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Background: Post-transplant lymphoproliferative disease (PTLD) occurs following allogeneic hematopoietic stem cell transplantation (HCT) as a consequence of immunosuppression. In most cases following HCT, PTLD is associated with Epstein-Barr Virus (EBV) infection of B cells, either due to reactivation, or from primary EBV infection (Styczynski J, Haematol. 2016; Allen UD, Am J Transplant, 2019; Nijand M, Transplant Direct, 2016). Clinical practice treatment guidelines recommend rituximab as preemptive therapy for EBV reactivation (based on EBV virus load) and for treatment of EBV-driven (EBV +) PTLD following HCT. However, EBV + PTLD patients (pts) who fail rituximab have very poor outcomes with limited treatment options. There are ongoing clinical studies investigating innovative therapies to address unmet needs in these pts. Published evidence on the clinical outcomes of these pts who fail rituximab is also limited. We aimed to describe the outcomes for pts diagnosed with EBV + PTLD following HCT who fail rituximab in a multinational real-world setting. Methods: We conducted a large multinational, multicenter retrospective chart review study of EBV + PTLD pts following HCT or solid organ transplantation who received rituximab or rituximab plus chemotherapy (CT) between January 2000-December 2018 and were refractory (failed to achieve complete response [CR] or partial response [PR]) or relapsed at any point after such therapy. Treatment response was assessed by either clinical diagnosis, radiographic/imaging, biopsy/cytology, or a combination of such assessments. Data was collected from 29 centers across North America (United States and Canada) and the European Union. The study population was aligned with the ongoing investigational trial (Clinicaltrials.gov Identifier: NCT03394365). This analysis includes pts with EBV + PTLD following HCT who were refractory or relapsed after rituximab ± CT as first line of therapy. The Kaplan-Meier (KM) method was used to estimate the overall survival (OS). Rituximab failure date was defined as the earliest date when pts became refractory or relapsed following rituximab ± CT. Results: A total of 81 pts with EBV + PTLD following HCT who failed rituximab ± CT were included in the analysis. Median age at PTLD diagnosis was 49 years (interquartile range [IQR]: 33‒57) and median time to PTLD onset from transplant was 3 months (IQR: 1.9‒4.2). Median follow-up time was 1.7 months (IQR: 0.6‒3.4) from the date of PTLD diagnosis. Of all the PTLDs, 52 (64.2%) were monomorphic, 18 (22.2%) polymorphic, 2 (2.5%) early lesions, and 9 (11.1%) were unknown. The most common PTLD subtype was diffuse large B-cell lymphoma (DLBCL) (46, 56.8%). Sixty-eight (84%) pts received rituximab monotherapy and 13 (16%) pts received rituximab plus CT as first line of therapy. Seven out of 13 pts who received rituximab plus CT had received preemptive rituximab treatment for EBV viremia prior to PTLD treatment. Median OS was 0.7 months (95% CI: 0.3‒1; IQR: 0.1‒2.7) for 81 pts who failed first line rituximab ± CT (Figure 1). Median OS from PTLD diagnosis was 1.7 months (95% CI: 1.1‒2.3; IQR: 0.6‒3.4). Seventy-four (91.4%) out of the 81 pts ultimately died. Causes of death comprised 50 (67.6%) related to PTLD and therapy, 10 (13.5%) graft-versus-host disease (GvHD), 5 (6.8%) from sepsis/infection, 3 (4.1%) due to primary disease leading to HCT, 2 (2.7%) organ failure, 1 (1.4%) graft failure, 1 (1.4%) from hepatic failure, and 2 (2.7%) unknown. Conclusions: The prognosis of EBV + PTLD pts following HCT who fail rituximab ± CT remains very poor with an estimated median OS of less than 1 month, highlighting the significant unmet need in this population. Figure 1 Figure 1. Disclosures Storek: Atara Biotherapeutics: Other: Site PI, Research Funding. Socié: Alexion: Research Funding. Thirumalai: Atara Biotherapeutics: Current Employment. Guzman-Becerra: Atara Biotherapeutics: Current Employment. Xun: Atara Biotherapeutics: Current Employment. Kumar: Roche: Research Funding; GSK: Research Funding; Amplyx: Research Funding; Merck: Research Funding; Takeda & Atara: Research Funding. Sadetsky: Atara Biotherapeutics: Current Employment. Dierickx: Sandoz: Consultancy; Sanofi: Consultancy; Novartis: Consultancy; Roche: Consultancy, Research Funding; Takeda, Incyte, Atara: Consultancy. Reitan: Atara, Kite, Janssen: Research Funding. Barlev: Atara Biotherapeutics: Current Employment. Mohty: Sanofi: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Astellas: Honoraria; Amgen: Honoraria; Adaptive Biotechnologies: Honoraria.

