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Secondary Neoplasms of the Female Lower Genital Tract After Hematopoietic Cell Transplantation

Howard A. Chang, Saro H. Armenian, and Thanh H. Dellinger

Hematopoietic cell transplantation (HCT) results in long-term survival (≥10 years) in 85% of patients who survive transplant-related complications within the first 2 years posttransplant. Transplant survivors, however, are at an increased risk of chronic health conditions compared with the general population, including the emergence of secondary malignant neoplasms. In particular, female transplant survivors may face a greater risk of lower genital tract (cervical, vulvar, or vaginal) neoplasms due to chronic immune dysregulation in the peritransplant and posttransplant environment. Persistent immune suppression may facilitate the carcinogenesis of human papillomavirus (HPV), the causative agent of nearly all cervical cancers and most vulvar and vaginal cancers. Nevertheless, the risk of these cancers has not been sufficiently quantified in female transplant survivors. Small clinical studies have shown that the rate of cervical cytological abnormalities increases after allogeneic HCT, but large population-based studies have not consistently demonstrated an increased risk of secondary cervical cancer after transplant compared with the general population; the risk of developing secondary vulvar or vaginal cancer after transplant remains unclear. A better understanding of the natural history of HPV-associated lower genital tract neoplasms and their transplant-related risk factors would help delineate optimal long-term follow-up protocols in this population. In this systematic review, we summarize the current literature on this topic and discuss the implications for cervical cancer screening and vaccination in female transplant recipients.

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Integration of Pediatric Hodgkin Lymphoma Treatment and Late Effects Guidelines: Seeing the Forest Beyond the Trees

Matthew J. Ehrhardt, Jamie E. Flerlage, Saro H. Armenian, Sharon M. Castellino, David C. Hodgson, and Melissa M. Hudson

The successful integration of clinical trials into pediatric oncology has led to steady improvement in the 5-year survival rate for children diagnosed with Hodgkin lymphoma (HL). It is estimated that >95% of children newly diagnosed with HL will become long-term survivors. Despite these successes, survival can come at a cost. Historically, long-term survivors of HL have a high risk of late-occurring adverse health effects and increased risk of nonrelapse mortality compared with the general population. The recognition of late-occurring events paired with the decades of life remaining for children cured of HL have made paramount the need to develop effective treatments that minimize the risk of late toxicity. Toward this goal, multiple, dose-intense, risk- and response-based regimens that use lower cumulative doses of chemotherapy and radiation have been developed. Appropriate frontline treatment selection requires a level of familiarity with the efficacy, acute toxicity, convenience, and late effects of treatments that may be impractical for providers who infrequently treat children with HL. There is an increasing need for guideline developers to begin to merge considerations from both frontline treatment and survivorship guidelines into practical documents that integrate potential long-term health risks. Herein, we take the first steps toward doing so by aligning cumulative treatment exposures, anticipated risks of late toxicity, and suggested surveillance recommendations for NCCN-endorsed Pediatric HL Guidelines. Future studies that integrate simulation modeling will strengthen this integrated approach and allow for opportunities to incorporate regimen-specific risks, health-related quality of life, and cost-effectiveness into decision tools to optimize HL therapy.

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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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Pediatric Aggressive Mature B-Cell Lymphomas, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology

Matthew Barth, Ana C. Xavier, Saro Armenian, Anthony N. Audino, Lindsay Blazin, David Bloom, Jong Chung, Kimberly Davies, Hilda Ding, James B. Ford, Paul J. Galardy, Rabi Hanna, Robert Hayashi, Cathy Lee-Miller, Andrea Judit Machnitz, Kelly W. Maloney, Lianna Marks, Paul L. Martin, David McCall, Martha Pacheco, Anne F. Reilly, Mikhail Roshal, Sophie Song, Joanna Weinstein, Sara Zarnegar-Lumley, Nicole McMillian, Ryan Schonfeld, and Hema Sundar

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Aggressive Mature B-Cell Lymphomas include recommendations for the diagnosis and management of pediatric patients with primary mediastinal large B-cell lymphoma (PMBL) and sporadic variants of Burkitt lymphoma and diffuse large B-cell lymphoma. PMBL is now considered as a distinct entity arising from mature thymic B-cells accounting for 2% of mature B-cell lymphomas in children and adolescents. This discussion section includes the recommendations outlined in the NCCN Guidelines for the diagnosis and management of pediatric patients with PMBL.

