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Cancers
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Measurable Residual Disease in Cancer
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Measurable Residual Disease in Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Drug Development".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 17581

Special Issue Editors

Prof. Dr. Krzysztof Jamroziak

E-Mail Website
Guest Editor
Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland
Interests: hematological neoplasm
Dr. Bartosz Pula

E-Mail Website
Guest Editor
Department of Hematology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland
Interests: chronic lymphocytic leukemia; multiple myeloma; light chain amyloidosis

Special Issue Information

Dear Colleagues,

Measurable residual disease (MRD; previously termed minimal residual disease) refers to the presence of cancer cells below the threshold of detection when using conventional methods of assessing response to treatment. Depending on the type of tumor MRD can be evaluated using a variety of techniques; most of which are in constant evolution and new techniques are still being developed. Importantly, with the significant advances in therapeutic approaches in recent decades to obtain deep responses, MRD has become an important post-therapy prognostic indicator in many types of cancer. Moreover, in some tumors, MRD assessment has become a key factor in risk stratification and treatment planning in clinical practice. MRD is also widely used endpoint in clinical trials assessing novel drugs and treatment strategies. 
It should be noted, however, that in many neoplasms, the methods for assessing MRD have not yet been standardized qualitatively or quantitatively, and widely accepted guidelines for the use of MRD in clinical practice are rarely available.
In this Special Issue, a panel of internationally recognized experts will focus on the current and future role of MRD in cancer with respect to MRD assessment techniques, MRD as a prognostic/predictive factor or therapeutic target as well as MRD-based directions in the anticancer drugs development. 

Potential topics include, but are not limited to:

  • Systematic reviews on the current role of MRD in particular types of cancer
  • Novel methods of MRD assessment and MRD standardization efforts in cancer
  • Design and results of clinical trials testing MRD-driven treatment strategies
  • Original studies reporting treatment of disease at MRD or subclonal levels in clinical practice
  • Significance of genomic and spatial heterogeneity of MRD 
  • Role of tumor microenvironment regarding MRD persistence/eradication
  • MRD as surrogate endpoint for new anti-cancer drug development and approval

Prof. Dr. Krzysztof Jamroziak
Dr. Bartosz Pula
Guest Editors

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. Cancers 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 2900 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

  • MRD
  • measurable residual disease
  • minimal residual disease
  • cancer
  • tumor microenvironment
  • next generation sequencing
  • flow cytometry
  • imaging techniques

Published Papers (6 papers)

