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Neurotoxicities After CAR T-Cell Immunotherapy

Introduction Chimeric antigen receptor (CAR)–modified T-cell immunotherapy can be a highly effective treatment for patients with relapsed and/or refractory hematologic malignancies, but significant adverse effects remain a concern. Systemic cytokine release syndrome (CRS) can occur in association with the inflammatory cytokine surge during in vivo CAR T-cell proliferation, and neurologic adverse effects commonly occur in this context. While most patients who experience neurotoxicity have mild and reversible…

Special Considerations for ICU Management of Patients Receiving CAR Therapy

Cancer is among the leading causes of death worldwide. The number of new cancer cases per year is expected to rise to 23.6 million by 2030. Advancements in oncology therapeutics and associated improvements in survival mean that more patients may require advanced life support for cancer-related complications, treatment-related toxicities, and severe infections. Cancer-specific guidelines for admission to the intensive care unit (ICU) as well as protocols…

Management of Cytokine Release Syndrome

Acknowledgments COI disclosures: Dr. Lee serves on the external advisory board for Juno Therapeutics/Celgene, has provided ad hoc consulting to Harpoon Therapeutics, and has received clinical trial research support from Kite Introduction Chimeric antigen receptor (CAR) T-cell therapy has been shown to have antitumor activity in a variety of cancers including pediatric and adult acute lymphoblastic leukemia (ALL), , , diffuse large B-cell non-Hodgkin's lymphoma (NHL),…

Peri-CAR T-Cell Management

Acknowledgments We thank ML Silverberg for assistance with development of nursing and postinfusion protocols. Screening Once identified as a candidate for chimeric antigen receptor (CAR) T-cell therapy, patients must undergo screening for eligibility. Prediagnostic evaluations are required to assess patient candidacy to undergo CAR treatment, fulfill regulatory criteria for cell product collection, and satisfy insurance standards for reimbursement. Patient's disease burden should be reevaluated per usual…

CAR T-Cell: Cell Processing Laboratory Considerations

Introduction Chimeric antigen receptor (CAR) T-cells are one of the most rapidly growing cancer immunotherapies, particularly for B-cell malignancies. While the manufacturing of CAR T-cells is relatively straightforward, there are many barriers associated with the manufacturing process. Additionally, most CAR T-cells are produced from a patient's own or autologous lymphocytes, which creates many unique cell production and logistical challenges. Many patients receiving CAR T-cells have life-threatening…

Optimizing the Apheresis Product

Conflicts of Interest The authors have no conflicts of interest to declare. The views expressed are the authors' own and do not represent the National Institutes of Health, the Department of Health and Human Services, or the US Federal government. Introduction Definition and Early Beginnings of Apheresis Apheresis, named after the ancient Greek word meaning “taking away,” is a medical procedure in which blood is drawn…

When to Refer a Patient for CAR T-Cell Therapy

Introduction Chimeric antigen receptor (CAR) T-cell immunotherapy is a rapidly emerging and highly publicized new treatment modality, which has gained significant attention for its effectiveness, side effects, and costs. Early-phase clinical trials have shown dramatic results in patients with often heavily pretreated disease, including those with relapsed/refractory childhood acute lymphoblastic leukemia (ALL) and adult diffuse large B-cell lymphomas (DLBCL). With recent US Food and Drug Administration…

Preclinical Approaches to the Protection of Ovarian Function

9.1 Introduction Recent advances in our understanding of the mechanisms underlying the impact of cytotoxic drugs on the ovary have opened up new directions for the protection of ovarian function from chemotherapy-induced damage. Studies are providing greater detail as to the pathways and factors triggered within the different cell types of the ovary by each drug class. As we gain increased knowledge of the specifics of…

Current Clinical Approaches to Protecting the Ovary: GnRH Analogues

8.1 Introduction Cancer is not uncommon and no longer considered as an incurable disease among reproductive-age women. Indeed, cancer is estimated to occur in approximately 2% of women under the age 40. Over the past decades, there has been a remarkable improvement in the survival rates due to the marked progress in detecting cancer at earlier stages and the improvement in treatment modalities. With improvements in…

Ovarian Tissue Cryopreservation for Fertility Preservation

7.1 Overview The survival rate among the ~2% of women of reproductive age who have suffered from invasive cancer has substantially increased. Unfortunately, the necessary chemo- and radiotherapy carry the risk of unwanted side effects such as permanent infertility, jeopardizing a woman’s chances of having her own biological children. Until recently, in vitro fertilization (IVF) and embryo transfer (ET) in combination with cryopreservation were considered the…

