Research Topic

The Minimal Residual Disease in Hematology: the Impact of the New Technologies

About this Research Topic

In recent years, minimal residual disease (MRD) has not only become a pure research issue in Hematology, but a real basis for innovative and “patient-oriented” treatments: in acute lymphoblastic leukemia (ALL), for example, the anti-CD3/CD19 bi-specific T-cell engager (BiTE) blinatumomab can be prescribed to patients who are in remission but still have minimal residual disease (MRD).

Moreover, the entire management of patients affected by chronic myeloid leukemia (CML) is based on the quantitative measurement of the BCR-ABL1 transcript and on the appearance of mutations that reflect primary or secondary resistance to tyrosine kinase inhibitors. Recently, new effective drugs, such as daratumumab and carfilzomib used for multiple myeloma (MM) or venetoclax used for chronic lymphocytic leukemia (CLL), are increasingly used to achieve molecular remission as one of the principal goals of treatment. On the other hand, next generation sequencing (NGS) techniques can identify low-level BTK mutations responsible for resistance to ibrutinib in CLL or mantle cell lymphoma (MCL). Finally, digital PCR, with its ability of absolute deeper quantitation, has been shown to be a promising technique for MRD assessment in several lymphomas, such as Waldenstrom macroglobulinemia or DLBCL, in addition to better define the molecular classes in CML.

In this scenario, a sound understanding of different molecular techniques to measure MRD has become fundamental for the practicing Hematologist: quantitative real-time PCR, digital PCR, and NGS are today employed in routine clinical tests, and their pros and cons must also be known by clinicians.

This Research Topic dedicated to MRD and modern molecular techniques in Hematology aims to review recent data concerning MRD and methods necessary for its detection, with a language understandable by both physicians and biologists/technicians, in order to further sustain their collaboration and interaction.

This Research Topic will describe the significance of MRD in acute leukemia, lymphoma, myeloma, chronicl myeloid leukemia, and CLL. For each group of diseases, authors will identify what kind of molecular tests are suitable and more useful and what significant role they could play in routine clinical practice. For example, for CML, NGS is able to detect clinically relevant ABL1 mutations 3 months before the conventional Sanger sequencing, including the T315I mutation that prompts clinicians to immediately switch patients to ponatinib. In follicular lymphoma, the FOLL12 trial is assessing if PCR- and PET-negative cases can avoid the maintenance with rituximab or if the pre-emptive therapy with anti-CD20 antibody will be useful for avoiding relapse in patients that are still PCR-positive. In MM, in a near future, MRD status could be used as a decision support tool for the duration of maintenance therapy, perhaps prolonging it in cases that remain MRD-positive. Obviously, all these technologies need to be standardized, ideally at the international level, an effort that has already started within the Europe MRD network. The experiences in this field will be also described.


Keywords: MRD, NGS, DIGITAL PCR, NHL, AML


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

In recent years, minimal residual disease (MRD) has not only become a pure research issue in Hematology, but a real basis for innovative and “patient-oriented” treatments: in acute lymphoblastic leukemia (ALL), for example, the anti-CD3/CD19 bi-specific T-cell engager (BiTE) blinatumomab can be prescribed to patients who are in remission but still have minimal residual disease (MRD).

Moreover, the entire management of patients affected by chronic myeloid leukemia (CML) is based on the quantitative measurement of the BCR-ABL1 transcript and on the appearance of mutations that reflect primary or secondary resistance to tyrosine kinase inhibitors. Recently, new effective drugs, such as daratumumab and carfilzomib used for multiple myeloma (MM) or venetoclax used for chronic lymphocytic leukemia (CLL), are increasingly used to achieve molecular remission as one of the principal goals of treatment. On the other hand, next generation sequencing (NGS) techniques can identify low-level BTK mutations responsible for resistance to ibrutinib in CLL or mantle cell lymphoma (MCL). Finally, digital PCR, with its ability of absolute deeper quantitation, has been shown to be a promising technique for MRD assessment in several lymphomas, such as Waldenstrom macroglobulinemia or DLBCL, in addition to better define the molecular classes in CML.

In this scenario, a sound understanding of different molecular techniques to measure MRD has become fundamental for the practicing Hematologist: quantitative real-time PCR, digital PCR, and NGS are today employed in routine clinical tests, and their pros and cons must also be known by clinicians.

This Research Topic dedicated to MRD and modern molecular techniques in Hematology aims to review recent data concerning MRD and methods necessary for its detection, with a language understandable by both physicians and biologists/technicians, in order to further sustain their collaboration and interaction.

This Research Topic will describe the significance of MRD in acute leukemia, lymphoma, myeloma, chronicl myeloid leukemia, and CLL. For each group of diseases, authors will identify what kind of molecular tests are suitable and more useful and what significant role they could play in routine clinical practice. For example, for CML, NGS is able to detect clinically relevant ABL1 mutations 3 months before the conventional Sanger sequencing, including the T315I mutation that prompts clinicians to immediately switch patients to ponatinib. In follicular lymphoma, the FOLL12 trial is assessing if PCR- and PET-negative cases can avoid the maintenance with rituximab or if the pre-emptive therapy with anti-CD20 antibody will be useful for avoiding relapse in patients that are still PCR-positive. In MM, in a near future, MRD status could be used as a decision support tool for the duration of maintenance therapy, perhaps prolonging it in cases that remain MRD-positive. Obviously, all these technologies need to be standardized, ideally at the international level, an effort that has already started within the Europe MRD network. The experiences in this field will be also described.


Keywords: MRD, NGS, DIGITAL PCR, NHL, AML


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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13 January 2019 Manuscript

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Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

13 January 2019 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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