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Background The Coronavirus disease-2019 (COVID-19) is a global pandemic. Acute respiratory compromise and systemic coagulopathy cause significant morbidity and mortality. Venous thromboembolism (VTE), which encompasses both deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as arterial thromboembolism (ATE), which includes stroke, are common sequelae described in this patient population. COVID-19 coagulopathy is attributed to severe inflammation and endothelial dysfunction resulting in a prothrombotic state. COVID-19 related treatment has focused on targeting the unregulated inflammatory state in an attempt to decrease incidence of COVID-19 related complications, such as thrombosis. Prophylactic anticoagulation is recommended, and many suggest intermediate to therapeutic anticoagulation in severe COVID-19. However, there is no clear data showing impact of anticoagulation on morbidity and mortality in patients with COVID-19. Methods A retrospective analysis was performed on all COVID-19 patients hospitalized between March 2020 and June 2020 at our institution. Patient charts were individually reviewed to ensure accuracy of data. Thromboembolic events (VTE or ATE) verified by imaging were included in the analysis. The impact of COVID-19 specific treatments such as Remdesivir, Tocilizumab, Hydroxychloroquine, and steroids on incidence of thrombosis was analyzed by using X2 testing. Using logistics regression, we analyzed the effect of prophylactic versus therapeutic anticoagulation received before development of thrombosis on mortality. Results Out of 1265 COVID-19 positive hospitalized patients during our time frame, 138 (10.9%) had thromboembolism. Incidence of 6.3% VTE, 5.6% DVT, 4.8% PE in COVID-19 patients was significantly higher than 0.24% VTE, 0.15% DVT, 0.12% PE in non COVID-19 hospitalized patients as reported by CDC (p Conclusion In Our study the incidence of thrombosis in hospitalized COVID-19 patients was significantly higher than non-COVID-19 hospitalized patients. COVID-19 patients with thrombosis had higher mortality compared to COVID-19 patient without thrombosis, particularly patients with PE. Hispanic patients with COVID-19 and thrombosis experienced a higher mortality rate compared to non-Hispanic patients. The lowest incidence of thrombosis occurred in COVID-19 patients who received steroids, followed by Tocilizumab suggesting that steroids and Tocilizumab may reduce the pro-inflammatory state leading to thrombosis. However, mortality rate was higher in patients who received COVID-19 related treatment, suggesting that these patients likely had severe disease. There was no mortality difference in patients who received prophylactic versus therapeutic anticoagulation prior to thrombosis. Randomized control trials will address the impact of anticoagulation dosing on morbidity and mortality in COVID-19 patients and study the post discharge prophylaxis and long-term outcomes in these patients. Disclosures No relevant conflicts of interest to declare.

The coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic on March 11, 2020. This novel virus can cause a rapid progression from cough to acute respiratory distress syndrome and death. Cancer patients infected with COVID-19 were reported to have a 39% incidence of severe events, including admission to intensive care unit (ICU), mechanical ventilation, or death. Patients with hematologic malignancies, especially those undergoing treatment, are a particularly at-risk population due to disease-related impairment of the immune system and chemotherapy-induced neutropenia. The goal of this study is to analyze outcomes of COVID-19 infected patients with hematologic malignancies in order to better understand the impact of SARS-CoV-2 on this vulnerable population. Methods We performed a retrospective analysis on 26 COVID-19 positive patients with hematologic malignancies identified at our center. On July 22, 2020, there were 264 COVID-19 positive patients with hematologic malignancies (including our center's 26 patients) reported to the American Society of Hematology Research Collaborative COVID-19 Registry (ASH RC), a global public reference tool. We extracted our patient's data from each category reported to the ASH RC and compared hospitalization, ICU admissions, and mortality rates between our cohort and the remaining 238 cases. Chi-square test was used for analyses. We also performed a subgroup analysis comparing demographics; type and status of hematologic malignancy, as well as COVID-19 directed treatments between our center's patients and the patients reported to the ASH RC. Results Between March and June 2020, a total of 1265 COVID-19 positive patients were hospitalized at our institution. A significantly higher percentage of COVID-19 patients with hematologic malignancies were hospitalized at our institution compared to the ASH RC (61.5% versus 35.3%, P=. 