Effect of malnutrition-driven nutritional support protocol on clinical outcomes in autologous stem cell transplantation patients.

PURPOSE: 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. We compared their clinical outcomes with those of a historical cohort admitted between May 2016 and October 2017 (n = 257) for whom nutrition assessment and initiation of EN/PN were not protocol-driven. RESULTS: Patients receiving ASCT during the intervention period experienced decreased odds of prolonged hospital stay (p = 0.023), central line-associated bloodstream infection (p = 0.015), mucosal barrier injury (p = 0.037), and high weight loss (p = 0.002), in a multivariate analysis as compared with those receiving ASCT during the control period. Outcomes for ICU transfer, deconditioning on discharge, time to platelet engraftment, and unplanned 30-day hospital readmission did not differ significantly between groups. CONCLUSION: A malnutrition-driven nutritional support protocol may improve outcomes for ASCT patients.

Fluoroquinolone Prophylaxis Is Highly Effective for the Prevention of Central Line-Associated Bloodstream Infections in Autologous Stem Cell Transplant Patients.

Patients 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. Patients undergoing autologous SCT at a tertiary care hospital received levofloxacin prophylaxis from January 13, 2016 to January 12, 2017. Levofloxacin was administered from autologous SCT (day 0) until day 13, absolute neutrophil count > 500/mm3, or neutropenic fever, whichever occurred first. Clinical outcomes were compared with a baseline group who underwent autologous SCT but did not receive antibacterial prophylaxis during the previous year. The primary endpoint was incidence of CLABSIs assessed using Cox proportional hazards regression. A total of 324 patients underwent autologous SCT during the entire study period, with 150 receiving levofloxacin prophylaxis during the intervention period. The rate of CLABSIs was reduced from 18.4% during the baseline period to 6.0% during the intervention period. On multivariable analysis levofloxacin prophylaxis significantly reduced CLABSI incidence (hazard ratio, .33; 95% confidence interval [CI], .16 to .69; P = .003). There was also a reduction in the risk of neutropenic fever (odds ratio [OR], .23; 95% CI, .14 to .39; P < .001) and a trend toward a reduction in intensive care unit transfer for sepsis (OR, .33; 95% CI, .09 to 1.24; P = .10) in patients receiving levofloxacin prophylaxis. Notably, there was no increase in Clostridium difficile infection in the levofloxacin group (OR, .66; 95% CI, .29 to 1.49; P = .32). Levofloxacin prophylaxis was effective in reducing CLABSIs and neutropenic fever in patients undergoing autologous SCT. Further studies are needed to identify specific patient groups who will benefit most from antibiotic prophylaxis.

Transfer of influenza vaccine-primed costimulated autologous T cells after stem cell transplantation for multiple myeloma leads to reconstitution of influenza immunity: results of a randomized clinical trial.

Severe 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. Patients were randomly assigned to receive an influenza-primed autologous T-cell product or a nonspecifically primed autologous T-cell product. The study endpoint was the development of hemagglutination inhibition titers to the strain-specific serotypes in the influenza vaccine. Enzyme-linked immunospot assays were performed to confirm the development of influenza-specific B-cell and T-cell immunity. Patients who received the influenza-primed autologous T-cell product were significantly more likely to seroconvert in response to the influenza vaccine (P = .001). Seroconversion was accompanied by a significant B-cell response. No differences were observed in the global quantitative recovery of T-cell and B-cell subsets or in global T-cell and B-cell function. The provision of a primed autologous T-cell product significantly improved subsequent influenza vaccine responses. This trial was registered at www.clinicaltrials.gov as #NCT00499577.

Patient Perceptions of CAR-T Therapy in the USA: Findings from In-Depth Interviews.

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. METHODS: In-depth qualitative interviews were conducted with 18 patients in the USA with relapsed/refractory multiple myeloma or relapsed/refractory diffuse large B-cell lymphoma, 10 of whom had completed investigational or commercially approved CAR-T therapy and 8 of whom had discussed it with their physicians. We aimed to better understand inpatient experiences and patient expectations regarding CAR-T therapy and to ascertain patient perspectives on the possibility of outpatient care. RESULTS: CAR-T offers unique treatment benefits, particularly high response rates with an extended treatment-free period. All study participants completing CAR-T were very positive about their inpatient recovery experience. Most reported mild-to-moderate side effects; two experienced severe side effects. All said that they would opt to undergo CAR-T therapy again. Participants felt that the primary advantage of inpatient recovery was immediate access to care and on-going monitoring. Perceived advantages of the outpatient setting were comfort and familiarity. Because immediate access to care was seen as crucial, patients recovering in an outpatient setting would seek either a direct contact person or phone line for assistance if needed. CONCLUSION: As institutions become more experienced with CAR-T therapies, outpatient care may help reduce financial strain. Patient input can help institutions improve the outpatient experience and ensure safety and effectiveness of CAR-T programs.

Adoptive Cell Therapies: Keeping Pace With New and Emerging Advances.

At 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.

CRISPR-engineered T cells in patients with refractory cancer.