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Research

12 pages, 738 KiB  
Article
IGH::NSD2 Fusion Gene Transcript as Measurable Residual Disease Marker in Multiple Myeloma
by András Bors, András Kozma, Ágnes Tomán, Zoltán Őrfi, Nóra Kondor, Szabolcs Tasnády, István Vályi-Nagy, Péter Reményi, Gábor Mikala and Hajnalka Andrikovics
Cancers 2024, 16(2), 283; https://doi.org/10.3390/cancers16020283 - 09 Jan 2024
Viewed by 763
Abstract
Multiple myeloma (MM) is the second most common hematological malignancy. Approximately 15% of MM patients are affected by the t(4;14) translocation resulting in the IGH::NSD2 fusion transcript. Breakage occurs in three major breakpoint regions within the NSD2 gene (MB4-1, MB4-2, and MB4-3), where [...] Read more.
Multiple myeloma (MM) is the second most common hematological malignancy. Approximately 15% of MM patients are affected by the t(4;14) translocation resulting in the IGH::NSD2 fusion transcript. Breakage occurs in three major breakpoint regions within the NSD2 gene (MB4-1, MB4-2, and MB4-3), where MB4-1 leads to the production of full-length protein, while truncated proteins are expressed in the other two cases. Measurable residual disease (MRD) has been conclusively established as a crucial prognostic factor in MM. The IGH::NSD2 fusion transcript can serve as a sensitive MRD marker. Using bone marrow (BM) and peripheral blood (PB) samples from 111 patients, we developed a highly sensitive quantitative real-time PCR (qPCR) and digital PCR (dPCR) system capable of detecting fusion mRNAs with a sensitivity of up to 1:100,000. PB samples exhibited sensitivity three orders of magnitude lower compared to BM samples. Patients with an MB4-2 breakpoint demonstrated significantly reduced overall survival (p = 0.003). Our novel method offers a simple and sensitive means for detecting MRD in a substantial proportion of MM patients. Monitoring may be carried out even from PB samples. The literature lacks consensus regarding survival outcomes among patients with different NSD2 breakpoints. Our data align with previous findings indicating that patients with the MB4-2 breakpoint type tend to exhibit unfavorable overall survival. Full article
(This article belongs to the Special Issue Measurable Residual Disease in Cancer)
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15 pages, 1911 KiB  
Article
Standardization of Molecular MRD Levels in AML Using an Integral Vector Bearing ABL and the Mutation of Interest
by Boaz Nachmias, Svetlana Krichevsky, Moshe E. Gatt, Noa Gross Even-Zohar, Adir Shaulov, Arnon Haran, Shlomzion Aumann and Vladimir Vainstein
Cancers 2023, 15(22), 5360; https://doi.org/10.3390/cancers15225360 - 10 Nov 2023
Viewed by 798
Abstract
Quantitative PCR for specific mutation is being increasingly used in Acute Myeloid Leukemia (AML) to assess Measurable Residual Disease (MRD), allowing for more tailored clinical decisions. To date, standardized molecular MRD is limited to typical NPM1 mutations and core binding factor translocations, with [...] Read more.
Quantitative PCR for specific mutation is being increasingly used in Acute Myeloid Leukemia (AML) to assess Measurable Residual Disease (MRD), allowing for more tailored clinical decisions. To date, standardized molecular MRD is limited to typical NPM1 mutations and core binding factor translocations, with clear prognostic and clinical implications. The monitoring of other identified mutations lacks standardization, limiting its use and incorporation in clinical trials. To overcome this problem, we designed a plasmid bearing both the sequence of the mutation of interest and the ABL reference gene. This allows the use of commercial standards for ABL to determine the MRD response in copy number. We provide technical aspects of this approach as well as our experience with 19 patients with atypical NPM1, RUNX1 and IDH1/2 mutations. In all cases, we demonstrate a correlation between response and copy number. We further demonstrate how copy number monitoring can modulate the clinical management. Taken together, we provide proof of concept of a novel yet simple tool, which allows in-house MRD monitoring for identified mutations, with ABL-based commercial standards. This approach would facilitate large multi-center studies assessing the clinical relevance of selected MRD monitoring. Full article
(This article belongs to the Special Issue Measurable Residual Disease in Cancer)
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0 pages, 2136 KiB  
Article
Measurable Residual Disease (MRD) by Flow Cytometry in Adult B-Acute Lymphoblastic Leukaemia (B-ALL) and Acute Myeloid Leukaemia (AML): Correlation with Molecular MRD Testing and Clinical Outcome at One Year
by Riana van der Linde, Prudence N. Gatt, Sandy Smith, Marian A. Fernandez, Lachlin Vaughan, Emily Blyth, Jennifer Curnow, David A. Brown, Elizabeth Tegg and Sarah C. Sasson
Cancers 2023, 15(20), 5064; https://doi.org/10.3390/cancers15205064 - 19 Oct 2023
Cited by 1 | Viewed by 1265
Abstract
Measurable residual disease (MRD) detected by flow cytometry (FC) is well established in paediatric B- lymphoblastic leukaemia (B-ALL) and adult chronic lymphocytic leukaemia (CLL), but its utility in adult B-ALL and adult acute myeloid leukaemia (AML) is less clear. In this prospective MRD [...] Read more.
Measurable residual disease (MRD) detected by flow cytometry (FC) is well established in paediatric B- lymphoblastic leukaemia (B-ALL) and adult chronic lymphocytic leukaemia (CLL), but its utility in adult B-ALL and adult acute myeloid leukaemia (AML) is less clear. In this prospective MRD study, one of the largest in Australia to date, we examined consecutive bone marrow aspirates from adult participants with B-ALL (n = 47) and AML (n = 87) sent for FC-MRD testing at a quaternary referral hospital in Sydney. FC-MRD results were correlated to corresponding Mol-MRD testing where available and clinical outcomes at three-month intervals over 1 year. B-ALL showed a moderate positive correlation (rs = 0.401, p < 0.001), while there was no correlation between FC-MRD and Mol-MRD for AML (rs = 0.13, p = 0.237). Five FC-MRD patterns were identified which had significant associations with relapse (X2(4) = 31.17(4), p > 0.001) and survival (X2(4) = 13.67, p = 0.008) in AML, but not in B-ALL. The three-month MRD results were also strongly associated with survival in AML, while the association in B-ALL was less evident. There was a moderate correlation between FC-MRD and Mol-MRD in B-ALL but not AML. The association of FC-MRD with relapse and survival was stronger in AML than in B-ALL. Overall, these findings suggest divergent utilities of FC-MRD in AML and B-ALL. Full article
