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Role of Minimal Residual Disease Assessment in Hematological Cancers
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Role of Minimal Residual Disease Assessment in Hematological Cancers

A special issue of Journal of Clinical Medicine (ISSN 2077-0383).

Deadline for manuscript submissions: closed (30 April 2017)

Special Issue Editor

Dr. Marco Ladetto

E-Mail Website
Guest Editor
Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy
Interests: diagnosis and treatment of non-Hodgkin lymphoma; hodgkin lymphoma; multiple myeloma and CLL; minimal residual disease in lymphoma; myeloma and CLL; prognostic factors in lymphoid malignancies; lymphomagenesis

Special Issue Information

Dear Colleagues,

Early identification of patients at high risk of relapse is a major goal of current translational research in oncohematology. Minimal residual disease (MRD) detection is increasingly employed in multiple different settings as additional tissue sources become useful targets for monitoring. Moreover, methods for MRD detection are rapidly evolving, thanks to substantial technical improvements of traditional approaches, such as real time polymerase chain reaction (PCR) and multiparameter flow cytometry and development of novel highly effective tools (digital droplet PCR and next generation sequencing). In the meantime, MRD diagnostics is applied to a number of novel clinical settings. In some entities, such as acute lymphoblastic leukemia, MRD detection by real time PCR using patient specific primers is already part of the routine clinical management of adult and pediatric patients. In other entities, such as follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia and multiple myeloma, MRD is a well-established prognostic tool and clinical trials employing MRD as a decision-making tool are currently ongoing. Finally in some entities, such as Hodgkin Lymphoma aggressive lymphoma and lymphoplasmacytic lymphoma, MRD diagnostics is highly promising but still in its infancy, In the present review, we shall discuss the 'state-of-the-art' of MRD evaluation in these neoplasms with the ultimate aim of providing critical take-home messages for clinicians working in the field. Moreover, we will outline the role of MRD detection in the design of future clinical trials.

Dr. Marco Ladetto
Gues Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • real time PCR
  • multiparameter flow cytometry
  • next generation sequencing
  • digital droplet PCR
  • patient specific primers
  • acute lymphoblastic leukemia
  • lymphoma
  • multiple myeloma
  • chronic lymphocytic leukemia

Published Papers (4 papers)

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Review

1844 KiB  
Review
Comparison of Minimal Residual Disease Detection by Multiparameter Flow Cytometry, ASO-qPCR, Droplet Digital PCR, and Deep Sequencing in Patients with Multiple Myeloma Who Underwent Autologous Stem Cell Transplantation
by Hiroyuki Takamatsu
J. Clin. Med. 2017, 6(10), 91; https://doi.org/10.3390/jcm6100091 - 25 Sep 2017
Cited by 31 | Viewed by 10378 | Correction
Abstract
Multiple myeloma (MM) is a hematological malignancy with a poor prognosis, characterized by clonal proliferation of plasma cells in the bone marrow (BM). Relapse due to undetected minimal residual disease (MRD) is the leading cause of death among patients with MM. This review [...] Read more.
Multiple myeloma (MM) is a hematological malignancy with a poor prognosis, characterized by clonal proliferation of plasma cells in the bone marrow (BM). Relapse due to undetected minimal residual disease (MRD) is the leading cause of death among patients with MM. This review summarizes the methods and prognostic value of MRD assessment in BM and autografts from MM patients who underwent autologous stem cell transplantation (ASCT) by multiparameter flow cytometry (MFC), allele-specific oligonucleotide real-time quantitative PCR (ASO-qPCR), droplet digital PCR (ddPCR), and next-generation sequencing (NGS)-based detection methods. MRD assessment using NGS-based approaches has clear prognostic value and better sensitivity compared to traditional methods. Full article
(This article belongs to the Special Issue Role of Minimal Residual Disease Assessment in Hematological Cancers)
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Figure 1

