Interferon-α Is Effective for Treatment of Minimal Residual Disease in Patients with t(8;21) Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation: Results of a Prospective Registry Study.

BACKGROUND: RUNX1-RUNX1T1 transcript levels were established as a powerful marker for predicting relapse in patients with t(8;21) acute myeloid leukemia (AML). We aimed to identify the efficacy of minimal residual disease (MRD)-directed interferon-alpha (IFN-α) treatment in patients with t(8;21) AML who were positive for MRD after allogeneic hematopoietic stem cell transplantation (allo-HSCT; n=42). SUBJECTS, MATERIALS, AND METHODS: MRD-positive status was defined as a <4.5-log reduction from diagnosis in RUNX1-RUNX1T1 transcripts and/or the loss of a ≥4.5-log reduction after 3 months after HSCT. Patients with positive MRD received six cycles of IFN-α treatment (twice or thrice weekly of every 4 weeks cycle). RESULTS: The 1-year cumulative incidence of severe acute and chronic graft-versus-host disease after MRD-directed IFN-α treatment was 7.1% and 4.8%, respectively. After the treatment, 15 (35.7%), 5 (11.9%), 3 (7.1%), and 9 (21.5%) patients achieved MRD negativity at 1, 2, 3, and >3 months, respectively. Three patients relapsed after the IFN-α treatment, in which the 1-year cumulative incidence of relapse was 7.2%. One patient died of severe infection at 460 days after treatment. The 1-year probabilities of event-free survival, disease-free survival, and overall survival after treatment were 76.0%, 92.4%, and 92.5%, respectively. The clinical outcomes in patients who received MRD-directed IFN-α treatment were significantly better than those of the MRD-positive patients without any interventions in the historical cohort. CONCLUSION: MRD-directed IFN-α treatment is effective for patients with t(8;21) AML who were MRD-positive after allo-HSCT. The study was registered at http://clinicaltrials.gov as NCT02027064. IMPLICATIONS FOR PRACTICE: In patients with t(8;21) acute myeloid leukemia (AML), the presence of post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) minimal residual disease (MRD), measured by RUNX1-RUNX1T1 transcript levels, has been established as a powerful marker for predicting relapse. Interferon-alpha (IFN-α) could exert a relatively strong graft-versus-leukemia effect, and MRD-directed IFN-α treatment is effective for patients with t(8;21) AML who were MRD-positive after allo-HSCT.