Abstract
Relapse after allogeneic hematopoietic cell transplantation (allo-HCT) remains a major cause of treatment failure and is associated with poor prognosis. DLI is a well-established immunotherapy enhancing the graft-versus-leukemia effect and can be used in prophylactic, preemptive, or therapeutic settings. While DLI strategies are extensively studied in North America and Europe, real-world data from Latin America are scarce. This study presents a 15-year single-center experience with DLI for patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), acute lymphoblastic leukemia (ALL) and myeloproliferative neoplasm (MPN) in a transplant center in Brazil.
We conducted a retrospective analysis of all patients who underwent allo-HCT and received at least one DLI between January 2010 and June 2025 at a single transplant center in Brazil. Patients were categorized into groups based on the indication for DLI: prophylactic (high risk disease defined by ELN2022), preemptive (positive minimal residual disease or mixed chimerism), or therapeutic (after clinical or hematological relapses). Baseline features, DLI timing/dosing, engraftment, GVHD, responses, and survival were assessed. Survival analyses were performed using Kaplan-Meier estimates, and comparisons between groups were evaluated using the log-rank test.
A total of 55 patients, 27 were female and 28 male, including 34 with AML, 10 with ALL, 9 with MDS, and 2 with MPN. The median age at the time of DLI was 45 years (range, 2–73). Of these, 21 patients (38.2%) received prophylactic or preemptive DLI (pDLI), while 34 patients (61.8%) received therapeutic DLI (tDLI). Baseline characteristics, including median age, underlying disease, conditioning regimen, donor type, and cytogenetic risk, were comparable between groups.
Median number of DLI infusions administered was 2.4 (range, 1–7). In the pDLI group, 11 of 21 patients (52,3%) received two or more infusions, with a median of 3.9 doses per patient. The median initial CD3+ cell dose was 3.8 × 10⁶/kg for pDLI and 6.5 × 10⁵/kg for haploidentical transplantation. Use of hypomethylating agents with or without Venetoclax prior to DLI was more frequent in the therapeutic group (64.7% vs. 45.5%), though not statistically significant (p = 0.155). The first DLI was given at a median of 91 days (range, 20–368) after HCT in the prophylactic setting, 251 days (range, 88–605) in the preemptive setting, and 300 days (range, 28–1744) in the therapeutic setting.
With a median follow-up of 517 days post-DLI, the cohort's median OS was 572 days (95%CI: 0–1167). The pDLI group achieved longer OS (1146 days; 95%CI: 351–1941) versus the tDLI group (246 days; 95% CI: 71–421; p = 0.077), which was associated with higher mortality (HR 2.07; 95% CI: 0.91–4.71)
At last follow-up, 57,1% (12/21) of patients in the pDLI group remained alive and in remission and 16,1% (5/31) in the tDLI. Active disease prior to allo-HCT had a median overall survival nearly three times shorter than those who were MRD-negative at transplant (561 vs 1772 days, 95%IC, p=0,064).
A total of 16 (29%) out of 55 developed acute GVHD of any grade, and 10 (18,2%) developed grade III-IV aGVHD following DLI. Severe GVHD was more frequent in the therapeutic group compared to the prophylactic/preemptive group (26.5% vs. 9.1%, p = 0.027, HR 5.03, 95%CI: 1.04–24.25). Importantly, the administration of DLI seems not toincrease the risk of severe GVHD, supporting the safety of prophylactic and preemptive strategies in this cohort. Compared with matched related donors, the HR for severe GVHD was 1.53 (95% CI: 0.40–5.79) in matched unrelated donor (URD) and 0.49 (95% CI: 0.09–2.52) in haplo/mismatched URD, without statistical significance (p = 0.391). These results suggest that donor type was not significantly associated with the risk of severe GVHD after DLI in our cohort.
This 15-year single-center experience from Brazil provides real-world evidence supporting the feasibility and safety of prophylactic and preemptive DLI strategies after allo-HCT. While therapeutic DLI was associated with poorer outcomes due to underlying relapse, early DLI administration showed encouraging response rates, and a favorable safety profile, including low rates of severe GVHD. These results are consistent with international data and reinforce the value of DLI as a potentially beneficial intervention in high-risk post-transplant patients, even in resource-constrained settings.