427 KiB  
Review
Technical Advances in the Measurement of Residual Disease in Acute Myeloid Leukemia
by Gregory W. Roloff, Catherine Lai, Christopher S. Hourigan and Laura W. Dillon
J. Clin. Med. 2017, 6(9), 87; https://doi.org/10.3390/jcm6090087 - 19 Sep 2017
Cited by 24 | Viewed by 6974
Abstract
Outcomes for those diagnosed with acute myeloid leukemia (AML) remain poor. It has been widely established that persistent residual leukemic burden, often referred to as measurable or minimal residual disease (MRD), after induction therapy or at the time of hematopoietic stem cell transplant [...] Read more.
Outcomes for those diagnosed with acute myeloid leukemia (AML) remain poor. It has been widely established that persistent residual leukemic burden, often referred to as measurable or minimal residual disease (MRD), after induction therapy or at the time of hematopoietic stem cell transplant (HSCT) is highly predictive for adverse clinical outcomes and can be used to identify patients likely to experience clinically evident relapse. As a result of inherent genetic and molecular heterogeneity in AML, there is no uniform method or protocol for MRD measurement to encompass all cases. Several techniques focusing on identifying recurrent molecular and cytogenetic aberrations or leukemia-associated immunophenotypes have been described, each with their own strengths and weaknesses. Modern technologies enabling the digital quantification and tracking of individual DNA or RNA molecules, next-generation sequencing (NGS) platforms, and high-resolution imaging capabilities are among several new avenues under development to supplement or replace the current standard of flow cytometry. In this review, we outline emerging modalities positioned to enhance MRD detection and discuss factors surrounding their integration into clinical practice. Full article
(This article belongs to the Special Issue Role of Minimal Residual Disease Assessment in Hematological Cancers)
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Figure 1

228 KiB  
Review
When Less Is Good, Is None Better? The Prognostic and Therapeutic Significance of Peri-Transplant Minimal Residual Disease Assessment in Pediatric Acute Lymphoblastic Leukemia
by Adam Lamble, Rachel Phelan and Michael Burke
J. Clin. Med. 2017, 6(7), 66; https://doi.org/10.3390/jcm6070066 - 07 Jul 2017
Cited by 9 | Viewed by 5163
Abstract
The measurement of minimal residual disease (MRD) in pediatric acute lymphoblastic leukemia (ALL) has become the most important prognostic tool of, and the backbone to, upfront risk stratification. While MRD assessment is the standard of care for assessing response and predicting outcomes for [...] Read more.
The measurement of minimal residual disease (MRD) in pediatric acute lymphoblastic leukemia (ALL) has become the most important prognostic tool of, and the backbone to, upfront risk stratification. While MRD assessment is the standard of care for assessing response and predicting outcomes for pediatric patients with ALL receiving chemotherapy, its use in allogeneic hematopoietic stem cell transplant (HSCT) has been less clearly defined. Herein, we discuss the importance of MRD assessment during the peri-HSCT period and its role in prognostication and management. Full article
(This article belongs to the Special Issue Role of Minimal Residual Disease Assessment in Hematological Cancers)
585 KiB  
Review
Minimal Residual Disease in Acute Myeloid Leukemia: Still a Work in Progress?
by Federico Mosna, Debora Capelli and Michele Gottardi
J. Clin. Med. 2017, 6(6), 57; https://doi.org/10.3390/jcm6060057 - 03 Jun 2017
Cited by 24 | Viewed by 6901
Abstract
Minimal residual disease evaluation refers to a series of molecular and immunophenotypical techniques aimed at detecting submicroscopic disease after therapy. As such, its application in acute myeloid leukemia has greatly increased our ability to quantify treatment response, and to determine the chemosensitivity of [...] Read more.
Minimal residual disease evaluation refers to a series of molecular and immunophenotypical techniques aimed at detecting submicroscopic disease after therapy. As such, its application in acute myeloid leukemia has greatly increased our ability to quantify treatment response, and to determine the chemosensitivity of the disease, as the final product of the drug schedule, dose intensity, biodistribution, and the pharmakogenetic profile of the patient. There is now consistent evidence for the prognostic power of minimal residual disease evaluation in acute myeloid leukemia, which is complementary to the baseline prognostic assessment of the disease. The focus for its use is therefore shifting to individualize treatment based on a deeper evaluation of chemosensitivity and residual tumor burden. In this review, we will summarize the results of the major clinical studies evaluating minimal residual disease in acute myeloid leukemia in adults in recent years and address the technical and practical issues still hampering the spread of these techniques outside controlled clinical trials. We will also briefly speculate on future developments and offer our point of view, and a word of caution, on the present use of minimal residual disease measurements in “real-life” practice. Still, as final standardization and diffusion of the methods are sorted out, we believe that minimal residual disease will soon become the new standard for evaluating response in the treatment of acute myeloid leukemia. Full article
(This article belongs to the Special Issue Role of Minimal Residual Disease Assessment in Hematological Cancers)
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