Polymorphism in ANRIL is associated with relapse in patients with multiple myeloma after autologous stem cell transplant.

Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells and overproduction of monoclonal immunoglobins. Treatment with melphalan is currently standard of care for younger and fit patients when followed by hematopoietic stem cell transplantation (HSCT), and in transplant ineligible patients when used in combination regimens. It has been previously shown that changes in the p53 pathway are associated with melphalan efficacy, but the regulatory role of the p14ARF-MDM2-p53 axis has yet to be fully explored. Recently, a non-coding RNA, ANRIL (antisense non-coding RNA in the INK4-ARF locus) has been shown to negatively regulate the transcription of the entire INK4-ARF locus and simultaneously modulate the p53 and pRb pathways. Moreover, some single nucleotide polymorphisms (SNPs) in ANRIL have previously been associated with susceptibility to several malignancies. Here we investigated select ANRIL SNPs in DNA from patient-derived peripheral blood mononuclear cells obtained from 108 MM patients treated with high-dose melphalan followed by HSCT. Our results show that the rs2151280 (CàT) SNP in ANRIL was associated with worse progression-free survival (TC/CC vs TT: HR = 0.53, 95%CI, [0.26, 1.07], P = 0.07; adjusted HR = 0.39, 95%CI, [0.18, 0.84], P = 0.016), and the TT variant had higher ANRIL expression and lower p15, p14ARF, and p16 expression compared to the TC/CC variants. Our results indicate that ANRIL may be involved in melphalan-mediated apoptosis via down-regulating p14ARF and subsequent p53, and that the rs2151280 polymorphism may be a potential prognostic biomarker for relapse in melphalan-treated MM patients.

CAR T-Cell Therapy: Update on the State of the Science.

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.

Detection of toxigenic Clostridium difficile colonization in patients admitted to the hospital for chemotherapy or haematopoietic cell transplantation.

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.

Pharmacokinetic-Pharmacodynamic Model of Neutropenia in Patients With Myeloma Receiving High-Dose Melphalan for Autologous Stem Cell Transplant.

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.

From unit based to population focused: transforming the role of oncology clinical nurse specialists.

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.