Introduction: Chimeric antigen receptor-T cell (CAR-T) therapy has revolutionized advanced blood cancer treatment. However, preparation, administration, and recovery from these therapies can be complex and burdensome to patients and their care partners. Utilization of an outpatient setting for CAR-T therapy administration could help improve convenience and quality of life.
View Article and Find Full Text PDFThe main goal of this research paper is to apply a deep neural network model for time series forecasting of environmental variables. Accurate forecasting of snow cover and NDVI are important issues for the reliable and efficient hydrological models and prediction of the spread of forest. Long Short Term Memory (LSTM) model for the time series forecasting of snow cover, temperature, and normalized difference vegetation index (NDVI) are studied in this research work.
View Article and Find Full Text PDFSystemic lupus erythematosus (SLE) is associated with an IL-2-deficient state, with regulatory T cells (Tregs) showing diminished immune regulatory capacity. A low dose of IL-2 has shown encouraging clinical benefits in SLE patients; however, its clinical utility is limited because of the requirement of daily injections and the observation of increase in proinflammatory cytokines and in non-Tregs. We recently showed that a fusion protein of mouse IL-2 and mouse IL-2Rα (CD25), joined by a noncleavable linker, was effective in treating diabetes in NOD mice by selectively inducing Treg expansion.
View Article and Find Full Text PDFAt JADPRO Live 2019, Patricia Mangan, RN, MSN, CRNP, and Edward Stadtmauer, MD, discussed the emerging world of chimeric antigen receptor (CAR) T-cell therapy, including the CAR T-cell process, approved indications and studies in hematologic malignancies, strategies for monitoring and managing emerging toxicities, and future directions in the use of this novel therapy.
View Article and Find Full Text PDFPurpose: Poor nutrition status in patients receiving high-dose chemotherapy and autologous stem cell transplant (ASCT) has been associated with inferior clinical outcomes. We aim to determine whether a malnutrition-driven nutritional support protocol can improve these outcomes.
Methods: In this prospective cohort study, we assessed adults for malnutrition who were consecutively admitted for ASCT between October 2017 and March 2019 (n = 251), and provided enteral or parenteral nutrition (EN/PN) to patients who were malnourished early in the transplantation admission.
CRISPR-Cas9 gene editing provides a powerful tool to enhance the natural ability of human T cells to fight cancer. We report a first-in-human phase 1 clinical trial to test the safety and feasibility of multiplex CRISPR-Cas9 editing to engineer T cells in three patients with refractory cancer. Two genes encoding the endogenous T cell receptor (TCR) chains, TCRα () and TCRβ (), were deleted in T cells to reduce TCR mispairing and to enhance the expression of a synthetic, cancer-specific TCR transgene (NY-ESO-1).
View Article and Find Full Text PDFPatients undergoing stem cell transplant (SCT) for the treatment of hematologic malignancy are at increased risk for central line-associated bloodstream infections (CLABSIs). The use of prophylactic antibiotics to prevent CLABSIs in the setting of autologous SCT is of unclear benefit. We aimed to evaluate the impact of levofloxacin prophylaxis on reducing CLABSIs in this high-risk population.
View Article and Find Full Text PDFBackground: Multiple myeloma is usually fatal due to serial relapses that become progressively refractory to therapy. CD19 is typically absent on the dominant multiple myeloma cell population but may be present on minor subsets with unique myeloma-propagating properties. To target myeloma-propagating cells, we clinically evaluated autologous T cells transduced with a chimeric antigen receptor (CAR) against CD19 (CTL019).
View Article and Find Full Text PDFBackground: A majority of patients with multiple myeloma experience damage to the kidneys and peripheral nerves either at diagnosis or throughout the disease. Symptoms of diarrhea, nausea, vomiting, or constipation can also occur. Prevention and management of disease- and treatment-related side effects are essential to treatment adherence.
View Article and Find Full Text PDFJ Adv Pract Oncol
April 2017
There have been promising results from clinical trials on the efficacy of engineering patients' immune cells to treat their cancers. CAR T-cell therapy also has unique toxicities advanced practitioners should be aware of.
View Article and Find Full Text PDFBackground: Financial toxicity is increasingly recognised as adversely affecting the quality of life and medication adherence in patients with cancer in the USA. Patients with multiple myeloma might be particularly vulnerable because of high use of novel treatments and extended treatment duration.
Methods: Between Aug 18, 2014, and Jan 7, 2015, we did a cross-sectional survey of individuals receiving at least 3 months of ongoing treatment for multiple myeloma at a tertiary academic medical centre in the USA.
Therapies targeting either interleukin (IL)-23 or IL-17 have shown promise in treating T helper 17 (Th17)-driven autoimmune diseases. Although IL-23 is a critical driver of IL-17, recognition of nonredundant and independent functions of IL-23 and IL-17 has prompted the notion that dual inhibition of both IL-23 and IL-17 could offer even greater efficacy for treating autoimmune diseases relative to targeting either cytokine alone. To test this hypothesis, we generated selective inhibitors of IL-23 and IL-17 and tested the effect of either treatment alone compared with their combination in vitro and in vivo.
