scholarly journals Minimal Residual Disease Assessment in Lymphoma: Methods and Applications

2017 ◽  
Vol 35 (34) ◽  
pp. 3877-3887 ◽  
Author(s):  
Alex F. Herrera ◽  
Philippe Armand
Keyword(s):  
Clinical Trials ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Response Assessment ◽  
Response To Therapy ◽  
Detection Methods ◽  
Disease Assessment ◽  
Routine Practice ◽  
Advantages And Disadvantages ◽  
Minimal Residual

Standard methods for disease response assessment in patients with lymphoma, including positron emission tomography and computed tomography scans, are imperfect. In other hematologic malignancies, particularly leukemias, the ability to detect minimal residual disease (MRD) is increasingly influencing treatment paradigms. However, in many subtypes of lymphoma, the application of MRD assessment techniques, like flow cytometry or polymerase chain reaction–based methods, has been challenging because of the absence of readily detected circulating disease or canonic chromosomal translocations. Newer MRD detection methods that use next-generation sequencing have yielded promising results in a number of lymphoma subtypes, fueling the hope that MRD detection may soon be applicable in clinical practice for most patients with lymphoma. MRD assessment can provide real-time information about tumor burden and response to therapy, noninvasive genomic profiling, and monitoring of clonal dynamics, allowing for many possible applications that could significantly affect the care of patients with lymphoma. Further validation of MRD assessment methods, including the incorporation of MRD assessment into clinical trials in patients with lymphoma, will be critical to determine how best to deploy MRD testing in routine practice and whether MRD assessment can ultimately bring us closer to the goal of personalized lymphoma care. In this review article, we describe the methods available for detecting MRD in patients with lymphoma and their relative advantages and disadvantages. We discuss preliminary results supporting the potential applications for MRD testing in the care of patients with lymphoma and strategies for including MRD assessment in lymphoma clinical trials.

scholarly journals Role of Imaging in the Evaluation of Minimal Residual Disease in Multiple Myeloma Patients

2020 ◽  
Vol 9 (11) ◽  
pp. 3519
Author(s):  
Elena Zamagni ◽  
Paola Tacchetti ◽  
Simona Barbato ◽  
Michele Cavo
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Minimal Residual Disease ◽  
Plasma Cells ◽  
Residual Disease ◽  
Imaging Techniques ◽  
Response Assessment ◽  
Response To Therapy ◽  
Whole Body ◽  
Minimal Residual

The International Myeloma Working Group (IMWG) recently introduced the evaluation of minimal residual disease (MRD) within the multiple myeloma (MM) response criteria, and MRD negativity assessed inside and outside the bone marrow is currently considered the most powerful predictor of favorable long-term outcomes. However, MRD evaluation has thus far relied on flow-cytometry or molecular-based methods, despite the limitations associated with the patchy infiltration of bone marrow (BM) plasma cells and the presence of extra-medullary (EMD). On the contrary, imaging-based sensitive response assessment through the use of functional rather than morphological whole-body (WB) imaging techniques, such as positron emission tomography with computed tomography (PET/CT) and magnetic resonance imaging (MRI), likely is a promising strategy to overcome these limitations in evaluating response to therapy and in the assessment of the MRD status in MM patients. However, despite the significant advances in the development and availability of novel functional imaging techniques for MRD evaluation, a worldwide standardization of imaging criteria for acquisition, interpretation, and reporting is yet to be determined and will be object of future investigations.

scholarly journals Exhaustive circulating tumor DNA sequencing reveals the genomic landscape of Hodgkin lymphoma and facilitates ultrasensitive detection of minimal residual disease

2021 ◽  
Author(s):  
Sophia Sobesky ◽  
Laman Mammadova ◽  
Melita Cirillo ◽  
Esther Drees ◽  
Julia Mattlener ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Response Assessment ◽  
Copy Number Variations ◽  
Disease Assessment ◽  
Molecular Response ◽  
Sequencing Platform ◽  
Genomic Landscape ◽  
Minimal Residual

Individualizing treatment is key to improve outcome and reduce long-term side-effects in any cancer. In Hodgkin lymphoma (HL), individualization of treatment is hindered by a lack of genomic characterization and technology for sensitive, molecular response assessment. Sequencing of cell-free (cf)DNA is a powerful strategy to understand an individual cancer genome and can be used to develop assays for extremely sensitive disease monitoring. In HL, a high proportion of cfDNA is tumor-derived making it a highly relevant disease model to study the role of cfDNA sequencing in cancer. Here, we introduce our targeted cfDNA sequencing platform and present the largest genomic landscape of HL to date, which was entirely derived by cfDNA sequencing. We comprehensively genotype and assess minimal residual disease in 324 samples from 121 patients, presenting an integrated landscape of mutations and copy number variations in HL. In addition, we perform a deep analysis of mutational processes driving HL, investigate the clonal structure of HL and link several genotypes to HL phenotypes and outcome. Finally, we show that minimal residual disease assessment by repeat cfDNA sequencing as early as a week after treatment initiation is feasible and predicts overall treatment response allowing highly improved treatment guidance and relapse prediction. Our study also serves as a blueprint showcasing the utility of our platform for other cancers with similar therapeutic challenges.

