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MRD Tailored Therapy in AML: What We Have Learned So Far
Acute myeloid leukemia (AML) is a heterogeneous clonal disease associated with a dismal survival, partly due to the frequent occurrence of relapse. Many patient- and leukemia-specific characteristics, such as age, cytogenetics, mutations, and measurable residual disease (MRD) after intensive chemoth...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871983/ https://www.ncbi.nlm.nih.gov/pubmed/33575214 http://dx.doi.org/10.3389/fonc.2020.603636 |
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author | Ngai, Lok Lam Kelder, Angèle Janssen, Jeroen J. W. M. Ossenkoppele, Gert J. Cloos, Jacqueline |
author_facet | Ngai, Lok Lam Kelder, Angèle Janssen, Jeroen J. W. M. Ossenkoppele, Gert J. Cloos, Jacqueline |
author_sort | Ngai, Lok Lam |
collection | PubMed |
description | Acute myeloid leukemia (AML) is a heterogeneous clonal disease associated with a dismal survival, partly due to the frequent occurrence of relapse. Many patient- and leukemia-specific characteristics, such as age, cytogenetics, mutations, and measurable residual disease (MRD) after intensive chemotherapy, have shown to be valuable prognostic factors. MRD has become a rich field of research where many advances have been made regarding technical, biological, and clinical aspects, which will be the topic of this review. Since many laboratories involved in AML diagnostics have experience in immunophenotyping, multiparameter flow cytometry (MFC) based MRD is currently the most commonly used method. Although molecular, quantitative PCR based techniques may be more sensitive, their disadvantage is that they can only be applied in a subset of patients harboring the genetic aberration. Next-generation sequencing can assess and quantify mutations in many genes but currently does not offer highly sensitive MRD measurements on a routine basis. In order to provide reliable MRD results, MRD assay optimization and standardization is essential. Different techniques for MRD assessment are being evaluated, and combinations of the methods have shown promising results for improving its prognostic value. In this regard, the load of leukemic stem cells (LSC) has also been shown to add to the prognostic value of MFC-MRD. At this moment, MRD after intensive chemotherapy is most often used as a prognostic factor to help stratify patients, but also to select the most appropriate consolidation therapy. For example, to guide post-remission treatment for intermediate-risk patients where MRD positive patients receive allogeneic stem cell transplantation and MRD negative receive autologous stem cell transplantation. Other upcoming uses of MRD that are being investigated include: selecting the type of allogeneic stem cell transplantation therapy (donor, conditioning), monitoring after stem cell transplantation (to allow intervention), and determining drug efficacy for the use of a surrogate endpoint in clinical trials. |
format | Online Article Text |
id | pubmed-7871983 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78719832021-02-10 MRD Tailored Therapy in AML: What We Have Learned So Far Ngai, Lok Lam Kelder, Angèle Janssen, Jeroen J. W. M. Ossenkoppele, Gert J. Cloos, Jacqueline Front Oncol Oncology Acute myeloid leukemia (AML) is a heterogeneous clonal disease associated with a dismal survival, partly due to the frequent occurrence of relapse. Many patient- and leukemia-specific characteristics, such as age, cytogenetics, mutations, and measurable residual disease (MRD) after intensive chemotherapy, have shown to be valuable prognostic factors. MRD has become a rich field of research where many advances have been made regarding technical, biological, and clinical aspects, which will be the topic of this review. Since many laboratories involved in AML diagnostics have experience in immunophenotyping, multiparameter flow cytometry (MFC) based MRD is currently the most commonly used method. Although molecular, quantitative PCR based techniques may be more sensitive, their disadvantage is that they can only be applied in a subset of patients harboring the genetic aberration. Next-generation sequencing can assess and quantify mutations in many genes but currently does not offer highly sensitive MRD measurements on a routine basis. In order to provide reliable MRD results, MRD assay optimization and standardization is essential. Different techniques for MRD assessment are being evaluated, and combinations of the methods have shown promising results for improving its prognostic value. In this regard, the load of leukemic stem cells (LSC) has also been shown to add to the prognostic value of MFC-MRD. At this moment, MRD after intensive chemotherapy is most often used as a prognostic factor to help stratify patients, but also to select the most appropriate consolidation therapy. For example, to guide post-remission treatment for intermediate-risk patients where MRD positive patients receive allogeneic stem cell transplantation and MRD negative receive autologous stem cell transplantation. Other upcoming uses of MRD that are being investigated include: selecting the type of allogeneic stem cell transplantation therapy (donor, conditioning), monitoring after stem cell transplantation (to allow intervention), and determining drug efficacy for the use of a surrogate endpoint in clinical trials. Frontiers Media S.A. 2021-01-15 /pmc/articles/PMC7871983/ /pubmed/33575214 http://dx.doi.org/10.3389/fonc.2020.603636 Text en Copyright © 2021 Ngai, Kelder, Janssen, Ossenkoppele and Cloos http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Ngai, Lok Lam Kelder, Angèle Janssen, Jeroen J. W. M. Ossenkoppele, Gert J. Cloos, Jacqueline MRD Tailored Therapy in AML: What We Have Learned So Far |
title | MRD Tailored Therapy in AML: What We Have Learned So Far |
title_full | MRD Tailored Therapy in AML: What We Have Learned So Far |
title_fullStr | MRD Tailored Therapy in AML: What We Have Learned So Far |
title_full_unstemmed | MRD Tailored Therapy in AML: What We Have Learned So Far |
title_short | MRD Tailored Therapy in AML: What We Have Learned So Far |
title_sort | mrd tailored therapy in aml: what we have learned so far |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871983/ https://www.ncbi.nlm.nih.gov/pubmed/33575214 http://dx.doi.org/10.3389/fonc.2020.603636 |
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