Prophylactic Donor Lymphocyte Infusion (DLI) Followed by Minimal Residual Disease and Graft-versus-Host Disease–Guided Multiple DLIs Could Improve Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Refractory/Relapsed Acute Leukemia

Abstract

Patients with refractory/relapsed acute leukemia who have received allogeneic hematopoietic stem cell transplantation (allo-HSCT) are still at a high risk for relapse post-transplant. To investigate the impact of prophylactic donor lymphocyte infusion (DLI) followed by minimal residual disease (MRD) test and graft-versus-host disease (GVHD)–guided multiple DLIs to prevent relapse and improve survival in patients with refractory/relapsed acute leukemia who received allo-HSCT. A multicenter prospective study was designed. In total, 100 patients who achieved complete remission at 30 days post-transplant and had no uncontrolled infection, organ failure, or active GVHD were eligible First, prophylactic DLI was administered at 30 days after HLA-matched related HSCT or 45 to 60 days after HLA-matched unrelated HSCT or haploidentical HSCT. Subsequently, multiple DLIs were administered based on the results of MRD test and whether they developed GVHD. In addition to DLI, chemotherapy was also given to patients who had a positive MRD test. Three-year cumulative incidence of relapse, leukemia-free survival, and survival post-transplant were 32.4% (95% confidence interval, 22.4% to 42.4%), 50.3% (95% confidence interval, 40.3% to 60.3%), and 51.4% (95% confidence interval, 41.2% to 61.6%), respectively. In multivariate analysis, a positive MRD test (HR, 3.840; 95% confidence interval, 1.678 to 5.784; P = .001) and receiving 1 course of DLI (HR, 4.346; 95% confidence interval, 1.223 to 9.450, P = .023) were associated with an increased relapse risks. These data suggest that prophylactic DLI followed by MRD test and GVHD-guided multiple DLIs reduced relapse and increased survival post-transplant in patients with refractory/relapsed acute leukemia who received allo-HSCT. The study is registered at www.ClinicalTrials.gov as NCT01455272.