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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with thrombotic complications in adults, but the incidence of COVID-19-related thrombosis in children and adolescents is unclear. Most children with acute COVID-19 have mild disease, but coagulopathy has been associated with multisystem inflammatory syndrome in children (MIS-C), a postinfectious complication. We conducted a multicenter retrospective cohort study to determine the incidence of thrombosis in children hospitalized with COVID-19 or MIS-C and evaluate associated risk factors. We classified patients into 1 of 3 groups for analysis: COVID-19, MIS-C, or asymptomatic SARS-CoV-2. Among a total of 853 admissions (COVID-19, n = 426; MIS-C, n = 138; and asymptomatic SARS-CoV-2, n = 289) in 814 patients, there were 20 patients with thrombotic events (TEs; including 1 stroke). Patients with MIS-C had the highest incidence (9 [6.5%] of 138) vs COVID-19 (9 [2.1%] of 426) or asymptomatic SARS-CoV-2 (2 [0.7%] of 289). In patients with COVID-19 or MIS-C, a majority of TEs (89%) occurred in patients age ≥12 years. Patients age ≥12 years with MIS-C had the highest rate of thrombosis at 19% (9 of 48). Notably, 71% of TEs that were not present on admission occurred despite thromboprophylaxis. Multivariable analysis identified the following as significantly associated with thrombosis: age ≥12 years, cancer, presence of a central venous catheter, and MIS-C. In patients with COVID-19 or MIS-C, hospital mortality was 2.3% (13 of 564), but it was 28% (5 of 18) in patients with TEs. Our findings may help inform pediatric thromboprophylaxis strategies.

Background: Sickle Cell Disease (SCD) is associated with a chronic prothrombotic state that increases the risk of venous thromboembolism (VTE). The rate of VTE in hospitalized children with SCD is nearly 2%, substantively higher than the 0.2-0.6% rate seen in the general pediatric population. 1-3 The frequency and risk factors associated with the development of recurrent VTE in this population are vastly unknown. This knowledge gap hinders the development of disease-specific guidelines for the management and secondary prevention of VTE in pediatric SCD. Aim: To investigate the frequency of recurrent VTE in children birth to 21 years of age (inclusive) with SCD and history of prior VTE. Methods: We analyzed patient-level data from the TriNetX Research Network Database, a global federated network of electronic medical record (EMR) data from 42 health care organizations. Children ≤21 years of age with a diagnosis of SCD and history of VTE between January 1 2008 to March 31 2021 were included in the analysis. Index VTE was defined as the first diagnosis of VTE in the patient's EMR. Recurrent VTE was defined as an acute VTE diagnosis that occurred 90 days after the index VTE discharge date in a different anatomic location from the index VTE. Patient demographic and clinical characteristics were summarized using counts and percentages. Missing values were not imputed. Overall, one year and five-year recurrence VTE are reported with the corresponding 95% confidence intervals (CI). Results: A total of 119 children with SCD and VTE were included. Table 1 shows the patients baseline characteristics. Mean age at the time of index VTE diagnosis was 16.7 years (standard deviation 5.5 years). The majority of patients were Black (87%) and female (61%). The most frequent index VTE diagnosis was pulmonary embolism (42%) followed by lower (23%) and upper (22%) extremity VTE. Of the 119 patients,10 (8.4%, 95%CI=4-15%) developed recurrent VTE within 1-year and 25 (21.0%, 95%CI=14-29%) developed recurrent VTE within 5-years from index VTE. Compared to patients without recurrent VTE, patients with recurrent VTE were more frequently female (50% vs. 68%, respectively), and slightly older (mean age 16.6 years vs. 17.2 years, respectively). The most frequent anatomic location for VTE recurrence was the upper extremity (32%) Conclusions: This retrospective database analysis identified, for the first time, high rates of recurrent VTE of 8.4% and 21% at 1- and 5-years post-VTE in children with SCD. These rates stand in contrast with the 3% VTE recurrence at 1-year reported for the general pediatric VTE population. 4 Further analyses of the database are ongoing to identify risk factors for recurrent VTE in this population. These initial findings highlight the need for cooperative multicenter prospective studies to reliably establish rates of- and prognostic factors associated with recurrent VTE in children with SCD, in order to generate evidence for disease-specific treatment guidelines, and to inform future prognostically-stratified interventional trials designed to optimize VTE outcomes in pediatric SCD. 1.Kumar R, Stanek J, Creary S, et al. Prevalence and risk factors for venous thromboembolism in children with sickle cell disease: an administrative database study. Blood Adv 2018;2:285-291. 2. Raffini L, Huang YS, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001to 2007. Pediatrics 2009;124:1001-8. 3. Setty BA, O'Brien SH, Kerlin BA. Pediatric venous thromboembolism in the United States: a tertiary care complication of chronic diseases. Pediatr Blood Cancer 2012;59:258-64. 4. Goldenberg NA, Schulman S, Kittelson JM, et al, Kids-DOTT Trial Investigators and the ATLAS Group. A Six-week versus Three-month Duration of Anticoagulation for Acute Provoked Venous Thromboembolism in Patients < 21 Years Old: Results of the Multinational Kids-DOTT Randomized Controlled Trial. [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). Figure 1 Figure 1. Disclosures Hankins: Global Blood Therapeutics: Consultancy; Vindico Medical Education: Consultancy; UpToDate: Consultancy; Bluebird Bio: Consultancy. Goldenberg: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Daiici: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Anthos: Membership on an entity's Board of Directors or advisory committees.

