Prophylactic Donor Lymphocyte Infusion Based on Two Different Time for Preventing Relapse in Advanced Acute Leukemia Undergoing Allo-HSCT: Comparison of Two Independent Prospective Cohorts

Background: Prophylactic donor lymphocyte infusion (pDLI) can reduce relapse in advanced acute leukemia (AL) undergoing allogeneic hematopoitic stem cell transplantation (allo-HSCT), but the optimal timing of pDLI remains uncertain. Our previous study demonstrated that pDLI on day +60 post-transplant regardless of minimal residual disease (MRD) could reduce relapse, but the incidence and mortality of graft-versus-host disease (GVHD) were high. To reduce GVHD post-pDLI, we modified our pDLI strategy by delaying the time to day +90 unless MRD was positive on day +60.

Methods: This study population came from two prospective multicenter cohorts. In cohort 1, pDLI was given once on day +60 regardless of MRD for all patients without grade II/>II acute GVHD (aGVHD), and then administered based on MRD and GVHD. In cohort 2, for patients who were MRD negative on day +60 and did not experience grade II/>II aGVHD by day +90, pDLI was given once on day +90 and then administered based on MRD and GVHD. For patients with positive MRD on day +60, the application of pDLI was conducted according to cohort 1. The outcomes of pDLI at two different time were compared.

Results: A total of 161 advanced AL undergoing allo-HSCT from January 2012 to December 2017 were enrolled, including 83 from January 2012 to December 2014 in cohort 1 (74 receiving pDLI) and 78 from January 2015 to December 2017 in cohort 2 (69 receiving pDLI). The extensive chronic GVHD (cGVHD) incidence in cohort 2 was lower than that in cohort 1 (10.3% vs 27.9%, P=0.006) and GVHD-free/relapse-free survival (GRFS) in cohort 2 was superior to that in cohort 1 (55.1% vs 41.0%, P=0.042). The 2-year relapse rate, overall and leukemia-free survival were similar between the two cohorts (29.0% vs 28.2%, P=0.986; 63.9% vs 64.1%, P=0.863; 57.8% vs 61.5%, P=0.666). Multivariate analysis revealed that modified pDLI strategy was the only protective factor for GRFS (P=0.015, HR=0.470).