untington disease (HD) is an autosomal-dominant neurodegenerative disorder resulting from an unstable cytosine-adenine-guanine (CAG) repeat in the Huntingtin gene 1 that is clinically characterized by involuntary movements, cognitive decline, and behavioral changes. 2-4 Several studies have previously described the natural history of the disease. 4-22 Many, however, have been either small, narrowly focused, short in duration, or uncontrolled. Highquality longitudinal data will inform the design of clinical trials aimed at slowing progression and may inform patients and clinicians about the disease course. We, therefore, analyzed longitudinal data from the recently concluded, prospective, multicenter, observational study Cooperative Huntington's Observational Research Trial (COHORT). Methods Study The Johns Hopkins Medicine institutional review board reviewed and approved this analysis of COHORT study data. All COHORT study participants provided written informed consent or, if unable, had an authorized representative provide consent on their behalf. The COHORT project was an observational study that collected phenotypic and genotypic data from individuals with HD and their families from February 14, 2006, until June 30, 2011. The study design and initial baseline characteristics have been previously described. 23 In brief, the study, which was conducted at 44 research sites in Aus-IMPORTANCE Understanding the natural history of Huntington disease will inform patients and clinicians on the disease course and researchers on the design of clinical trials. OBJECTIVE To determine the longitudinal change in clinical features among individuals with Huntington disease compared with controls. DESIGN, SETTING, AND PARTICIPANTS Prospective, longitudinal cohort study at 44 research sites in Australia (n = 2), Canada (n = 4), and the United States (n = 38). Three hundred thirty-four individuals with clinically manifest Huntington disease who had at least 3 years of annually accrued longitudinal data and 142 controls consisting of caregivers and spouses who had no genetic risk of Huntington disease. MAIN OUTCOMES AND MEASURES Change in movement, cognition, behavior, and function as measured by the Unified Huntington's Disease Rating Scale, the Mini-Mental State Examination, and vital signs. RESULTS Total motor score worsened by 3.0 points (95% CI, 2.5-3.4) per year and chorea worsened by 0.3 point per year (95% CI, 0.1-0.5). Cognition declined by 0.7 point (95% CI, 0.6-0.8) per year on the Mini-Mental State Examination. Behavior, as measured by the product of frequency and severity score on the Unified Huntington's Disease Rating Scale, worsened by 0.6 point per year (95% CI, 0.0-1.2). Total functional capacity declined by 0.6 point per year (95% CI, 0.5-0.7). Compared with controls, baseline body mass index was lower in those with Huntington disease (25.8 vs 28.8; P < .001), and average pulse was higher (74.2 vs 69.6 beats/min; P < .001). CONCLUSIONS AND RELEVANCE Over 3 years, the cardinal features of Huntington disease all d...

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Recipients of ex vivo T-cell depleted (TCD) HCT are at risk of infection by double stranded (ds) DNA viruses. We report rates of dsDNA viremia, end-organ disease (EOD), infection-related mortality, and overall survival (OS) in a contemporary cohort of adult TCD HCT recipients routinely monitored for cytomegalovirus (CMV), adenovirus (ADV), human herpesvirus 6 (HHV6) and Epstein-Barr virus (EBV). Health care utilization in the first 6 months post HCT was compared between patients with dsDNA viremia versus no viremia. Observational study of adult patients with acute leukemia and myelodysplastic syndrome who received CD34+ selected, peripheral blood HCT at Memorial Sloan Kettering Cancer Center from March 2012 through December 2014. Patients were prospectively monitored by quantitative polymerase chain (qPCR) assays for CMV, ADV, HHV6 and EBV in whole blood or plasma. The cumulative incidence of viremia(s) at day +180, end-organ disease (EOD) at 1 year, and overall survival at 1 year were estimated by the Kaplan-Meier method and compared by the log-rank test among patient with and without viremia/EOD. Standardized incidence ratios (SIR) were used to compare overall length of hospital stay (LOS), number of readmissions after HCT and length of readmissions through day +180. Of 156 patients, 96 (62%) were CMV recipient seropositive. Patients received grafts from matched related 42 (27%), matched unrelated 86 (55%) or mismatched 28 (18%) donors. Overall, 132 (85%) patients had ≥1viremia, and 52 (33%) patients had ≥2 viremias by day +180. The cumulative incidences for CMV, HHV6, ADV, and EBV viremia were 44%, 61%, 7% and 16%, respectively with median [interquartile range(IQR)] time of onset 28 (25–33), 33(25–47), 60(19–84), and 79 (54–106) days post HCT, respectively. Twenty-eight (18%) patients developed EOD by ds DNA viruses at 1 year post HCT. Treatment for CMV accounted for 91% total antiviral treatment-days. Compared to patients with no viremia, patients with CMV viremia, HHV6 viremia, or ≥ 2 viremias experienced longer LOS (P<0.001) and a higher number of readmissions (P<0.001) by day+ 180. OS at 1-year was 79% and similar between patients with or without ds DNA viremias. EOD was associated with lower 1-year OS (63.4%) vs without EOD (81.1%) (P=0.02). Of 33 patients that died, 10 died due to infection and 7 of the 10 infection-related deaths were due to dsDNA viruses. Viremia by dsDNA viruses occurred in 85% of CD34+ HCT recipients by day +100 and 33% of patients experienced ≥2 viremias by day +180. CMV accounted for the majority of antiviral use. CMV, HHV6 or ≥2 viremias were associated with more readmissions and longer LOS. Overall, one-year OS was 78%. EOD by dsDNA viruses was associated with decreased one-year OS. Infections by ds DNA viruses pose a substantial burden after TCD HCT.

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