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.

Figure 1. Detection thresholds of various MRD modalities compared to traditional clinical complete remission

Axis scales approximate and solely for illustrative purposes. http://www.nature.com/nrclinonc/journal/v10/n8/fig_tab/nrclinonc.2013.100_F1.html and http://www.nature.com/nrclinonc/journal/v10/n8/fig_tab/nrclinonc.2013.100_F2.html