The Prognostic Value of Minimal Residual Disease Assessed During the Remission Induction Stage in Acute Myeloid Leukemia Patients
DOI:
https://doi.org/10.21320/2500-2139-2025-18-3-233-241BACKGROUND. The assessment of minimal residual disease (MRD) in acute myeloid leukemias (AML) is an important tool for predicting treatment outcomes, especially in patients with favorable and intermediate cytogenetic/molecular risk. MRD assessed by multicolor flow cytometry (MFC) allows to identify patients with high relapse risk. MRD-positive status after the second chemotherapy cycle is associated with low long-term survival rates.
AIM. To assess the long-term therapy outcomes in AML patients with vs. without MRD measured during the remission induction stage.
MATERIALS & METHODS. The study enrolled 73 AML patients treated at the National Research Center for Hematology from 2017 to 2021. They were aged 17 to 58 years (median 37 years); there were 45 women and 28 men. Patients were treated with the ‘ОМЛ-17’ and ‘mОМЛ-17’ regimens. MRD was measured by MFC after the first and second induction chemotherapy cycles.
RESULTS. After 2 induction cycles, complete remission was achieved in 89.1 % (65/73) of patients. After the first cycle, MRD-negative status was confirmed in 66.7 % (38/57) of patients and after the second one it was documented in 74.6 % (44/59) of patients. MRD-positive status after the first and the second chemotherapy cycles was associated with the lowest rates of overall and disease-free survival as well as higher relapse risk. Multivariate analysis confirmed MRD-negative status in the period of complete remission to be a key factor in reducing the relapse risk and mortality.
CONCLUSION. The present study demonstrates that MRD status at two end-points of the program AML therapy (after the first and second induction cycles) serves as an optimal basis for predicting treatment outcomes. MRD-positive status at each of these end-points is associated with a high relapse risk and worse survival. Therefore, MRD monitoring during the remission induction stage is a powerful tool for personalizing the therapy and improving the prognosis of AML patients.
- Maurillo L, Buccisano F, Del Principe MI, et al. Toward optimization of postremission therapy for residual disease-positive patients with acute myeloid leukemia. J Clin Oncol. 2008;26(30):4944–51. doi: 10.1200/JCO.2007.15.9814. DOI: https://doi.org/10.1200/JCO.2007.15.9814
- Terwijn M, van Putten WLJ, Kelder A, et al. High prognostic impact of flow cytometric minimal residual disease detection in acute myeloid leukemia: data from the HOVON/SAKK AML 42A study. J Clin Oncol. 2013;31(31):3889–97. doi: 10.1200/JCO.2012.45.9628. DOI: https://doi.org/10.1200/JCO.2012.45.9628
- Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424–47. doi: 10.1182/blood-2016-08-733196. DOI: https://doi.org/10.1182/blood-2016-08-733196
- Wood B. Multicolor immunophenotyping: human immune system hematopoiesis. Methods Cell Biol. 2004;75:559–76. doi: 10.1016/s0091-679x(04)75023-2. DOI: https://doi.org/10.1016/S0091-679X(04)75023-2
- Wood BL. Flow cytometric monitoring of residual disease in acute leukemia. Methods Mol Biol. 2013;999:123–36. doi: 10.1007/978-1-62703-357-2_8. DOI: https://doi.org/10.1007/978-1-62703-357-2_8
- Venditti A, Piciocchi A, Candoni A, et al. GIMEMA AML1310 trial of risk-adapted, MRD-directed therapy for young adults with newly diagnosed acute myeloid leukemia. Blood. 2019;134(12):935–45. doi: 10.1182/blood.2018886960. DOI: https://doi.org/10.1182/blood.2018886960
- Brüggemann M, Raff T, Kneba M. Has MRD monitoring superseded other prognostic factors in adult ALL? Blood. 2012;120(23):4470–81. doi: 10.1182/blood-2012-06-379040. DOI: https://doi.org/10.1182/blood-2012-06-379040
- Freeman SD, Hills RK, Virgo P, et al. Measurable Residual Disease at Induction Redefines Partial Response in Acute Myeloid Leukemia and Stratifies Outcomes in Patients at Standard Risk Without NPM1 Mutations. J Clin Oncol. 2018;36(15):1486–97. doi: 10.1200/JCO.2017.76.3425. DOI: https://doi.org/10.1200/JCO.2017.76.3425
- Burnett AK, Russell NH, Hills RK, et al. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML15 trial. J Clin Oncol. 2013;31(27):3360–8. doi: 10.1200/JCO.2012.47.4874. DOI: https://doi.org/10.1200/JCO.2012.47.4874
- Capizzi RL, Powell BL, Cooper MR, et al. Sequential high-dose ara-C and asparaginase in the therapy of previously treated and untreated patients with acute leukemia. Semin Oncol. 1985;12(2 Suppl 3):105–13.
- Wu D, Duan C, Chen L, Chen S. Efficacy and safety of different doses of cytarabine in consolidation therapy for adult acute myeloid leukemia patients: a network meta-analysis. Sci Rep. 2017;7(1):9509. doi: 10.1038/s41598-017-10368-0. DOI: https://doi.org/10.1038/s41598-017-10368-0
- Preisler H, Raza A, Larson R, et al. Some reasons for the lack of progress in the treatment of acute myelogenous leukemia: a review of three consecutive trials of the treatment of poor prognosis patients. Leuk Res. 1991;15(9):773–80. doi: 10.1016/0145-2126(91)90460-b. DOI: https://doi.org/10.1016/0145-2126(91)90460-B
- Maurillo L, Buccisano F, Piciocchi A, et al. Minimal residual disease as biomarker for optimal biologic dosing of ARA-C in patients with acute myeloid leukemia. Am J Hematol. 2015;90(2):125–31. doi: 10.1002/ajh.23893. DOI: https://doi.org/10.1002/ajh.23893
- Rubnitz JE, Inaba H, Dahl G, et al. Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trial. Lancet Oncol. 2010;11(6):543–52. doi: 10.1016/S1470-2045(10)70090-5. DOI: https://doi.org/10.1016/S1470-2045(10)70090-5
Keywords:
acute myeloid leukemias, minimal residual disease, flow cytometry
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