Eradication of Measurable Residual Disease in AML: A Challenging Clinical Goal

In non-promyelocytic (non-M3) AML measurable residual disease (MRD) detected by multi-parameter flow cytometry and molecular technologies, which are guided by Consensus-based guidelines and discover very low leukemic cell numbers far below the 5% threshold of morphological assessment, has emerged as...

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Bibliographic Details
Published in:Cancers 2021-06, Vol.13 (13), p.3170
Main Authors: Bernasconi, Paolo, Borsani, Oscar
Format: Article
Language:English
Subjects:
Antigens
Apoptosis
Biomarkers
Bone marrow
Chemotherapy
Clinical outcomes
Flow cytometry
Hematopoietic stem cells
Leukemia
Methylation
Morphology
Multivariate analysis
Mutation
Patients
Peripheral blood
Radiation therapy
Remission
Review
Signal transduction
Stem cell transplantation
Transplants & implants
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Summary:In non-promyelocytic (non-M3) AML measurable residual disease (MRD) detected by multi-parameter flow cytometry and molecular technologies, which are guided by Consensus-based guidelines and discover very low leukemic cell numbers far below the 5% threshold of morphological assessment, has emerged as the most relevant predictor of clinical outcome. Currently, it is well-established that MRD positivity after standard induction and consolidation chemotherapy, as well as during the period preceding an allogeneic hematopoietic stem cell transplant (allo-HSCT), portends to a significantly inferior relapse-free survival (RFS) and overall survival (OS). In addition, it has become absolutely clear that conversion from an MRD-positive to an MRD-negative state provides a favorable clinical outcome similar to that associated with early MRD negativity. Thus, the complete eradication of MRD, i.e., the clearance of the few leukemic stem cells—which, due to their chemo-radiotherapy resistance, might eventually be responsible of disease recurrence—has become an un-met clinical need in AML. Nowadays, this goal might potentially be achieved thanks to the development of novel innovative treatment strategies, including those targeting driver mutations, apoptosis, methylation patterns and leukemic proteins. The aim of this review is to analyze these strategies and to suggest any potential combination able to induce MRD negativity in the pre- and post-HSCT period.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13133170