ALBERT

Description: Venous thromboembolism (VTE) is a known complication in children with leukemia, with prevalence in acute lymphoblastic leukemia (ALL) reported as high as 37% (Mitchell, et al, Cancer, 2003). Indwelling catheters, hyperviscosity, mediastinal masses, and medications such as asparaginase, can all contribute to increased VTE risk. In addition to national interest in preventing VTE in hospitalized children, decreasing risk of VTE in children with cancer is of great importance to pediatric hematologist/oncologists. The International Society of Hemostasis and Thrombosis released a guidance statement (Tullius, et al, JTH, 2017) that suggested considering thromboprophylaxis on a case-by-case basis for children with cancer and multiple VTE risk factors, and suggested discontinuing anticoagulant prophylaxis when predisposing conditions resolve. Children with leukemia certainly may have multiple risk factors and therefore deserve consideration for prophylaxis. The Children's Oncology Group is currently conducting a clinical trial studying thromboprophylaxis during induction for ALL. Given the importance of reducing VTE and the interest in thromboprophylaxis, we sought to assess practitioners' practices regarding thromboprophylaxis in children with leukemia. We performed a cross sectional, anonymous survey of pediatric members of VENUS (the VTE Network of the Hemostasis and Thrombosis Research Society) and ASH (the American Society of Hematology) using Qualtrics, a secure online survey tool. Responses were excluded if physicians answered no to either of 2 screening questions (related to clinical practice and board certification/eligibility), or if no questions were answered after screening. A gift card incentive was offered anonymously. Institutional IRBs approved this study. 870 surveys were distributed, with a response rate of 17.7%; after exclusions, a total of 142 surveys were included. Demographics were well balanced regarding size of program and years in practice. When asked about which anticoagulant agents may be used for thromboprophylaxis (n=36), 92% of those responding reported using enoxaparin (Table 1). In addition, 36% use Apixaban and 14% use Rivaroxaban. When asked if they ever provide primary VTE prophylaxis to children with leukemia (n=127), 71% said no, while 29% answered yes (Table 1). When asked in what scenarios primary prophylaxis was used, the most common answer was in leukemia patients with a known inherited thrombophilia (57%). Also common were children with mediastinal masses with vessel compression, and children enrolled on the COG prophylaxis study. Some additional scenarios offered were AYA patients, and those with additional risk factors, such as obesity and immobility. When asked about duration of primary prophylaxis (n=36), the most common times for discontinuing therapy were resolution of mediastinal mass and/or vessel compression (58%), end of all asparaginase therapy (50%), and until the central line is removed (42%). A smaller number of physicians (22%) would consider continuing anticoagulant prophylaxis until the end of all cancer chemotherapy. When questioned about secondary prophylaxis following VTE (n=127), 8% of respondents never provide post-VTE prophylaxis, 11% always give post-VTE prophylaxis, and 81% used post-VTE prophylaxis in certain cases (Table 1.) The most common stopping point for secondary prophylaxis (n=116) was after central line removal (55%), followed by completion of all asparaginase therapy (41%). Our study is limited by a low response rate. Due to technical issues, we had missing data for many questions and could not obtain free-text answers for some of the prophylaxis questions, limiting full data acquisition. Despite these issues, our results provide some insights into current practices of pediatric hematologist/oncologists. This study shows that many physicians are not utilizing primary anticoagulant prophylaxis in their pediatric leukemia patients, despite the high-risk nature of these patients, possibly trying to balance bleeding risk due to thrombocytopenia. Duration of anticoagulant therapy varies, and it is likely that there are no clear definitions regarding resolution of predisposing factors. Given their unique set of risk factors, and the potential morbidity associated with VTE, further study of VTE prophylaxis is essential for development of pediatric leukemia-specific guidelines. Disclosures Cooley: off-label: Other: drug use. Acharya:Bayer Pharmaceuticals, LLC: Research Funding; Novonordisk: Membership on an entity's Board of Directors or advisory committees; BioProducts Laboratory: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: We surveyed physicians on which anticoagulants they use in their pediatric leukemia patients and the majority of drugs offered as answer choices are technically off-label.

