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Cytometry. Part B, Clinical Cytometry Sep 2021
Topics: Flow Cytometry; Humans; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Neoplasm, Residual
PubMed: 34536066
DOI: 10.1002/cyto.b.22031 -
Best Practice & Research. Clinical... Dec 2022Quantification of measurable residual disease (MRD) in acute lymphoblastic leukemia (ALL) is a well-established clinical tool used to risk stratify patients during the... (Review)
Review
Quantification of measurable residual disease (MRD) in acute lymphoblastic leukemia (ALL) is a well-established clinical tool used to risk stratify patients during the course of chemotherapy, immunotherapy, and/or transplant therapy. As technologies evolve, the sensitivity for quantifying exceptionally low disease burden using either next generation sequencing (NGS) or next generation flow cytometry (NGF) has improved. It is now possible to detect MRD and quantify it precisely in patients who would previously have been deemed MRD negative by older, lower sensitivity methods. Persistence or recurrence of ALL disease burden above 10 (0.01%) is accepted as the minimum threshold for making clinical decisions, but with NGS and NGF, clinicians now confront decision-making with disease burdens sometimes quantified to as low as 10 (0.0001%, or one leukemia cell in a million leukocytes). Emerging data suggest these higher sensitivity methods are superior for identifying patients at lowest risk for relapse, but it remains controversial whether to institute therapies such as blinatumomab or chimeric antigen receptor (CAR)-T cells or move patients to allogeneic hematopoietic cell transplant (alloHCT) when they have quantifiable disease burden less than 10. With additional evidence to facilitate integration of highly sensitive MRD quantification into clinical care and to contextualize MRD within the genotype of individual patients, it will likely be increasingly possible to identify patients able to avoid alloHCT and potentially even de-escalate therapy.
Topics: Humans; Hematopoietic Stem Cell Transplantation; High-Throughput Nucleotide Sequencing; Neoplasm, Residual; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 36517126
DOI: 10.1016/j.beha.2022.101407 -
Current Oncology Reports Nov 2021There has been a huge development in the assessment of malignancies through liquid biopsies last years, especially for NSCLC, where its use has become part of clinical... (Review)
Review
PURPOSE OF REVIEW
There has been a huge development in the assessment of malignancies through liquid biopsies last years, especially for NSCLC, where its use has become part of clinical practice in some settings. We aim to summarize current evidence about minimal residual disease and its use in lung cancer.
RECENT FINDINGS
Recent studies using ctDNA in NSCLC but also in other types of cancer found strong correlations between the presence of ctDNA and the risk of disease progression or death after curative intent, despite current technical difficulties in performing this analysis (high sensitivity and specificity required). Evaluation of MRD in NSCLC, especially through ctDNA, could be an important point in future trial designs and could permit a more "targeted" adjuvant treatment.
Topics: Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Circulating Tumor DNA; Humans; Neoplasm Recurrence, Local; Neoplasm, Residual
PubMed: 34735646
DOI: 10.1007/s11912-021-01131-w -
American Journal of Hematology Mar 2017Acute myeloid leukemia (AML) is characterized by a clonal expansion of undifferentiated myeloid precursors resulting in impaired hematopoiesis and bone marrow failure.... (Review)
Review
Acute myeloid leukemia (AML) is characterized by a clonal expansion of undifferentiated myeloid precursors resulting in impaired hematopoiesis and bone marrow failure. In 2016, the World Health Organization (WHO) published revisions to the classification of myeloid neoplasms and acute leukemias. Similar to the 2008 classification, the updated classification incorporates clinical features, morphology, immunophenotyping, and cytogenetics, with greater emphasis on molecular genetics, to define disease entities. This brief review addresses the various components of pathologic assessment to establish a diagnosis of AML and to help risk stratify patients, with an emphasis on newer techniques used in the detection of mutations with prognostic significance, as well as assays employed in the evaluation of minimal residual disease following treatment.
