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 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.

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

Flow cytometric minimal residual disease assessment of peripheral blood in acute lymphoblastic leukaemia patients has potential for early detection of relapsed extramedullary disease

2018 ◽  
Vol 71 (7) ◽  
pp. 653-658 ◽  
Author(s):  
Alissa Keegan ◽  
Karry Charest ◽  
Ryan Schmidt ◽  
Debra Briggs ◽  
Daniel J Deangelo ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukaemia ◽  
Minimal Residual Disease ◽  
Lymphoblastic Leukaemia ◽  
Peripheral Blood ◽  
Residual Disease ◽  
Diagnostic Value ◽  
Disease Assessment ◽  
Extramedullary Disease ◽  
Systemic Relapse ◽  
Minimal Residual

ObjectivesTo evaluate peripheral blood (PB) for minimal residual disease (MRD) assessment in adults with acute lymphoblastic leukaemia (ALL).MethodsWe analysed 76 matched bone marrow (BM) aspirate and PB specimens independently for the presence of ALL MRD by six-colour flow cytometry (FC).ResultsThe overall rate of BM MRD-positivity was 24% (18/76) and PB was also MRD-positive in 22% (4/18) of BM-positive cases. We identified two cases with evidence of leukaemic cells in PB at the time of the extramedullary relapse that were interpreted as MRD-negative in BM.ConclusionsThe use of PB MRD as a non-invasive method for monitoring of systemic relapse may have added clinical and diagnostic value in patients with high risk of extramedullary disease.

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