Abstract
The ability to detect residual levels of leukemic blasts (measurable residual disease, MRD) has already been integrated in the daily routine for treatment of patients with chronic myeloid and acute lymphoblastic leukemia. In acute myeloid leukemia (AML), a variety of mostly retrospective studies have shown that individuals in AML remission who tested positive for MRD at specific time-points or had increasing MRD levels are at significantly higher risk of relapse and death compared to MRD-negative patients. However, these studies differ with respect to the “MRD-target”, time-point of MRD determination, material analyzed, and method applied. How this probably very valuable MRD information in individual patients may be adapted in the daily clinical routine, e.g., to separate patients who need more aggressive therapies from those who may be spared additional—potentially toxic—therapies is still a work-in-progress. With the exception of MRD assessment in acute promyelocytic leukemia (APL), the lack of randomized, prospective trials renders MRD-based decisions and clinical implications in AML a difficult task. As of today, we still do not have proof that early intervention in MRD-positive AML patients would improve outcomes, although this is very likely. In this article, we review the current knowledge on non-APL AML MRD assessment and possible clinical consequences.
Highlights
Acute myeloid leukemia (AML) is a highly heterogeneous and aggressive neoplasia that is characterized by clonal expansion of myeloid precursors
In acute myeloid leukemia (AML) with RUNX1-RUNX1T1, bone marrow (BM) measurable residual disease (MRD)-negativity at the end of treatment was found to associate with overall survival (OS) and disease-free survival (DFS) or relapse probability in some studies [11,48] while another analysis only described a prognostic impact of MRD analyzed in peripheral blood (PB) [52]
Comparing patients treated according to protocol to patients not treated according to protocol, this study indicated that allogeneic hematopoietic stem cell transplantation (HSCT) significantly reduces relapse rates and improve survival compared to chemotherapy
Summary
Acute myeloid leukemia (AML) is a highly heterogeneous and aggressive neoplasia that is characterized by clonal expansion of myeloid precursors. Over the past few decades, a growing understanding of the molecular landscape and the associated AML biology allowed improved risk stratification at diagnosis. These findings are reflected in the current World Health. Associates with adverse outcomes, allowing risk stratification in AML remission [4,5,6] These days, much effort has been put into the development of new assays, to improve sensitivities and specificities, to optimize standardization between laboratories and to provide applicable techniques for the majority of patients [7,8]. AML together with their clinical applicability and current practical consequences in daily routines
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