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Pediatric Aggressive Mature B-Cell Lymphomas, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology

Kimberly Davies, Matthew Barth, Saro Armenian, Anthony N. Audino, Phillip Barnette, Branko Cuglievan, Hilda Ding, James B. Ford, Paul J. Galardy, Rebecca Gardner, Rabi Hanna, Robert Hayashi, Alexandra E. Kovach, Andrea Judit Machnitz, Kelly W. Maloney, Lianna Marks, Kristin Page, Anne F. Reilly, Joanna L. Weinstein, Ana C. Xavier, Nicole R. McMillian, and Deborah A. Freedman-Cass

Pediatric aggressive mature B-cell lymphomas are the most common types of non-Hodgkin lymphoma in children, and they include Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). These diseases are highly aggressive but curable, the treatment is complex, and patients may have many complicated supportive care issues. The NCCN Guidelines for Pediatric Aggressive Mature B-Cell Lymphomas provide guidance regarding pathology and diagnosis, staging, initial treatment, disease reassessment, surveillance, therapy for relapsed/refractory disease, and supportive care for clinicians who treat sporadic pediatric BL and DLBCL.

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Pediatric Hodgkin Lymphoma, Version 3.2021

Jamie E. Flerlage, Susan M. Hiniker, Saro Armenian, Ellen C. Benya, Adam J. Bobbey, Vivian Chang, Stacy Cooper, Don W. Coulter, Branko Cuglievan, Bradford S. Hoppe, Leidy Isenalumhe, Kara Kelly, Leslie Kersun, Adam J. Lamble, Nicole A. Larrier, Jeffrey Magee, Kwadwo Oduro, Martha Pacheco, Anita P. Price, Kenneth B. Roberts, Christine M. Smith, Aliyah R. Sohani, Erin M. Trovillion, Emily Walling, Ana C. Xavier, Jennifer L. Burns, and Mallory Campbell

Hodgkin lymphoma (HL) is a highly curable form of cancer, and current treatment regimens are focused on improving treatment efficacy while decreasing the risk of late effects of treatment. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for pediatric HL provide recommendations on the workup, diagnostic evaluation, and treatment of classic HL, including principles of pathology, imaging, staging, systemic therapy, and radiation therapy. This portion of the NCCN Guidelines focuses on the management of pediatric classic HL in the upfront and relapsed/refractory settings.

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NCCN Guidelines Insights: Survivorship, Version 2.2020

Featured Updates to the NCCN Guidelines

Crystal S. Denlinger, Tara Sanft, Javid J. Moslehi, Linda Overholser, Saro Armenian, K. Scott Baker, Gregory Broderick, Wendy Demark-Wahnefried, Debra L. Friedman, Mindy Goldman, Norah Lynn Henry, Christine Hill-Kayser, Melissa Hudson, Nazanin Khakpour, Divya Koura, Allison L. McDonough, Michelle Melisko, Kathi Mooney, Halle C. F. Moore, Natalie Moryl, Tracey O’Connor, Electra D. Paskett, Chirayu Patel, Lindsay Peterson, William Pirl, M. Alma Rodriguez, Kathryn J. Ruddy, Lillie Shockney, Sophia Smith, Karen L. Syrjala, Amye Tevaarwerk, Phyllis Zee, Nicole R. McMillian, and Deborah A. Freedman-Cass

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for consequences of adult-onset cancer and its treatment, with the goal of helping healthcare professionals who work with survivors, including those in primary care. The guidelines also provide recommendations to help clinicians promote physical activity, weight management, and proper immunizations in survivors and facilitate care coordination to ensure that all of the survivors’ needs are addressed. These NCCN Guidelines Insights summarize additions and changes made to the guidelines in 2020 regarding cardiovascular disease risk assessment and screening for subsequent primary malignancies.

