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Minimal Residual Disease in Acute Lymphoblastic Leukemia: Technical and Clinical Advances
Introduction: Acute lymphoblastic leukemia (ALL) is the first neoplasm where the assessment of early response to therapy by minimal residual disease (MRD) monitoring has proven to be a fundamental tool to guide therapeutic choices. The most standardized methods to study MRD in ALL are multi-parametr...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692455/ https://www.ncbi.nlm.nih.gov/pubmed/31448230 http://dx.doi.org/10.3389/fonc.2019.00726 |
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author | Della Starza, Irene Chiaretti, Sabina De Propris, Maria S. Elia, Loredana Cavalli, Marzia De Novi, Lucia A. Soscia, Roberta Messina, Monica Vitale, Antonella Guarini, Anna Foà, Robin |
author_facet | Della Starza, Irene Chiaretti, Sabina De Propris, Maria S. Elia, Loredana Cavalli, Marzia De Novi, Lucia A. Soscia, Roberta Messina, Monica Vitale, Antonella Guarini, Anna Foà, Robin |
author_sort | Della Starza, Irene |
collection | PubMed |
description | Introduction: Acute lymphoblastic leukemia (ALL) is the first neoplasm where the assessment of early response to therapy by minimal residual disease (MRD) monitoring has proven to be a fundamental tool to guide therapeutic choices. The most standardized methods to study MRD in ALL are multi-parametric flow cytometry (MFC) and polymerase chain reaction (PCR) amplification-based methods. Emerging technologies hold the promise to improve MRD detection in ALL patients. Moreover, novel therapies, such as monoclonal antibodies, bispecific T-cell engagers, and chimeric antigen receptor T cells (CART) represent exciting advancements in the management of B-cell precursor (BCP)-ALL. Aims: Through a review of the literature and in house data, we analyze the current status of MRD assessment in ALL to better understand how some of its limitations could be overcome by emerging molecular technologies. Furthermore, we highlight the future role of MRD monitoring in the context of personalized protocols, taking into account the genetic complexity in ALL. Results and Conclusions: Molecular rearrangements (gene fusions and immunoglobulin and T-cell receptor-IG/TR gene rearrangements) are widely used as targets to detect residual leukemic cells in ALL patients. The advent of novel techniques, namely next generation flow cytometry (NGF), digital-droplet-PCR (ddPCR), and next generation sequencing (NGS) appear important tools to evaluate MRD in ALL, since they have the potential to overcome the limitations of standard approaches. It is likely that in the forthcoming future these techniques will be incorporated in clinical trials, at least at decisional time points. Finally, the advent of new powerful compounds is further increasing MRD negativity rates, with benefits in long-term survival and a potential reduction of therapy-related toxicities. However, the prognostic relevance in the setting of novel immunotherapies still needs to be evaluated. |
format | Online Article Text |
id | pubmed-6692455 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66924552019-08-23 Minimal Residual Disease in Acute Lymphoblastic Leukemia: Technical and Clinical Advances Della Starza, Irene Chiaretti, Sabina De Propris, Maria S. Elia, Loredana Cavalli, Marzia De Novi, Lucia A. Soscia, Roberta Messina, Monica Vitale, Antonella Guarini, Anna Foà, Robin Front Oncol Oncology Introduction: Acute lymphoblastic leukemia (ALL) is the first neoplasm where the assessment of early response to therapy by minimal residual disease (MRD) monitoring has proven to be a fundamental tool to guide therapeutic choices. The most standardized methods to study MRD in ALL are multi-parametric flow cytometry (MFC) and polymerase chain reaction (PCR) amplification-based methods. Emerging technologies hold the promise to improve MRD detection in ALL patients. Moreover, novel therapies, such as monoclonal antibodies, bispecific T-cell engagers, and chimeric antigen receptor T cells (CART) represent exciting advancements in the management of B-cell precursor (BCP)-ALL. Aims: Through a review of the literature and in house data, we analyze the current status of MRD assessment in ALL to better understand how some of its limitations could be overcome by emerging molecular technologies. Furthermore, we highlight the future role of MRD monitoring in the context of personalized protocols, taking into account the genetic complexity in ALL. Results and Conclusions: Molecular rearrangements (gene fusions and immunoglobulin and T-cell receptor-IG/TR gene rearrangements) are widely used as targets to detect residual leukemic cells in ALL patients. The advent of novel techniques, namely next generation flow cytometry (NGF), digital-droplet-PCR (ddPCR), and next generation sequencing (NGS) appear important tools to evaluate MRD in ALL, since they have the potential to overcome the limitations of standard approaches. It is likely that in the forthcoming future these techniques will be incorporated in clinical trials, at least at decisional time points. Finally, the advent of new powerful compounds is further increasing MRD negativity rates, with benefits in long-term survival and a potential reduction of therapy-related toxicities. However, the prognostic relevance in the setting of novel immunotherapies still needs to be evaluated. Frontiers Media S.A. 2019-08-07 /pmc/articles/PMC6692455/ /pubmed/31448230 http://dx.doi.org/10.3389/fonc.2019.00726 Text en Copyright © 2019 Della Starza, Chiaretti, De Propris, Elia, Cavalli, De Novi, Soscia, Messina, Vitale, Guarini and Foà. 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 Della Starza, Irene Chiaretti, Sabina De Propris, Maria S. Elia, Loredana Cavalli, Marzia De Novi, Lucia A. Soscia, Roberta Messina, Monica Vitale, Antonella Guarini, Anna Foà, Robin Minimal Residual Disease in Acute Lymphoblastic Leukemia: Technical and Clinical Advances |
title | Minimal Residual Disease in Acute Lymphoblastic Leukemia: Technical and Clinical Advances |
title_full | Minimal Residual Disease in Acute Lymphoblastic Leukemia: Technical and Clinical Advances |
title_fullStr | Minimal Residual Disease in Acute Lymphoblastic Leukemia: Technical and Clinical Advances |
title_full_unstemmed | Minimal Residual Disease in Acute Lymphoblastic Leukemia: Technical and Clinical Advances |
title_short | Minimal Residual Disease in Acute Lymphoblastic Leukemia: Technical and Clinical Advances |
title_sort | minimal residual disease in acute lymphoblastic leukemia: technical and clinical advances |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692455/ https://www.ncbi.nlm.nih.gov/pubmed/31448230 http://dx.doi.org/10.3389/fonc.2019.00726 |
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