SummaryIntroduction The ADVATE (rAHF-PFM) Prophylaxis Study compared the efficacy of (i) standard factor (F) VIIII prophylaxis (SP) (20–40 IU kg−1 every other day) vs. pharmacokinetic-tailored prophylaxis (PKP) (20–80 IU kg−1 every third day) and (ii) both prophylactic regimens with on-demand therapy (OD) in 66 previously on-demand-treated patients (median age: 26 years; range: 7–59) with FVIII ≤2% and ≥8 joint haemorrhages in the year before enrolment. Aim The aim of this study was to evaluate joint bleeding episodes during the on-demand and prophylactic study periods. Methods A post hoc analysis of joint bleeding episodes in the per protocol analysis set (n = 53) was conducted. Results The annualized joint bleeding rate (AJBR) was significantly lower for subjects treated with 12 months of SP (n = 30) or PKP (n = 23) as compared with 6 months of OD (n = 53): 55 {median AJBR 0.48 [interquartile range (IQR) 1.96]}, 72 [1.00 (4.07)] and 1164 [38.65 (24.81)] respectively (P

Factor replacement therapy for the treatment of moderate to severe haemophilia A and B can be complicated by the production of inhibitory alloantibodies to factor VIII (FVIII) or factor IX. Treatment with the nanofiltered anti-inhibitor coagulant complex, Factor Eight Inhibitor Bypassing Activity (FEIBA NF), is a key therapeutic option for controlling acute haemorrhages in patients with high-titre inhibitors or low-titre inhibitors refractory to replacement therapy. Given the high risk for morbidity and mortality in haemophilia patients with inhibitors to FVIII or FIX, we conducted this Phase 3 prospective study to evaluate whether prophylaxis with FEIBA NF is a safe and effective treatment option. Over a 1-year period, 17 subjects were treated prophylactically (85 ± 15 U kg(-1) every other day) while 19 subjects were treated on demand. The median (IQR) annualized bleeding rate (ABR) during prophylaxis was 7.9 (8.1), compared to 28.7 (32.3) during on-demand treatment, which amounts to a 72.5% reduction and a statistically significant difference in ABRs between arms (P = 0.0003). Three (17.6%) subjects (ITT) on prophylaxis experienced no bleeding episodes, whereas none treated on demand were bleeding episode-free. Total utilization of FEIBA NF for the treatment of bleeding episodes was significantly higher during on-demand therapy than prophylaxis (P = 0.0067). There were no differences in the rates of related adverse events between arms. This study demonstrates that FEIBA prophylaxis significantly reduces all types of bleeding compared with on-demand treatment, and the safety of prophylaxis is comparable to that of on-demand treatment.

