ALBERT

Description: Background: Von Willebrand disease (VWD) is the most common inherited bleeding disorder in humans affecting up to 1% of the population, while symptomatic prevalence is likely closer to 0.1%. A deficiency of von Willebrand factor (VWF) can be quantitative (type 1 or type 3) or qualitative (type 2) and lead to a bleeding diathesis of variable intensity roughly correlating with functional activity. Diagnosis can be challenging due to variable penetrance and large influence of multiple pre-analytic variables and a wide testing coefficient of variation. Treatment for VWD is focused on replacement of defective or deficient VWF with a plasma-derived or recombinant VWF-containing product, release and elevation of endogenous stores of VWF with Desmopressin (DDAVP), or prevention of premature fibrinolysis with an antifibrinolytic, such as aminocaproic acid. Although there is relative consensus on the management of mild VWD, there is scarce literature about the optimal treatment of patients with severe disease, especially in regard to factor replacement. Real World evidence for the use of primary (prior to significant bleeding) or secondary (following development of significant bleeding) prophylaxis is lacking with the majority of studies relying heavily on retrospective data. Additionally, ongoing VWD prophylaxis studies typically only allow participants to enroll if they previously have not been on prophylaxis, limiting our ability to learn about this growing population of patients. Study Design and Methods: Approximately 1,900 VWD patients were identified in the ATHNdataset with a VWF:Ag or VWF:RCo of ≤ 30%, with ~170 of these on prophylaxis. This group, in addition to those VWD patients with clinically significant bleeding and ≤ 40% of normal VWF:Ag or VWF:RCo, provide a potential unmet opportunity to examine prophylaxis and treatment patterns. Furthermore, a standardized laboratory assessment (including a standardized diagnostic battery, genetic evaluation of VWF gene, and inhibitor testing) will provide significant enrichment of the ATHNdataset by fully characterizing patients that are highly likely to utilize factor concentrates. Inclusion criteria are patients with severe VWD defined as type 3 VWD, or VWF:RCo, VWF:GP1bM or VWF:Ag≤ 30%, patients with clinically severe VWD as defined by VWF:Rco, VWF:GP1bM or VWF:Ag ≤ 40% with severe bleeding phenotype requiring recurrent use of factor concentrates, and co-enrollment in the ATHNdataset. Patients with platelet-type or acquired VWD are excluded. The primary objective is to assess the safety of various VWF regimens for different indications (on-demand, surgery, and prophylaxis) in adult and pediatric patients with clinically severe VWD. Safety is measured by the number of reported events as defined by the European Haemophilia Safety Surveillance (EUHASS) program. Secondary objectives are to enrich and analyze data from clinically severe congenital VWD patients by collecting laboratory data; to establish sub-studies for patients who are treated with VWF products on demand or who have started on or switched to a particular VWF containing product; to evaluate the use of factor replacement as prophylaxis in a cohort of severe VWD participants over 6 month time periods; to describe bleeding events, changes in overall bleeding, and annualized bleed rate as measured by the International Society on Thrombosis and Haemostasis (ISTH) Bleeding Assessment Tool (BAT) and if applicable the Pictorial Bleed Assessment Chart (PBAC); and to describe real-world effectiveness of VWD treatment as measured by health care utilization and quality of life measures (PROMIS® and V-WIQ questionnaires). Descriptive statistics will be calculated to analyze the primary and secondary outcomes. For each categorical variable, its frequency and percentage will be reported. In terms of a continuous measurement, its mean, median, standard deviation, interquartile range, minimum, and maximum values will be disclosed. The study will attempt to enroll a target number of at least 50 participants who are receiving VONVENDI but will not mandate the use of VONVENDI. More study design details are outlined in Table 1. Disclosures Sidonio: Genetech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda-Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bioverativ: Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding; Biomarin: Membership on an entity's Board of Directors or advisory committees; Uniqure: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Kedrion: Research Funding.

