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Venous Thromboembolic Disease

Michael B. Streiff, Paula L. Bockenstedt, Spero R. Cataland, Carolyn Chesney, Charles Eby, John Fanikos, Annemarie E. Fogerty, Shuwei Gao, Samuel Z. Goldhaber, Hani Hassoun, Paul Hendrie, Bjorn Holmstrom, Nicole Kuderer, Jason T. Lee, Michael M. Millenson, Anne T. Neff, Thomas L. Ortel, Tanya Siddiqi, Judy L. Smith, Gary C. Yee, Anaadriana Zakarija, Nicole McMillian, and Maoko Naganuma

Venous thromboembolism (VTE) remains a common and life-threatening complication among patients with cancer. Thromboprophylaxis can be used to prevent the occurrence of VTE in patients with cancer who are considered at high risk for developing this complication. Therefore, it is critical to recognize the various risk factors for VTE in patients with cancer. Risk assessment tools are available to help identify patients for whom discussions regarding the potential benefits and risks of thromboprophylaxis would be appropriate. The NCCN Clinical Practice Guidelines in Oncology for VTE provide recommendations on risk evaluation, diagnosis, prevention, and treatment of VTE in patients with cancer.

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Cancer-Associated Venous Thromboembolic Disease, Version 1.2015

Michael B. Streiff, Bjorn Holmstrom, Aneel Ashrani, Paula L. Bockenstedt, Carolyn Chesney, Charles Eby, John Fanikos, Randolph B. Fenninger, Annemarie E. Fogerty, Shuwei Gao, Samuel Z. Goldhaber, Paul Hendrie, Nicole Kuderer, Alfred Lee, Jason T. Lee, Mirjana Lovrincevic, Michael M. Millenson, Anne T. Neff, Thomas L. Ortel, Rita Paschal, Sanford Shattil, Tanya Siddiqi, Kristi J. Smock, Gerald Soff, Tzu-Fei Wang, Gary C. Yee, Anaadriana Zakarija, Nicole McMillian, and Anita M. Engh

The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of venous thromboembolism (VTE) in adult patients with a diagnosis of cancer or for whom cancer is clinically suspected. VTE is a common complication in patients with cancer, which places them at greater risk for morbidity and mortality. Therefore, risk-appropriate prophylaxis is an essential component for the optimal care of inpatients and outpatients with cancer. Critical to meeting this goal is ensuring that patients get the most effective medication in the correct dose. Body weight has a significant impact on blood volume and drug clearance. Because obesity is a common health problem in industrialized societies, cancer care providers are increasingly likely to treat obese patients in their practice. Obesity is a risk factor common to VTE and many cancers, and may also impact the anticoagulant dose needed for safe and effective prophylaxis. These NCCN Guidelines Insights summarize the data supporting new dosing recommendations for VTE prophylaxis in obese patients with cancer.

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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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Association Between Pretreatment Skeletal Muscle and Outcomes After CAR T-Cell Therapy

Kyuwan Lee, Aleksi Iukuridze, Tianhui He, Alysia Bosworth, Lanie Lindenfeld, Jennifer Berano Teh, Meagan Echevarria, Sophia Albanese, Liezl Atencio, Rusha Bhandari, F. Lennie Wong, Andrew S. Artz, Tanya Siddiqi, Liana Nikolaenko, Jasmine Zain, Matthew Mei, Geoffrey Shouse, Leslie L. Popplewell, Alex F. Herrera, L. Elizabeth Budde, Stephen J. Forman, and Saro H. Armenian

