Background We tested the hypothesis that changes in our transplant practice have improved outcomes over the last decade. To explore correlates of improved outcomes, we analyzed the frequency and severity of graft-versus-host disease and hepatic, renal, pulmonary and infectious complications. Methods During 1993–1997 and 2003–2007, 1418 and 1148 patients received their first allogeneic transplants at our Center. Outcome measures included non-relapse mortality, recurrent malignancy, overall mortality, and the frequency and severity of major complications across this decade. Components of the Pretransplant Assessment of Mortality (PAM) score were used in regression models to adjust for severity of illness at the time of transplantation. Results In comparing outcomes during 1993–1997 and 2003–2007, we observed statistically significant decreases in the hazards of day -200 non-relapse mortality (by 60%), overall non-relapse mortality (by 52%), relapse or progression of malignancy (by 21%), and overall mortality (by 41%), after adjusting for components of the PAM score. Similar results were seen when the analyses were confined to patients receiving myeloablative conditioning therapy. We found statistically significant declines in the risk of more severe GVHD, disease caused by infections (viral, bacterial, and fungal), and damage to the liver, kidneys, and lungs. Conclusions We document a substantial reduction in the hazard of death related to allogeneic hematopoietic cell transplantation as well as improved long-term survival over the last decade. Improved outcomes appear to be related to reductions in organ damage, infection, and severe acute GVHD.

Since 1999, there have been nearly 20,000 cases of confirmed symptomatic West Nile virus (WNV) infection in the United States, and it is likely that more than 1 million people have been infected by the virus. WNV is now the most common cause of epidemic viral encephalitis in the United States, and it will likely remain an important cause of neurological disease for the foreseeable future. Clinical syndromes produced by WNV infection include asymptomatic infection, West Nile Fever, and West Nile neuroinvasive disease (WNND). WNND includes syndromes of meningitis, encephalitis, and acute flaccid paralysis/poliomyelitis. The clinical, laboratory, and diagnostic features of these syndromes are reviewed here. Many patients with WNND have normal neuroimaging studies, but abnormalities may be present in areas including the basal ganglia, thalamus, cerebellum, and brainstem. Cerebrospinal fluid invariably shows a pleocytosis, with a predominance of neutrophils in up to half the patients. Diagnosis of WNND depends predominantly on demonstration of WNV-specific IgM antibodies in cerebrospinal fluid. Recent studies suggest that some WNV-infected patients have persistent WNV IgM serum and/or cerebrospinal fluid antibody responses, and this may require revision of current serodiagnostic criteria. Although there is no proven therapy for WNND, several vaccines and antiviral therapy with antibodies, antisense oligonucleotides, and interferon preparations are currently undergoing human clinical trials. Recovery from neurological sequelae of WNV infection including cognitive deficits and weakness may be prolonged and incomplete.

BACKGROUNDCannabis is purported to alleviate symptoms related to cancer treatment, although the patterns of use among cancer patients are not well known. This study was designed to determine the prevalence and methods of use among cancer patients, the perceived benefits, and the sources of information in a state with legalized cannabis.METHODSA cross‐sectional, anonymous survey of adult cancer patients was performed at a National Cancer Institute–designated cancer center in Washington State. Random urine samples for tetrahydrocannabinol provided survey validation.RESULTSNine hundred twenty‐six of 2737 eligible patients (34%) completed the survey, and the median age was 58 years (interquartile range [IQR], 46‐66 years). Most had a strong interest in learning about cannabis during treatment (6 on a 1‐10 scale; IQR, 3‐10) and wanted information from cancer providers (677 of 911 [74%]). Previous use was common (607 of 926 [66%]); 24% (222 of 926) used cannabis in the last year, and 21% (192 of 926) used cannabis in the last month. Random urine samples found similar percentages of users who reported weekly use (27 of 193 [14%] vs 164 of 926 [18%]). Active users inhaled (153 of 220 [70%]) or consumed edibles (154 of 220 [70%]); 89 (40%) used both modalities. Cannabis was used primarily for physical (165 of 219 [75%]) and neuropsychiatric symptoms (139 of 219 [63%]). Legalization significantly increased the likelihood of use in more than half of the respondents.CONCLUSIONSThis study of cancer patients in a state with legalized cannabis found high rates of active use across broad subgroups, and legalization was reported to be important in patients' decision to use. Cancer patients desire but are not receiving information about cannabis use during their treatment from oncology providers. Cancer 2017;123:4488‐97. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

This cross-sectional study examines whether racial and/or ethnic minority, female, and older adults are underrepresented in vaccine clinical trials compared with the US population.

Cytomegalovirus (CMV) surveillance and preemptive therapy is the most commonly used strategy for CMV disease prevention in hematopoietic cell transplant (HCT) recipients. In 2007, we introduced a CMV prevention strategy for those patients at risk for CMV disease using quantitative PCR surveillance, with treatment thresholds determined by patient risk factors. Patients (N=367) received preemptive therapy either at a plasma viral load of ≥500 copies/ml, at ≥100 copies/ml if receiving ≥ 1 mg/kg of prednisone or anti-T cell therapies, or if a ≥ 5-fold viral load increase from baseline was detected. Compared to patients prior to 2007 undergoing antigenemia-based surveillance (n=690) with preemptive therapy initiated for any positive level, the risk-adapted PCR based strategy resulted in similar use of antiviral agents, and similar risks of CMV disease, toxicity and non-relapse mortality (NRM) in multivariable models. The cumulative incidence of CMV disease by day 100 was 5.2% in the PCR group compared to 5.8% in the antigenemia group (1 year: 9.1% PCR vs 9.6% antigenemia). Breakthrough CMV disease in the PCR group was predominantly in the gastrointestinal (GI) tract (15/19 cases, 79%). However, unlike CMV pneumonia, CMV GI disease was not associated with increased NRM (adjusted hazard ratio 1.19, P=0.7 [GI disease] vs. 8.18, P<0.001 [pneumonia]). Thus, the transition to a preemptive therapy strategy based on CMV viral load and host risk factors successfully prevented CMV disease without increasing the proportion of patients receiving preemptive therapy and attributable toxicity. Breakthrough disease in PCR-based preemptive therapy occurs at a low incidence and presents primarily as GI disease which is more likely to be responsive to antiviral therapy.