Description: Background. Hemophilia A is a rare X-linked bleeding disorder resulting from deficiency in coagulation factor VIII. Numerous genetic variants (〉2000) affecting the F8 gene have been implicated as causative of hemophilia A, including structural variants (SVs) such as copy number variants (CNVs) and large intra-chromosomal inversions caused by recombination between distant regions with high homology to sequences within F8 intron 1 or intron 22. SVs detected in patients with hemophilia are associated with more severe disease, and different types of SVs may inform inhibitor risk. For the vast majority of patients, causative variants can be identified using targeted DNA sequencing of F8 coding regions and/or the use of methods which detect known SVs (e.g. inverse shifting PCR, long-range PCR, MLPA). However, these approaches fail to explain 1-3% of hemophilia A cases. We hypothesized that a dedicated structural variant analysis at the F8 locus using whole genome sequencing data could identify previously undetected deleterious F8 gene variants in unsolved cases of hemophilia A. Methods. Cases were selected from the My Life, Our Future (MLOF) hemophilia study cohort recently whole genome sequenced by the NHLBI TOPMed program. In this study, we performed a custom SV analyses using whole genome sequencing (WGS) data from 11 cases of severe hemophilia A (factor VIII activity level 〈 1%) that remained genetically unexplained after exhausting all available laboratory testing methods. Two of the eleven unsolved severe hemophilia A cases (18%) were reported to have had an inhibitor. Results. SV analyses of the F8 genomic region revealed previously undetected deletions and inversions in 6 out of the 11 cases. In these 6 samples, SV calls were supported by multiple sequencing reads (〉 25 reads) and multiple types of read evidence (read depth, paired-end and/or split read evidence). Two deletions within intron 6 were detected in a single hemophilia A case, a finding which suggests F8 intron 6 may contain one or more regulatory elements critical for F8 expression. Three distinct large inversions predicted to disrupt the F8 structural gene were detected in five other cases; a 720Kb inversion with breakpoints in F8 intron 6 and SPRY3 intron 1 (n=1), a 20Mb inversion with breakpoints in F8 intron 1 and INTS6L intron 8 (n=1), and a 7.4Kb inversion with breakpoints in F8 intron 25 and the SMIM9 intron 1 (n=3). These events are novel in hemophilia and were also not present in the larger, sequenced My Life, Our Future dataset (N=2186), supporting these SVs as likely causative of severe hemophilia A. Both cases with inhibitors had the F8 intron 25-SMIM9 inversion. Conclusions. This work demonstrates that dedicated analyses of WGS for SVs originating in non-coding regions can identify novel variants in previously unsolved cases of hemophilia A. We conclude that any genetic studies of diseases caused by loss-of-function variants should consider dedicated analyses for SVs. We predict additional deleterious SVs remain to be discovered in rare unexplained cases of hemophilia. Disclosures Konkle: BioMarin: Consultancy; Bioverativ: Research Funding; CSL Behring: Consultancy; Genentech: Consultancy; Spark: Consultancy, Research Funding; Pfizer: Research Funding; Gilead: Consultancy; Sangamo: Research Funding; Shire: Research Funding. Johnsen:CSL Behring: Consultancy; Octapharma: Consultancy.

Description: Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a heterogenous disease that can develop after solid organ or allogeneic hemopoietic stem cell transplant (HCT). PTLD after HCT is primarily of the monomorphic subtype and driven by the Epstein-Barr Virus. It is an ultra-rare disease that follows an aggressive clinical course with poor outcomes and for which there is no approved standard treatment. The risk of PTLD after HCT in the current clinical setting is insufficiently quantified, and large-scale data from the US are lacking. The objective of this study was to estimate the incidence of PTLD after allogeneic HCT using a large US claims database. Methods: A retrospective cohort study using the MarketScan Commercial and Medicare Supplemental database was conducted. Patients who received an allogeneic HCT between January 1, 2011 and December 31, 2016 with at least 6 months of continuous enrollment prior to allogeneic HCT were included in the analysis. PTLD cases were identified as having a diagnosis of PTLD (ICD-9 code 238.77 or ICD-10 code D47Z1) or one inpatient or two outpatient claims for preselected, clinically relevant lymphoma codes within 1-year post-transplant. Patients with a clinically relevant lymphoma diagnosis in the 6 months prior to HCT were excluded. The percentage of patients who developed PTLD during the first year after allogeneic HCT was calculated, the average time to PTLD diagnosis was estimated, and patient characteristics at PTLD diagnosis were described. Results: A total of 2,735 eligible patients were included in the analysis; the mean (range) post-transplant follow-up time was 576 (1-2555) days. Overall, 103 patients (3.8%; 95% CI: 3.1%-4.6%) developed PTLD during the first year after allogeneic HCT, and the median (range) time from allogeneic HCT to PTLD diagnosis was 90 (0-364) days. The mean (SD) age at time of first PTLD diagnosis was 46.8 (17.2) years, with 84.5% of patients 18 to 〈 65 years old, 8.7% of patients 〈 18 years old, and 6.8% of patients ≥ 65 years old. There was a higher percentage of male versus female PTLD patients: 55.3% versus 44.7%. Conclusions: This analysis of a large-scale US claims database showed that 3.8% (95%CI: 3.1%-4.6%) of post-allogeneic HCT patients had PTLD within the first year after transplant. Most patients impacted by PTLD were younger than 65 (93.2%), and a substantial proportion were pediatric patients (8.7%). Future studies are needed to better understand the disease state and burden of PTLD as well as the unmet medical need for this patient population. Disclosures Barlev: Atara Biotherapeutics, Inc: Employment, Equity Ownership. Xu:Atara Biotherapeutics, Inc: Employment, Equity Ownership. Fulcher:IBM Watson Health: Employment. Watson:Atara Biotherapeutics, Inc: Employment, Equity Ownership. Sruti:IBM Watson Health: Employment. Sudhindra:Atara Biotherapeutics, Inc: Employment, Equity Ownership.

