AUTHOR=Fan Shuang , Shen Meng-Zhu , Zhang Xiao-Hui , Xu Lan-Ping , Wang Yu , Yan Chen-Hua , Chen Huan , Chen Yu-Hong , Han Wei , Wang Feng-Rong , Wang Jing-Zhi , Zhao Xiao-Su , Qin Ya-Zhen , Chang Ying-Jun , Liu Kai-Yan , Huang Xiao-Jun , Mo Xiao-Dong 

TITLE=Preemptive Immunotherapy for Minimal Residual Disease in Patients With t(8;21) Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.773394

DOI=10.3389/fonc.2021.773394

ISSN=2234-943X

ABSTRACT=In patients with t(8;21) acute myeloid leukemia (AML), minimal residual disease (MRD) measured by RUNX1-RUNX1T1 transcript levels could predict relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the present study, we aimed to compare the efficacy of preemptive interferon (IFN)-α therapy and donor lymphocyte infusion (DLI) in AML patients with t(8;21) following allo-HSCT. We also evaluated the appropriate method for patients with different RUNX1-RUNX1T1 transcript levels. In this retrospective study, consecutive patients who had high-risk t(8;21) AML and received allo-HSCT were enrolled if they met the following criteria: (1) was ≤65 years old; (2) and regained MRD positive following allo-HSCT. MRD positive was defined as a loss of a ≥4.5-log reduction and/or the <4.5-log reduction in RUNX1-RUNX1T1 transcripts, and low-level, intermediate-level, and high-level MRDs were respectively defined as 3.5 to 4.5-log, 2.5 to 3.5-log, and <2.5-log reductions in the transcripts comparing with the pretreatment baseline level. Patients with positive RUNX1-RUNX1T1 could receive preemptive IFN-α therapy or DLI, which was mainly according to donor availability and the intentions of physicians and patients. Patients received recombinant human IFN-α-2b therapy by subcutaneous injection twice a week in every 4 weeks cycle. IFN-α therapy was scheduled for 6 cycles or until RUNX1-RUNX1T1 transcripts were negative at least for 2 consecutive tests. The rate of MRD turning negative was 87.5%, 58.1%, and 22.2% for low-, intermediate- and high-level RUNX1-RUNX1T1 patients who received IFN-α as initial therapy, and it was 50.0% and 14.3% for intermediate- and high-level RUNX1-RUNX1T1 patients who received DLI as initial therapy. For the patients with low- and intermediate-level RUNX1-RUNX1T1, the probability of survival at 2 years for IFN-α group was better than that of DLI group (87.6% vs. 55.6%, p=0.003). For the patients with high-level RUNX1-RUNX1T1, the probability of survival was comparable between IFN-α group and DLI group (53.3% vs. 83.3%, p=0.780). Thus, patients with low- and intermediate-level RUNX1-RUNX1T1 might benefit more from preemptive IFN-α therapy compared with DLI. The clinical outcomes were comparable between preemptive IFN-α therapy and DLI for patients with high-level RUNX1-RUNX1T1; however, they should be further improved.