Abstract
In patients with t(8;21) acute myeloid leukemia (AML), recurrent minimal residual disease (MRD) measured by RUNX1-RUNX1T1 transcript levels can predict relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to compare the efficacy of preemptive interferon (IFN)-α therapy and donor lymphocyte infusion (DLI) in patients with t(8;21) AML following allo-HSCT. We also evaluated the appropriate method for patients with different levels of RUNX1-RUNX1T1 transcripts. In this retrospective study, consecutive patients who had high-risk t(8;21) AML and received allo-HSCT were enrolled. The inclusion criteria were as follows: (1) age ≤65 years; (2) regained MRD positive following allo-HSCT. MRD positive was defined as the loss of a ≥4.5-log reduction and/or <4.5-log reduction in the RUNX1-RUNX1T1 transcripts, and high-level, intermediate-level, and low-level MRDs were, respectively, defined as <2.5-log, 2.5−3.5-log, and 3.5−4.5-log reductions in the transcripts compared with the pretreatment baseline level. Patients with positive RUNX1-RUNX1T1 could receive preemptive IFN-α therapy or DLI, which was primarily based on donor availability and the intentions of physicians and patients. The patients received recombinant human IFN-α-2b therapy by subcutaneous injection twice a week every 4 weeks. IFN-α therapy was scheduled for six cycles or until the RUNX1-RUNX1T1 transcripts were negative for at least two consecutive tests. The rates of MRD turning negative for patients with low-level, intermediate-level, and high-level RUNX1-RUNX1T1 receiving IFN-α were 87.5%, 58.1%, and 22.2%, respectively; meanwhile, for patients with intermediate-level and high-level RUNX1-RUNX1T1 receiving DLI, the rates were 50.0% and 14.3%, respectively. For patients with low-level and intermediate-level RUNX1-RUNX1T1, the probability of overall survival at 2 years was higher in the IFN-α group than in the DLI group (87.6% vs. 55.6%; p = 0.003). For patients with high levels of RUNX1-RUNX1T1, the probability of overall survival was comparable between the IFN-α and DLI groups (53.3% vs. 83.3%; p = 0.780). Therefore, patients with low-level and intermediate-level RUNX1-RUNX1T1 could benefit more from preemptive IFN-α therapy compared with DLI. Clinical outcomes were comparable between preemptive IFN-α therapy and DLI in patients with high-level RUNX1-RUNX1T1; however, they should be further improved.
Highlights
Acute myeloid leukemia (AML) with t(8;21) is a heterogeneous disease, and relapse can occur in 40–50% of patients treated with chemotherapy alone, even if it is considered to have a good prognosis [1, 2]
We observed that donor type, Kit mutation, other karyotypic abnormalities, and duration of immunosuppressive therapy before Minimal residual disease (MRD) were not associated with posttransplant RUNX1-RUNX1T1 levels (Supplementary Tables S2, S3 and Supplementary Figure S1); pre-transplant transcripts were associated with posttransplant RUNX1-RUNX1T1 levels (Supplementary Table S2 and Supplementary Figure S1C)
The cumulative incidences of relapse, nonrelapse mortality (NRM), Leukemia-free survival (LFS), and overall survival (OS) at 2 years after preemptive interventions were 16.8% [95% confidence interval (CI), 8.7% −24.8%] versus 19.6% (p = 0.810), 3.6% versus 20.1% (p = 0.001), 78.2% versus 60.3% (p = 0.023), and 84.2% versus 66.7% (p = 0.004), respectively, for the IFN-a and donor lymphocyte infusion (DLI) groups
Summary
Acute myeloid leukemia (AML) with t(8;21) is a heterogeneous disease, and relapse can occur in 40–50% of patients treated with chemotherapy alone, even if it is considered to have a good prognosis [1, 2]. The MRD measured by the level of RUNX1-RUNX1T1 transcript has been identified as an effective predictor of relapse in patients with t(8;21) AML after allo-HSCT [13, 14]. Interferon-a (IFN-a) is another important immunotherapy after allo-HSCT [18,19,20,21,22]; Mo et al [20] reported that the survival of patients with MRD positive without any intervention was significantly lower than those receiving preemptive IFN-a therapy [20]. IFN-a therapy and DLI could improve the prognosis of patients with MRD following allo-HSCT. Mo et al [21] reported that the prognosis of preemptive DLI and IFN-a therapy was comparable, but their study included a small sample size of patients with t(8;21) AML. No studies have compared the efficacy of preemptive DLI and IFN-a therapy in patients with t(8;21) AML
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