Description: Introduction: Transplant recipients younger than 18 years old are believed to have a 2- to 4-fold higher risk of developing post-transplant lymphoproliferative disorder (PTLD) than adult transplant patients. Within the pediatric group, there is evidence to suggest an increased risk of PTLD in younger children. We conducted a systematic literature review (SLR) to estimate the weighted mean age (WMA) at PTLD diagnosis and describe patient demographics in the real-world setting. Methods: An SLR was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with the scope defined in terms of Population, Intervention Comparators, Outcomes, and Study design (PICOS) criteria. Studies were identified based on a systematic search using key biomedical literature databases: EMBASE, MEDLINE, and Cochrane. The literature search was conducted on July 19, 2018 and included studies published between database inception in January 1, 1959 and July 19, 2018. Relevant congress abstracts published between January 2015 and June 2018 were also identified. The PICOS-based inclusion and exclusion criteria were used to review identified citations. To ensure inclusion of all relevant evidence, no treatment limitations were imposed; however, the study designs were limited to prospective and retrospective observational studies. Case reports were included regardless of sample size. Two independent reviewers screened all citations and full-text articles; any discrepancies were resolved by a third independent reviewer. Data from included studies were extracted into a pre-defined template, and results were summarized using the PRISMA flow diagram. Using the sample size from the selected studies, the WMA for each relevant subgroup was determined and was compared to the average age at the time of diagnosis for other cancers reported in SEER Cancer Statistics (2011-2015; https://seer.cancer.gov/csr/). Results: A total of 447 studies fulfilled the search criteria: 114 adult studies, 136 pediatric studies with varied definitions (〈 16, 〈 18 or 〈 21 years old), and 197 that did not specify inclusion by age. Seventy studies enrolled only PTLD patients after allogeneic hematopoietic stem cell transplantation (HCT). Among these studies, 17 included pediatric patients with a WMA of 12.5 years, 10 included adult patients with a WMA of 40.2 years, and 41 had no age restriction with a WMA of 34.4 years. For pediatric patients, the risk of post-HCT PTLD was 1.3-23.5% and the time from transplant to PTLD was 0.9-6.0 months. There was only one pediatric HCT study (N=4; mean age, 9 years), which reported median survival of 27.6 months. A total of 350 studies only enrolled PTLD patients after solid-organ transplant (SOT). Among these studies, 115 included pediatric patients with a WMA of 6.6 years, 98 included adult patients with a WMA of 46.9 years, and 136 had no age restriction with a WMA of 38.6 years. Among the pediatric SOT studies, the risk of PTLD was 0.3-25.0%, the time from transplant to PTLD was 1.4-92.8 months, and the reported survival was 0.9-37.2 months. The average age of lymphoma patients at cancer diagnosis according to the SEER Cancer Statistics database was 65 years. Conclusions: This SLR of published real-world studies demonstrates that the WMA at PTLD diagnosis (for studies with no age restrictions: 34.4 years for HCT and 38.6 years for SOT) is substantially lower than the reported average age at diagnosis for lymphomas (65 years), irrespective of study design and inclusion criteria. PTLD greatly impacts the pediatric population, with a quarter of HCT studies and a third of SOT studies focusing on this population. Currently, there is no indicated treatment for this ultra-rare disease with poor prognosis, indicating a clear unmet need for patients with PTLD that disproportionately affects younger patients. Disclosures Watson: Atara Biotherapeutics, Inc: Employment, Equity Ownership. Xu:Atara Biotherapeutics, Inc: Employment, Equity Ownership. Forsythe:Novartis: Consultancy. Barlev:Atara Biotherapeutics, Inc: Employment, Equity Ownership.

