Long-term Outcome of a DLI-based Treatment Strategy in Patients With Relapsed AML After TCD Allogeneic Stem Cell Transplantation is Hampered by GvHD and Late Relapse

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Relapse of acute myeloid leukemia (AML) after allogeneic stem cell transplantation (alloSCT) remains a major cause of treatment failure, with poor long-term survival. Donor lymphocyte infusion (DLI) can induce a graft-versus-leukemia effect but may also lead to graft-versus-host disease (GvHD) associated morbidity and mortality. In this study we evaluated the 5-year overall survival of a treatment strategy combining cytoreduction, dose-escalated DLI and interferon-α in patients with relapsed AML after T-cell depleted alloSCT. In this single-center, retrospective cohort study we analyzed 84 adult patients with relapsed AML after first alloSCT with in vitro T-cell depletion (TCD), and in a proportion of patients combined with in vivo TCD. The study was performed at Leiden University Medical Center between 2005 and 2020, with follow-up through January 2025. Patients with low-burden morphologic relapse (≤10% bone marrow blasts) received DLI without prior cytoreduction; patients with higher-burden morphologic relapse received cytoreductive therapy followed by DLI 3 weeks later. In the absence of GvHD 3 weeks after DLI, interferon-α was administered to augment the alloimmune response. Quality of life in long-term survivors was assessed exploratively. Six patients received supportive care only, leaving 78 patients treated per protocol. Patients with low-burden morphologic relapse (n = 8) received DLI without cytoreduction and achieved a 5-year OS of 60% (95% confidence interval [CI] 22 to 98). In 7 additional patients, higher-burden morphologic relapse was unexpectedly diagnosed at the time of a pre-scheduled prophylactic or pre-emptive DLI. Cytoreduction was deferred to await the effect of this DLI, yet none of these patients survived beyond 18 months. Among 63 patients with higher-burden morphologic relapse who received re-induction therapy with intent to proceed to DLI, 44 (70%) ultimately received DLI, of whom 25 (57%) developed GvHD. The 5-year OS for the re-induction cohort was 7% (95% CI 1 to 13). Of 44 patients who reached DLI, 24 (55%) achieved complete remission. In this subset, 2- and 5-year RFS were 35% and 19%, respectively, with 5-year cumulative incidences of relapse and nonrelapse mortality of 25% (95% CI 12 to 45) and 42% (95% CI 25 to 51). Transplantation in first complete remission (hazard ratio [HR] 0.40, P = .017) and relapse occurring more than 6 months after alloSCT (HR 0.44, P = .036) were associated with improved OS. Long-term survivors reported good global mental health but persistent GvHD-related symptoms and impaired social and functional well-being. A DLI-based strategy can induce durable remission in patients with low-burden morphologic AML relapse after TCD alloSCT, even without prior cytoreduction. In higher-burden morphologic relapse, however, effective cytoreduction followed by DLI and interferon-α is essential, yet long-term outcomes remain poor, constrained by GvHD-associated nonrelapse mortality as well as recurrent leukemia. These results define the long-term boundaries of therapeutic DLI and provide a contemporary reference standard for novel post-transplant relapse interventions.

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