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  • Review Article
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Minimal residual disease in acute myeloid leukaemia

Abstract

Technological advances in the laboratory have led to substantial improvements in clinical decision making through the introduction of pretreatment prognostic risk stratification factors in acute myeloid leukaemia (AML). Unfortunately, similar progress has not been made in treatment response criteria, with the definition of 'complete remission' in AML largely unchanged for over half a century. Several clinical trials have demonstrated that high-sensitivity measurements of residual disease burden during or after treatment can be performed, that results are predictive for clinical outcome and can be used to improve outcomes by guiding additional therapeutic intervention to patients in clinical complete remission, but at increased relapse risk. We review these recent trials, the characteristics and challenges of the modalities currently used to detect minimal residual disease (MRD), and outline opportunities to both refine detection and improve clinical use of MRD measurements. MRD measurement is already the standard of care in other myeloid malignancies, such as chronic myelogenous leukaemia and acute promyelocytic leukaemia (APL). It is our belief that response criteria for non-APL AML should be updated to include assessment for molecular complete remission and recommendations for post-consolidation surveillance should include regular monitoring for molecular relapse as standard of care.

Key Points

  • Complete remission as currently defined in patients with acute myeloid leukaemia (AML) represents a highly heterogeneous state with a wide range of tumour burden and diverse clinical outcomes

  • Multiple high sensitivity methods exist for detecting AML minimal residual disease in patients in a morphological complete remission

  • Use of minimal residual disease status as a response criterion allows for the high sensitivity assessment of the efficacy of AML therapy

  • Minimal residual disease measurement during or after therapy for AML is prognostic and can risk-stratify patients to identify those most likely to benefit from escalated or additional therapy

  • For patients in complete remission minimal disease quantification of remaining leukaemic burden may supersede descriptors of disease biology (such as cytogenetics and molecular markers) for predicting subsequent risk of relapse

  • Thresholds can be established during post-treatment surveillance that when exceeded are predictive of future haematological relapse; therapeutic intervention at this stage can be effective in delaying or preventing relapse

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Figure 1: Detection thresholds of various MRD modalities compared to traditional clinical complete remission.
Figure 2: Potential integration of minimal residual disease measurement into acute myeloid leukaemia treatment.

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Acknowledgements

The authors wish to thank Gouri Bardhan, A. John Barrett, Minoo Battiwalla, Luis Diaz, Meghali Goswami, Philip J. McCoy and Sandhya Panch for useful discussions and Alan Hoofring of the NIH Medical Arts Service for assistance in creating Figure 1. This research was supported by National Institutes of Health grant P30CA006973 (JEK) and the Intramural Research Program of the NIH, National Heart, Lung and Blood Institute (CSH). Any views expressed here represent personal opinion and do not necessarily reflect those of the U. S. Department of Health and Human Services, or the United States federal government.

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Both authors researched the data for the article and made a substantial contribution to a discussion of the content. C. S. Hourigan wrote the article, and both authors reviewed and edited the manuscript before submission.

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Hourigan, C., Karp, J. Minimal residual disease in acute myeloid leukaemia. Nat Rev Clin Oncol 10, 460–471 (2013). https://doi.org/10.1038/nrclinonc.2013.100

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