Description: Introduction: Recipients of solid-organ transplant (SOT) or allogeneic hematopoietic stem cell transplantation (HCT) have an increased risk of cancers from Epstein-Barr virus (EBV), specifically lymphomas due to immunosuppression. Post-transplant lymphoproliferative disorder (PTLD) is a disease with a range of clinical presentations, including that of an aggressive lymphoma, that occurs after transplantation. PTLD occurs rarely after transplantation and is associated with poor survival outcomes. Publications on the clinical evidence for PTLD are scarce; therefore, a systematic literature review (SLR) was conducted to better understand the real-world evidence in PTLD. Methods: An SLR was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with the scope defined in terms of Population, Intervention Comparators, Outcomes and Study design (PICOS) criteria. Studies were identified based on a systematic search using key biomedical literature databases: EMBASE, MEDLINE, and Cochrane. The literature search was conducted on July 19, 2018 and included studies published between database inception in January 1, 1959 and July 19, 2018. Relevant congress abstracts published between January 2015 and June 2018 were also identified. The PICOS-based inclusion and exclusion criteria were used to review identified citations. To ensure inclusion of all relevant evidence, no treatment limitations were imposed; however, the study designs were limited to prospective and retrospective observational studies. Case reports were included regardless of sample size. Two independent reviewers screened all citations and full-text articles; any discrepancies were resolved by a third independent reviewer. Data from included studies were extracted into a pre-defined template, and results were summarized using the PRISMA flow diagram. Results: A total of 447 articles were identified that met the SLR criteria: 350 SOT, 70 HCT, and 27 that included both SOT and HCT. Among 97 studies of PTLD post HCT, 81 involved allogeneic HCT, 2 involved autologous HCT, and 14 did not report the type of HCT. Of the 376 identified studies with PTLD post-SOT, the most prevalent SOTs involved were: kidney (193 studies), heart (126 studies), liver (91 studies), lung (84 studies), pancreas (43 studies), and intestine (25 studies). Data on the risk of PTLD, treatment patterns for PTLD, and utilization and survival outcomes following PTLD were reported in 334, 331, and 210 studies, respectively. There was notable clinical and methodological heterogeneity among studies. For example, there was variability in the study populations: 114 were adult populations, 136 were pediatric populations, and 197 did not specify age. Most of the studies were retrospective (419 studies) versus prospective (28 studies), and most were single-center studies (340 studies) versus multicenter studies/registries (98 studies), limiting the generalizability of the results. In addition, the sample sizes were small among most PTLD studies, with fewer than 50 patients in 376 studies, 50-100 patients in 9 studies, and more than 100 patients in 46 studies. The clinical and methodological heterogeneity noted above may explain the large variations in reported risk of PTLD in both HCT and SOT. Among adult SOT patients, the risk of developing PTLD was 0.2% to 11.5%, while among pediatric SOT patients, the risk was 0.3% to 25.0%. Among adults with HCT, the risk of developing PTLD was 1.0 to 20.0%, while among pediatric patients with HCT, the risk was 1.3% to 23.5%. Conclusions: To the best of our knowledge, this is the first comprehensive SLR to examine the published real-world evidence in patients with PTLD. Our SLR reveals important differences with respect to methodology and reporting of real-world published studies assessing the current landscape in PTLD. Additional large, high-quality studies employing more rigorous study methodology are required to understand the current landscape of PTLD in the real-world setting. Disclosures Xu: Atara Biotherapeutics, Inc: Employment, Equity Ownership. Forsythe:Novartis: Consultancy. Barlev:Atara Biotherapeutics, Inc: Employment, Equity Ownership. Watson:Atara Biotherapeutics, Inc: Employment, Equity Ownership.

