NCCN Guidelines® Insights: B-Cell Lymphomas, Version 6.2023

Journal of the National Comprehensive Cancer Network · 2023 · 113 citations

• Medicine
• Oncology
• Internal medicine

Novel targeted therapies (small molecule inhibitors, antibody-drug conjugates, and CD19-directed therapies) have changed the treatment landscape of relapsed/refractory B-cell lymphomas. Bruton's tyrosine kinase (BTK) inhibitors continue to evolve in the management of mantle cell lymphoma (MCL), in both the relapsed/refractory and the frontline setting. Anti-CD19 CAR T-cell therapies are now effective and approved treatment options for relapsed/refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and MCL. Bispecific T-cell engagers represent a novel immunotherapeutic approach for relapsed FL and DLBCL after multiple lines of therapies, including prior CAR T-cell therapy. These NCCN Guideline Insights highlight the significant updates to the NCCN Guidelines for B-Cell Lymphomas for the treatment of FL, DLBCL, and MCL.

The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms

Leukemia · 2022 · 3589 citations

• Pathology
• Medicine
• Cancer research

edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.

The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms

Leukemia · 2022 · 3808 citations

• Computer Science
• Medicine
• Computational biology

The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.

NCCN Guidelines® Insights: B-Cell Lymphomas, Version 5.2021

Journal of the National Comprehensive Cancer Network · 2021 · 166 citations

• Medicine
• Cancer research
• Oncology

In the last decade, a better understanding of the molecular pathogenesis of B-cell non-Hodgkin lymphomas has resulted in the development of novel targeted therapies, such as small molecule inhibitors of select kinases in the B-cell receptor pathway, antibody-drug conjugates, and small molecules that target a variety of proteins (eg, CD-19, EZH2, and XPO-1-mediated nuclear export). Anti-CD19 CAR T-cell therapy, first approved for relapsed/refractory (R/R) diffuse large B-cell lymphoma, has also emerged as a novel treatment option for R/R follicular lymphoma and mantle cell lymphoma. These NCCN Guideline Insights highlight the new targeted therapy options included in the NCCN Guidelines for B-Cell Lymphomas for the treatment of R/R disease.

International evidence-based consensus diagnostic and treatment guidelines for unicentric Castleman disease

Blood Advances · 2020 · 206 citations

• Medicine
• Internal medicine

Castleman disease (CD) includes a group of rare and heterogeneous disorders with characteristic lymph node histopathological abnormalities. CD can occur in a single lymph node station, which is referred to as unicentric CD (UCD). CD can also involve multicentric lymphadenopathy and inflammatory symptoms (multicentric CD [MCD]). MCD includes human herpesvirus-8 (HHV-8)-associated MCD, POEMS-associated MCD, and HHV-8-/idiopathic MCD (iMCD). The first-ever diagnostic and treatment guidelines were recently developed for iMCD by an international expert consortium convened by the Castleman Disease Collaborative Network (CDCN). The focus of this report is to establish similar guidelines for the management of UCD. To this purpose, an international working group of 42 experts from 10 countries was convened to establish consensus recommendations based on review of treatment in published cases of UCD, the CDCN ACCELERATE registry, and expert opinion. Complete surgical resection is often curative and is therefore the preferred first-line therapy, if possible. The management of unresectable UCD is more challenging. Existing evidence supports that asymptomatic unresectable UCD may be observed. The anti-interleukin-6 monoclonal antibody siltuximab should be considered for unresectable UCD patients with an inflammatory syndrome. Unresectable UCD that is symptomatic as a result of compression of vital neighboring structures may be rendered amenable to resection by medical therapy (eg, rituximab, steroids), radiotherapy, or embolization. Further research is needed in UCD patients with persisting constitutional symptoms despite complete excision and normal laboratory markers. We hope that these guidelines will improve outcomes in UCD and help treating physicians decide the best therapeutic approach for their patients.

Mastermind: A Comprehensive Genomic Association Search Engine for Empirical Evidence Curation and Genetic Variant Interpretation

Frontiers in Genetics · 2020 · 95 citations

• Computer Science
• Computational biology
• Genetics

Design and interpretation of genome sequencing assays in clinical diagnostics and research labs is complicated by an inability to identify information from the medical literature and related databases quickly, comprehensively and reproducibly. This challenge is compounded by the complexity and heterogeneity of nomenclatures used to describe diseases, genes and genetic variants. Mastermind is a widely-used bioinformatic platform of genomic associations that has indexed more than 7.5 M full-text articles and 2.5 M supplemental datasets. It has automatically identified, disambiguated and annotated >6.1 M genetic variants and identified >50 K disease-gene associations. Here, we describe how Mastermind improves the sensitivity and reproducibility of clinical variant interpretation and produces comprehensive genomic landscapes of genetic variants driving pharmaceutical research. We demonstrate an alarmingly high degree of heterogeneity across commercially available panels for hereditary cancer that is resolved by evidence from Mastermind. We further examined the sensitivity of Mastermind for variant interpretation by examining 108 clinically-encountered variants and comparing the results to alternate methods. Mastermind demonstrated a sensitivity of 98.4% compared to 4.4, 45.6, and 37.4% for alternatives PubMed, Google Scholar, and ClinVar, respectively, and a specificity of 98.5% compared to 45.1, 57.6, and 68.8% as well as an increase in content yield of 22.6-, 2.2-, and 2.6-fold. When curated for clinical significance, Mastermind identified more than 4.9-fold more pathogenic variants than ClinVar for representative genes. For structural variants, we compared Mastermind's ability to sensitively identify evidence for 10 representative disease-causing CNVs versus results identified in PubMed, as well as its ability to identify evidence for fusion events compared to COSMIC. Mastermind demonstrated a 4.0- to 43.9-fold increase in references for specific CNVs compared to PubMed, as well as 5.4-fold more fusion genes when compared with COSMIC's curated database. Additionally, Mastermind produced an 8.0-fold increase in reference citations for fusion events common to Mastermind and outside databases. Taken together, these results demonstrate the utility and superiority of Mastermind in terms of both sensitivity and specificity of automated results for clinical diagnostic variant interpretation for multiple genetic variant types and highlight the potential benefit in informing pharmaceutical research.