Risk-Adapted Donor Lymphocyte Infusion after Hematopoietic Cell Transplant in Pediatric and Young Adult Patients Is Associated with Low Risk of Graft Versus Host Disease

Donor lymphocyte infusion (DLI) is a form of adoptive immunotherapy administered in patients experiencing mixed chimerism (MC) or disease relapse after an allogeneic hematopoietic cell transplantation (HCT). Success is limited by the occurrence of acute and chronic graft-versus-host disease (GVHD). To determine the efficacy and toxicity of DLIs and to identify potential factors influencing the outcomes, we conducted a retrospective single center study including patients who received DLIs after HCT. We collected data on all HCTs and conventional DLIs that had been administered from 1993 to 2022 for any indication at our center. Competing-risk regression models using the Fine-Gray method were developed to evaluate risk factors for acute and chronic GVHD. Death and relapse were considered as competing risk events. Logistic regression analysis was performed to assess factors associated with the response to DLI within 180 days after the first DLI. In the study, 236 patients received 252 HCTs followed by DLIs (median age at HCT 9.2 [range 0.2-25.1] years). Additionally, 743 patients received 806 HCTs with no subsequent DLI (median age at HCT 10.3 [range 0.1-27.2] years). Dosing most frequently used was 1 × 105, 1 × 106 and 1 × 107 CD3+ cells/kg, for haploidentical donor (HAPLO), matched unrelated donor (MUD) and matched sibling donor (MSD) recipients, respectively. After receiving DLI, 19.4% developed acute GVHD, and 9.2% developed chronic GVHD with no significant differences between MSD, MUD and HAPLO recipients. After adjusting for donor source, longer duration between HCT and DLI was associated with a decreased risk of both acute (HR 0.97 P<0.001) and chronic GVHD (HR 0.98 P=0.04). A higher CD3+ cell dose was associated with an increased risk of acute GVHD (HR 1.03 P<0.001) but not chronic GVHD (HR 0.96 P=0.12). The overall response rate after DLI for treating MC was 45.2% for MSD, 32.6% for MUD and 41.4% for HAPLO recipients. Logistic regression analysis revealed leukemia patients had a higher response rate after receiving a DLI for mixed chimerism from MSD (OR=19.5 P=0.002) and HAPLO (OR=9.03 P=0.042), but not from MUD HCT (OR=0.65 P= 0.57), compared to patients with non-malignant disorders. The response rate after DLI for frank disease relapse was 50% (1/2) for MSD, 44.4% (4/9) for HAPLO, but 0% (0/4) for MUD recipients. In summary, the incidence of GVHD was not higher in HCT recipients who received DLI as compared to those who did not. The risk of developing acute and chronic GVHD after DLI was low and comparable between different donor sources. This risk decreased further away from HCT and increased with higher DLI dose. Thus, DLIs may be safely administered to pediatric and young adult patients after HCT. The therapeutic effect may be modulated by adjusting the dose, timing and frequency of DLI administration.