scholarly journals Unsupervised Flow Cytometry Analysis Allows for an Accurate Identification of Minimal Residual Disease Assessment in Acute Myeloid Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 629
Author(s):  
Jean Philippe Vial ◽  
Nicolas Lechevalier ◽  
Francis Lacombe ◽  
Pierre-Yves Dumas ◽  
Audrey Bidet ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Response To Therapy ◽  
Disease Assessment ◽  
Multiparameter Flow Cytometry ◽  
Accurate Identification ◽  
Self Organizing Maps ◽  
Minimal Residual

The assessment of minimal residual disease (MRD) is increasingly considered to monitor response to therapy in hematological malignancies. In acute myeloblastic leukemia (AML), molecular MRD (mMRD) is possible for about half the patients while multiparameter flow cytometry (MFC) is more broadly available. However, MFC analysis strategies are highly operator-dependent. Recently, new tools have been designed for unsupervised MFC analysis, segregating cell-clusters with the same immunophenotypic characteristics. Here, the Flow-Self-Organizing-Maps (FlowSOM) tool was applied to assess MFC-MRD in 96 bone marrow (BM) follow-up (FU) time-points from 40 AML patients with available mMRD. A reference FlowSOM display was built from 19 healthy/normal BM samples (NBM), then simultaneously compared to the patient’s diagnosis and FU samples at each time-point. MRD clusters were characterized individually in terms of cell numbers and immunophenotype. This strategy disclosed subclones with varying immunophenotype within single diagnosis and FU samples including populations absent from NBM. Detectable MRD was as low as 0.09% in MFC and 0.051% for mMRD. The concordance between mMRD and MFC-MRD was 80.2%. MFC yielded 85% specificity and 69% sensitivity compared to mMRD. Unsupervised MFC is shown here to allow for an easy and robust assessment of MRD, applicable also to AML patients without molecular markers.

scholarly journals Harmonization of Flow Cytometric Minimal Residual Disease Assessment in Multiple Myeloma in Centers of Polish Myeloma Consortium

Diagnostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1872
Author(s):  
Agnieszka Krzywdzińska ◽  
Bartosz Puła ◽  
Anna Czyż ◽  
Beata Krzymieniewska ◽  
Jolanta Kiernicka-Parulska ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
High Sensitivity ◽  
Disease Assessment ◽  
Reproducibility Study ◽  
Highly Sensitive ◽  
Data Files ◽  
Minimal Residual

Minimal residual disease (MRD) status is now considered as one of the most relevant prognostic factors in multiple myeloma (MM) while MRD negativity became an important endpoint in clinical trials. Here, we report the results of the first study evaluating the reproducibility of high-sensitivity flow cytometry MM MRD assessment in four laboratories in Poland. EuroFlow protocols for instrument setting standardization and sample preparation in MM MRD assessment were implemented in each laboratory. In the inter-laboratory reproducibility study, 12 bone marrow samples from MM patients were distributed and processed in participant laboratories. In the inter-operator concordance study, 13 raw data files from MM MRD measurements were analyzed by five independent operators. The inter-laboratory study showed high 95% overall concordance of results among laboratories. In the inter-operator study, 89% of MRD results reported were concordant, and the highest immunophenotype interpretation differences with regard to expression of CD27, CD45, CD81 were noticed. We confirmed the applicability and feasibility of the EuroFlow protocol as a highly sensitive method of MRD evaluation in MM. Results of our inter-center comparison study demonstrate that the standardization of MM MRD assessment protocols is highly desirable to improve quality and comparability of results within and between different clinical trials.

Early Detection of Minimal Residual Disease in Biological Prognostic Risk Groups in Chronic Lymphocytic Leukaemia (CLL) Utilizing the Novel CD160FCA Assay

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2832-2832
Author(s):  
Timothy W Farren ◽  
Fengting Liu ◽  
Marion Macey ◽  
Michael Jenner ◽  
Samir Agrawal
Keyword(s):  
Minimal Residual Disease ◽  
Prognostic Markers ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Response To Therapy ◽  
Disease Assessment ◽  
Prognostic Indicators ◽  
Long Term Outcome ◽  
Highly Sensitive ◽  
Minimal Residual