Background Immunosuppressed patients are at increased risk for herpes zoster (HZ), but incidence in solid organ transplant (SOT) recipients has varied in multiple studies. To assess incidence of HZ, we examined patients who underwent SOT and received follow-up care within the large multicenter Us Department of Veteran’s Affairs Healthcare system. Methods Incident cases of HZ were determined using ICD-9 coding from administrative databases. A multivariable Cox proportional hazards model, adjusted for a priori risk factors, was used to assess demographic factors associated with development of HZ. Results Among the 1077 eligible SOT recipients, the cohort-specific incidence rate of HZ was 22.2 per 1000 patient-years (95% confidence interval [CI], 18.1–27.4). African Americans (37.6 per 1000 [95% CI, 25.0–56.6]) and heart transplants recipients (40.0 per 1000 [95% CI, 23.2–68.9]) had the highest incidence of HZ. Patients transplanted between 2005 and 2007 had the lowest incidence (15.3 per 1000 [95% CI, 8.2–28.3]). In a multivariable model, African Americans (hazard ratio [HR] 1.88; 95% CI: 1.12, 3.17) and older transplant recipients (HR 1.13; 95% CI: 1.01, 1.27 [per 5-year increment]) had increased relative hazards of HZ. Conclusions These data demonstrate that HZ is a common infectious complication following SOT. Future studies focused on HZ prevention are needed in this high-risk population.

Infection is a major complication of hematopoietic cell transplantation. Prolonged neutropenia and graft versus host disease are the two major complications with an associated risk for infection, and these complications differ according to the graft source. A phase 3, multicenter, randomized trial (BMT CTN 0201) of transplantation of bone marrow (BM) versus peripheral-blood stem cells (PBSC) from unrelated donors (URD) showed no significant differences in two-year survival between these graft sources. In an effort to provide data regarding whether bone marrow or peripheral-blood stem cells could be used as a preferential graft source for transplantation, we report a detailed analysis of the infectious complications for 2 years following transplantation from the BMT CTN 0201 trial. A total of 499 patients in this study had full audits of infection data. A total of 1347 infection episodes of moderate or greater severity were documented in 384 (77%) patients; 201/249 (81%) of the evaluable patients had received a BM graft and 183/250 (73%) had received a PBSC graft. Of 1347 infection episodes, 373 were severe and 123 were life-threatening and/or fatal; 710 (53%) of these episodes occurred on the BM arm and 637 (47%) on the PBSC arm, resulting in a two-year cumulative incidence 84.7% (95% confidence interval [CI]: 79.6–89.8) for BM vs. 79.7% (95%CI, 73.9–85.5) for PBSC, P = .013. The majority of these episodes, 810 (60%), were due to bacteria, with a two-year cumulative incidence of 72.1% and 62.9% in BM versus PBSC recipients, respectively (P = .003). The cumulative incidence of bloodstream bacterial infections during the first 100 days was 44.8% (95%CI, 38.5–51.1) for BM vs. 35.0% (95%CI, 28.9–41.1) for PBSC (P = .027). The total infection density (# infection events / 100 patient days at risk) was .67 for BM and .60 for PBSC. The overall infection density for bacterial infections was .4 in both arms; for viral infections was .2 in both arms; and for fungal/parasitic infections was .04 and .05 for BM and PBSC, respectively. The cumulative incidence of infection prior to engraftment was 47.9% (95%CI, 41.5–53.9) for BM vs. 32.8% (95%CI, 27.1–38.7) for PBSC (P = .002), possibly related to quicker neutrophil engraftment using PBSC. Infections remain frequent following URD HCT, particularly following BM grafts.

No therapeutic agent has yet been established as the definitive therapy for adenovirus infections. We describe the clinical experience of 13 immunocompromised patients who received CMX001 (hexadecyloxypropyl cidofovir), an orally bioavailable lipid conjugate of cidofovir, for adenovirus disease. We retrospectively analyzed 13 patients with adenovirus disease and viremia treated with CMX001; data were available for ≥4 weeks after initiation of CMX001 therapy. Virologic response (VR) was defined as a 99% drop from baseline or undetectable adenovirus DNA in serum. The median age of the group was 6 years (range, 0.92-66 years). One patient had severe combined immunodeficiency, 1 patient was a small bowel transplant recipient, and 11 were allogeneic stem cell transplant recipients. Adenovirus disease was diagnosed at a median of 75 days (range, 15-720 days) after transplantation. All patients received i.v. cidofovir for a median of 21 days (range, 5-90 days) before CMX001 therapy. The median absolute lymphocyte count at CMX001 initiation was 300 cells/μL (range, 7-1500 cells/μL). Eight patients (61.5%) had a ≥1 log10 drop in viral load after the first week of therapy. By week 8, 9 patients (69.2%) demonstrated a VR, with a median time to achieve VR of 7 days (range, 3-35 days). The change in absolute lymphocyte count was inversely correlated with the change in log10 viral load only at week 6 (r = −0.74; P = .03). Patients with VR had longer survival than those without VR (median 196 days versus 54.5 days; P = .04). No serious adverse events were attributed to CMX001 during therapy. CMX001 may be a promising therapeutic option for the treatment of severe adenovirus disease in immunocompromised patients.