Abstract
Outcomes for those diagnosed with acute myeloid leukemia (AML) remain poor. It has been widely established that persistent residual leukemic burden, often referred to as measurable or minimal residual disease (MRD), after induction therapy or at the time of hematopoietic stem cell transplant (HSCT) is highly predictive for adverse clinical outcomes and can be used to identify patients likely to experience clinically evident relapse. As a result of inherent genetic and molecular heterogeneity in AML, there is no uniform method or protocol for MRD measurement to encompass all cases. Several techniques focusing on identifying recurrent molecular and cytogenetic aberrations or leukemia-associated immunophenotypes have been described, each with their own strengths and weaknesses. Modern technologies enabling the digital quantification and tracking of individual DNA or RNA molecules, next-generation sequencing (NGS) platforms, and high-resolution imaging capabilities are among several new avenues under development to supplement or replace the current standard of flow cytometry. In this review, we outline emerging modalities positioned to enhance MRD detection and discuss factors surrounding their integration into clinical practice.
Highlights
Acute myeloid leukemia (AML) is a malignancy of blood-forming stem cells in which recurrent genetic mutations and chromosomal aberrations are associated with the clonal expansion of immature myeloid populations [1,2]
It is increasingly appreciated that minimal residual disease (MRD) testing adds to prognostication in AML beyond established metrics such as patient age and cytogenetics [60,69,70]
Flow cytometry is the standard method for the measurement of residual disease in most subtypes of AML
Summary
Acute myeloid leukemia (AML) is a malignancy of blood-forming stem cells in which recurrent genetic mutations and chromosomal aberrations are associated with the clonal expansion of immature myeloid populations [1,2] For those fit to undergo intensive induction therapy, treatment typically with a combination of anthracycline and cytarabine successfully induces cytomorphological complete remission (CR) in up to 70% of patients [3,4,5]. For more than 50 years, CR in AML has been defined by the recovery of marrow function and peripheral blood counts after completion of chemotherapy and by a morphologic examination of the bone marrow revealing
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