Background: Cirmtuzumab (Cirm) is a humanized monoclonal antibody that inhibits the tumor promoting activity of ROR1 and has demonstrated additive/synergistic activity with many anticancer agents, including ibrutinib (Ibr). Methods: Patients (Pts) with relapsed or refractory (RR) MCL or treatment-naïve (TN) or RR CLL were enrolled. In Part 1 (Dose Escalation), doses of Cirm IV q2wks x5 then q4wks of 2-16 mg/kg and 300 or 600 mg were examined. Safety of Cirm alone was assessed during the first 28 days, then Ibr was started at approved doses for each indication. Cirm 600 mg IV q2wks x3 then q4wks in combination with Ibr starting day 0 was chosen as the recommended dosing regimen for use in Part 2 (Expansion) and Part 3 (CLL only, Cirm/Ibr vs. Ibr). MCL Part 1 is closed, and Part 2 is open for enrollment. CLL Parts 1, 2 & 3 are closed for enrollment. Results: As of 18Jun2021 data cutoff, 28, 34 and 28 pts were treated in MCL Parts 1 & 2, CLL Parts 1 & 2, and CLL Part 3 (Cirm/Ibr (n=18) or Ibr (n=10)). In Parts 1 & 2 MCL, the median number (#) of prior systemic regimens was 1.5 (1-4) including pts relapsing after Ibr (n=4), auto-SCT (n=6), auto-SCT/allo-SCT (n=1), or auto-SCT/CAR-T (n=1). Ki-67 ≥30% and extra-nodal disease was present in 54% and 68% of pts, respectively. The median # of prior systemic regimens for CLL Parts 1 & 2 and CLL Part 3 (RR), was 2 (1-15) including auto-SCT (n=1), and 2 (1-6). Pts entered with Rai staging ≥ Grade 2 in 71% and 64%. Safety (MCL and CLL): Most frequent treatment emergent (TEAEs) (≥30%) for both MCL and CLL pts treated with Cirm/Ibr (N=80), (all grades; regardless of causality) included contusion & fatigue (both 40.0%), and diarrhea (37.5%). Most frequent (≥5%) Grade ≥3 TEAEs, regardless of causality included hypertension (10.0%), fatigue, neutropenia, pneumonia, and atrial fibrillation (all 6.3%), leukocytosis and anemia (both 5.0%). Grade ≥3 TEAEs of myelosuppression, regardless of causality, include anemia (5.0%), thrombocytopenia (1.3%), and neutropenia (6.3%). Most TEAEs in MCL or CLL pts were considered related by Investigator to Ibr alone 64% or 84% vs. Cirm alone 14.3% or 16%. Efficacy (MCL): The best response of 20 evaluable pts in Parts 1 & 2 included CR 35%, PR 45%, SD 10%, and 10% PD. At a median follow-up of 14.9 mos., the objective response rate (ORR), clinical benefit rate (CBR) and median duration of response (DOR) for overall, ≥30% Ki-67, and >1 prior systemic regimen subgroups, were 80%, 90% and (not reached) NR (95% CI: 11.9, NR), 81.8%, 81.8% and 13.8 (95% CI: 8.7, NR), and 90%, 100% and NR (95% CI: 8.7, NR). Responses occurred in all evaluable pts who received prior SCT+/- CAR-T (4CR, 2PR) or prior Ibr (2CR, 2PR). The median PFS (mPFS) for overall, pts achieving CR, and >1 prior systemic regimen subgroups were all NR with varying 95% CI: (16.5, NR), (0.03, NR), and (0.03, NR). Efficacy (CLL): The best response of 34 evaluable pts in Parts 1 & 2 included 94.1% ORR, 11.8% CR, 82.3% PR/PR-L, and 5.9% SD for a CBR of 100%. In Part 3, evaluable Cirm/Ibr TN (n=8) or RR (n=7) and Ibr TN (n=4) or RR (n=3) arms achieved 100% or 85.7% and 100% or 100% ORR, 12.5% or 0% and 0% or 0% CR, 87.5% or 85.7% and 100% or 100% PR/PR-L, 0% or 14.3% and 0% or 0% SD. No pts had PD as best response. All pts had a CBR of 100%. For Parts 1 & 2, at a median follow-up of 24.8 mos., the DOR for overall and >1 prior systemic regimen subgroups, was NR (8.3, 35.9) and NR (12.0, 29.6). In Part 3, at a median follow-up of 14.7 mos., the DOR for TN or RR Cirm/Ibr and Ibr arms is NR (7.7, 18.6) or NR (9.2, 14.8) and NR (11.2, 18.5) or NR (8.3, 14.2). The mPFS (Parts 1 & 2) for overall, pts achieving CR, and >1 prior systemic regimen subgroups were NR (9.1, 35.8), NR (95% CI: 22.5, NR), and NR (9.1, 35.2). In Part 3, mPFS for TN or RR Cirm/Ibr and Ibr arms is all NR. Conclusions: Cirm/Ibr is well-tolerated. ORR, CR, DOR, and mPFS were similar across all subgroups of MCL and CLL pts regardless of number of prior systemic regimens or poor risk factors. Striking responses were observed in patients with MCL as evidenced by a mPFS that was NR (95% CI: 16.5, NR), CR of 35%, and a DOR of NR (95% CI: 11.9, NR) within the study period. These data compare very favorably to the mPFS of 12.8 mos, CR of 20%, and a DOR of 18.6 mos., reported for Ibr alone (Rule 2017). For CLL pts treated with Cirm/Ibr, results continue to be encouraging as they mature. The study is ongoing, with MCL enrollment expanded to include Cirm + Ibr in pts who have had an inadequate response to an Ibr regimen, or who are refractory to approved BTKi agents. Figure 1 Figure 1. Disclosures Lee: Oncternal: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Seagen: Research Funding; BMS: Honoraria, Research Funding; Aptitude Health: Honoraria; Guidepoint: Honoraria; Century Therapeutics: Consultancy; Pharmacyclics: Research Funding; Janssen: Honoraria. Choi: Abbvie: Other: Institution: Research Grant/Funding; Pharmacyclics: Other: Institution: Research Grant/Funding; Oncternal: Other: Institution: Research