Optimized clinical application of minimal residual disease in acute myeloid leukemia with RUNX1-RUNX1T1.

Abstract

Minimal residual disease (MRD) levels monitored by polymerase chain reaction are associated with outcomes in acute myeloid leukemia with RUNX1-RUNX1T1. The objectives of our study were to quantitatively compare the predictive value of MRD reduction and absolute copies and assess the influence of other prognostic factors on MRD. A total of 224 consecutive patients with RUNX1-RUNX1T1 aged ≤55 years were included in the MRD study. Patients received different induction regimens including conventional- or intermediate-dose cytarabine plus low-dose daunorubicin and omacetaxine mepesuccinate or daunorubicin at 60 mg/m2/day on days 1-3. As continuous variables, both MRD reduction and absolute MRD level were significantly associated with cumulative incidence of relapse (CIR; hazard ratio [HR] = 1.610, 95% confidence interval [CI]: 1.370-1.890, p < 0.001, and HR = 1.170, 95% CI: 1.120-1.230, p < 0.001, respectively). For the CIR, the area under the curves (AUCs) of MRD reduction and absolute MRD level after the first consolidation chemotherapy were 0.629 and 0.629, respectively. Intermediate-dose cytarabine induction (HR = 0.494; p = 0.039 for CIR, HR, 0.451; p = 0.014 for RFS, and HR, 0.262; p = 0.006 for OS) remained significantly associated with outcomes after adjusting for MRD reduction after the first consolidation therapy (HR = 1.456, p < 0.001, for CIR; HR = 1.467, p = 0.001, for relapse-free survival; and HR = 1.468, p = 0.014, for overall survival) in multivariate analyses. In conclusion, the prognostic significance of MRD after the first consolidation therapy was influenced by the induction regimen in acute myeloid leukemia with RUNX1-RUNX1T1.

• Authors: Hui Wei, Xueou Liu, Ying Wang, Dong Lin, Chunlin Zhou, Bingcheng Liu, Shaowei Qiu, Runxia Gu, Yan Li, Shuning Wei, Benfa Gong, Kaiqi Liu, Xiaoyuan Gong, Yuntao Liu, Guangji Zhang, Qiuyun Fang, Junping Zhang, Jingjing Jin, Yueshen Ma, Yingchang Mi, Jianxiang Wang
• Journal: Experimental hematology (Exp Hematol) Vol. 96 Pg. 63-72.e3 (04 2021) ISSN: 1873-2399 [Electronic] Netherlands
• PMID: 33524443 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Core Binding Factor Alpha 2 Subunit
• Oncogene Proteins, Fusion
• RUNX1 Translocation Partner 1 Protein
• RUNX1 protein, human
• RUNX1T1 protein, human
• Cytarabine

Topics

• Adolescent
• Adult
• Antineoplastic Agents (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Core Binding Factor Alpha 2 Subunit (genetics)
• Cytarabine (therapeutic use)
• Female
• Humans
• Leukemia, Myeloid, Acute (diagnosis, drug therapy, genetics)
• Male
• Middle Aged
• Neoplasm, Residual (diagnosis, drug therapy, genetics)
• Oncogene Proteins, Fusion (genetics)
• Prognosis
• RUNX1 Translocation Partner 1 Protein (genetics)
• Young Adult