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 (TRAC) and TCRß (TRBC), were deleted in T cells to reduce TCR mispairing and to enhance the expression of a synthetic, cancer-specific TCR transgene (NY-ESO-1). Removal of a third gene encoding programmed cell death protein 1 (PD-1; PDCD1), was performed to improve antitumor immunity. Adoptive transfer of engineered T cells into patients resulted in durable engraftment with edits at all three genomic loci. Although chromosomal translocations were detected, the frequency decreased over time. Modified T cells persisted for up to 9 months, suggesting that immunogenicity is minimal under these conditions and demonstrating the feasibility of CRISPR gene editing for cancer immunotherapy.

Steroid-associated side effects in patients with multiple myeloma: consensus statement of the IMF Nurse Leadership Board.

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. By following patients carefully and educating them and their caregivers, nurses can promote adherence to therapy and improve quality of life. The International Myeloma Foundation's Nurse Leadership Board developed this consensus statement for the management of steroid-associated side effects to be used by healthcare providers in any medical setting.

Management of side effects of novel therapies for multiple myeloma: consensus statements developed by the International Myeloma Foundation's Nurse Leadership Board.

Nurses 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. Myelosuppression, thromboembolic events, peripheral neuropathy, steroid toxicities, and gastrointestinal side effects were selected for the first consensus statements. The board developed recommendations for healthcare providers in any medical setting, including grading of side-effect toxicity and strategies for managing the side effects in general, with specific recommendations pertaining to the novel agents.

Anti-CD19 CAR T cells with high-dose melphalan and autologous stem cell transplantation for refractory multiple myeloma.

BACKGROUND: 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). METHODS: Subjects received CTL019 following salvage high-dose melphalan and autologous stem cell transplantation (ASCT). All subjects had relapsed/refractory multiple myeloma and had previously undergone ASCT with less than 1 year progression-free survival (PFS). RESULTS: ASCT + CTL019 was safe and feasible, with most toxicity attributable to ASCT and no severe cytokine release syndrome. Two of 10 subjects exhibited significantly longer PFS after ASCT + CTL019 compared with prior ASCT (479 vs. 181 days; 249 vs. 127 days). Correlates of favorable clinical outcome included peak CTL019 frequency in bone marrow and emergence of humoral and cellular immune responses against the stem-cell antigen Sox2. Ex vivo treatment of primary myeloma samples with a combination of CTL019 and CAR T cells against the plasma cell antigen BCMA reliably inhibited myeloma colony formation in vitro, whereas treatment with either CAR alone inhibited colony formation inconsistently. CONCLUSION: CTL019 may improve duration of response to standard multiple myeloma therapies by targeting and precipitating secondary immune responses against myeloma-propagating cells. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02135406. FUNDING: Novartis, NIH, Conquer Cancer Foundation.

CAR T-Cell Therapy: On the Verge of Breakthrough in Many Hematologic Malignancies.

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.

Renal, GI, and Peripheral Nerves: Evidence-Based Recommendations for the Management of Symptoms and Care for Patients With Multiple Myeloma

BACKGROUND: 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.
. OBJECTIVES: This article aims to provide insight into prevention and management of organ health-related toxicities and give best practice recommendations for optimal nursing care.
. METHODS: The authors performed a literature search, and articles were reviewed for relevance to each organ-related topic. FINDINGS: Prevention and management strategies include close monitoring and prompt intervention when organ damage develops to reverse impairment and maintain adherence to therapy when indicated.

Caregiving at the end of life: Perceptions of health care quality and quality of life among patients and caregivers.

This study explored the association between perceptions of health care quality and quality of life in patients with advanced metastatic cancer and their informal caregivers (n=39). Patients' and caregivers' perceptions of health care quality, mental health, health-related quality of life, symptoms, and burden were measured. The key findings included the following: 1) patients' mental health and depression scores correlated with those of caregivers, suggesting that the mental health of patients and their caregivers are associated; 2) patients and caregivers shared similar perceptions regarding health care quality; 3) the presence of depression in caregivers correlated with caregivers being less satisfied with the health care being given to their patients (this correlation did not exist for patients, a finding that may be due in part to the protective buffering effect that caregivers provide their patients as illness progresses); and 4) a modified Primary Care Assessment Survey, originally designed for primary care patients, was a useful measure of health care assessment for both patients and caregivers. These data suggest that patients with advanced disease and their caregivers share similar perceptions and evolve as a "unit of care," and caregivers, as unique and important members of the patient's health care team, are also in need of care. When depressed, caregivers may unilaterally lose trust by becoming less satisfied with the quality of health care being provided to their patients.

Geographic disparities in cervical cancer mortality: what are the roles of risk factor prevalence, screening, and use of recommended treatment?