(This article belongs to the Special Issue Measurable Residual Disease in Cancer)
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12 pages, 2891 KiB  
Article
Genetic Profiling of Cell-Free DNA in Liquid Biopsies: A Complementary Tool for the Diagnosis of B-Cell Lymphomas and the Surveillance of Measurable Residual Disease
by Gloria Figaredo, Alejandro Martín-Muñoz, Santiago Barrio, Laura Parrilla, Yolanda Campos-Martín, María Poza, Laura Rufián, Patrocinio Algara, Marina De La Torre, Ana Jiménez Ubieto, Joaquín Martínez-López, Luis-Felipe Casado and Manuela Mollejo
Cancers 2023, 15(16), 4022; https://doi.org/10.3390/cancers15164022 - 08 Aug 2023
Cited by 2 | Viewed by 1207
Abstract
Purpose: To assess the potential value of LiqBio as a complementary tool for diagnosis and surveillance of BCL. Methods: This prospective multi-center study included 78 patients (25 follicular lymphomas (FL) and 53 large B-cell lymphomas (LBCL)). We performed next-generation sequencing (NGS) of cfDNA [...] Read more.
Purpose: To assess the potential value of LiqBio as a complementary tool for diagnosis and surveillance of BCL. Methods: This prospective multi-center study included 78 patients (25 follicular lymphomas (FL) and 53 large B-cell lymphomas (LBCL)). We performed next-generation sequencing (NGS) of cfDNA LiqBio and paired gDNA tissue biopsies at diagnosis and compared the mutational statuses. Also, through NGS of LiqBio, we identified MRD biomarkers and compared this novel LiqBio–MRD method with PET/CT in detecting MRD at follow-up. Results: We identified mutations in 71% of LiqBio and 95% of tissue biopsies, and found a correlation between variant allele frequency of somatic mutations. Additionally, we identified mutations in 73% of LiqBio from patients with no available tissue samples or no mutations in them. Regarding the utility of LiqBio–MRD as a dynamic monitoring tool, when compared with the PET/CT method, a lower sensitivity was observed for LiqBio–MRD at 92.3% (vs. 100% for PET/CT), but a higher specificity of 91.3% (vs. 86.9% for PET/CT). Conclusion: Genetic profiling of tumor cfDNA in plasma LiqBio is a complementary tool for BCL diagnosis and MRD surveillance. Full article
(This article belongs to the Special Issue Measurable Residual Disease in Cancer)
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17 pages, 2646 KiB  
Article
Go with the Flow—Early Assessment of Measurable Residual Disease in Children with Acute Lymphoblastic Leukemia Treated According to ALL IC-BFM2009
by Katarzyna Pawinska-Wasikowska, Karolina Bukowska-Strakova, Marta Surman, Monika Rygielska, Beata Sadowska, Teofila Ksiazek, Tomasz Klekawka, Aleksandra Wieczorek, Szymon Skoczen and Walentyna Balwierz
Cancers 2022, 14(21), 5359; https://doi.org/10.3390/cancers14215359 - 30 Oct 2022
Cited by 1 | Viewed by 3945
Abstract
Measurable residual disease (MRD) is a well-known tool for the evaluation of the early response to treatment in patients with acute lymphoblastic leukemia (ALL). In respect to predicting the relapse the most informative cut-off and time point of MRD measurement during therapy were [...] Read more.
Measurable residual disease (MRD) is a well-known tool for the evaluation of the early response to treatment in patients with acute lymphoblastic leukemia (ALL). In respect to predicting the relapse the most informative cut-off and time point of MRD measurement during therapy were evaluated in our study. Between 1 January 2013 and 31 December 2019, multiparametric flow cytometry (MFC) MRD was measured in the bone marrow of 140 children with ALL treated according to the ALL IC-BFM2009 protocol. The MRD cut-off of 0.1% and day 33, end of induction, were the most discriminatory for all patients. Patients with negative MRD on day 15 and 33 had a higher 5-year overall survival—OS (100%) and a higher relapse-free survival—RFS rate (97.6%) than those with positive levels of MRD (≥0.01%) at both time points (77.8% and 55.6%, p = 0.002 and 0.001, respectively). Most patients with residual disease below 0.1% on day 15 exhibit hyperdiploidy or ETV6-RUNX1 in ALL cells. Measurement of MRD at early time points can be used with simplified genetic analysis to better identify low and high-risk patients, allowing personalized therapies and further improvement in outcomes in pediatric ALL. Full article
(This article belongs to the Special Issue Measurable Residual Disease in Cancer)
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12 pages, 1362 KiB  
Article
Flow Cytometric Analysis of Bone Marrow Particle Cells for Measuring Minimal Residual Disease in Multiple Myeloma
by Duanfeng Jiang, Yanan Zhang, Shiming Tan, Jing Liu, Xin Li and Congming Zhang
Cancers 2022, 14(19), 4937; https://doi.org/10.3390/cancers14194937 - 08 Oct 2022
Viewed by 5424
Abstract
Minimal residual disease (MRD) is one of the most relevant prognostic factors in patients with multiple myeloma (MM). However, the hemodilution of bone marrow (BM) aspirates, the most common preanalytical problem, is known to affect MRD detection. In the present study, we analyzed [...] Read more.
Minimal residual disease (MRD) is one of the most relevant prognostic factors in patients with multiple myeloma (MM). However, the hemodilution of bone marrow (BM) aspirates, the most common preanalytical problem, is known to affect MRD detection. In the present study, we analyzed a preanalytical method for routine BM aspirates and a bone marrow particle cell (BMPL) enrichment assay and validated it as a reliable preanalytical method for flow cytometric MRD determination. A total of 120 BM samples were taken from 103 MM patients consecutively recruited; 77 BM samples had BMPL enrichment analysis and 99 BM samples were routinely analyzed. Then, the two different samples from patients with MM were sent for MRD detection using an eight-color flow cytometry. Our data showed that assessment of the BMPL enrichment samples attenuated the overestimation of MRD-negative assessed in the routine BM samples, which was mainly caused by hemodilution. In conclusion, the BMPL enrichment assay is a functional and practical preanalytical method for flow cytometric MRD analysis. Full article
(This article belongs to the Special Issue Measurable Residual Disease in Cancer)
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