View Article and Find Full Text PDFWhen caring for patients with multiple myeloma, questions often arise about the role and timing of autologous hematopoietic stem cell transplantation. As a complement to the other articles in this supplement, as well as to ensure that readers are provided with the insight needed to feel comfortable speaking to patients and other practitioners about this topic, the authors address eight frequently asked questions about common decision points in the process of autologous hematopoietic stem cell transplantation as a treatment for patients with multiple myeloma.
View Article and Find Full Text PDFAutologous hematopoietic stem cell transplantation (AHSCT) is approved for the treatment of select solid tumors, autoimmune disorders, and most hematologic malignancies. Multiple myeloma (MM) is the most common indication for AHSCT. Despite improvement in response and survival rates in the era of novel agents, AHSCT remains an important treatment option for patients with MM who are eligible.
View Article and Find Full Text PDFKidney dysfunction is a common clinical feature of symptomatic multiple myeloma. Some degree of renal insufficiency or renal failure is present at diagnosis or will occur during the course of the disease and, if not reversed, will adversely affect overall survival and quality of life. Chronic insults to the kidneys from other illnesses, treatment, or multiple myeloma itself can further damage renal function and increase the risk for additional complications, such as anemia.
View Article and Find Full Text PDFSevere immune deficiency follows autologous stem cell transplantation for multiple myeloma and is associated with significant infectious morbidity. This study was designed to evaluate the utility of a pretransplantation vaccine and infusion of a primed autologous T-cell product in stimulating specific immunity to influenza. Twenty-one patients with multiple myeloma were enrolled from 2007 to 2009.
View Article and Find Full Text PDFBone Marrow Transplant
January 2011
Lenalidomide is an active treatment for multiple myeloma (MM) and is increasingly used as part of the initial treatment of this disease. Recent reports have suggested decreases in the number of CD34+ cells collected and increases in the failure rate among patients whose initial therapy contained lenalidomide when mobilized with G-CSF alone. A retrospective data analysis of 364 patients with MM who underwent stem cell mobilization and attempted harvest at the Hospital of the University of Pennsylvania between January 2002 and December 2007 was performed.
View Article and Find Full Text PDFCentral and peripheral tolerance is required to prevent immune responses to self-antigens. We now present a mouse model in which wild-type (WT) SH2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) has been constitutively targeted to the membrane, where CD4+ T cells become spontaneously dysregulated and develop an inflammatory phenotype. Mice bearing membrane-targeted SLP-76 (MTS) have a partial T-cell lymphopenia and impaired signaling though the mature T-cell receptor.
View Article and Find Full Text PDFBone Marrow Transplant
March 2009
Therapeutic options for patients with multiple myeloma whose disease has relapsed after a prior auto-SCT include novel biologic therapies, traditional chemotherapy or a second transplant, with no clear standard of care. Few published studies address the safety and efficacy of a second auto-SCT for relapsed disease. We reviewed the Abramson Cancer Center experience with salvage auto-SCT for relapsed multiple myeloma.
View Article and Find Full Text PDFObjective: To determine whether the routine use of preimplantation genetic screening (PGS) in "good prognosis" women improves in vitro fertilization (IVF) cycle outcome.
Design: Randomized, controlled, prospective clinical study.
Setting: Private infertility clinic.
Steroids have been the foundation of multiple myeloma therapy for more than 30 years and continue to be prescribed as single agents and in combination with other antimyeloma drugs, including novel therapies. Steroids cause a wide range of side effects that affect almost every system of the body. Identification and prompt management of the toxicities contribute to the success of steroid-containing antimyeloma regimens.
View Article and Find Full Text PDFNurses play an essential role in managing the care of patients with multiple myeloma, who require education and support to receive and adhere to optimal therapy. The International Myeloma Foundation created a Nurse Leadership Board comprised of oncology nurses from leading cancer centers and community practices. An assessment survey identified the need for specific recommendations for managing key side effects of novel antimyeloma agents.
View Article and Find Full Text PDFA rapid modification in the postsynaptic gamma-aminobutyric acid (GABA(A)) receptor population occurs during the prolonged seizures of status epilepticus (SE). This rapid modification contributes to a reduction in GABA-mediated inhibition and the development of benzodiazepine pharmacoresistance. Previous hypotheses to explain the modification have included an alteration in the structural composition or posttranslational modification of the receptors.
View Article and Find Full Text PDFRoutine use of EmbryoGlue did not significantly improve pregnancy or implantation rates in nonselected patients receiving either a day 3 or day 5 embryo transfer compared with standard culture media. Future prospective randomized studies need to be performed to determine whether EmbryoGlue is beneficial in a selected patient population.
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