Topics: Classification; Cytogenetics; Humans; Immunophenotyping; Leukemia, Myeloid, Acute; Molecular Biology; Neoplasm, Residual; Risk Assessment; World Health Organization
PubMed: 28066929
DOI: 10.1002/ajh.24648 -
Journal of Cellular and Molecular... Aug 2021Major advances in the field of genomic technologies have led to an improvement in cancer diagnosis, classification and prognostication. However, many cancers remain... (Review)
Review
Major advances in the field of genomic technologies have led to an improvement in cancer diagnosis, classification and prognostication. However, many cancers remain incurable due to the development of drug resistance, minimal residual disease (MRD) and disease relapse, highlighting an incomplete understanding of the mechanisms underlying these processes. In recent years, the impact of non-genetic factors on neoplastic transformations has increasingly been acknowledged, and growing evidence suggests that low oxygen (O ) levels (ie hypoxia) in the tumour microenvironment play a critical role in the development and treatment of cancer. As a result, there is a growing need to develop research tools capable of reproducing physiologically relevant O conditions encountered by cancer cells in their natural environments in order to gain in-depth insight into tumour cell metabolism and function. In this review, the authors highlight the importance of hypoxia in the pathogenesis of malignant diseases and provide an overview of novel engineering tools that have the potential to further drive this evolving, yet technically challenging, field of cancer research.
Topics: Bioengineering; Humans; Hypoxia; Neoplasm, Residual; Neoplasms; Neoplastic Stem Cells; Tumor Microenvironment
PubMed: 34213838
DOI: 10.1111/jcmm.16759 -
Current Oncology Reports Jul 2021Until recently, improvement in terms of survival for patients with acute myeloid leukemia (AML) was achieved mostly in younger patients with dose intensification of... (Review)
Review
PURPOSE OF REVIEW
Until recently, improvement in terms of survival for patients with acute myeloid leukemia (AML) was achieved mostly in younger patients with dose intensification of conventional chemotherapy and a broadening use of allogeneic hematopoietic cell transplantation (allo-HCT) whereas the results remained dismal and very stable in patients older than 60 years. The current review highlights the recent developments in standard intensive post-remission chemotherapy, evidence for the use of recently approved agents, and discusses the relevance of measurable residual disease (MRD) measurement in treatment adaptation.
RECENT FINDINGS
Current approvals of midostaurin, venetoclax, gemtuzumab ozogamicin, VYXEOS, ivosidenib, enasidenib, glasdegib, and CC-486 have changed the structure, aim, and schedule of consolidation therapy, and new, well-tolerated agents are being evaluated as maintenance therapies. Furthermore, MRD assessment has been implemented to guide the duration and type of consolidation and maintenance therapy as well as indicate the optimal timing of allo-HCT. Novel therapies have changed the structure and perspective of post-remission therapy in AML for both young and elderly patients. In addition, MRD assessment could guide the type, duration, and intensity of consolidation and maintenance therapy.
Topics: Acute Disease; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid; Male; Middle Aged; Neoplasm, Residual; Remission Induction; Survival Analysis; Transplantation, Homologous
PubMed: 34272619
DOI: 10.1007/s11912-021-01092-0 -
Cancer Mar 2023This study analyzed data from two consecutive protocols for children newly diagnosed with acute lymphoblastic leukemia (ALL) to determine the clinical impact of...
BACKGROUND
This study analyzed data from two consecutive protocols for children newly diagnosed with acute lymphoblastic leukemia (ALL) to determine the clinical impact of minimal/measurable residual disease (MRD) and recently identified tumor genetic subtypes.
METHODS
Genetic subtypes were determined by sequential approaches including DNA indexing, reverse transcriptase-polymerase chain reaction, multiplex ligation-dependent probe amplification, and RNA-sequencing. MRD was assessed by flow cytometry. The Taiwan Pediatric Oncology Group TPOG-ALL-2013 study enrolled patients who received MRD-directed therapy.
RESULTS
The 5-year event-free survival (EFS) and overall survival rates in the 2013 cohort were 77.8% and 86.9% compared to those of the 2002 cohort, which were 62.4% and 76.5%. Among patients treated with MRD-guided therapy, those with ETV6-RUNX1 fusion and high hyperdiploidy had the highest 5-year EFS (91.4% and 89.6%, respectively). The addition of dasatinib improved outcomes in patients with BCR-ABL1 ALL. Recently identified subtypes like DUX4-rearranged, ZNF384-rearranged, MEF2D-rearranged, and PAX5alt subtypes were frequently positive for MRD after remission induction, and these patients consequently received intensified chemotherapy. Treatment intensification according to the MRD improved the outcomes of patients presenting DUX4 rearrangements. In high-risk or very-high-risk subtypes, the TPOG-ALL-2013 regimen did not confer significant improvements compared to TPOG-ALL-2002, and the outcomes of BCR-ABL1-like, MEF2D-rearranged, and KMT2A-rearranged ALL subtypes (in addition to those of T-cell ALL) were not sufficiently good. Novel agents or approaches are needed to improve the outcomes for these patients.