Grant/Funding; Velosbio: Other: Institution: Research Grant/Funding; Merck: Other: Institution: Research Grant/Funding; Geron: Other: Institution: Research Grant/Funding. Siddiqi: Celgene: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kite Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Speakers Bureau; Oncternal: Research Funding; TG Therapeutics: Research Funding. Wierda: Acerta Pharma Inc.: Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; AstraZeneca: Research Funding; Cyclacel: Research Funding; Karyopharm: Research Funding; Xencor: Research Funding; Oncternal Therapeutics, Inc.: Research Funding; KITE Pharma: Research Funding; Miragen: Research Funding; Janssen: Research Funding; Gilead Sciences: Research Funding; Juno Therapeutics: Research Funding; Genentech: Research Funding; GSK/Novartis: Research Funding; Sunesis: Research Funding; Loxo Oncology, Inc.: Research Funding; Genzyme Corporation: Consultancy; AbbVie: Research Funding. Tuscano: BMS: Research Funding; Seattle Genetics: Research Funding; Takeda: Research Funding; Acrotech: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding; Abbvie: Research Funding. Leslie: Abbvie: Consultancy, Honoraria; PCYC/Janssen: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy, Honoraria, Speakers Bureau; Karyopharm Therapeutics: Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; BeiGene: Consultancy, Honoraria, Speakers Bureau; ADC Therapeutics: Consultancy; Celgene/BMS: Consultancy, Honoraria, Speakers Bureau; TG Therapeutics: Consultancy, Honoraria, Speakers Bureau; Kite, a Gilead Company: Consultancy, Honoraria, Speakers Bureau; Epizyme: Consultancy, Honoraria, Speakers Bureau; Seagen: Consultancy, Honoraria, Speakers Bureau; Merck: Consultancy. Breitmeyer: Oncternal Therapeutics: Current Employment, Membership on an entity's Board of Directors or advisory committees. Yazji: Oncternal Therapeutics: Current Employment. Wang: Oncternal Therapeutics: Current Employment. Wang: OMI: Honoraria; Moffit Cancer Center: Honoraria; Chinese Medical Association: Honoraria; Newbridge Pharmaceuticals: Honoraria; DTRM Biopharma (Cayman) Limited: Consultancy; InnoCare: Consultancy, Research Funding; Scripps: Honoraria; Mumbai Hematology Group: Honoraria; VelosBio: Consultancy, Research Funding; BioInvent: Research Funding; Hebei Cancer Prevention Federation: Honoraria; Epizyme: Consultancy, Honoraria; Anticancer Association: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Lilly: Research Funding; Physicians Education Resources (PER): Honoraria; Dava Oncology: Honoraria; Clinical Care Options: Honoraria; Molecular Templates: Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Research Funding; Acerta Pharma: Consultancy, Honoraria, Research Funding; Imedex: Honoraria; Juno: Consultancy, Research Funding; Celgene: Research Funding; Genentech: Consultancy; Loxo Oncology: Consultancy, Research Funding; Kite Pharma: Consultancy, Honoraria, Research Funding; Miltenyi Biomedicine GmbH: Consultancy, Honoraria; The First Afflicted Hospital of Zhejiang University: Honoraria; Bayer Healthcare: Consultancy; BGICS: Honoraria; CAHON: Honoraria; Oncternal: Consultancy, Research Funding; CStone: Consultancy. Jamieson: Forty Seven Inc.: Patents & Royalties. Kipps: Genentech-Roche: Consultancy; Gilead Sciences: Consultancy, Honoraria, Other, Speakers Bureau; Janssen: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Roche: Honoraria, Other; MD Anderson Cancer Center: Research Funding; Velos: Research Funding; CRIM: Research Funding; Indy Hematology Review: Other; TG Therapeutics: Other; Verstem: Other, Speakers Bureau; University of California, San Diego: Current Employment; Pharmacyclics/AbbVie: Honoraria, Research Funding; Breast Cancer Research Foundation: Research Funding; SCOR - The Leukemia and Lymphoma Society: Research Funding; National Cancer Institute/NIH: Honoraria, Research Funding; Genentech/Roche: Honoraria; European Research Initiative on CLL (ERIC): Honoraria; Genetech: Honoraria, Other; Celgene: Consultancy, Honoraria, Other, Research Funding; Bionest Partner: Other; DAVA Pharmaceuticals: Speakers Bureau; DAVAOncology: Consultancy, Honoraria, Other; AbbVie: Consultancy, Honoraria, Other, Speakers Bureau; Oncternal Therapeutics, Inc.: Current holder of stock options in a privately-held company, Other: Stock or other ownership, Patents & Royalties: Cirmtuzumab was developed by Thomas J. Kipps in the Thomas J. Kipps laboratory and licensed by the University of California to Oncternal Therapeutics, Inc., which provided stock options and research funding to the Thomas J. Kipps laboratory., Research Funding; Moores Cancer Center: Current Employment; MedImmune Inc: Research Funding; GlaxoSmithKline: Research Funding; Gilead Sciences, Inc.: Honoraria, Research Funding; Genentech, Inc.: Honoraria, Research Funding, Speakers Bureau; Pharmacyclics LLC, an Abbvie Company: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Celgene Corporation: Consultancy, Honoraria, Research Funding; Abbott Laboratories: Consultancy, Research Funding.