Background: The purpose of this study was to examine the association between baseline skeletal muscle measurements, acute toxicity (immune effector cell–associated neurotoxicity syndrome [ICANS], cytokine release syndrome), and treatment efficacy in patients undergoing CAR T-cell therapy for B-lineage lymphoma. Patients and Methods: Skeletal muscle measurements were obtained from automated CT measurements in 226 consecutive patients who received CAR T-cell therapy between 2015 and 2021. The Kaplan-Meier method was used to examine progression-free survival (PFS) and overall survival (OS) at 1-year. Multivariable regression was used to calculate the hazard ratio (HR) with 95% confidence intervals, adjusted for covariates. Results: The median age of the cohort was 63.1 years (range, 18.5–82.4 years), and most patients were male (66%) and had primary refractory disease (58%). Patients with abnormally low skeletal muscle at baseline were at greater risk of ICANS (HR, 1.74; 95% CI, 1.05–2.87) and had longer length of hospitalization (mean 27.7 vs 22.9 days; P<.05) compared with those with normal muscle mass. Abnormal skeletal muscle was independently associated with risk of disease progression (HR, 1.70; 95% CI, 1.11–2.57) and worse survival (HR, 2.44; 95% CI, 1.49–4.00) at 1 year compared with normal skeletal muscle. Individuals who had abnormal skeletal muscle and high lactate dehydrogenase (LDH) levels at baseline had poor 1-year PFS (17%) and OS (12%) compared with those with normal skeletal muscle and LDH levels (72% and 82%, respectively; P<.001). Patients who had abnormal skeletal muscle and LDH levels had a 5-fold risk (HR, 5.34; 95% CI, 2.97–9.62) of disease progression and a 10-fold risk (HR, 9.73; 95% CI, 4.81–19.70) of death (reference: normal skeletal muscle, normal LDH), independent of prior lines of therapy, extent of residual disease at time of CAR T-cell therapy, functional status, or product. Conclusions: This information can be used for risk stratification prior to CAR T-cell therapy or to implement prehabilitation and nutritional optimization before lymphodepletion as well as thereafter. These efforts will be complementary to ongoing efforts toward sustained efficacy after CAR T-cell therapy.

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Cancer-Associated Venous Thromboembolic Disease, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Michael B. Streiff, Bjorn Holmstrom, Dana Angelini, Aneel Ashrani, Amro Elshoury, John Fanikos, Kleber Yotsumoto Fertrin, Annemarie E. Fogerty, Shuwei Gao, Samuel Z. Goldhaber, Krishna Gundabolu, Ibrahim Ibrahim, Eric Kraut, Andrew D. Leavitt, Alfred Lee, Jason T. Lee, Ming Lim, Janelle Mann, Karlyn Martin, Brandon McMahon, John Moriarty, Colleen Morton, Thomas L. Ortel, Rita Paschal, Jordan Schaefer, Sanford Shattil, Tanya Siddiqi, Deepak Sudheendra, Eliot Williams, Liz Hollinger, and Mai Q. Nguyen

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer-Associated Venous Thromboembolic Disease focus on the prevention, diagnosis, and treatment of patients with cancer who have developed or who are at risk for developing venous thromboembolism (VTE). VTE is a significant concern among cancer patients, who are at heightened risks for developing as well as dying from the disease. The management of patients with cancer with VTE often requires multidisciplinary efforts at treating institutions. The NCCN panel comprises specialists from various fields: cardiology, hematology/hematologic oncology, internal medicine, interventional radiology, medical oncology, pharmacology/pharmacy, and surgery/surgical oncology. This article focuses on VTE prophylaxis for medical and surgical oncology inpatients and outpatients, and discusses risk factors for VTE development, risk assessment tools, as well as management methods, including pharmacological and mechanical prophylactics. Contraindications to therapeutic interventions and special dosing, when required, are also discussed.

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NCCN Guidelines Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 2.2019

William G. Wierda, John C. Byrd, Jeremy S. Abramson, Syed F. Bilgrami, Greg Bociek, Danielle Brander, Jennifer Brown, Asher A. Chanan-Khan, Julio C. Chavez, Steve E. Coutre, Randall S. Davis, Christopher D. Fletcher, Brian Hill, Brad S. Kahl, Manali Kamdar, Lawrence D. Kaplan, Nadia Khan, Thomas J. Kipps, Shuo Ma, Sami Malek, Anthony Mato, Claudio Mosse, Vishala T. Neppalli, Mazyar Shadman, Tanya Siddiqi, Deborah Stephens, Nina Wagner, Mary A. Dwyer, and Hema Sundar

Chronic lymphocytic leukemia (CLL) is generally characterized by an indolent disease course. Histologic transformation (also known as Richter's transformation) to more aggressive lymphomas, such as diffuse large B-cell lymphoma or Hodgkin lymphoma, occurs in approximately 2% to 10% of patients and is associated with a poor prognosis. These NCCN Guidelines Insights discuss the recommendations for the diagnosis and management of patients with histologic transformation.

