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Cancer
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
Elyce Cardonick, Charlotte Maggen, Puja Patel
Leukemic blasts can accumulate in peripheral blood causing significant leukocytosis which occludes the vasculature and can lead to respiratory or neurologic disease. This can be further aggravated by pregnancy. Treatment may require urgent leukapheresis at any gestational age [77]. Chemotherapy after the first trimester would be similar to regimens used for non-pregnant women including cytarabine and an anthracycline. For concerns with idarubicin mentioned previously, daunorubicin is recommended instead of idarubicin in pregnancy.
Therapeutic apheresis
Published in Jennifer Duguid, Lawrence Tim Goodnough, Michael J. Desmond, Transfusion Medicine in Practice, 2020
In 1914, Abel, Rowntree and Turner1 coined the term plasmaphaeresis (from the Greek word aphairesis – a withdrawal). Their early experiments were for the relief of symptoms following bilateral nephrectomy in dogs. Although these experiments were associated with deaths (due to apparent overbleeding and hemorrhage), the improvement in the clinical condition of the animals successfully treated was ‘marked’. The term apheresis has since been generalized to refer to the separation of blood into its components, removing one component, and returning the remainder. Thus, leukapheresis means the removal of leukocytes and erythrocytapheresis means the removal of erythrocytes. Alternative terminologies such as plasma exchange and red cell exchange are frequently used interchangeably for plasmapheresis and erythrocytapheresis, respectively. Some authors have suggested that the term ‘plasma exchange’ or therapeutic plasma exchange be reserved for low-volume procedures involving no more then 500–600 ml of plasma and plasmapheresis for large-volume procedures; however, these terms are frequently used interchangeably. Hemapheresis is also used as a broad term encompassing all apheresis procedures.
Therapy with lnterleukin-2 and Tumor-Derived Activated Lymphocytes
Published in Ronald H. Goldfarb, Theresa L. Whiteside, Tumor Immunology and Cancer Therapy, 2020
Mononuclear cells removed during leukapheresis procedures were not significantly cytolytic toward tumor cells, even though the cancer patients received rIL-2 by continuous infusion for 5 days. The cells became highly cytolytic after further culture in vitro in high concentrations of rIL-2 (1000–3000 IU/3×106 cells) (Table 2). In brief, we developed an automated closed system to produce LAK cells in 1 or 3 liter Fenwal PL732 plastic platelet storage bags (31–33), with cell harvesting performed by a continuous flow harvest system developed on the CS3000. Such an automated system allows for efficient and safe handling of the large numbers of cells obtained in the leukapheresis procedure. By utilizing an automated closed system for handling the cells, we reduced the incidence of bacterial and fungal contamination of the LAK cell product. The mean levels of endotoxin as determined by the limulus ameobocyte lysate test (LAL) has been 0.19±0.10 endotoxin U/ml (n = 125), giving no endotoxin-related clinical toxicities.
Comparison of early mortality between leukapheresis and non-leukapheresis in adult acute myeloid leukemia patients with hyperleukocytosis: a systematic review and meta-analysis
Published in Hematology, 2022
Ikhwan Rinaldi, Noorwati Sutandyo, Kevin Winston
Many of the studies used here had low number of patients. For example, the retrospective cohort study by Malkan et al. evaluated the impact of leukapheresis on 15-day mortality rate in 28 de novo acute myeloid leukemia patients with hyperleukocytosis [43]. The patients were divided into 10 patients receiving leukapheresis and 18 patients not receiving leukapheresis. However, the study did not describe whether the comparator group was given chemotherapy or not. The results of the study by Malkan et al. showed no significant difference in early mortality between leukapheresis group and non-leukapheresis group [43]. Another study by Pastore et al. had 52 newly diagnosed AML patients divided into 20 patients receiving both chemotherapy and leukapheresis, and 32 patients receiving chemotherapy only [27]. This study also showed no benefit of mortality reduction from the use of leukapheresis.
Monitoring and safety of CAR-T therapy in clinical practice
Published in Expert Opinion on Drug Safety, 2022
José M. Serra López-Matencio, Valle Gómez Garcia de Soria, Manuel Gómez, Estefanía Alañón-Plaza, Cecilia Muñoz-Calleja, Santos Castañeda
The first step in generating autologous CAR-T cells is the collection of peripheral blood mononuclear cells from the patient. This procedure is usually carried out by leukapheresis. Subsequently, T cells are cultured in the presence of a nonspecific stimulus necessary not only for cell expansion, but also to achieve efficient genetic modification: many of the transfection systems used require dividing cells. Antigen presenting cells (APCs) are the natural choice for this function. However, they are expensive to produce and present differences in their effectiveness among donors. This problem can be avoided using the K562 cell line as an APC. In addition, this artificial APC can be modified to express co-stimulatory molecules (such as CD40, CD80, and CD86) that enhance T-cell activation. In addition, they can also be modified to express the cognate antigen for specific CARs, thus achieving a selective expansion of CAR-T cells once the receptor is expressed. However, T cells are most commonly stimulated with anti-CD3 and anti-CD28 monoclonal antibodies bound to microbeads or coated with tissue culture plastic [7].
Ophthalmic Implications of Chimeric Antigen Receptor T-Cell Therapy
Published in Seminars in Ophthalmology, 2021
Kevin D Chodnicki, Sashank Prasad
CAR T-cells can be produced from a patient’s own blood (autologous) or the blood of a donor (allogeneic). White blood cells are first harvested in a process called leukapheresis (figure 1). The harvested cells are then enriched in a process that removes inhibitory cell populations and stimulates the favored cells to proliferate. This population of T-cells is then infected with a retroviral vector (e.g., lentivirus), which integrates the necessary genetic information into the T-cells to allow expression of the desired receptor (e.g., CD19). Some techniques employ clustered regularly interspaced short palindromic repeats (CRISPR) gene editing techniques to insert the required gene modification instead of using viral vectors.9 This chimeric cell population is then expanded to the degree necessary for clinical use.10 In order to create space for the CAR T-cells to proliferate, patients often undergo lymphodepleting conditioning chemotherapy with medications including cyclophosphamide, fludarabine, or bendamustine. The process of obtaining, genetically engineering, and proliferating the T-cells can take several weeks. In most cases, the leukapheresis process is performed at the treating center with the cells then shipped to a commercial lab for preparation of the chimeric cells. The cells are cryopreserved in transit from the treating center and commercial lab. This commercial production process can cost over 350,000 USD per patient.10