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NCCN Guidelines Insights: Survivorship, Version 2.2019

Featured Updates to the NCCN Guidelines

Tara Sanft, Crystal S. Denlinger, Saro Armenian, K. Scott Baker, Gregory Broderick, Wendy Demark-Wahnefried, Debra L. Friedman, Mindy Goldman, Melissa Hudson, Nazanin Khakpour, Divya Koura, Robin M. Lally, Terry S. Langbaum, Allison L. McDonough, Michelle Melisko, Kathi Mooney, Halle C.F. Moore, Javid J. Moslehi, Tracey O’Connor, Linda Overholser, Electra D. Paskett, Lindsay Peterson, William Pirl, M. Alma Rodriguez, Kathryn J. Ruddy, Sophia Smith, Karen L. Syrjala, Amye Tevaarwerk, Susan G. Urba, Phyllis Zee, Nicole R. McMillian, and Deborah A. Freedman-Cass

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for consequences of cancer and cancer treatment to aid healthcare professionals who work with survivors of adult-onset cancer. Guidance is also provided to help promote physical activity, weight management, and proper immunizations in survivors and to facilitate care coordination to ensure that all needs are addressed. These NCCN Insights summarize some of the topics discussed by the NCCN Survivorship Panel during the 2019 update of the guidelines, including the survivorship population addressed, ways to improve care coordination, and pain management.

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NCCN Guidelines® Insights: Survivorship, Version 1.2022

Featured Updates to the NCCN Guidelines

Tara Sanft, Andrew Day, Lindsay Peterson, M. Alma Rodriguez, Shannon Ansbaugh, Saro Armenian, K. Scott Baker, Tarah Ballinger, Gregory Broderick, Wendy Demark-Wahnefried, Kristin Dickinson, Nathan Paul Fairman, Debra L. Friedman, Mindy Goldman, Norah Lynn Henry, Christine Hill-Kayser, Melissa Hudson, Nazanin Khakpour, Divya Koura, Allison L. McDonough, Michelle Melisko, Kathi Mooney, Halle C.F. Moore, Natalie Moryl, Heather Neuman, Tracey O’Connor, Linda Overholser, Electra D. Paskett, Chirayu Patel, William Pirl, Andrea Porpiglia, Kathryn J. Ruddy, Lidia Schapira, Lillie Shockney, Sophia Smith, Karen L. Syrjala, Amye Tevaarwerk, Eric H. Yang, Phyllis Zee, Nicole R. McMillian, and Deborah A. Freedman-Cass

The NCCN Guidelines for Survivorship are intended to help healthcare professionals who work with survivors to ensure that the survivors’ complex and varied needs are addressed. The NCCN Guidelines provide screening, evaluation, and treatment recommendations for the consequences of adult-onset cancer and its treatment; recommendations to help promote physical activity, weight management, and immunizations in survivors; and a framework for care coordination. This article summarizes updates to the NCCN Guidelines pertaining to preventive health for cancer survivors, including recommendations about alcohol consumption and vaccinations.

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Survivorship, Version 1.2021

Featured Updates to the NCCN Guidelines

Amye Tevaarwerk, Crystal S. Denlinger, Tara Sanft, Shannon M. Ansbaugh, Saro Armenian, K. Scott Baker, Gregory Broderick, Andrew Day, Wendy Demark-Wahnefried, Kristin Dickinson, Debra L. Friedman, Patricia Ganz, Mindy Goldman, Norah Lynn Henry, Christine Hill-Kayser, Melissa Hudson, Nazanin Khakpour, Divya Koura, Allison L. McDonough, Michelle Melisko, Kathi Mooney, Halle C.F. Moore, Natalie Moryl, Javid J. Moslehi, Tracey O’Connor, Linda Overholser, Electra D. Paskett, Chirayu Patel, Lindsay Peterson, William Pirl, M. Alma Rodriguez, Kathryn J. Ruddy, Lidia Schapira, Lillie Shockney, Sophia Smith, Karen L. Syrjala, Phyllis Zee, Nicole R. McMillian, and Deborah A. Freedman-Cass

The NCCN Guidelines for Survivorship are intended to help healthcare professionals working with cancer survivors to ensure that each survivor’s complex and varied needs are addressed. The Guidelines provide screening, evaluation, and treatment recommendations for consequences of adult-onset cancer and its treatment; recommendations to help promote healthful lifestyle behaviors, weight management, and immunizations in survivors; and a framework for care coordination. This article summarizes the recommendations regarding employment and return to work for cancer survivors that were added in the 2021 version of the NCCN Guidelines.