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NCCN Guidelines® Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 3.2022

Featured Updates to the NCCN Guidelines

William G. Wierda, Jennifer Brown, Jeremy S. Abramson, Farrukh Awan, Syed F. Bilgrami, Greg Bociek, Danielle Brander, Asher A. Chanan-Khan, Steve E. Coutre, Randall S. Davis, Herbert Eradat, Christopher D. Fletcher, Sameh Gaballa, Armin Ghobadi, Muhammad Saad Hamid, Francisco Hernandez-Ilizaliturri, Brian Hill, Paul Kaesberg, Manali Kamdar, Lawrence D. Kaplan, Nadia Khan, Thomas J. Kipps, Shuo Ma, Anthony Mato, Claudio Mosse, Stephen Schuster, Tanya Siddiqi, Deborah M. Stephens, Chaitra Ujjani, Nina Wagner-Johnston, Jennifer A. Woyach, J. Christine Ye, Mary A. Dwyer, and Hema Sundar

The treatment landscape of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has significantly evolved in recent years. Targeted therapy with Bruton’s tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors has emerged as an effective chemotherapy-free option for patients with previously untreated or relapsed/refractory CLL/SLL. Undetectable minimal residual disease after the end of treatment is emerging as an important predictor of progression-free and overall survival for patients treated with fixed-duration BCL-2 inhibitor-based treatment. These NCCN Guidelines Insights discuss the updates to the NCCN Guidelines for CLL/SLL specific to the use of chemotherapy-free treatment options for patients with treatment-naïve and relapsed/refractory disease.

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Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 4.2020, NCCN Clinical Practice Guidelines in Oncology

William G. Wierda, John C. Byrd, Jeremy S. Abramson, Syed F. Bilgrami, Greg Bociek, Danielle Brander, Jennifer Brown, Asher A. Chanan-Khan, Julio C. Chavez, Steve E. Coutre, Randall S. Davis, Christopher D. Fletcher, Brian Hill, Brad S. Kahl, Manali Kamdar, Lawrence D. Kaplan, Nadia Khan, Thomas J. Kipps, Megan S. Lim, Shuo Ma, Sami Malek, Anthony Mato, Claudio Mosse, Mazyar Shadman, Tanya Siddiqi, Deborah Stephens, Suchitra Sundaram, Nina Wagner, Mary Dwyer, and Hema Sundar

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are characterized by a progressive accumulation of leukemic cells in the peripheral blood, bone marrow, and lymphoid tissues. Treatment of CLL/SLL has evolved significantly in recent years because of the improved understanding of the disease biology and the development of novel targeted therapies. In patients with indications for initiating treatment, the selection of treatment should be based on the disease stage, patient’s age and overall fitness (performance status and comorbid conditions), and cytogenetic abnormalities. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with CLL/SLL.

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NCCN Guidelines Insights: Cancer-Associated Venous Thromboembolic Disease, Version 2.2018

Michael B. Streiff, Bjorn Holmstrom, Dana Angelini, Aneel Ashrani, Paula L. Bockenstedt, Carolyn Chesney, John Fanikos, Randolph B. Fenninger, Annemarie E. Fogerty, Shuwei Gao, Samuel Z. Goldhaber, Krishna Gundabolu, Paul Hendrie, Alfred I. Lee, Jason T. Lee, Janelle Mann, Brandon McMahon, Michael M. Millenson, Colleen Morton, Thomas L. Ortel, Sadat Ozair, Rita Paschal, Sanford Shattil, Tanya Siddiqi, Kristi J. Smock, Gerald Soff, Tzu-Fei Wang, Eliot Williams, Anaadriana Zakarija, Lydia Hammond, Mary A. Dwyer, and Anita M. Engh

Venous thromboembolism (VTE) is common in patients with cancer and increases morbidity and mortality. VTE prevention and treatment are more complex in patients with cancer. The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of VTE in adult patients diagnosed with cancer or in whom cancer is clinically suspected. These NCCN Guidelines Insights explain recent changes in anticoagulants recommended for the treatment of cancer-associated VTE.

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Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology

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.