SummaryWe report a prospective trial of 55 previously untreated patients (PUPs) and minimally treated patients (MTPs) with severe/moderately severe haemophilia A (baseline factor VIII [FVIII] ≤2%) treated with a single FVIII replacement product. It was the objective of this study to evaluate the immunogenicity, efficacy, and safety of rAHF-PFM (Advate®). Ondemand or prophylactic treatment regimens were determined at the discretion of the investigator. rAHF-PFM was also permitted for perioperative management. There were 633 bleeding episodes (BEs), including 517 treated, and 466 rated for efficacy. Haemostatic efficacy was considered excellent/good in 93% of 466 rated treatments. Of 517 treated BEs, 463/517 (90%) were managed with one (356/517 [69%]) or two infusions (107/517 [21%]). There were 27 surgeries. Intraoperative (n=22) and postoperative (n=25) haemostatic efficacies were considered excellent or good in 100% of rated surgeries. Related serious adverse events (SAEs) were inhibitor development in 16/55 (29.1%) subjects who received at least one infusion of rAHF-PFM. Nonserious, related adverse events (AEs) were few in number (14 in eight subjects). The odds ratio (OR [95% Confidence Interval, CI]) of developing inhibitors was significantly higher in subjects with a family history of inhibitor (4.95 [1.29–19.06]), non-Caucasian ethnicity (4.18, [1.18–14.82]), and intensive treatment at high dose (4.5 [1.05–19.25]) within ≤20 exposure days (EDs). In conclusion, rAHF-PFM was safe and effective for the management and perioperative coverage of PUPs/MTPs with severe/moderately severe haemophilia A. This report supports previous findings from studies in which family history of inhibitor, non-Caucasian ethnicity, and high intensity treatment were associated with high risk of inhibitor development.

– Objectives: Several types of HIV-related oral mucosal conditions have been reported to occur during the course of HIV disease progression. Of these, few may be manifested as ‘white’ lesions and many are noticeable to the patient. This paper examines the relationships between social, behavioral and medical aspects of HIV infection and reporting an occurrence of oral white patches (OWP) by HIV-infected patients. Methods: The subjects are participants in all three interviews in the HIV Cost and Services Utilization Study (HCSUS). The subjects were selected using a three-stage probability sampling design. The multivariate analysis is based on 2109 subjects with nonmissing binary outcome variable for all three waves representing a national sample of 214 000 individuals. The multivariate model was fitted using generalized estimating equations (GEE) by implementing the XTGEE command in STATA. Results: We estimate that 75 000 persons (35%) reported at least one incident of OWP, of these 14 000 reported having OWP during all three interviews, and that the rate of reporting declined over the three HCSUS waves. The multivariate analysis showed seven variables that were significant predictors of at least one report of OWP. Conclusions: Compared with persons on HAART therapy, patients on other regimens or taking no antiviral medications were 23–46% more likely to report an incident of OWP. Compared with whites, African Americans were 32% less likely to report OWP, while current smokers were 62% more likely than nonsmokers. Being diagnosed with AIDS and having CD4 counts less than 500 significantly increased the likelihood of reporting OWP.

Background: The impact of oral health on HIV patients has not been sufficiently documented. Objective: To estimate the associations between measures of oral and generic health-related quality of life in persons receiving medical care for HIV. Design: This is a longitudinal study of interview data collected in a probability sample of adults with HIV receiving health care in the US. The data were collected at three points in time. Patients: Two thousand eight hundred and sixty-four HIV-infected adults using medical care. Measurements: Physical and mental health were assessed using 28 items and oral health was assessed using seven items on oral-related pain and discomfort, worry, appearance, and function. Clinical measures included CD4 count, oral symptoms, physical symptoms, and stage of HIV. Physical functioning and emotional well-being were measured on a 0–100 scale with higher scores indicating better health. Oral health was measured using seven items with a five point scale. Results: In multivariate analyses, oral symptoms had the strongest association with oral health-related quality of life. Each additional oral symptom was associated with an average decrease in oral health (0–100 possible range) of 3.97 points (p = 0.000). In addition, oral health was significantly associated with both physical and mental health. A one-point increase in oral health was associated with a 0.05 (p = 0.000) increase in mental health and 0.02 increase in physical health (p = 0.031). Conclusions: Oral health is strongly associated with physical and mental health but provides noteworthy unique information in persons with HIV infection. Thus, physical and mental health measures of HIV patients should incorporate indicators of oral functioning and well-being.

This longitudinal study examines perceived unmet dental need in a nationally representative probability sample of HIV-infected persons in medical care. A logistic regression analysis modeled the relationship between unmet need and explanatory variables. We estimate that 40% of HIV/AIDS patients report an unmet need associated with being male, being unemployed, injecting drugs, being heterosexual, lacking dental insurance, and having less education. Disparities in unmet need are related to socioeconomic status rather than to disease stage or ethnicity.

