HR=0.41), supporting adherence to current recommendations.