In Vitro Models of Ovarian Toxicity

6.1 Introduction Investigating the precise effect of chemotherapy on female fertility is a key research aspect underpinning fertility-preservation work. Protecting the ovarian follicle pool will require detailed understanding of precisely how the different chemotherapy drugs damage the ovary: whether chemotherapy drugs directly kill oocytes or whether damage is first to surrounding somatic cells; if the drugs are equally toxic to all follicles or if specific stages…

In Vivo Models of Ovarian Toxicity

5.1 Introduction The success of cancer treatment creates a growing population of female cancer survivors who wrestle with long-term side effects of chemotherapy, including primary ovarian insufficiency (POI). This growing survivorship presents researchers and clinicians with the challenging mandate to develop therapeutics that improve ovarian function post-chemotherapy. Continuing research is therefore devoted to developing non-invasive, drug-based ovarian shields and ovarian-regenerative technology. An ideal ovoprotective drug would…

The Current Understanding of Clinical Data on Ovarian Toxicity from Cancer Treatment

4.1 Introduction Chemotherapy has considerably improved survival of many cancer types; however, a patient’s quality of life is influenced by long-term complications of chemotherapeutic regimens. These complications include cardiac abnormalities, secondary malignancies, renal and hepatic impairment, and gonadal dysfunction. Gonadal dysfunction may result in an early menopause and infertility in reproductive-age patients, which is associated with poorer quality of life. Chemotherapy-induced gonadotoxicity is not limited to…

Clinical Assessment of Ovarian Toxicity

3.1 Introduction Assessment of ovarian toxicity in the clinical setting is important in determining the effects of exposures on individual women and to compare different exposures in groups of women, for example those on different chemotherapy regimens. Such knowledge can also be used prospectively to inform discussion about likely effects on future fertility, for example in patients facing cancer therapies or other treatments involving cytotoxic agents,…

Relevant Cancer Diagnoses, Commonly Used Chemotherapy Agents and Their Biochemical Mechanisms of Action

2.1 Introduction More than 75% of children treated for malignant disease will be alive 10 years following initial diagnosis in the UK. In addition, many women of reproductive age will undergo curative treatment for malignant disease. An understanding of the impact that these treatments will have on their future reproductive health is critical in order to inform both treatment choices and counselling with respect to educational,…

Ovarian Follicle Biology and the Basis for Gonadotoxicity

1.1 Overview of Ovarian Function The ovary serves two roles – the production of hormones necessary to support the endocrine health of the individual and the generation of mature oocytes that are able to be fertilized and contribute half of the genetic makeup of a new organism. The ovarian follicle is the functional unit of the ovary that carries out both of these goals. The ovarian…

Informed and Shared Decision Making in Breast Screening

Plain Language Summary Breast cancer screening has been going on for many years now, and research suggests that most women in the community feel positive about screening as a way to reassure them that they are well or to find early signs of cancer that can then be treated. Women have been told a lot about the potential benefits of screening, such as helping some women…

Treatment of Screen-Detected Breast Cancer: Can We Avoid or Minimize Overtreatment?

Plain Language Summary Women with screen-detected breast cancers have better survival than those with symptomatic breast cancers. Many screen-detected cancers are low risk because they are unlikely to recur or to cause death, with between 11% and 19% of screen-detected cancers considered as being overdiagnosed, that means that these women have been diagnosed and treated for breast cancer but if they had not been screened then…

Ethical and Societal Considerations in Breast Cancer Screening

Plain Language Summary Breast screening is a large public health program with a significant reach. It is shaped by existing patterns of acting and reasoning, and challenges us to think differently about society and ethics. Social attitudes about the breast affect attitudes toward breast cancer. The symbolism of the breast (motherhood, sexuality) means breast cancer is a highly emotive issue and breast screening is a popular…

Evolution of Mammography Screening: From Film Screen to Digital Breast Tomosynthesis

Plain Language Summary Mammography screening has been adopted in many countries and population health programs because randomized trials showed that it reduces the risk of dying from breast cancer. These randomized trials used screen-film mammography (SFM) which means that the X-ray beams are captured on a film cassette. The films are then developed and reviewed on a light-box by the physician. However, technical developments have witnessed…