Background: The authors describe and compare drinking patterns among malt liquor beer (MLB), regular beer (RB), and hard liquor (HL) drinkers in a low-income, racial/ethnic minority community. Methods: Drinkers were recruited from randomly selected alcohol outlets in South Los Angeles. Respondents were assessed on sociodemographic characteristics, alcohol use history, drinking patterns, and drinking context among other items in a face-to-face interview with research staff. Results: Three hundred twenty-nine drinkers were interviewed, of whom 297 reported drinking MLB, RB, or HL brands of alcohol most often in the past 90 days. This subsample was 88% African-American, 72% male, and 35% unemployed. As compared with RB and HL drinkers, MLB drinkers were more likely to be homeless, to receive public assistance for housing, and to be unemployed. MLB drinkers also reported significantly higher rates of daily or near-daily drinking (74%, as compared with 48% for RB and 29% for HL) of drinks per day on drinking days (5.2, as compared with 4.2 for RB and 3.1 for HL), and daily average ethanol consumption (6.97 oz, as compared with 2.13 oz for RB drinkers and 6.13 oz for HL drinkers). In multinomial regression analysis that controlled for potential confounders, the odds of preferring RB as compared with MLB were significantly increased among persons with blue-collar occupations and those who reported drinking in public settings and were reduced among persons who drank outdoors, those who combined drinking with tobacco smoking, and those who drank alcohol with members of the same sex. Average daily ethanol consumption odds were reduced for RB drinkers as compared with MLB drinkers. TheoddsofpreferringHLascomparedwithMLBweresignificantlyincreasedforpersonswithwhite-collar occupations and those who drank in public settings and were reduced for persons who drank outdoors and those who combined drinking and smoking. Conclusion: The authors observed substantial differences in sociodemographic characteristics, drinking patterns, and ethanol consumption by beverage type in this community sample. MLB drinkers seem to have distinctive drinking patterns that require additional study to determine whether this pattern is associated with increased individual or community risk.

This article examines the impact of different dental plan types, dental markets, premiums, out-of-pocket costs and enrollee demographics on the enrollees' perceived oral health status.The authors randomly sampled enrollees in dental benefit plans offered by eight Fortune 500 companies and interviewed them regarding their experiences with their plans, including perceived oral health status. The sample consisted of 2,340 respondents, of whom 42.3 percent were enrolled in capitation, or CAP, plans, and 57.7 percent were enrolled in fee-for-service, or FFS, plans.The authors used chi2 tests, analysis of variance and multinomial logistic regression. They set significance at P.05. Results indicate that nonwhites, CAP-plan enrollees and those with higher out-of-pocket cost were less likely to rate their oral health "good," "very good" or "excellent" compared with whites, FFS-plan enrollees and those with lower out-of-pocket costs, respectively.CAP-plan enrollees rated their oral health more poorly than did FFS-plan enrollees. Further studies are necessary to determine if adverse selection occurs and if CAP plans provide inferior quality of care.Practitioners' awareness of and willingness to address the variety of factors that influence perceived oral health status may improve their patients' perceived oral health status and satisfaction with care.

Background This article examines the impact of capitated, or CAP, and fee-for-service, or FFS, dental benefit plans on the enrollees' satisfaction with their plans and their satisfaction with their dentists. Methods The authors selected four dental markets: California, New Jersey, Michigan and North Carolina. Eight Fortune 500 companies participated. Enrollees were selected randomly and interviewed about their experiences with their dental plans. The sample consisted of 2,340 respondents, of whom 42.3 percent were enrolled in CAP plans and 57.7 percent in FFS plans. Results The major findings were that those enrolled in FFS plans were four times more likely to be very satisfied than dissatisfied with their dental plans than were those in CAP plans. The FFS plan enrollees were 16 times more likely to be very satisfied than dissatisfied with their dentists than were those in CAP plans. Conclusion Enrollees generally were satisfied with their plans and their dentists but those in FFS plans were the most satisfied. The higher the premium paid, the higher the level of satisfaction. Practice Implications Enrollees with perceived unmet needs were less satisfied with their dental benefit plans and dentists. Taking care of needs is the most significant thing dentists can do to affect patients' satisfaction.