Analysis of Safety and Efficacy of Donor Lymphocyte Infusion in Prophylactic, Pre-Emptive and Treatment Strategies Post Allogeneic Stem Cell Transplant

Donor lymphocyte infusions (DLI) are often used to prevent or treat disease relapse following allogeneic stem cell transplantation (alloSCT). However, patients remain at risk of graft-versus-host disease (GVHD) from DLI or death from progressive disease (PD). We reviewed outcomes in our institution after DLI was administered prophylactically (mixed chimerism), pre-emptively (positive measurable residual disease) or therapeutically (relapsed disease).Between 2015 and 2023, 81 patients received 181 doses of DLI with prophylactic (n=21), pre-emptive (n=16) or therapeutic (n=44) intent. More patients with acute leukaemia received pre-emptive and therapeutic DLI. Majority of patients received reduced intensity conditioned alloSCT. There is also a higher percentage of ATG use in prophylactic group. Patient characteristics were otherwise well matched. Cytoreductive therapy were concurrently utilised in 73% of therapeutic DLI.Median follow up was 383 days (range: 11-2574 days) post DLI. The 1-year overall survival (OS) was 63.5% for the entire cohort, with superior OS seen in the prophylactic and pre-emptive cohort compared to therapeutic cohort (85% vs 100% vs 44%, P=0.001) (Figure 1). The 180-day incidence of grade II-IV GVHD was lower in the therapeutic DLI cohort (22%) compared to prophylactic (54%) and pre-emptive cohorts (70%) (P=0.003, respectively) (Figure 2). The 1-year incidence of relapse, relapse-free survival and GVHD, relapse-free survival in prophylactic and pre-emptive cohorts were similar. The leading cause of death in the entire cohort was PD (n=29, 68%) and occur almost exclusively within the therapeutic DLI cohort (90%). Death from GVHD was 11% across the whole group.In this analysis, PD remains the main cause of treatment failure following DLI. DLI-induced GVHD mortality was low in prophylactic and treatment cohorts. Patients receiving pre-emptive DLI had excellent survival outcomes but high incidence of GVHD, suggesting that the graft-versus-tumour effect remains inseparable from GVHD. Our analysis indicates that DLI is safe, and especially effective with acceptable risk in the pre-emptive group but largely ineffective as currently undertaken in the treatment group. A better salvage option is indicated to improve outcome in the treatment group.