Muticenter Retrospective Comparable Study of Prophylactic Versus Preemptive Modified Donor Lymphocyte Infusion for Patients with High-Risk Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

Objective: To compare the efficacy and safety of prophylactic modified DLI (pro-DLI) and preemptive modified DLI (pre-DLI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with high-risk acute leukemia

Method: Patients with high-risk acute leukemia who received myeloablative conditioning and allo-HSCT during August 1, 2014 to August 30, 2020 were eligible for this study. Pro-DLI was scheduled at three months after HSCT for patients in pro-DLI cohort. In the pre-DLI cohort, patients would stop immunosuppressive drugs and receive pre-DLI immediately after MRD turning positive with morphology remission.

Result: Pro-DLI was performed in ninty-five patients while two hundred and six patients were included in the pre-DLI cohort. Thirty-eight patients in the pre-DLI cohort became positive MRD and received pre-DLI. Patients in the pro-DLI cohort achieved a lower cumulative incidence of relapse (CIR) (27.6% versus 37.1%, p=0.027) and comparable overall survival (OS) (65.2% versus 59.3%, p=0.303) comparing with patients in the pre-DLI cohort. The 100-days cumulative incidence of grade III-IV acute graft-versus-host-disease (aGVHD) and chronic graft-versus-host-disease (cGVHD) were comparable between cohorts. Further subgroup analysis of patients who received allo-HSCT at CR1, pro-DLI achieved lower 3-year cumulative incidence of relapse (CIR) (27.6% versus 37.1%, p=0.027) while no benefit in OS (72.2% versus 69.2%, p=0.864) comparing with pre-DLI cohort. On the other hand, pro-DLI significantly decreased the CIR (13.25% versus 28.77%, p=0.044) and increased OS (60.7% versus 42.3%, p=0.022) when compared with pre-DLI in patients who received HSCT beyond CR1. Multivariate analysis demonstrated the strong protective effect of pro-DLI on long-term OS and PFS in patients who received HSCT beyond CR1.

Conclusion: From these date, pro-DLI was highly recommended for patients with high-risk features who received allo-HSCT beyond CR1 with significantly decreased incidence of relapse and increased survival rates. Pre-DLI could be chosen by those who received allo-HSCT in CR1 in view of comparable survival rates regardless of higher relapse rates compared with pro-DLI.

No relevant conflicts of interest to declare.