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BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy leverages the power of the patient's own immune system by serving as a bridge to connect genetically modified T cells to the surface antigens of tumor cells based on targeted ligands. Clinical trials have demonstrated compelling overall response and survival rates in individuals with B-cell malignancies. The current approved agents target CD19, an antigen commonly overexpressed in B-cell hematologic and other malignancies. OBJECTIVES: This article provides information on the current state of the science related to commercially available CAR T-cell products and examines how CAR T-cell science is evolving. METHODS: An overview of pathophysiology, indications, and nursing implications of the currently approved CAR T-cell agents is presented. Future directions for CAR T-cell development and treatment indications are discussed. FINDINGS: Tisagenlecleucel (Kymriah®) and axicabtagene ciloleucel (Yescarta®) received approval in 2017 for the treatment of B-cell precursor acute lymphoblastic leukemia in pediatric and young adult patients, and relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy in adult patients, respectively. Additional indications have since been approved, and new agents are in development. [ABSTRACT FROM AUTHOR]

High‐dose melphalan (HDM) is part of the conditioning regimen in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT). However, individual sensitivity to melphalan varies, and many patients experience severe toxicities. Prolonged severe neutropenia is one of the most severe toxicities and contributes to potentially life‐threatening infections and failure of ASCT. Granulocyte‐colony stimulating factor (G‐CSF) is given to stimulate neutrophil proliferation after melphalan administration. The aim of this study was to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model capable of predicting neutrophil kinetics in individual patients with MM undergoing ASCT with high‐dose melphalan and G‐CSF administration. The extended PK/PD model incorporated several covariates, including G‐CSF regimen, stem cell dose, hematocrit, sex, creatinine clearance, p53 fold change, and race. The resulting model explained portions of interindividual variability in melphalan exposure, therapeutic effect, and feedback regulation of G‐CSF on neutrophils, thus enabling simulation of various doses and prediction of neutropenia duration. [ABSTRACT FROM AUTHOR]

The article focuses on autologous hematopoietic stem cell transplant for fit patients with multiple myeloma. Topics discussed include acceleration in neutrophil recovery due to use of granulocyte colony-stimulating factor (G-CSF), high-dose melphalan given to several patients followed by autologous stem cell rescue, and benefits demonstrated by transplant including reduction in the duration of neutropenia and number of infections.

Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have poor treatment outcomes when treated with traditional chemoimmunotherapy. Superior outcomes have been observed with the 2 CAR-T cell products approved by the US FDA; tisagenlecleucel (CTL109) and axicabtagene ciloleucel (Axi-cel) with 12 months overall survival rates of 49% and 59% respectively. The 2 major acute toxicities of these therapies are cytokine release syndrome (CRS) and neurotoxicity. The incidence of grade 3 or higher neutropenia, anemia, and thrombocytopenia was 78%, 43%, and 38% in patients treated with axi-cel. Little is known regarding the patterns and outcomes of these cytopenias. Here we present our preliminary experience on the patterns and outcomes of cytopenias in 32 patients who received commercially-available CAR-T cell therapy at our institution. We retrospectively reviewed all DLBCL patients receiving either CTL109 or axi-cel between January and September 2018 at our institution. All patients received a conditioning regimen of low-dose cyclophosphamide and fludarabine, followed by CAR-T infusion. Persistent cytopenias were defined as incomplete absolute neutrophil count (<1 × 109/L), Hb (<12 g/dL) or platelet count (<100 × 109/L) recovery after day 28 of CAR-T cell infusion. Treatment response was assessed with PET-CT imaging and classified according to International Working Group Criteria. The median age of patients was 59 years (range, 23-80); 63% were male, 4 patients (13%) received CTL109 and 28 (87%) received axi-cel. Twenty-two patients (69%) had a 3 month follow up imaging for assessment of response, of whom 7 patients (32%) achieved complete response (CR), 6 patients (27%) achieved partial response (PR), and 9 patients (41%) had progressive disease (PD). Persistent neutropenia was observed in 3 patients (9%), while persistent thrombocytopenia was seen in 21 cases (65%) and persistent anemia was the most common with a frequency of 72% (23/32 cases). Median time to neutrophil, platelet and Hb recoveries were 11 days (range, 5-218 days), 59.5 days (range, 4-241 days), and 76 days (range, 0-218 days), respectively. Filgrastim was used in 15 (47%) patients to facilitate neutrophil recovery. Twenty-three patients (72%) experienced neurotoxicity, of whom 11 (34%) had grade 3-4 toxicity. The frequency of CRS was 94% (29 out of 32 patients), with grade 3-4 CRS observed in 4 cases (12.5%). We observed no significant association between CRS and persistent cytopenias. In our preliminary series of 32 patients, persistent anemia and thrombocytopenia were more common than neutropenia after CAR-T cell therapy. However, most of these patients required growth factor support for neutrophil recovery. Longer duration of follow up is necessary to determine the impact of persistent cytopenias on outcomes and survival after CAR-T cell therapy. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that asymptomatic carriers are an important source of healthcare-associated Clostridium difficile infection. However, it is not known which test for the detection of C. difficile colonization is most sensitive in patients with haematological malignancies. We performed a prospective cohort study of 101 patients with haematological malignancies who had been admitted to the hospital for scheduled chemotherapy or haematopoietic cell transplantation. Each patient provided a formed stool sample. We compared the performance of five different commercially available assays, using toxigenic culture as the reference method. The prevalence of toxigenic C. difficile colonization as determined by toxigenic culture was 14/101 (14 %). The Cepheid Xpert PCR C. difficile /Epi was the most sensitive test for the detection of toxigenic C. difficile colonization, with 93 % sensitivity and 99 % negative predictive value. Our findings suggest that the Xpert PCR C. difficile /Epi could be used to rule out toxigenic C. difficile colonization in this population.

Purpose/objectives: The aim of this study was to describe how the clinical nurse specialist (CNS) role can be positioned to proactively plan and facilitate evidenced-based best practices in collaboration with a transdisciplinary, population-focused team that manages the patient across the cancer care continuum. This model capitalizes on the spheres of CNS practice (patient, nurse, and organization) through the functional roles of the CNS (clinical expert, researcher, educator, and consultant) to maximize quality care., Background/rationale: The CNS practice in a Midwest comprehensive cancer center has been unit based, focused on nursing staff education, skills, and competencies. Practice varied based on the needs of the unit. With the aging population, rapid growth in research accrual, increasing referrals, and expansion of facilities and programs, a reexamination of CNS practice was undertaken., Description of the Project/innovation: Nursing administration and CNSs evaluated the efficacy of transitioning to a population-focused model. Some responsibilities transitioned to other roles, the reporting structure was changed, and the role was realigned to a specific disease focus that encompassed care across the entire cancer continuum., Outcome: There was significant improvement in the areas of physician collaboration, autonomy, administrative support, teamwork, and contribution to the mission of the cancer program., Interpretation/conclusion: In this model, CNSs proactively plan and facilitate evidenced-based best practices in collaboration with a transdisciplinary team that manages the patient from diagnosis through the cancer trajectory, maximizing quality care and nursing-sensitive patient outcomes., Implications: Healthcare organizations need to examine various roles for opportunities to focus on incorporating evidenced-based practices that will result in improved patient care and satisfaction.