Measurable Residual Disease Monitoring by Locked Nucleic Acid Quantitative Real-Time PCR Assay for IDH1/2 Mutation in Adult AML

• Published in: Cancers Vol. 14; no. 24; p. 6205
• Main Authors: Kao, Hsiao-Wen, Kuo, Ming-Chung, Huang, Ying-Jung, Chang, Hung, Hu, Shu-Fen, Huang, Chein-Fuang, Hung, Yu-Shin, Lin, Tung-Liang, Ou, Che-Wei, Lien, Ming-Yu, Wu, Jin-Hou, Chen, Chih-Cheng, Shih, Lee-Yung
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15.12.2022; MDPI
• Subjects: acute myeloid leukemia; Bone marrow; Chemotherapy; Copy number; IDH1/2 mutation; Induction therapy; locked nucleic acid quantitative PCR; measurable residual disease; Medical prognosis; Mutants; Mutation; NPM1 mutation; Nucleic acids; Remission; Remission (Medicine); Statistical analysis; Survival; Taiwan; IDH1/2 mutation; acute myeloid leukemia; NPM1 mutation; measurable residual disease; locked nucleic acid quantitative PCR
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14246205

Locked nucleic acid quantitative Real-Time PCR (LNA-qPCR) for IDH1/2 mutations in AML measurable residual disease (MRD) detection is rarely reported. LNA-qPCR was applied to quantify IDH1/2 mutants MRD kinetics in bone marrow from 88 IDH1/2-mutated AML patients, and correlated with NPM1-MRD, clinical characteristics, and outcomes. The median normalized copy number (NCN) of IDH1/2 mutants decreased significantly from 53,228 (range 87−980,686)/ALB × 106 at diagnosis to 773 (range 1.5−103,600)/ALB × 106 at first complete remission (CR). IDH1/2 LNA-qPCR MRD was concordant with remission status or NPM1-MRD in 79.5% (70/88) of patients. Younger patients and patients with FLT3 mutations had higher concordance. The Spearman correlation coefficient (rs) and concordance rate between the log reduction of IDH1/2 LNA-qPCR and NPM1-MRD were 0.68 and 81% (K = 0.63, 95% CI 0.50−0.74), respectively. IDH1/2-MRD > 2 log reduction at first CR predicted significantly better relapse-free survival (3-year RFS rates 52.9% vs. 31.9%, p = 0.007) and cumulative incidence of relapse (3-year CIR rates 44.5% vs. 64.5%, p = 0.012) compared to IDH1/2-MRD ≤ 2 log reduction. IDH1/2-MRD > 2 log reduction during consolidation is also associated with a significantly lower CIR rate than IDH1/2-MRD ≤ 2 log reduction (3-year CIR rates 42.3% vs. 68.8%, p = 0.019). LNA-qPCR for IDH1/2 mutation is a potential MRD technique to predict relapse in IDH1/2-mutated AML patients, especially for those with IDH1/2 MRD > 2 log reduction at first CR or a concurrent FLT3 mutation.