Background: Sickle Cell Disease (SCD) has established socioeconomic disadvantage resulting in increased healthcare utilization. Among the pediatric population, the implementation of preventative care measures within the medical home model has improved outcomes and lifespan. Area deprivation index (ADI) is an established method for quantifying socioeconomic disadvantage and has been shown to be associated with increased hospital readmission in adults and pediatric patients with chronic disease (Singh Am J Public Health. 2003, Kind et al. Ann Intern Med. 2014). ADI has been applied to adults with SCD and vaso-occlusive events (VOE) but has not been investigated in pediatric patients. We explored the role of ADI in pediatric patients with SCD admitted with VOE in order to characterize disadvantage and the hospitalization characteristics that impact hospital readmission. Methods: This retrospective review included 675 consecutive emergency department and hospital admissions for VOE among 101 pediatric (≤ 21 years old) patients with SCD from 2016-2019 at a single urban, US-based medical center. One hospital admission for each patient was selected at random. Information extracted included demographics, SCD characteristics, admission complications, entry and discharge pain scores, length of stay, and management characteristics. Variables were compiled in a descriptive table and compared in logistic regression models against a primary outcome of 7-day readmission. The 2018 ADI dataset was used to assign an ADI value based on the census block corresponding to the patient-reported zip-code for the specific hospital admission (https://www.neighborhoodatlas.medicine.wisc.edu). ADI values were grouped by most and least deprived with higher scores (6-10) indicating more deprivation. Summary statistics described patient and disease characteristics in these groups. Results: Within our cohort, the state and national ADI was calculated for 101 patients with a median age of 14 years (50.4% female; 98.0% Black) (Table 1). Most patients were publicly insured (80.2%). The Hb SS genotype was the most common genotype, followed by Hb SC (22.7%). Median ADI rank was 9 with 11 patients (10.9%) classified as less disadvantaged (ADI 1-5) and 90 patients (89.1%) as more disadvantaged (ADI 6-10). We found the less disadvantaged group had even numbers of public and private insurance use while 83.3% of the patients in the more disadvantaged group had public insurance. The Hb SS genotype was more common in the less disadvantaged (90.9%) than the more disadvantaged (74.4%), where Hb SC was overrepresented (24.4%). Greatest prevalence of mental health disease and hospital complications, including acute chest syndrome, avascular necrosis, and pneumonia, were observed in the more disadvantaged. Additionally, the more disadvantaged group included a greater number of patients with scheduled follow-up (61.1%) and shorter time to follow-up (median: 31 days). For treatment and management, both groups had high numbers of prescriptions for hydroxyurea (HU) and opiates, with slightly higher numbers in the less disadvantaged group (82% HU; 100% opioids) compared to the more disadvantaged (61% HU; 81% opioids). Length of hospital-stay and pain scores were similar across groups. The 7-day readmission rate was 9% for the less disadvantaged group and 14% for the more disadvantaged group. Conclusions: We applied a validated measure of socioeconomic disadvantage to a group of pediatric patients with SCD and VOE. Our cohort consists of more disadvantaged patients across ADI scales. Readmission rate was low for both groups and there was no relationship between greater ADI scores and hospital readmission. Within the more disadvantaged group, the higher prevalence of mental health illness as well as associated disease complications may have been countered by protective factors including established follow-up, shorter time to follow-up, and high number of prescriptions for hydroxyurea and opiates. Our results are consistent with the protective effect of ADI on recurrent acute chest syndrome in pediatric SCD patients (Alishlash et al. Pediatr. Blood Cancer. 2021) highlighting the importance of preventative care within the SCD medical home. Further research is warranted on identifying key protective factors that may reduce acute care utilization and social disparity in this population. Figure 1 Figure 1. Disclosures Novelli: Novartis Pharmaceuticals: Consultancy.