Description: Introduction: Venous thromboembolism (VTE) is a known complication of pediatric leukemia with reported incidence ranging widely from 1.5-40%. It is associated with significant morbidity including loss of venous access, post thrombotic syndrome, and thrombosis recurrence or embolization. Increased risk of VTE in these patients is often multifactorial. There are currently no standard guidelines for VTE prophylaxis in pediatric leukemia patients, and it is unclear which patients are at highest risk. Identifying potential markers for patients at risk for VTE could be helpful for guiding prophylaxis practices and ultimately decreasing rates of VTE in these children. Thrombolytic agents are commonly used to treat catheter obstruction by breaking down fibrin that forms within the catheter. Therefore, we hypothesize that patients requiring more tissue plasminogen activator (TPA) for treatment of catheter obstruction may be at higher risk of developing fulminant thromboses. Therefore, the primary objectiveof this study is to determine the association between central line clearance with TPA and development of symptomatic VTE (sVTE) in pediatric leukemia patients. Methods: This is a multi-center,retrospective cohort study of patients under 21 years old with a central line (CVC), including peripherally inserted central catheters (PICC), who began treatment at Weill Cornell Medicine (WCM) or Memorial Sloan Kettering Cancer Center (MSKCC) from January 2012-December 2015 for newly diagnosed or relapsed leukemia. Patients were excluded if they had a prior VTE, or an incidental VTE was identified. Transplant and CAR-T -cell patients were excluded, as were those who transferred into the institution over 30 days from start of treatment. Data collected included demographics, disease-specific information (including type of leukemia, treatment regimen, and CVC details), dates of TPA administration, and details of sVTE. Data analysis was performed with Fisher's exact test andWilcoxon rank-sum test. Results: A total of 96 patients with leukemia were included. The median age was 6.5 years (Q1, Q3: 3.15-15.05 years), and 55% (n=53) were male. 78% (n=75) were new diagnoses. Acute lymphoblastic leukemia (ALL; 72%, n=69) was most common, followed by acute myelogenous leukemia (AML; 25%, n=24), and mixed lineage leukemias (3%, n=3). There were no significant differences between gender, age, type of leukemia, or TPA use between the two centers. The overall incidence of sVTE over the 4-year period in this cohort was 6% (6/96). At the time of thrombosis, five of the six patients had a PICC line in place and one patient had a mediport (Table 1). Four sVTE patients were diagnosed with ALL. Four of the thromboses were line-associated, one was a sinus venous thrombosis, and one was an inferior vena cava thrombus. Five of the six sVTEs were diagnosed at WCM. There was no association found between use of TPA for line de-occlusion and development of sVTE (OR 0.55, CI 0.07-6.57, p=0.61) or between number of TPA doses needed and development of sVTE (p=0.830). The patients who developed sVTE were significantly older than those who did not develop sVTE (Figure 1, p=0.048). There was no significant difference between gender and development of sVTE. A significant difference (p

Description: Introduction: Venous thromboembolism (VTE) is a known complication in children with inflammatory bowel disease (IBD) and can be associated with significant morbidity and mortality. Central lines, inflammation, hospital stays, and protein losses are among risk factors that contribute to this elevated risk. While it is known that children with IBD have an increased VTE risk, there are no standard guidelines for prevention of this unwanted complication. Decreasing the rate of hospital-acquired VTE in all hospitalized children is of national interest, especially in this unique patient population. However, there are no clear data regarding the true impact of VTE on the pediatric IBD population to guide practitioners in prevention and management. Given that IBD patients are known to have an increased risk of VTE, we sought to assess the burden associated with VTE development in hospitalized IBD patients. Methods: The Pediatric Health Information System database (PHIS), a database that includes both clinical and resource utilization data for over 45 children's hospitals, was utilized to gather inpatient data from 2009-2017. ICD9 (IBD - 555.xx, 556.xx and VTE - 325, 415.1x, 451.x, 452, 453.0-.9, and 572.1) and ICD10 (IBD - K50.0-.919, K51.0-.919 and VTE - I80.0-.9, I81, I82.0-.91, I63.6, I67.6) diagnostic codes for IBD and VTE were applied to identify hospitalized IBD patients who experienced a VTE event. First admissions during the time period were used to avoid capturing the same VTE event more than once. Demographic data, as well as data regarding hospitalization, were reviewed. The Institutional Review Board of Weill Cornell Medicine approved this study. Results: 19,004 first admissions were identified for patients with IBD. Of those, 475 had documented episodes of VTE, demonstrating an incidence of having a VTE at first admission of 2.5%. There were no significant differences in gender, age at first admission, ethnicity, or geographic region between hospitalized IBD patients who did and did not have a VTE event. Hospitalized IBD patients with VTE had a significantly greater median length of stay, significantly higher likelihood of ICU stay, and a significantly higher discharge mortality rate (Table 1). Children with IBD and VTE had an odds ratio of 8.63 [95% CI 7.02-10.62, p=

