Comparison of Prophylactic and Preemptive Donor Lymphocyte Infusion in Patients with Very High Risk Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

Relapse remains to be the biggest problem for patients with very high risk acute leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Donor lymphocyte infusion (DLI) has been widely applied to the prevention and preemptive intervention of relapse post-transplantation. However, the optimal time to implement DLI in patients with a high risk of relapse remains controversial. During August 1, 2014 and August 30, 2020, four hundred and thirty-one consecutive acute leukemia patients with very high-risk features underwent allo-HSCT in our center. Ninety-five patients received prophylactic DLI (pro-DLI) while one hundred and fifty-five patients received preemptive DLI (pre-DLI). Patients were stratified into five risk groups by the disease-risk stratification system (DRSS) which recently introduced by European Society for Blood and Marrow Transplantation: low risk (N=44), intermediate-1 (N=67), intermediate-2 (N=60), high (N=36), and very high (N=43). In the very high group, patients who received pro-DLI achieved higher 3-year overall survival (OS) (50.8% versus 31.8%, P=0.05), leukemia-free survival (LFS) (52.5% versus 31.6%, P=0.03) and graft-versus-host disease (GVHD)-free and relapse-free survival (GRFS) (47.9% versus 31.6%, P=0.04) compared with pre-DLI. Pro-DLI cohort was associated with a trend of lower 3-year cumulative rates of relapse (42.8% versus 57.9%, P=0.12) and non-relapse mortality (NRM) (4.6% versus 10.5%, P=0.43). In the subgroup of intermediate-2 and high (N=96), pro-DLI cohort was associated with superior survival and relapse rate, though without statistical significance. Further analysis was conducted separately between patients with positive minimal residual disease (MRD) and negative MRD pre-transplant in intermediate-2/high subgroup. In the patients with positive MRD before all-HSCT, pro-DLI achieved significant higher 3-year OS (66.7 % versus 26.2%, P=0.028), PFS (68.6 % versus 24.7%, P=0.015) and GRFS (68.6 % versus 14.4%, P=0.007), along with lower cumulative of relapse (31.4 % versus 59.3%, P=0.1) and NRM (0 versus 16%, P=0.1) compared with pre-DLI. However, pro-DLI patients was associated with inferior OS (52.7 % versus 77.8%, P=0.046), PFS(54.8 % versus 75.3%, P=0.247) and NRM (25% versus 3%, P=0.02) in patients with negative MRD. In addition, no difference was found in patients in the group of low and intermediate-1 risk. Taken together, we recommend early pro-DLI in patients of very-high risk group and positive MRD of intermediate-2/high group. Pre-DLI given timely after MRD turning positive achieved better outcome in the remaining patients.