Prophylaxis for Hepatitis B Virus Reactivation after Allogeneic Stem Cell Transplantation in the Era of Drug Resistance and Newer Antivirals: A Systematic Review and Meta-Analysis.

Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are at a very high risk of hepatitis B virus reactivation (HBVr). Lamivudine is commonly used as prophylaxis against HBVr in high-risk patients undergoing allo-HSCT. Unfortunately, its efficacy is diminishing due to the development of HBV mutant drug-resistant strains. With the availability of newer antiviral agents such as entecavir, telbivudine, adefovir, and tenofovir, it is important to assess their role in HBVr prophylaxis. A comprehensive search of 7 databases was performed to evaluate efficacy of antiviral prophylaxis against HBVr in allo-HSCT patients (PubMed/Medline, Embase, Scopus, Cochrane Library, Web of Science, CINAHL, and ClinicalTrials.gov (June 21, 2017)). We identified 10 studies, with 2067 patients undergoing allo-HSCT; these primarily evaluated the use of lamivudine and entecavir as prophylaxis against HBVr in patients undergoing allo-HSCT because there were little or no data about adefovir, telbivudine, or tenofovir as prophylaxis in this specific patient population. Thus, included studies were categorized into 2 main prophylaxis groups: lamivudine and entecavir. Results of our meta-analysis suggest that entecavir is very effective against HBVr, although further clinical trials are required to test efficacy of new antivirals and explore the emerging threat of drug resistance.

Cardiovascular Function in Long-Term Hematopoietic Cell Transplantation Survivors.

Peak oxygen consumption (VO2peak), as measured by cardiopulmonary exercise testing (CPET), is a powerful independent predictor of cardiovascular disease (CVD) and all-cause mortality in a broad range of populations. We assessed the safety and feasibility of CPET in aging long-term hematopoietic cell transplantation (HCT) survivors, a population at high risk for premature onset of CVD. Next, we examined how organ-specific impairments (eg, cardiac, pulmonary, hematologic) impact VO2peak after HCT. Twenty consecutive HCT survivors underwent a comprehensive assessment of cardiopulmonary health that included CPET, echocardiography with strain, pulmonary function testing, 6-minute walk test, and timed up and go. Median age at assessment was 67.4 years (range, 42 to 75), and median time from HCT was 9.8 years (range, 3 to 20). No adverse events were observed during CPET procedures, and 95% of studies were considered to be at "peak" effort (respiratory exchange ratio ≥ 1.10). VO2peak was on average 22% less than predicted, and allogeneic HCT survivors had markedly lower VO2peak when compared with autologous HCT survivors (18.2 mL/kg/min versus 22.2 mL/kg/min; P = .05). Six participants (30%) had VO2peak ≤ 16 mL/kg/min, a threshold associated with a 9-foldrisk of death in patients undergoing HCT. Despite the presence of normal (>50%) resting left ventricular ejection fraction in all participants, 25% had markedly abnormal left ventricular longitudinal strain, an advanced echocardiographic measure of myocardial dysfunction. These findings highlight the role of stress-based measures and advanced myocardial imaging to characterize CVD risk in HCT survivors, setting the stage for tailored interventions to prevent CVD with its attendant morbidity and mortality.

Rationale and design of the Children's Oncology Group (COG) study ALTE1621: a randomized, placebo-controlled trial to determine if low-dose carvedilol can prevent anthracycline-related left ventricular remodeling in childhood cancer survivors at high risk for developing heart failure.

BACKGROUND: Anthracyclines are widely used in the treatment of childhood cancer. One of the well-recognized side-effects of anthracycline therapy is dose-dependent cardiomyopathy that may progress to heart failure (HF) years after completion of cancer-directed therapy. This study will evaluate the efficacy of low-dose beta-blocker (carvedilol) for HF risk reduction in childhood cancer survivors at highest risk for HF. The proposed intervention has the potential to significantly reduce chronic cardiac injury via interruption of neurohormonal systems responsible for left ventricular (LV) remodeling, resulting in improved cardiac function and decreased risk of HF. The intervention is informed by previous studies demonstrating efficacy in pediatric and adult non-oncology populations, yet remains unstudied in the pediatric oncology population. METHODS/DESIGN: The primary objective of the trial is to determine impact of the intervention on echocardiographic markers of cardiac remodeling and HF risk, including: LV wall thickness/ dimension ratio (LVWT/D; primary endpoint), as well as LV ejection fraction, volume, and blood biomarkers (natriuretic peptides, galectin-3) associated with HF risk. Secondary objectives are to establish safety and tolerability of the 2-year course of carvedilol using: 1) objective measures: hepatic and cardiovascular toxicity, treatment adherence, and 2) subjective measures: participant self-reported outcomes. Two hundred and fifty survivors of childhood cancer (diagnosed <21 years of age), and previously treated with high-dose (≥300 mg/m2) anthracyclines will be enrolled in a randomized, double-blind, placebo controlled trial. After baseline assessments, participants will be randomized in a 1:1 ratio to low-dose carvedilol (maximum dose: 12.5 mg/day) or placebo. Carvedilol or placebo is up-titrated (starting dose: 3.125 mg/day) according to tolerability. DISCUSSION: When completed, this study will provide much-needed information regarding a physiologically plausible pharmacological risk-reduction strategy for childhood cancer survivors at high risk for developing anthracycline-related HF. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02717507.

TotShots: An Innovative Pediatric Free Clinic Providing High Patient Satisfaction to the Underserved.