Background/Aims: Despite the increase in clinicians identifying venous thromboembolism (VTE), we lack robust research to support clinical care guidelines. Although most children are at low risk for VTE recurrence, some have higher risks due to persistent prothrombotic risk factors. However, pediatric-specific guidance and expert consensus to recommend long-term anticoagulation in children is lacking. Understanding provider practices is a vital first step to addressing current limitations in pediatric guidelines for secondary thromboprophylaxis among such high-risk children. Methods: We performed an international survey of pediatric thrombosis physicians to approximate the number of children with persistent prothrombotic risk factors and characterize the contemporary practice patterns for the use of secondary thromboprophylaxis. Potential participants were identified using the membership registries of three of the primary pediatric thrombosis networks: Duration of Therapy for Thrombosis in children investigators, Children's Hospital Acquired Thrombosis consortium and the VENUS pediatric thrombosis subgroup. Surveys were disseminated December 2020 through January 2021 using Qualtrics (Provo, UT). Results: The survey was distributed electronically to 124 potential participants with 80 respondents. After exclusions, 61 complete surveys were evaluable. The majority of responders were from the United States, practicing more than 10 years at freestanding, academic pediatric hospitals with dedicated pediatric thrombosis programs. Providers were more likely to prescribe secondary thromboprophylaxis to adolescents and teenage patients as compared to infants and children. Respondents reported they were most likely to initiate chronic secondary thromboprophylaxis (therapeutic or low dose) in children with a potent thrombophilia (homozygous prothrombin or factor V Leiden mutations, protein C/S levels Conclusion: Our results show variation in practice patterns but less so in areas where we have more definitive guidelines. These findings highlight the need for a multi-center prospective cohort study to determine the impact of various risk factors on recurrence rates. This will inform the design of ultimate interventional studies aimed at safely decreasing the risk of recurrent VTE in children who have persistent prothrombotic risk factors upon completion of a conventional course of anticoagulation for provoked VTE. Disclosures Lebensburger: Novartis: Consultancy; Bio Products Laboratory: Consultancy. Goldenberg: Novartis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Daiici: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Anthos: Membership on an entity's Board of Directors or advisory committees.

Introduction: Identification of patients seropositive for cytomegalovirus (CMV) prior to stem cell transplant (SCT) is a well-accepted practice across institutions designed to reduce a known cause of morbidity and mortality in this population, but the role of monitoring and preemptive approaches to CMV identification and treatment are controversial and not standardized in autologous transplantation. The preemptive approach necessitates the use of significant resources and requires persistent patient involvement. Patients undergoing autologous SCT are at a relatively low risk for CMV reactivation, especially those seronegative for CMV at the time of transplant. Here, we show that the necessity of routine monitoring of autologous transplant patients is of minimal clinical value. Methods: To determine the efficacy of the CMV monitoring protocol currently in place at our institution in detecting patients who would later develop CMV reactivation and disease following autologous SCT, we retrospectively analyzed the charts of 218 adult patients between 11/1/14 and 8/1/19 who underwent transplant at St. Louis University Hospital. No patients underwent CD34 selected stem cell infusions. The protocol stipulated the following: CMV IgG/IgM and CMV DNA PCR prior to preparative regimen followed by weekly CMV DNA PCR to day +30 . We correlated the predictive ability of positive results on any of these screening tests to identify whether patients would later develop quantifiable CMV DNA PCR positivity, clinical manifestations of CMV disease, and/or require pharmacologic treatment for CMV. Results: Quantifiable pre-BMT DNA PCR was positive in only 0.46% of patients, and 97.79% of patients were DNA PCR negative prior to transplant. CMV IgG was positive in 56.4% patients, and only 22.1% of patients in this group went on to develop a quantifiable post-transplant PCR. Of the remaining 43.6% of patients initially testing negative for CMV IgG, no patients went on to develop a quantifiably positive post-transplant PCR. Regardless of seropositivity, only 0.08% of the 1,191 PCRs performed during the study period were found to be quantifiable. Further, no patients in our cohort developed CMV disease or required CMV treatment during the monitoring period. This trend persisted despite stratification by age, diagnosis, transplant number, and preparative regimen. Conclusion: When clinically-significant CMV is defined by cases requiring treatment or the development of end-organ disease, no screening tests performed elicited clinical action. Laboratory-based CMV surveillance, based on our data, has minimal diagnostic implications and represents an overly-stringent practice in a set of patients already utilizing a substantial share of healthcare resources. We believe that pre-transplant screening for CMV IgM serology and CMV DNA PCR can be safely eliminated in the autologous SCT population at our institution while CMV IgG still plays a role in determining candidacy for CMV-negative blood products. We also propose the elimination of serial post-transplant monitoring with DNA PCR in patients without clinical signs, symptoms, or pathologic findings suggestive of CMV disease. We have changed the protocol to test for CMV PCR only if there are clinical scenarios that indicate a utility, such as prolonged fever post-transplant, unexplained cytopenias, or unexplained pneumonitis, colitis, or hepatitis. By extension, other centers should consider determining the necessity of CMV screening in their autologous transplant population given the potential resource conservation and reduction in healthcare expenditures. Disclosures Fesler: abbvie: Consultancy, Speakers Bureau; incyte: Consultancy, Speakers Bureau; sanofi: Speakers Bureau; morphosys: Speakers Bureau; epizyme: Consultancy; jazz: Consultancy; Skipta: Consultancy; Best Doctors: Consultancy; Aptitude Health: Consultancy; Care Dx: Consultancy; Opinionsite: Consultancy. Goldenberg: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Introduction: Cirmtuzumab (Cirm) is a high-affinity humanized monoclonal antibody designed to inhibit the tumor promoting activity of ROR1. In this study, we examined the safety and efficacy of Cirm in combination with ibrutinib (Ibr) in patients (pts) with MCL or CLL. ROR1 is an onco-embryonic tyrosine kinase-like receptor that is found at high levels on the cell surface of many hematologic and solid cancers. Activation of ROR1 by binding its ligands such as Wnt5a results in increased intracellular signaling, tumor growth and survival, enhanced cancer cell stemness and epithelial mesenchymal transition. Methods: Pts with relapsed or refractory (RR) MCL or treatment naïve (TN) or RR CLL were enrolled and treated in separate groups. In Part 1 Dose Escalation (DE), groups of MCL and CLL pts received Cirm IV q2wks x5 doses then q4wks at assigned doses of 2-16 mg/kg, and in CLL, additional fixed dose levels of 300 or 600 mg were evaluated. The safety and PK of single-agent Cirm was assessed during the first 28 days, and then Ibr was started at 560 mg/day PO for MCL or 420 mg/day PO for CLL. After reviewing the safety and PK data from Part 1, a recommended regimen of fixed dose Cirm 600 mg IV q2wks x3 then q4wks plus Ibr starting D0 was chosen for use in Parts 2 and 3. In Part 3, CLL pts (only) were randomized to either Cirm/Ibr vs. Ibr alone Results: As of April 30, 2020, 12 evaluable MCL pts were enrolled into Part 1 DE. Of these pts, 83% (10) had received ≥ 2 separate prior treatment regimens. In CLL, 34 pts (12 TN and 22 RR pts) enrolled into Part 1 DE (n= 18) or Part 2 Expansion (n= 16). At least 79% of CLL pts in Parts 1 and 2 were high risk as determined by unmutated IGHV, del17p, and/or del11q. Safety: For both MCL and CLL, the most common adverse events (AEs) considered at least possibly related to Cirm alone were grade 1/2 (e.g. fatigue, 6%) with no dose limiting toxicities or discontinuations. The combination of Cirm plus Ibr was well tolerated, with no new or accentuated AEs compared to the known safety profile of Ibr alone. Cirm may be lowering the rates of certain AEs normally seen with Ibr; for example, neutropenic events were 8 mos after stopping all therapy. At a median follow-up of 12.8 mos, 100% of CLL pts were free of disease progression and 82% remained on study. CLL cells collected after the first 28 days of treatment showed a decrease in stemness signature (Choi et al, Cell Stem Cell 2019), with similar reductions seen with single agent Cirm or Cirm + Ibr. Additional pts have been enrolled into Part 2 Expansion MCL and into Part 3 CLL. Early data from these arms are not yet available and will be reported later. Conclusions: Cirmtuzumab in combination with ibrutinib is a well-tolerated and active regimen for RR MCL and TN or RR CLL. The 58% CR/CMR rate for MCL compares favorably to published data with single agent Ibr of 27% (Rule, et al. Haematologica 2019) and it is encouraging that responses occurred in heavily pretreated pts, including those with high Ki-67 expression. In CLL, the high ORR and interim PFS are encouraging; the significance of these observations will be determined with longer follow-up. These data support the continued investigation of this regimen in ROR1-expressing hematologic and solid malignancies. This study is ongoing, and due to the high CR rate in MCL pts, the number of pts to be enrolled in the Part 2 Expansion will be increased to further characterize the safety and efficacy of this combination. Disclosures Lee: Bristol-Myers Squibb: Consultancy, Research Funding; Aptitude Health: Speakers Bureau; Celgene: Research Funding; Guidepoint Blogal: Consultancy; Oncternal Therapeutics: Research Funding; Seattle Genetics: Research Funding; Takeda: Research Funding. Choi:Pharmacyclics/Abbvie: Research Funding; Genentech: Consultancy. Siddiqi:Juno Therapeutics, Pharmacyclics LLC, an AbbVie Company, AstraZeneca, Celgene, Kite Pharma, and BeiGene: Consultancy; Pharmacyclics LLC, an AbbVie Company, Seattle Genetics, Janssen, and AstraZeneca: Speakers Bureau; BeiGene: Other: DMC member; AstraZeneca: Other: Travel/accommodations/expenses; Astrazenca: Membership on an entity's Board of Directors or advisory committees; PCYC: Membership on an entity's Board of Directors or advisory committees; Juno: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics LLC, an AbbVie Company, Juno Therapeutics, KITE Pharma, AstraZeneca, TG Therapeutics, Celgene, Oncternal, and BeiGene: Research Funding. Barrientos:Oncternal Therapeutics: Research Funding; Gilead: Consultancy; AstraZeneca: Consultancy; Bayer: Consultancy; Sandoz: Consultancy; Janssen: Honoraria; Genentech: Consultancy. Lamanna:Octapharma: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bei-Gene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding; Juno: Other: Institutional research grants, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; MingSight: Other: Institutional research grants, Research Funding; Oncternal, Verastem, TG Therapeutics: Other: Institutional research grants, Research Funding; Astra Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding; Columbia University Medical Center: Current Employment; Loxo: Research Funding. Tuscano:Abbvie: Research Funding; Pharmacyclics: Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Seattle Genetics: Honoraria; Novartis: Research Funding; Spectrum: Research Funding; Takeda: Research Funding; Genentech: Research Funding. Leslie:KitePharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Epizyme: Honoraria, Speakers Bureau; Karyopharm: Honoraria, Speakers Bureau; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Speakers Bureau; BeiGene: Honoraria, Speakers Bureau; Celgene: Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ianopulos:Oncternal Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Breitmeyer:Oncternal Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Hsu:Oncternal Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company; Immune Design: Ended employment in the past 24 months. Wang:Beijing Medical Award Foundation: Honoraria; Lu Daopei Medical Group: Honoraria; MoreHealth: Consultancy; OMI: Honoraria, Other: Travel, accommodation, expenses; Targeted Oncology: Honoraria; Loxo Oncology: Consultancy, Research Funding; Pulse Biosciences: Consultancy; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Juno: Consultancy, Research Funding; BioInvent: Research Funding; VelosBio: Research Funding; Acerta Pharma: Research Funding; InnoCare: Consultancy; Oncternal: Consultancy, Research Funding; Nobel Insights: Consultancy; Guidepoint Global: Consultancy; Dava Oncology: Honoraria; Verastem: Research Funding; Molecular Templates: Research Funding; OncLive: Honoraria; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding. Jamieson:Bristol-Myers Squibb: Other; Forty Seven Inc: Patents & Royalties. Kipps:VelosBio: Research Funding; Pharmacyclics/ AbbVie, Breast Cancer Research Foundation, MD Anderson Cancer Center, Oncternal Therapeutics, Inc., Specialized Center of Research (SCOR) - The Leukemia and Lymphoma Society (LLS), California Institute for Regenerative Medicine (CIRM): Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech/Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Research Funding; Ascerta/AstraZeneca, Celgene, Genentech/F. Hoffmann-La Roche, Gilead, Janssen, Loxo Oncology, Octernal Therapeutics, Pharmacyclics/AbbVie, TG Therapeutics, VelosBio, and Verastem: Membership on an entity's Board of Directors or advisory committees; Oncternal Therapeutics, Inc.: Other: Cirmtuzumab was developed by Thomas J. Kipps in the Thomas J. Kipps laboratory and licensed by the University of California to Oncternal Therapeutics, Inc., which provided stock options and research funding to the Thomas J. Kipps laboratory, Research Funding.

Introduction Indolent Non-Hodgkin lymphomas (NHL) comprise a heterogeneous group of diseases including marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma (LPL), small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), and follicular lymphoma (FL). These compose a heterogenous group of disorders that frequently measures survival in years due to the long natural history of these diseases. Frequency and morbidity of cardiac arrhythmias in patients with indolent lymphoma is unknown, but recent observations note that arrhythmias are an increasing problem. Due to advances in treatment for indolent NHL with emergence of novel therapeutics, combined with an aging population and a long natural history, understanding of arrhythmia burden in indolent lymphoma is an area of research with important implications for patients undergoing active treatment as well as for long term lymphoma survivors. Methods Adult patients 18 years or older with indolent NHL treated at the University of Rochester Wilmot Cancer Institute between 2013-2019 were included in the Cardio-Oncology Lymphoid Malignancies Database and analyzed. The primary objective of this study was to define the rate of arrhythmic events and sudden cardiac death in patients with indolent lymphoma during treatment. Cardiac arrhythmias including ventricular arrhythmias (VT/VF), atrial arrhythmias (atrial fibrillation (afib), flutter, SVT and atrial tachycardia), and bradyarrhythmias were identified using ICD-10 codes. Kaplan-Meier survival analysis was used to assess cumulative probability of arrhythmia. Results There were nine hundred and eighteen patients who were diagnosed with indolent lymphoma. Diagnoses included: CLL, N=414; FL, N=284; MZL, N=144; LPL, N=76. Median age was 64, and 43% were female. There were 383 (42%) patients who received treatment. Treatments were classified as chemotherapy, targeted therapy, monoclonal antibodies/immunotherapy, and combination therapy. There were no significant differences in baseline characteristics between treated and never treated patients. At the time of diagnosis, 277 patients (30%) had hypertension, 101 (11%) had prior history of arrhythmia. During median follow up of 24 months, 168 patients (18%) developed a new or recurrent arrhythmia based on ICD-10 codes documented in the electronic medical record. Sixty-three out of one hundred sixty-eight patients had both prior history of and recurrence of arrhythmia, while one hundred five had a new diagnosis of arrhythmia. Afib was the most common arrhythmia, noted in 81 patients (9%). At 6 months from diagnosis, cumulative probability of developing any arrhythmia was 8% (Figure 1). Of all arrhythmias, 89/168 (53%) occurred in SLL/CLL, 35/168 (21%) in FL, 17/168 (10%) in LPL, 27/168 (16%) in MZL. Arrhythmias on treatment occurred in 4/95 patients receiving chemotherapy alone (4.2%), 12/95 patients receiving monoclonal antibodies/immunotherapy (12.6%), and 28/95 patients receiving targeted therapy (29.4%). Most arrhythmias (51/95; 53.6%) occurred in patients receiving combination therapy (chemoimmunotherapy or targeted/immunotherapy). Overall, there were 80 (9%) deaths. Ten deaths were related to cardiovascular diseases; of which 8/10 (80%) were from sudden cardiac death. Conclusions This real-world cohort demonstrates that patients with indolent lymphoma could have an increased risk of cardiac arrhythmias that is increased by treatment. Afib was the most common arrhythmia identified in this study and appears increased compared to the incidence in the general age matched population (1-1.8 per 100 person-years). Surprisingly, of 80 deaths, 8 (10%) were attributed to sudden cardiac death. This data set contributes important information that can help identify patients at increased risk of cardiovascular morbidity and mortality that can impact treatment. Prospective monitoring in these patients may better define the incidence and associated risks of arrhythmias. Future directions will focus on risk factors for arrhythmias and developing an approach to prevent and treat arrhythmias in this patient population. Updated results will be presented at the meeting. Disclosures Zent: Acerta / Astra Zeneca: Research Funding; TG Therapeutics, Inc: Research Funding; Mentrik Biotech: Research Funding. Barr:Janssen: Consultancy; Abbvie/Pharmacyclics: Consultancy, Research Funding; Verastem: Consultancy; Celgene: Consultancy; Seattle Genetics: Consultancy; TG therapeutics: Consultancy, Research Funding; Morphosys: Consultancy; Gilead: Consultancy; AstraZeneca: Consultancy, Research Funding; Merck: Consultancy; Genentech: Consultancy. Reagan:Kite, a Gilead Company: Consultancy; Seattle Genetics: Research Funding; Curis: Consultancy. Friedberg:Seattle Genetics: Research Funding; Roche: Other: Travel expenses; Bayer: Consultancy; Astellas: Consultancy; Acerta Pharma - A member of the AstraZeneca Group, Bayer HealthCare Pharmaceuticals.: Other; Kite Pharmaceuticals: Research Funding; Portola Pharmaceuticals: Consultancy.