Description: Introduction: Allogeneic hematopoietic cell transplantation (HCT) is a common treatment for many hematologic diseases. Most deaths occur in the first 2 years after HCT due to relapse, graft-versus-host disease, infections, malignancies, or other toxicities. Among patients who are alive and recurrence free at 2 years after HCT, survival at 10 years is between 80% and 92%. Advances in transplantation practices have led to improved outcomes and more long-term HCT survivors. As survival outcomes continue to improve and new treatments emerge, understanding and quantifying the full lifetime benefit of HCT in terms of mean overall survival (OS) is clinically relevant. In this analysis, we estimate the mean OS of a cohort of HCT patients. Methods: A systematic literature review of all studies reporting OS post-HCT was conducted. Extracted data were incorporated into a long-term survival model using a step-wise approach: short-term survival (up to 2 years post-HCT) using data reported by Uhlin et al (Haematologica. 2014;99:346-52), and longer-term survival (more than 2 years post-HCT) using data reported by Wingard et al (J Clin Oncol. 2011;29:2230-9) and the age-adjusted life tables for the general UK population. Available published data provided OS estimates up to 15 years post-HCT, and beyond this time, OS estimates are uncertain. To estimate mean OS and address this uncertainty, three different survival scenarios were modeled: best-case, worst-case, and base-case. For the best-case, it was assumed that HCT patients were cured and had the same OS as the age-adjusted general population. For the worst-case, it was assumed that HCT patients carried excess mortality for the rest of their lives. The excess mortality was calculated from Wingard et al 2011, which showed 20% mortality from year 2-15 post-HCT; this is an order of magnitude greater than the general population (2%). For the base-case, a Weibull parametric function was fit to the data published by Wingard et al 2011 to estimate the survival curve from year 2 post-HCT until death. To incorporate the excess mortality, the lowest survival was chosen cycle over cycle between the parametric estimate and the age-adjusted life tables. Sensitivity analysis for the mean survival estimate was performed by fitting several different parametric functions using exponential, Gompertz, log-logistic, and log-normal. A lifetime analysis was undertaken for a cohort of patients starting at the weighted mean age at the time of HCT, calculated from Wingard et al 2011. Results: Only two published articles were found that provided OS in patients without complications after HCT (Uhlin et al 2014 and Wingard et al 2011). Data from Uhlin et al 2014 was used to estimate the percent alive at 2 years post-HCT, which was 65%. For a cohort of HCT patients that received their transplant at age 23.5, the estimated mean OS for the base-case was 25.9 years post-HCT, with parametric models ranging between 25.9 and 29.5 years. The best-case and worst-case estimates were 31.7 and 23.9 years, respectively. Conclusions: The mean OS for a cohort of HCT patients was estimated to be 25.9 years. This estimate helps to understand and quantify the full lifetime survival benefit to HCT patients, including the tail end of the survival curve, and the potential added benefits of future treatments post-HCT. The sensitivity analysis revealed a narrow range for the estimated mean OS, minimizing the uncertainty of the results. Our estimates are based on data published by Wingard et al 2011, which incorporates excess mortality after 2 years post-HCT. This is consistent with the clinical assumption that HCT patients continue to have excess mortality throughout their lifetime. Since the first 2 years post-HCT has the highest mortality rate, new treatments that can improve survival during this time may change the impact on the lifetime benefit of the therapy. Disclosures Palmer: PRMA Consulting, Ltd: Consultancy. Watson:Atara Biotherapeutics, Inc: Employment, Equity Ownership. Barlev:Atara Biotherapeutics, Inc: Employment, Equity Ownership.

