Assessment of Minimal Residual Disease by Next Generation Sequencing in Peripheral Blood as a Complementary Tool for Personalized Transplant Monitoring in Myeloid Neoplasms

Aguirre-Ruiz, Paula; Ariceta, Beñat; Viguria, María Cruz; Zudaire, Maite; Blasco-Iturri, Zuriñe; Arnedo, Patricia; Aguilera-Diaz, Almudena; Jauregui, Axier; Mañú, Amagoia; Prósper, Felipe; Mateos, M.C.; Fernández-Mercado, Marta; Larráyoz, María José; Redondo, Margarita; Calasanz, Marı́a José; Vázquez, Iria; Bandrés, Eva

doi:10.3390/jcm9123818

Cited by 11 publications

(10 citation statements)

References 43 publications

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“…However, although principally feasible, broad clinical application of this technique is currently still hampered by the considerable costs. Aguirre-Ruiz and coworkers recently performed a retrospective correlation of the results of NGS-MRD (level of sensitivity 10 -3 ) and sensitive chimerism analysis using a commercial qPCR-assay in a pilot study of 20 patients with MDS or AML post alloHCT ( 51 ). The authors could document on overall concordance of the data, especially in patients with mixed chimerism, the detection of leukemic SNVs increased the predictive value of the chimerism findings.…”

Section: Current Limitations and Future Developmentsmentioning

confidence: 99%

Analysis of Subset Chimerism for MRD-Detection and Pre-Emptive Treatment in AML

et al. 2022

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Allogeneic hematopoietic stem cell transplantation (alloHCT) represents the only potentially curative treatment in high-risk AML patients, but up to 40% of patients suffer from relapse after alloHCT. Treatment of overt relapse poses a major therapeutic challenge and long-term disease control is achieved only in a minority of patients. In order to avoid post-allograft relapse, maintenance as well as pre-emptive therapy strategies based on MRD-detection have been used. A prerequisite for the implementation of pre-emptive therapy is the accurate identification of patients at risk for imminent relapse. Detection of measurable residual disease (MRD) represents an effective tool for early relapse prediction in the post-transplant setting. However, using established MRD methods such as multicolor flow cytometry or quantitative PCR, sensitive MRD monitoring is only applicable in about half of the patients with AML and advanced MDS undergoing alloHCT. Donor chimerism analysis, in particular when performed on enriched leukemic stem and progenitor cells, e.g. CD34+ cells, is a sensitive method and has emerged as an alternative option in the post alloHCT setting. In this review, we will focus on the current strategies for lineage specific chimerism analysis, results of pre-emptive treatment using this technology as well as future developments in this field.

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Section: Current Limitations and Future Developmentsmentioning

confidence: 99%

Analysis of Subset Chimerism for MRD-Detection and Pre-Emptive Treatment in AML

et al. 2022

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“…Due to these limitations, more research is necessary before its routine application in chimerism monitoring. Moreover, these authors believe that the long time and the high cost of analysis represent the two most important limits to adopting NGS technologies in clinical field [ 31 , 60 , 61 ].…”

Section: Resultsmentioning

confidence: 99%

“…In sum, some works agree that NGS is a sensitive, accurate, and promising technology but one that is also too complex, expensive, and immature to gain a central role in chimerism monitoring. However, they consider that NGS automatization as well as the continuous reduction cost per NGS run could lead to the integration in laboratories of NGS-based methods for chimerism quantification over the next few years [ 31 , 33 , 60 , 61 ].…”

Section: Resultsmentioning

confidence: 99%

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Chimerism Monitoring Techniques after Hematopoietic Stem Cell Transplantation: An Overview of the Last 15 Years of Innovations

et al. 2021

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Chimerism analysis is a well-established method for monitoring the state of hematopoietic stem cell transplantation (HSCT) over time by analyzing peripheral blood or bone marrow samples of the recipient in several malignant and non-malignant hematologic diseases. From a clinical point of view, a continuous monitoring is fundamental for an effective early therapeutic intervention. This paper provides a comparative overview of the main molecular biology techniques which can be used to study chimerism after bone marrow transplantation, focusing on their advantages and disadvantages. According to the examined literature, short tandem repeats (STR) analysis through simple PCR coupled with capillary electrophoresis (STR-PCR) is the most powerful method which guarantees a high power of differentiation between different individuals. However, other methods such as real-time quantitative PCR (qPCR), digital PCR (dPCR), and next-generation sequencing (NGS) technology were developed to overcome the technical limits of STR-PCR. In particular, these other techniques guarantee a higher sensitivity, which allows for the detection of chimerism at an earlier stage, hence expanding the window for therapeutic intervention. After a comparative evaluation of the various techniques, it seems clear that STR-PCR still remains the gold standard option for chimerism study, even if it is likely that both dPCR and NGS could supplement or even replace the common methods of STR analysis.

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“…In a retrospective analysis of NGS-based MRD with serial PB and BM samples of 12 AML and 8 MDS patients after HSCT, similar results were obtained with PB and BM suggesting that both could be used for NGS-based MRD in AML. However, the size of this AML cohort was limited, and confirmation using larger sample sizes is needed [ 86 ]. Contrarily, in another study, discrepancies in leukemic driver mutations were seen between PB and BM samples due to a shortage of leukemic blasts in the blood.…”

Section: Challenges Related To Mrd Detection By Ngsmentioning

confidence: 99%

Molecular Minimal Residual Disease Detection in Acute Myeloid Leukemia

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Hinai

Hanekamp

et al. 2021

Cancers

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Initial induction chemotherapy to eradicate the bulk of acute myeloid leukemia (AML) cells results in complete remission (CR) in the majority of patients. However, leukemic cells persisting in the bone marrow below the morphologic threshold remain unaffected and have the potential to proliferate and re-emerge as AML relapse. Detection of minimal/measurable residual disease (MRD) is a promising prognostic marker for AML relapse as it can assess an individual patients’ risk profile and evaluate their response to treatment. With the emergence of molecular techniques, such as next generation sequencing (NGS), a more sensitive assessment of molecular MRD markers is available. In recent years, the detection of MRD by molecular assays and its association with AML relapse and survival has been explored and verified in multiple studies. Although most studies show that the presence of MRD leads to a worse clinical outcome, molecular-based methods face several challenges including limited sensitivity/specificity, and a difficult distinction between mutations that are representative of AML rather than clonal hematopoiesis. This review describes the studies that have been performed using molecular-based assays for MRD detection in the context of other MRD detection approaches in AML, and discusses limitations, challenges and opportunities.

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Assessment of Minimal Residual Disease by Next Generation Sequencing in Peripheral Blood as a Complementary Tool for Personalized Transplant Monitoring in Myeloid Neoplasms

Cited by 11 publications

References 43 publications

Analysis of Subset Chimerism for MRD-Detection and Pre-Emptive Treatment in AML

Analysis of Subset Chimerism for MRD-Detection and Pre-Emptive Treatment in AML

Chimerism Monitoring Techniques after Hematopoietic Stem Cell Transplantation: An Overview of the Last 15 Years of Innovations

Molecular Minimal Residual Disease Detection in Acute Myeloid Leukemia

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