CONCLUSIONS
The TPOG-ALL-2013 study yielded outcomes superior to those of patients treated in the preceding TPOG-ALL-2002 study. This study provides important data to inform the design of future clinical trials in Taiwan.
PLAIN LANGUAGE SUMMARY
MRD-directed therapy improved the outcomes for pediatric ALL, especially standard-risk patients. Genomic analyses and MRD might be used together for risk-directed therapy of childhood ALL. Our work provides important data to inform the design of future clinical trials in Taiwan.
Topics: Child; Humans; Neoplasm, Residual; Prognosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Dasatinib; Remission Induction
PubMed: 36537587
DOI: 10.1002/cncr.34606 -
Expert Review of Hematology Apr 2019Commonly used scoring systems rely on blood counts, histological and cytological examination of bone marrow and peripheral blood as well as cytogenetic assessments to... (Review)
Review
Commonly used scoring systems rely on blood counts, histological and cytological examination of bone marrow and peripheral blood as well as cytogenetic assessments to estimate prognosis of patients with myelodysplastic syndromes (MDS) and guide therapy decisions. Next-generation sequencing (NGS) has identified recurrent genetic abnormalities in up to 90% of patients with MDS and may provide important information regarding the pathogenesis of the disease, diagnostic and prognostic evaluation, and therapy selection. Areas covered: Herein, the authors review the role of NGS in diagnosis, treatment, and prognosis of MDS at various disease stages, and discuss advantages and caveats of incorporating molecular genetics in routine management of MDS. While a vast majority of patients harbor recurrent mutations implicated in MDS pathogenesis, similar mutations can be detected in otherwise healthy individuals with other hematologic malignancies. Besides establishing a diagnosis, NGS may be used to monitor minimal residual disease following treatment. Expert opinion: As more targeted therapies become available, assessment of genetic mutations will become central to individualized therapy selection and may improve diagnostic accuracy and further guide management for each patient. However, multiple challenges remain before NGS can be incorporated into routine clinical practice.
Topics: Animals; High-Throughput Nucleotide Sequencing; Humans; Mutation; Myelodysplastic Syndromes; Neoplasm, Residual; Prognosis; Stem Cell Transplantation
PubMed: 30977414
DOI: 10.1080/17474086.2019.1592673 -
Hematology/oncology Clinics of North... Aug 2021With the advent of highly effective novel therapies for chronic lymphocytic leukemia, conventional response assessment is not able to sensitively capture depth of... (Review)
Review
With the advent of highly effective novel therapies for chronic lymphocytic leukemia, conventional response assessment is not able to sensitively capture depth of response. To achieve a more precise assessment of response, minimal residual disease has been introduced to more accurately classify and quantify treatment outcomes. It is now considered a strong predictor of outcome in chronic lymphocytic leukemia, although its interpretation depends on the therapeutic context. This review discusses available methods of minimal residual disease measurement. It summarizes minimal residual disease data from pivotal clinical trials and discusses potential implications for future studies and minimal residual disease-based clinical strategies.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasm, Residual; Treatment Outcome
PubMed: 34102145
DOI: 10.1016/j.hoc.2021.03.007 -
Leukemia & Lymphoma Aug 2018The primary hurdle in the path to curing multiple myeloma (MM) is defining a validated minimal residual disease (MRD) and its utility in the therapeutic decision making.... (Review)
Review
The primary hurdle in the path to curing multiple myeloma (MM) is defining a validated minimal residual disease (MRD) and its utility in the therapeutic decision making. A better definition of MRD will aid in tailoring MM therapy further to address the clonal heterogeneity and genomic instability and overcome patient's ineffective immune surveillance. MRD analysis can define the logical endpoint for maintenance therapy, in addition also aids in providing a better clinical end point for studies comparing novel agents in myeloma. MRD is a surrogate for the survival in MM. Guidelines for global incorporation of MRD in myeloma are fraught with lack of standardization, universal availability and abridged physicians' understanding of MRD modalities. We aimed at addressing some of the frequently asked questions in the MRD assessment and will also place in perspective some arguments in favor of MRD assessment in routine practice and clinical trial scenario.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Diagnostic Imaging; Disease-Free Survival; Gene Rearrangement; High-Throughput Nucleotide Sequencing; Humans; Multiple Myeloma; Neoplasm, Residual; Prognosis
PubMed: 29019452
DOI: 10.1080/10428194.2017.1386304