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Specific Targets in Sarcoma and Developmental Therapeutics

David M. Thomas and Andrew J. Wagner

Connective tissue tumors comprise a rich array of subtypes, many of which possess strong pathognomonic phenotypes and genotypes of therapeutic significance. This article describes recent applications of targeted and nontargeted therapeutic agents in connective tissue tumors that illustrate important themes in drug development. Targeted therapy has exploited the paradigms of oncogene and lineage addiction. In other cases, potential targets are more difficult to classify, such as the role of the insulin-like growth factor 1 pathway in Ewing's sarcoma. Understanding why these pathways seem critical in some cancers, and in some individuals but not others, is important in identifying novel therapeutic opportunities in an age of personalized medicine.

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Hairy Cell Leukemia, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology

William G. Wierda, John C. Byrd, Jeremy S. Abramson, Seema Bhat, Greg Bociek, Danielle Brander, Jennifer Brown, Asher Chanan-Khan, Steve E. Coutre, Randall S. Davis, Christopher D. Fletcher, Brian Hill, Brad S. Kahl, Manali Kamdar, Lawrence D. Kaplan, Nadia Khan, Thomas J. Kipps, Jeffrey Lancet, Shuo Ma, Sami Malek, Claudio Mosse, Mazyar Shadman, Tanya Siddiqi, Deborah Stephens, Nina Wagner, Andrew D. Zelenetz, Mary A. Dwyer, and Hema Sundar

Hairy cell leukemia (HCL) is a rare type of indolent B-cell leukemia, characterized by symptoms of fatigue and weakness, organomegaly, pancytopenia, and recurrent opportunistic infections. Classic HCL should be considered a distinct clinical entity separate from HCLvariant (HCLv), which is associated with a more aggressive disease course and may not respond to standard HCL therapies. Somatic hypermutation in the IGHV gene is present in most patients with HCL. The BRAF V600E mutation has been reported in most patients with classic HCL but not in those with other B-cell leukemias or lymphomas. Therefore, it is necessary to distinguish HCLv from classic HCL. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of classic HCL.

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Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 2.2024

William G. Wierda, Jennifer Brown, Jeremy S. Abramson, Farrukh Awan, Syed F. Bilgrami, Greg Bociek, Danielle Brander, Matthew Cortese, Larry Cripe, Randall S. Davis, Herbert Eradat, Bita Fakhri, Christopher D. Fletcher, Sameh Gaballa, Muhammad Saad Hamid, Brian Hill, Paul Kaesberg, Brad Kahl, Manali Kamdar, Thomas J. Kipps, Shuo Ma, Claudio Mosse, Shazia Nakhoda, Sameer Parikh, Andrew Schorr, Stephen Schuster, Madhav Seshadri, Tanya Siddiqi, Deborah M. Stephens, Meghan Thompson, Chaitra Ujjani, Riccardo Valdez, Nina Wagner-Johnston, Jennifer A. Woyach, Hema Sundar, and Mary Dwyer

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are essentially different manifestations of the same disease that are similarly managed. A number of molecular and cytogenetic variables with prognostic implications have been identified. Undetectable minimal residual disease at the end of treatment with chemoimmunotherapy or venetoclax-based combination regimens is an independent predictor of improved survival among patients with previously untreated or relapsed/refractory CLL/SLL. The selection of treatment is based on the disease stage, presence or absence of del(17p) or TP53 mutation, immunoglobulin heavy chain variable region mutation status, patient age, performance status, comorbid conditions, and the agent’s toxicity profile. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with CLL/SLL.