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

Abstract

Prophylactic and pre-emptive donor lymphocyte infusion (pro/preDLI) is used to prevent haematological relapse of AML and MDS after allogeneic stem cell transplantation. For lack of prospective trials, outcome reports, risk factor analyses and published recommendations for DLI administration had to rely on registry studies, frequently limited by inconsistent reporting and missing data. Therefore, we performed an extensive chart review on recipients of pro/preDLI in two German centers to investigate the clinical applicability of current guidelines in a well-defined cohort. Beyond, as outcome after pro/preDLI is unsatisfactorily described by conventional parameters, we constructed a model for treatment success, defined as leukaemia-free survival (LFS) without intensive immunosuppressive treatment for Graft-versus-Host-Disease (GvHD).

Eighty-three patients had received proDLI (n=36), preDLI for incomplete chimerism (preDLIIC, n=27) or for persisting minimal residual disease/molecular relapse (preDLI-MRD, 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%/28% had received DLI in lower/higher cell doses and/or at a later/earlier time point (low-/highintensity).

Two-year rates of overall survival (OS), LFS, relapse incidence and non-relapse mortality within the entire cohort were 80%/67%/27%/8%. One-year rates of high-grade acute/chronic GvHD were 34%/27% among all patients and 53%/33% after high-intensity DLI. One-year treatment success rate were 72%/69% after low-/standard intensity, in contrast to 34% after high-intensity DLI. Apart from advanced disease at alloSCT, high-intensity DLI was the major risk factor for lower OS (HR=6.12), LFS (HR=5.43), higher aGvHD (HR=2.51), and lower treatment success (HR=0.41), supporting adherence to current recommendations.