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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00699

The minimal residual disease within the bone marrow of Multiple Myeloma: caveats, clinical significance and future perspectives

  • 1University of Catania, Italy
  • 2Department of General Surgery and Medical-Surgical Specialties, University of Catania, Italy
  • 3Department of Medical, Surgical Sciences and Advanced Technologies G.F. Ingrassia, University of Catania, Italy
  • 4Department of Hematology, University Hospital Polyclinic Vittorio Emanuele, Italy
  • 5Department of Diagnostic and Experimental Medicine, University of Bologna, Italy
  • 6Sant'Orsola-Malpighi Polyclinic, Italy

There is an increasing clinical interest in the measure and achievement of minimal residual disease (MRD) negativity in the bone marrow of Multiple Myeloma (MM) patients, as defined equally either by Multicolor Flow Cytometry (MFC) or by Next Generation Sequencing (NGS) technologies. At present, modern technologies allow to detect up to one on 104 or on 105 or even on 106 cells, depending on their throughput. MFC approaches, which have been progressively improved up to the so-called Next Generation Flow (NGF), and NGS, which proved clear advantages over ASO-PCR, can detect very low levels of residual disease in the BM. These methods are actually almost superimposable, in terms of MRD detection power, supporting the lack of unanimous preference for either technique on basis of local availability. However, some technical issues are still open: the optimal assay to use to detect either phenotype (e.g. next generation multidimensional flow cytometry, imaging) or genotype aberrations (e.g. ASO-RQ PCR, digital droplet PCR, NGS) and their standardization, the sample source (BM or peripheral blood, PB) and its pre-processing (red-cell lysis versus Ficoll, fresh versus frozen samples, requirement of CD138+ cells enrichment). Overall, MRD negativity is considered as the most powerful predictor of favourable long-term outcomes in MM and is likely to represent the major driver of treatment strategies in the near future.
In this manuscript, we reviewed the main pitfalls and caveats of MRD detection within bone marrow in MM patients after front-line therapy, highlighting the improving of the currently employed technology and describing alternative methods for MRD testing in MM, such as liquid biopsy.

Keywords: Multiple Myeloma, NGS (Next Generation Sequencing), Flow cytofluorimetry, liquid biopsy, Minimal residual disease (MRD), real-time quantitative PCR (RQ PCR)

Received: 21 May 2019; Accepted: 15 Jul 2019.

Edited by:

Alessandro Gozzetti, University of Siena, Italy

Reviewed by:

Yago Nieto, University of Texas MD Anderson Cancer Center, United States
Muthalagu Ramanathan, UMass Memorial Medical Center, United States  

Copyright: © 2019 Romano, Palumbo, Parrinello, Conticello, Martello and Terragna. 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.

* Correspondence: Dr. Carolina Terragna, Sant'Orsola-Malpighi Polyclinic, Bologna, Italy,