Description: Objectives: CHOP (vincristine, cyclophosphamide, prednisone, doxorubicin) is a treatment option for post-transplant lymphoproliferative disorder (PTLD) following solid organ transplant, an aggressive and potentially fatal disease. The most common and impactful CHOP-related adverse events (AEs) are febrile neutropenia (FN), chemotherapy-induced (CI) peripheral neuropathy (PN), infection, CI-anemia (A), and CI-nausea and vomiting (NV). These CHOP-related AEs have a large humanistic burdensignificant impact to quality of life (QoL) of patients, especially shortly after treatment. The evidence for a positive QoL benefit associated with some AE treatments (e.g., erythropoietin stimulating agents [ESA], granulocyte colony stimulating factors) is inconsistent and many patients likely remain with QoL deficits even after treatment. The impact of these short-term CHOP-related AEs is likely to be accompanied by an increase in healthcare resource utilization and costs. The objective of this study was to explore the economic burden of short-term CHOP-associated AEs in PTLD patients. Since PTLD is a rare disease with limited available data, we expanded our search to include all patients with lymphoproliferative disorders (LPD). Methods: Short-term (within several months after treatment) AEs associated with CHOP with an incidence of 〉4% in patients with LPDs were determined and sourced from the published literature and cancer websites. A comprehensive literature search was conducted using PubMed and EMBASE to identify economic burden studies published from 2010 to 2018 of the AEs associated with CHOP and its components in the United States (US). Studies incorporating rituximab alongside CHOP (CHOP + R) were also included as this is a valid treatment option for PTLD patients. Economic burden was defined as the management costs and resource utilization associated with treating CHOP-emergent adverse events. The conduct of this comprehensive literature review was guided by the PRISMA protocol wherein the research question (using the PICOS format), search strategy, target short-term AEs, and inclusion and exclusion criteria were pre-specified in detail. Results: Overall, 3,946 non-duplicate citations were screened, 39 studies were included for abstraction and no studies included patients with PTLD. Studies were methodologically heterogenous, with approximately half (56%) based on some form of retrospective analysis or prospective observational study. FN was the AE most commonly encountered, followed by CIA, infection, CI-nausea and vomiting, and CIPN. FN was an important driver of hospitalization (proportion of FN patients with hospitalization was up to 83.2%) and extended length of stay (LOS) was substantial for several AEs (LOS range in days: infection, 8.4-23.6; FN, 7.9-19.7). Mean LOS was longer in FN patients with multiple hospitalizations as well as in FN patients with comorbidities. Rates of transfusion in CI-anemia patients varied dramatically, from 10.8% to 47.4%. Transfusion rates were attenuated by ESA use in LPD patients, although a significant proportion of anemic cancer patients receiving ESAs still required transfusions. Total management costs were highly variable, ranging from nominal for events such as CIPN to over $197,000 in hospitalization costs per infection discharge per patients complicated with clostridium difficile. One recent study showed the inpatient costs attributable to FN were $33,006 per patient per episode. Studies identified CINV as a top reason for unplanned service use, but no studies were identified assessing its economic impact in LPD patients. Outpatient care costs for each AE varied but tended to have a low to moderate economic impact. The costs attributable to several AEs (FN, infection) were highest in the first cycle of chemotherapy. Conclusions: Several common short-term AEs due to CHOP in the LPD population were associated with substantial healthcare resource utilization and costs that were primarily driven by increased hospitalization and length of inpatient stays. Costs for FN and infections associated with CHOP ranged from $33,000 to over $197,000, demonstrating the high economic burden to the US healthcare system. No PTLD-specific studies were found, highlighting the absence of published data addressing the economic burden associated with chemotherapy in PTLD patients and the need for effective and tolerable therapies. Disclosures Watson: Atara Biotherapeutics: Employment, Equity Ownership. Barlev:Atara Biotherapeutics: Employment, Equity Ownership. Worrall:Atara Biotherapeutics, Inc: Consultancy. Duff:Atara Biotherapeutics, Inc: Consultancy. Beckerman:Atara Biotherapeutics, Inc: Consultancy.