BACKGROUND AND OBJECTIVES: The University of Arizona College of Medicine-Tucson TotShots clinic is a student-developed, student-directed free clinic that provides sports physicals and vaccines to uninsured pediatric patients in Tucson, Arizona. TotShots runs under the greater umbrella of the Commitment to Underserved People Program, which aims to teach medical students how socioeconomic and cultural factors impact health and access to health care. Our objective was to study cost savings and patient satisfaction of this clinic. METHODS: Value of care provided through sports physicals and vaccine administration was calculated using the Centers for Medicare and Medicaid Services Physician Fee Schedule and Centers for Disease Control Vaccines for Children Decisions Analysis Model. In addition, patient satisfaction was measured through the utilization of an optional three-question survey completed by patients in their preferred language at the resolution of their visit. Vaccines and sports physicals were administered from April 2017 to November 2017. RESULTS: TotShots administered 51 vaccines and completed 115 sports physicals resulting in a value of $415.65 of administration fees and $5,878.80 of sports physical examinations. Sixty-three of 66 total patients completed patient satisfaction surveys. Of those patients, 57 (90.5%) were highly satisfied with their provider's communication, 58 (92%) rated their perception of the quality of medical care they received as excellent, and 54 (85.7%) of patients were highly satisfied with their overall TotShots experience. CONCLUSIONS: TotShots fills a valuable role in increasing access to vaccines and sports physicals while maintaining high patient satisfaction and high value of cost savings.

Accuracy of a Novel Handheld Wireless Platform for Detection of Cardiac Dysfunction in Anthracycline-Exposed Survivors of Childhood Cancer.

Purpose: Childhood cancer survivors are at risk for anthracycline-related cardiac dysfunction, often developing at a time when they are least engaged in long-term survivorship care. New paradigms in survivorship care and chronic disease screening are needed in this population. We compared the accuracy of a novel handheld mHealth platform (Vivio) as well as echocardiography for assessment of cardiac function [left ventricular ejection fraction (EF)] in childhood cancer survivors with cardiac magnetic resonance (CMR) imaging (reference).Experimental Design: Cross-sectional study design was used. Concurrent evaluation of EF was performed using Vivio, two-dimensional (2D) echocardiography, and CMR. Differences in mean EF (2D echocardiography vs. CMR; Vivio vs. CMR) were compared using Bland-Altman plots. Linear regression was used to evaluate proportional bias.Results: A total of 191 consecutive survivors participated [50.7% female; median time from diagnosis: 15.8 years (2-44); median anthracycline dose: 225 mg/m2 (25-642)]. Echocardiography overestimated mean EF by 4.9% (P < 0.001); linear regression analysis confirmed a proportional bias, when compared with CMR (t = 3.1, P < 0.001). There was no difference between mean EF derived from Vivio and from CMR (-0.2%, P = 0.68). The detection of cardiac dysfunction via echocardiography was poor when compared with CMR [Echo EF < 45% (sensitivity 14.3%), Echo EF < 50% (sensitivity 28.6%)]. Sensitivity was substantially better for Vivio-based measurements [EF < 45% or EF < 50% (sensitivity 85.7%)].Conclusions: This accessible technology has the potential to change the day-to-day practice of clinicians caring for the large number of patients diagnosed with cardiac dysfunction and heart failure each year, allowing real-time monitoring and management of their disease without the lag-time between imaging and interpretation of results. Clin Cancer Res; 24(13); 3119-25. ©2018 AACR.

Long-term pulmonary function in survivors of childhood cancer.

PURPOSE: This study was undertaken to determine the magnitude of pulmonary dysfunction in childhood cancer survivors when compared with healthy controls and the extent (and predictors) of decline over time. PATIENTS AND METHODS: Survivors underwent baseline (t1) pulmonary function tests, followed by a second comprehensive evaluation (t2) after a median of 5 years (range, 1.0 to 10.3 years). Survivors were also compared with age- and sex-matched healthy controls at t2. RESULTS: Median age at cancer diagnosis was 16.5 years (range, 0.2 to 21.9 years), and time from diagnosis to t2 was 17.1 years (range, 6.3 to 40.1 years). Compared with odds for healthy controls, the odds of restrictive defects were increased 6.5-fold (odds ratio [OR], 6.5; 95% CI, 1.5 to 28.4; P < .01), and the odds of diffusion abnormalities were increased 5.2-fold (OR, 5.2; 95% CI, 1.8 to 15.5; P < .01). Among survivors, age younger than 16 years at diagnosis (OR, 3.0; 95% CI, 1.2 to 7.8; P = .02) and exposure to more than 20 Gy chest radiation (OR, 5.6; 95% CI, 1.5 to 21.0; P = .02, referent, no chest radiation) were associated with restrictive defects. Female sex (OR, 3.9; 95% CI, 1.7 to 9.5; P < .01) and chest radiation dose (referent: no chest radiation; ≤ 20 Gy: OR, 6.4; 95% CI, 1.7 to 24.4; P < .01; > 20 Gy: OR, 11.3; 95% CI, 2.6 to 49.5; P < .01) were associated with diffusion abnormalities. Among survivors with normal pulmonary function tests at t1, females and survivors treated with more than 20 Gy chest radiation demonstrated decline in diffusion function over time. CONCLUSION: Childhood cancer survivors exposed to pulmonary-toxic therapy are significantly more likely to have restrictive and diffusion defects when compared with healthy controls. Diffusion capacity declines with time after exposure to pulmonary-toxic therapy, particularly among females and survivors treated with high-dose chest radiation. These individuals could benefit from subsequent monitoring.