Description: According to the CDC’s 2006 National Hemophilia Data Set, females comprise 0.7% of the moderately and severely affected hemophilia A (HA) population and 1.3% of those similarly affected with hemophilia B (HB) in the US. Since no comprehensive data have been published on this patient group since 1978, we conducted this study to collect and analyze epidemiological, clinical, psychosocial, and molecular genetic data on females with severe (s) or moderate (mod) HA or HB. Potential subjects with factor VIII or IX activity levels

Description: The development of venous thromboembolism (VTE) is a known complication occurring in children with leukemia with a reported incidence ranging from 1 to 37% (Ghanem, et al, Pediatric Blood & Cancer, 2017) and can be a source of significant morbidity. Known risk factors for VTE include central venous catheter (CVC) use, thrombophilia, and certain medications, such as asparaginase (Caruso, et al, Blood, 2006.) Despite the known occurrence of VTE in this population, there are no leukemia-specific guidelines for VTE management. Anticoagulant use in children with frequent periods of thrombocytopenia and coagulopathy is not risk free. Various elements of management lack standardization and consensus among practitioners. Given that the majority of pediatric leukemia patients are treated according to standardized protocols, it may be beneficial to standardize anticoagulation care guidelines. Therefore, the primary objective of this study was to assess current practices regarding the management of VTE in the pediatric leukemia population. We performed a cross sectional, anonymous, electronic survey of members of the American Society of Hematology (ASH) who self-identified as focusing in pediatric hematology or pediatric hematology/oncology, and the pediatric subcommittee of VENUS (VTE Network of the Hemostasis and Thrombosis Research Society) using Qualtrics, a secure online survey tool. Survey items included questions on demographics and clinical practice. Respondents were excluded if they were not board certified/eligible, if they did not participate in patient care, or if they did not answer survey research questions. A $25 gift card incentive was offered anonymously. This study was approved by both the Weill Cornell Medicine and Northwell Health IRBs. Of 870 surveys distributed, 154 were submitted, giving a 17.7% response rate. Twelve surveys were excluded, leaving 142 surveys for final analysis. There was even distribution of years in practice and size of clinical program among respondents (Figure 1A). Most respondents identified as being in hematology or combined practice. 50% of responding physicians (n=136) reported treating CVC-associated VTE for 3 months. 92% of respondents (n=138) report repeating imaging of the VTE with 58% (n=124) repeating at 6 weeks, and 31% at 3 months. 40% of respondents (n=131) treat cerebral venous sinus thrombosis (CVST) for 3 months, followed by 24% treating for 6 months. 95% of respondents (n=131) repeat imaging for CVST and of these individuals, 40% repeat imaging at 6 weeks followed by 50% at 3 months. The most frequently utilized anticoagulant class was heparins (n=140); respondents also reported using the direct Xa inhibitors Rivaroxaban (21%) and Apixaban (14%). Within the group utilizing direct Xa inhibitors, those in practice the longest (≥16 years) had the highest percentage of use (Figure 1B.) When asked at what platelet counts they hold therapeutic anticoagulation (n=140), 39% of respondents chose 50 x 109/L, 33% chose 30 x 109/L, and 16% chose 20 x 109/L. One person chose 100, x 109/L, 11% said they did not hold anticoagulation for thrombocytopenia, and 2 respondents gave platelet transfusions rather than hold anticoagulation (one at a cutoff below 30 x 109/L and one below 50 x 109/L). While no significant associations were seen, the highest percentage among individual groups using a platelet cutoff of less than 50 x 109/L were among those in practice longest, and those in the largest centers (Figure 1C). The results of this survey revealed variation in practice among practitioners regarding VTE management and prevention. Despite the lack of data in this population, a number of physicians are using direct Xa inhibitors in children with leukemia for anticoagulation. Imaging is being done earlier than treatment is being discontinued, potentially implying it is being used to monitor for progression, rather than help guide duration of therapy. Our survey had some limitations, including the low response rate and missing data for questions, which may be due to electronic data collection errors or respondent choice. Recent ASH guidelines endorsed by the Children's Oncology Group propose limited general guidelines and do not consider a cancer patient's unique VTE risk profile. Given the variation seen, multi-center, prospective clinical trials are urgently needed for developing consensus guidelines for the management of VTE in children with leukemia. Figure 1 Disclosures Cooley: off-label: Other: drug use. Acharya:Takeda: Membership on an entity's Board of Directors or advisory committees; BioProducts Laboratory: Membership on an entity's Board of Directors or advisory committees; Bayer Pharmaceuticals, LLC: Research Funding; Novonordisk: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Anticoagulations that will be discussed are off-label in children.