Introduction: Appropriate timing of central venous Catheter (CVC) removal in children after the diagnosis of a CVC-related thrombosis (CRT) is poorly characterized. Due to the risk of embolization, ASH guidelines recommend initiating anticoagulation before CVC removal, but without a specified treatment period before CVC removal. An abstract from the 2019 ASH meeting did not find an increase in embolization rates when comparing anticoagulation treatment < or >48 hours prior to removal (Houghton et al, Blood 2019) in adult cancer patients with upper extremity CRT. This current study aimed to use data within the multi-institutional Children's Hospital-Acquired Thrombosis (CHAT) Consortium Registry to evaluate the incidence of symptomatic pulmonary embolism (PE) after CVC removal. Methods: The CHAT Registry is a retrospective cohort study which consists of detailed data from children aged 0-21 years with a hospital-acquired venous thromboembolism (HA-VTE) from eight U.S. centers. Eligible participants were those with a CRT. Participants were excluded if the diagnosis of thrombosis was >/= 3 days after CVC removal or if the CRT was due to a failed attempt at inserting a CVC. CHAT included details on demographics, medical history, CVC insertion and removal dates, anticoagulation start and stop dates and secondary outcomes, such as PE were extracted for analysis. Participants were divided into three groups, those in which (1) CVC removal occurred without anticoagulation initiation, (2) CVC removal occurred Results: A total of 687 CRT events from 663 participants were included. The median age at hospital admission was 1.4 years (IQR 0.1, 11.3) The majority of participants were male, 57% (378), 54% were non-Hispanic (359) and 46% were White (307). The most common past medical history for all participants with a CRT was congenital heart disease (22%, n=148) followed by cancer (11%, n=71), metabolic or mitochondrial disorder (3%, n=22) and inflammatory bowel disease (3%, n=21). For 76 CRT events the CVC was not removed during the participant's hospitalization or the removal date was unknown, therefore these events were excluded from further analysis. Anticoagulation was not initiated for 72 CRT events and for these events the median time from VTE diagnosis to CVC removal was one day (range 0-5.5). For the events that received anticoagulation there were 311 with CVC removal Conclusions: While current guidelines suggest anticoagulation before removal of CVCs in the setting of CRT to prevent embolization and PE, removal appears safe regardless of duration of anticoagulation before CVC removal in this pediatric cohort. These findings support need to substantiate the findings our CHAT consortium's ongoing prospective cohort study, but while waiting for these results, potential PEs should not weigh heavily in providers clinical decision making on timing of CVC removal. Disclosures Jaffray: CSL Behring: Research Funding; Octapharma: Other: Unrestricted funds for physician education. Baumann Kreuziger:CSL Behring: Consultancy; Quercegen pharmaceuticals: Consultancy. Mahajerin:Spark Therapeutics, Alexion, Genentech, Inc.: Speakers Bureau. Croteau:Hemophilia Federation of America: Honoraria; National Hemophilia Foundation: Honoraria; Sigilon Therapeutics: Consultancy; ATHN: Research Funding; Spark Therapeutics: Research Funding; CSL-Behring: Consultancy; Novo Nordisk: Research Funding; Pfizer: Consultancy; Genentech: Consultancy; Bayer: Consultancy. Young:BioMarin, Freeline, Genentech/Roche, Grifols, Kedrion, Novo Nordisk, Sanofi Genzyme, Spark, Takeda, and UniQure: Honoraria; Bayer, CSL Behring, Freeline, UniQure: Consultancy; Genentech/Roche, Grifols, and Takeda: Research Funding. Goldenberg:Academic Research Organization CPC Clinical Research: Consultancy; Daiici Sankyo: Consultancy; Novartis: Consultancy; Chiesi: Consultancy; Roshan Pharmaceuticals: Consultancy.

In this issue of Blood, Brandão et al report the findings of an open-label, single-arm, phase 3 trial of the direct oral thrombin inhibitor dabigatran for extended secondary thromboprophylaxis in children with a history of venous thromboembolism (VTE) (ClinicalTrials.gov identifier: NCT02197416).(1)