Long-term outcome of DLI-based treatment strategy in patients with relapsed AML after allogeneic stem cell transplantation
Relapse of acute myeloid leukemia (AML) after allogeneic stem cell transplantation (SCT) is a major clinical challenge, with poor long-term survival. Donor lymphocyte infusion (DLI) can induce an enduring 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 DLI-based treatment strategy as previously described (Eefting, Haematologica, 2014).
We retrospectively analyzed patients with AML who relapsed after first allogeneic SCT between 2005 and 2020 at the Leiden University Medical Center. Patients with a high tumor burden (>10% blasts in bone marrow or ≥5% blasts in peripheral blood) were treated with re-induction therapy prior to DLI, while patients with a smoldering relapse (≤10% blasts in bone marrow and <5% in peripheral blood) received DLI only. Survival probabilities were calculated using the Kaplan Meier method and exploratory analyses were performed using a Cox proportional hazards regression model.
A total of 84 patients were assessed. Median age was 53 years (range 18-77), median time from allogeneic SCT to relapse was 182 days (39 – 1779). Overall survival (OS) for the total cohort was 12% (95% CI 4-22) at 5 years after relapse. Sixty-four patients (76%) received re-induction therapy; the majority including high dose cytarabine. Forty-five (70%) patients received DLI thereafter, with a median time between relapse and DLI of 34 days (range 24-178). The 5-year OS for these 45 patients was 12% (95% CI 2-22). Patients with a smoldering relapse (n=7) received DLI only, with a median of 15 days (range 7-60) between relapse and DLI. 5-year OS was 54% (95% CI 34-94). For 7 patients whose relapse was diagnosed at time of prophylactic or pre-emptive DLI (median blast percentage 35%, range 15-91%), it was decided to await the effect of DLI without re-induction therapy. Six patients only received supportive care. From these two groups, no patient survived longer than 18 months.
Thirty-three (56%) out of all patients receiving DLI (n=59) achieved complete remission, of whom 26 (79%) developed GvHD and 13 (39%) died due to GvHD-related complications. The cumulative incidences of relapse and non-relapse mortality were 51% (95% CI 38-65) and 31% (95% CI 18-44) at 5 years after DLI, respectively. In univariate analysis, both smoldering and late relapse (>1 year after transplantation) were significantly associated with an improved overall survival (hazard ratio [HR] 0.29, 95% CI 0.09-0.92 and HR 0.47, 95% CI 0.22-0.98, respectively).
A DLI-based treatment strategy is a potentially curative approach for patients with relapsed AML post-allogeneic SCT, particularly for patients with a lower leukemic burden at relapse. However, long-term survival is hampered by GvHD-associated mortality and relapsing disease.