Description: Background: Post-transplant lymphoproliferative disorder (PTLD) is a rare and often aggressive disease in the setting of immunosuppression following solid organ transplant (post-SOT). About 50% of cases are associated with Epstein-Barr virus (EBV) infection of B cells, either due to reactivation of the virus after transplantation, or from primary EBV infection. Data remain very limited with respect to overall clinical and economic burden among EBV+PTLD patients (pts), particularly in the setting of pts who fail first line therapy. This retrospective chart review aimed to quantify the burden of hospitalization due to EBV+PTLD in post-SOT pts who failed first-line therapy in the real-world setting in Germany. Study Design and Methods: The German PTLD registry database was screened for pts with EBV+PTLD post-SOT who were refractory (failed to achieve complete [CR] or partial remission [PR]) to rituximab or rituximab plus chemotherapy (CT) or relapsed at any point after such therapy between 2000 to 2015. Pts with primary CNS PTLD were excluded. Pts without any outpatient visit or hospitalization record were excluded from the analysis (n of pts=1). Hospitalization data were reviewed by an experienced physician and adjudicated as PTLD relevant; details on diagnoses and procedures performed during hospitalization were collected from the first diagnosis of PTLD to the earliest of the following: death, loss to follow up or end of study period (Sep 1st, 2018). We estimated the mean number of hospitalizations, average length of inpatient stay per admission and the percentages of time spent in the hospital out of the total time following PTLD index date or treatment failure index date. The PTLD index date was defined as the first date of EBV+PTLD diagnosis; and the treatment failure index date was defined as the earliest date of pts who became refractory or relapsed to first-line therapy of rituximab or rituximab plus CT. Results: A total of 35 EBV+PTLD pts were analyzed. All had failed first line rituximab monotherapy. Median follow up time was 24.8 months from the PTLD index date. Median age at PTLD diagnosis was 47 years (range 18-75). Of these, 6 (17.1%) were polymorphic, 21 (60%) were diffuse large B cell lymphoma, 3 (8.6%) were Burkitt lymphoma, and 5 (14.3%) were other B-cell lymphoma. Among the 35 pts, 23 (65.7%) died: 12 from PTLD, 6 treatment-related, 1 from organ failure, and 4 from other causes. The vast majority of pts (29 out of 35) received CHOP-based CT following rituximab failure (2 other CT, 4 did not receive CT). All pts (100%) had at least one inpatient hospitalization after PTLD diagnosis and 16 (45.7%) pts had at least one ICU admission following PTLD index date. The mean number of PTLD hospitalizations following PTLD index date was 4 (SD 3.2, range 1-12) and the mean average length of stay per hospitalization was 23.8 days (SD 22.6, range 2-94). The mean proportion of time spent in the hospital out of total time at risk from PTLD index date was 20.5% (SD 27.6, range 0.1-100) with an average of 9.5% of time spent in the ICU setting during hospitalization stay (SD 22, range 0-99.5). The mean number of PTLD hospitalizations (n of pts=19) following first course CT failure index date was 2.1 (SD 1.9, range 0-7) and the mean average length of stay per hospitalization was 14.8 days (SD 8.6, range 6-31.6). The mean proportion of time spent in the hospital out of total time at risk from CT failure index date was 41.8% (SD 39.6, range 0-100) with an average of 26% time spent in the ICU setting (SD 39, range 0-100). Conclusions: This is the first study to quantify the hospitalization burden directly related to EBV+PTLD post-SOT in Germany. The results show that hospitalization burden in EBV+PTLD post-SOT pts failing first line rituximab monotherapy is substantial accounting for approximately 20% of patient's time after initial diagnosis of PTLD with around 10% spent in the ICU setting. This hospitalization burden is even higher and accounts for over 40% of time in pts after additional treatment failure to first CT with 26% spent in the ICU setting. Disclosures Zimmermann: Roche: Research Funding; Janssen: Other: Travel, accomodations expenses; Atara Biotherapeutics: Other: Travel, accomodations expenses, Research Funding; Celgene: Other: Travel, accomodations expenses. Xu:Atara Biotherapeutics: Employment, Equity Ownership. Barlev:Atara Biotherapeutics: Employment, Equity Ownership. Zhang:Atara Biotherapeutics: Employment, Equity Ownership. Thirumalai:Atara Biotherapeutics: Employment. Watson:Atara Biotherapeutics: Employment, Equity Ownership. Trappe:Atara Biotherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Other: Congress related travel support; Roche: Consultancy, Honoraria, Other: Congress related travel support, Research Funding; AbbVie: Consultancy, Other: Congress related travel support; Celgene: Other: Congress related travel support.