Abstract Abstract 2832 Introduction: CLL is a heterogenous disease. At diagnosis, prognostication is possible using a number of clinical and biological factors, which can inform the choice of treatment. In terms of response to treatment, minimal residual disease (MRD) detection is becoming increasingly important in CLL. Utilizing the CD160FCA assay, we have evaluated the time to MRD detection for a number of established prognostic markers. Methods: Utilizing the anti-CD160 monoclonal antibody (BY55, Coulter Immunotech, Marseille, France), we have developed a highly sensitive CD160 Flow Cytometric Assay (CD160FCA) incorporating a sequential gating strategy. Between July 2010 and July 2011, 63 patients were investigated for MRD by the routine clinical diagnostic service. 47 (73%) had completed treatment and were evaluable for long-term outcome. Response rates and event-free survival (EFS) were determined. The time to MRD detection post therapy was determined using CD160FCA for the prognostic indicators, ZAP-70, CD38, beta-2 microglobulin (B2M) and cytogenetic abnormalities. Results: As expected, establishing clonality by light-chain restriction could not be reliably measured in patients with very low B-cell numbers, and hence could not reliably be used to determine MRD. The CD160FCA could reliably monitor patients for MRD, including immunotherapy with Rituximab and Campath. 28 Patients (44%) were in complete remission (CR) following therapy by current NCI guidelines. Of these patients, 9/28 (32%) were CR-MRD positive and had significantly shortened EFS compared with CR-MRD negative patients (61 days vs 957 days P<0.0001). Those patients with adverse cytogenetic markers had shorter time to disease detection (TTD): p53 mutation (30.5 days), 17pdel (61 days) and 11qdel (122 days) compared to +12 (427d), 13qdel (957d) and 13qdel with additional abnormalities (760 d). Of interest, patients with bi-allelic 13qdel had significantly shorter TTD compared to those with monoallelic 13qdel (46d vs 957d). Likewise CD38 status (CD38+: 92d vs CD38-: 669d; P=0.03) and B2M prior to treatment (B2M high: 91d vs B2M normal: 822d; P=0.004) were predictors of TTD based on residual disease assessment by the CD160FCA. 25 patients (40%) were assessed for ZAP-70 prior to commencing therapy. Those patients who were ZAP-70 positive had shorter TTD compared to those who were negative (ZAP+: 61d vs ZAP- 822d; P=0.01). Conclusion: Many clinical studies base their entry criteria on clinical and biological prognostication, as this provides insights into the biology of CLL and its response to therapy. The CD160FCA is a single tube tumor specific assay for MRD detection, which is highly sensitive, independent of the therapy and can be employed throughout treatment. Patients in CR had significantly different EFS based on their MRD status following treatment using the CD160FCA. For those patients with adverse prognostic markers (including CD38, ZAP-70 and B2M), the detection of MRD or relapsing disease using CD160FCA, is significantly shorter than those with a normal or good prognosis. Disclosures: No relevant conflicts of interest to declare.

Post-transplant minimal residual disease assessment in Multiple myeloma

2019 ◽  
Vol 19 (10) ◽  
pp. e180
Author(s):  
Anjali Mookerjee ◽  
Meetu Dahiya ◽  
Ritu Gupta ◽  
Rakesh Kumar ◽  
Atul Sharma ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Disease Assessment ◽  
Post Transplant ◽  
Minimal Residual

scholarly journals Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children's Oncology Group

Blood ◽  
2008 ◽  
Vol 111 (6) ◽  
pp. 2984-2990 ◽  
Author(s):  
Stella M. Davies ◽  
Michael J. Borowitz ◽  
Gary L. Rosner ◽  
Kristin Ritz ◽  
Meenakshi Devidas ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Response To Therapy ◽  
Oncology Group ◽  
Risk Status ◽  
Prognostic Features ◽  
Minimal Residual

Abstract Minimal residual disease (MRD) as a marker of antileukemic drug efficacy is being used to assess risk status and, in some cases, to adjust the intensity of therapy. Within known prognostic categories, the determinants of MRD are not known. We measured MRD by flow cytometry at day 8 (in blood) and at day 28 (in bone marrow) of induction therapy in more than 1000 children enrolled in Pediatric Oncology Group therapy protocols 9904, 9905, and 9906. We classified patients as “best risk” if they had cleared MRD by day 8 of therapy and as “worst risk” if they had MRD remaining in bone marrow at day 28, and tested whether MRD was related to polymorphisms in 16 loci in genes hypothesized to influence response to therapy in acute lymphoblastic leukemia (ALL). After adjusting for known prognostic features such as presence of the TEL-AML1 rearrangement, National Cancer Institute (NCI) risk status, ploidy, and race, the G allele of a common polymorphism in chemokine receptor 5 (CCR5) was associated with more favorable MRD status than the A allele (P = .009, logistic regression), when comparing “best” and “worst” risk groups. These data are consistent with growing evidence that both acquired and host genetics influence response to cancer therapy.

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