CONTEXT: Despite advances in early detection and prevention of cervical cancer, women living in rural areas, and particularly in Appalachia, the rural South, the Texas/Mexico border, and the central valley of California, have had consistently higher rates of cervical cancer mortality than their counterparts in other areas during the past several decades. METHODS: This paper reviews the published literature from 1966 to July 2002 to assess three potential pathways underlying this excess mortality--high human papilloma virus (HPV) prevalence, lack of or infrequent screening and advanced disease at diagnosis, and under-use of recommended treatment and shorter survival. FINDINGS: Living in rural areas may impose barriers to cervical cancer control, including lack of transportation and medical care infrastructures. Population characteristics that place women at greater risk for developing and dying from cervical cancer, such as low income, lack of health insurance, and physician availability, are concentrated in rural areas. Published data, however, are insufficient to identify the key reasons for the observed mortality patterns. CONCLUSIONS: At this time, given the lack of definitive evidence in the published literature, decisions about priorities in areas with high rates of cervical cancer mortality will depend on knowledge of current levels of screening, incidence, and stage distribution; and service delivery infrastructures, resources, and acceptability of interventions to the target population.

Financial toxicity in insured patients with multiple myeloma: a cross-sectional pilot study.

BACKGROUND: 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. The survey was derived from previous reported studies and included the 11-item COST measure (financial toxicity score range 0-44). A paper survey was offered to eligible patients on arrival for routine follow-up visits, and participants were asked to complete the survey before or after their visit to the clinic. Insurance and treatment data were obtained from patients' electronic health records. FINDINGS: Of 111 patients approached for the study, 100 individuals completed the survey. 59 (59%) of 100 patients reported that treatment costs were higher than expected, 70 (71%) of 99 had at least minor financial burden, and 36 (36%) of 100 reported applying for financial assistance. Use of savings to pay for myeloma treatment was common (43 [46%] of 94 patients) and 21 (21%) of 98 individuals borrowed money to pay for medications. COST scores were highly correlated with patient-reported use of strategies to cope with myeloma treatment expenses. On multivariable analysis, younger age (correlation coefficient ß 0·36, 95% CI 0·15 to 0·56, p=0·00092), non-married status (5·6, 1·5 to 9·6, p=0·0074), longer duration since diagnosis (-4·8, -9·3 to -0·2, p=0·042), and lower household income (US$40 000-79 999: 7·8, 2·7 to 12·9, p=0·0031; ≥$80 000: 11·8, 7·1 to 16·4, p<0·0001) were associated with higher financial burden as measured with the COST score. INTERPRETATION: Patient-reported financial toxicity and use of coping mechanisms were common in our insured population with multiple myeloma. Additional attention to rising treatment costs and cost sharing is needed to address the increasing evidence of financial toxicity affecting patients with cancer. FUNDING: University of Pennsylvania Perelman School of Medicine.

Care for the caregivers: a review of self-report instruments developed to measure the burden, needs, and quality of life of informal caregivers.

Significant demands are being placed on the informal caregivers of chronically ill patients, including those suffering from cancer. Health care professionals need to be aware of these demands, and they need effective tools to assess the impact these demands place on the caregivers. Over the past 25 years, researchers have developed self-report instruments to assess informal caregivers. These instruments assess various aspects of the caregiving experience, including caregiver burden, needs, and quality of life. The purpose of this review was to identify and critically evaluate these instruments. MEDLINE and PUBMED were searched from 1966 to 2002. After an extensive literature search and review, and utilizing specific inclusion criteria, 28 instruments were identified and evaluated in terms of their development, content, and psychometric properties. In addition, a history of the construct and measurement development in the areas of caregiver burden, needs, and quality of life are discussed. Although some further development and refinement of instruments could benefit the field, depending on the questions researchers or clinicians seek to pursue, there are many proven tools available for their use. Future research needs to use these instruments to assess the effectiveness of interventions aimed at improving the care of the caregivers.

Autologous hematopoietic stem cell transplantation for multiple myeloma: frequently asked questions.

When 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.

Autologous hematopoietic stem cell transplantation for patients with multiple myeloma: an overview for nurses in community practice.

Autologous 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. Clinical management of patients with MM requires a multidisciplinary approach that incorporates healthcare professionals in a number of clinical settings as well as caregivers and the patient. Patients about to undergo AHSCT are generally referred to tertiary care centers that specialize in ASCT. Pre- and post-transplantation treatments and long-term follow-up often are managed by a community-based referring oncologist in collaboration with the transplantation team. Oncology nurses play an integral role in the care of patients with MM in each clinical setting. This article aims to provide non-transplantation oncology nurses with guidelines for education, clinical management, and support of patients with MM undergoing AHSCT with a primary focus on the pre- and post-transplantation period.

Renal complications in multiple myeloma and related disorders: survivorship care plan of the International Myeloma Foundation Nurse Leadership Board.

Kidney 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. Patients with multiple myeloma who have light chain (Bence Jones protein) proteinuria may experience renal failure or progress to end-stage renal disease (ESRD) and require dialysis because of light chain cast nephropathy. Kidney failure in patients with presumed multiple myeloma also may result from amyloidosis, light chain deposition disease, or acute tubular necrosis caused by nephrotoxic agents; therefore, identification of patients at risk for kidney damage is essential. The International Myeloma Foundation's Nurse Leadership Board has developed practice recommendations for screening renal function, identifying positive and negative contributing risk and environmental factors, selecting appropriate therapies and supportive care measures to decrease progression to ESRD, and enacting dialysis to reduce and manage renal complications in patients with multiple myeloma.