Description: Background Venous thromboembolism (VTE) is the third leading cause of cardiovascular morbidity and mortality worldwide in adults and is increasingly seen in children. Optimal transition of care (TOC) from the inpatient to the outpatient setting may lead to improved outcomes for patients with VTE. Although several examples of TOC for patients with VTE exist, this project (ATHN 4: Transition of Care for Patients with VTE) is the first to create a uniform TOC model in the U.S that includes both pediatric and adult patients. The aim of this study was to improve the transition of care of adult and pediatric patients discharged on an anticoagulant after a first episode of VTE and evaluate patient/parent understanding and adherence to anticoagulation therapy-related instructions at seven and 30 days after hospital discharge. Methods Pediatric and adult hospitalized patients with a first episode of VTE requiring anticoagulation therapy were eligible to participate in ATHN 4, a multi-center quality improvement (QI) project conducted by the American Thrombosis and Hemostasis Network (ATHN). The project has two phases: a pre-intervention (PI) phase with no change in standard TOC practice, and a QI intervention phase consisting of enhanced education with standardized Comprehensive Discharge Instruction Modules (CDIM) for each anticoagulant. Demographics, disease, treatment characteristics, and outcomes were collected. Knowledge and feedback questionnaires were administered at 30 days post-discharge. Adult and pediatric data from the PI phase are presented. Results Complete data were submitted for 188 (91%) patients who were enrolled in the PI phase between May 2016 and March 2017 (Table 3). Results show that 73 (39%) were under 18 years of age, 90 (48%) were female, and 156 (83%) were non-Hispanic. A significant difference (p

Description: Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized disease after allogeneic hematopoietic stem cell transplantation (HCT) and is one of the most common post-transplant malignancies. In most cases, PTLD is associated with Epstein-Barr Virus (EBV) infection. The management of PTLD remains a challenge, with no approved treatments for patients. Clinical practice treatment guidelines recommend rituximab as first-line therapy for PTLD post-allogeneic HCT; however, treatment options for PTLD patients who fail rituximab are not clearly defined. We conducted a systematic literature review of the published literature to better understand treatment patterns for patients with PTLD who fail rituximab post-allogeneic HCT in a real-world setting. Methods: The systematic literature review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with the scope defined in terms of Population, Intervention Comparators, Outcomes, and Study design (PICOS) criteria. Using extensive search terms for the indication and study designs, studies were identified using key biomedical literature databases: EMBASE, MEDLINE, and Cochrane. The literature search was conducted on July 19, 2018 and included studies published between database inception in January 1, 1959 and July 19, 2018. Relevant congress abstracts published between January 2015 and June 2018 were also identified. The PICOS-based inclusion and exclusion criteria were used to review identified citations. No treatment limitations were imposed to ensure inclusion of all relevant evidence; the study designs were limited to prospective and retrospective observational studies. Case reports were included regardless of sample size. Two independent reviewers screened all citations and full-text articles; any discrepancies were resolved by a third independent reviewer. Data from included studies were extracted into a pre-defined template, and results were summarized using the PRISMA flow diagram. Results: A total of 69 studies were identified that described patients with PTLD post-allogeneic HCT. The majority (61 studies) were retrospective chart reviews, of which 54 studies were single-center studies. Forty-eight studies reported data on treatment of patients with PTLD. Among these, 5 studies included data prior to 2000, 33 studies included data from 2000-2010, and 26 studies included data from 2010-2016. The sample size for PTLD patients was between 1 and 144 patients, with only one study of 〉 100 patients. First-line therapy in PTLD included rituximab (41 studies), various chemotherapy regimens (15 studies), and lymphocyte infusion (10 studies). Nine studies reported treatment for patients who failed first-line rituximab (13-67% of PTLD patients); the number of patients with second-line treatments ranged from 2-10 across studies. Second-line treatments varied greatly across studies and included cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP, n=1); rituximab plus CHOP (R-CHOP, n=1-2); cyclophosphamide, etoposide/cytarabine (VP16/ARA-C, n=1); rituximab plus cyclophosphamide (n=1); rituximab plus high-dose cytarabine (n=1); chemotherapy unspecified (n=2-4), and lymphocyte infusion (n=3-5). Only 2 studies reported treatment outcomes in rituximab-refractory patients. One study (N=62, second-line n=10, median age 49 years) reported no complete or partial remission in the chemotherapy group; 60% had complete remission in the lymphocyte infusion group. The second study (N=12, second-line n=3, mean age 5 years) reported complete remission in 1 patient with lymphocyte infusion as second-line treatment. Conclusions: This systematic literature review demonstrates that data on treatment patterns for PTLD patients who failed rituximab post-allogeneic HCT are limited (9 studies with a sample size ≤ 10). Published data suggest that the percentage of patients who fail rituximab vary greatly (13-67%), there is no consistent standard of care for PTLD patients who fail rituximab, and outcomes are poor. There continues to be a significant unmet need among PTLD patients who fail rituximab, and further studies are needed to better understand rituximab response rates in the real-world setting. Disclosures Xu: Atara Biotherapeutics, Inc: Employment, Equity Ownership. Watson:Atara Biotherapeutics, Inc: Employment, Equity Ownership. Forsythe:Novartis: Consultancy. Barlev:Atara Biotherapeutics, Inc: Employment, Equity Ownership.