009). There was no difference in ICU admission rate at our center compared to the ASH RC (23.1% versus 30.2%, P=.45). Significantly less COVID-19 directed therapies were administered at our center compared to the ASH RC (46.2% versus 66.4%, P=.041). Our patients received: 7.7% Remdesivir, 11.5% Tocilizumab, 15.4% hydroxychloroquine, 11.5% azithromycin, 0% convalescent plasma, compared to the ASH RC: 1.7% Remdesivir, 5.5% Tocilizumab, 30.3% hydroxychloroquine, 25.6% azithromycin, 4.6% convalescent plasma. Lastly, our institution had a significantly decreased mortality rate compared to the ASH RC (11.5% versus 29.8%, P=.049). Demographics as well as type and status of hematologic malignancy comparing the two cohorts are shown in Table 1. Conclusions In our comparative analysis, we found that our center's patients were hospitalized significantly more than the ASH RC cohort yet had lower mortality rates. These differences were seen despite similar distribution of malignancy types between the two groups. It should be noted that more patients in our cohort were in remission and none presented at initial cancer diagnosis at the time of infection, which may have contributed to better outcomes. The difference in mortality rates may also be attributed to variance in provider experience, higher percentage of patients >80 years of age reported to the ASH RC, and closer patient monitoring at our center due to a higher hospitalization rate. Differences in ICU admissions were not significant, suggesting a similar rate of severe COVID-19 infection between the two cohorts. Our demographics reflect the urban population we serve with more African Americans and Hispanics compared to the ASH RC. The greater number of COVID-19 directed therapies in the ASH RC cohort compared to ours is likely attributed to the use of convalescent plasma, which was not commonly used as COVID-19 directed treatment at our institution. Limitations of our study include a restricted time frame, small sample size, and the possibility of incomplete datasets within the ASH RC, as stated on the registry's website. In conclusion, we recommend close monitoring and a lower threshold for hospitalizing patients with hematologic malignancies in the setting of COVID-19 infection; however, additional prospective studies are needed to confirm our findings, and further investigate the complications and outcomes of SARS-CoV-2 on this at-risk population. Disclosures Ustun: Kadmon: Honoraria. Shammo:Celgene: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau; Onconova: Research Funding; Incyte: Consultancy, Research Funding, Speakers Bureau; Apellis: Consultancy; Regeneron: Consultancy; Novartis: Consultancy; Agios: Consultancy; Sanofi: Speakers Bureau; Abbive: Current equity holder in publicly-traded company; Baxter: Current equity holder in publicly-traded company; Takeda: Current equity holder in publicly-traded company; Alexion: Consultancy, Research Funding, Speakers Bureau.

Background Coronavirus disease-2019 (COVID-19) has become a global pandemic causing respiratory compromise, coagulopathy and renal failure in severe cases. Studies demonstrate a high incidence of venous thromboembolism (VTE), up to 69% in patients with severe COVID-19 infection. Coagulopathy in COVID-19 patients is attributed to excessive inflammation and endotheliopathy. Pregnant patients have approximately a 4-fold increase of VTE incidence. This is in part due to an increase in clotting factors and fibrinogen and a decrease in fibrinolytic activity and protein S. Increased stasis and the presence of acquired and inherited thrombophilias can contribute to increased VTE incidence during pregnancy and postpartum period (PP). Risk factors for thrombosis in pregnancy include African American race, heart disease, diabetes, smoking, multiparity, age >35 years, and obesity. Pregnancy/PP state and COVID-19 infection independently increase the risk of VTE which raises concern for an even higher incidence of thromboembolic events in pregnant/PP patients with COVID-19. Data pertaining to hypercoagulability in COVID-19 infected pregnant patients is currently limited. We conducted this study to evaluate the incidence of thrombosis and mortality in pregnant/PP COVID-19 positive patients. Methods A retrospective analysis was performed on all COVID-19 positive hospitalized patients between March 2020-June 2020 at our institution. Pregnant and PP patients were extracted from this cohort and individually chart reviewed by clinicians. Data from the Centers for Disease Control and Prevention on COVID-19 positive pregnant women in the United States from January 22-July 7, 2020 was utilized for comparison analyses. Statistical analysis was performed with chi-square testing. The incidences of thrombosis and mortality were compared between hospitalized COVID-19 positive pregnant/PP patients and hospitalized adult COVID-19 positive women of childbearing age (18-51 years). A subgroup analysis was performed to evaluate risk factors for thrombosis such as demographics, trimester of pregnancy, and single/multiple gestation (Table 1). Anticoagulation and COVID-19 related therapies administered in this cohort were also studied. Results Forty-three pregnant/PP COVID-19 positive patients were identified out of 1265 hospitalized COVID-19 positive patients at our institution. Thrombosis (DVT, PE, or stroke) incidence in our cohort was 0%, which was not significantly different compared to 6.12% incidence of thrombosis in hospitalized COVID-19 positive women of childbearing age (P = .097). The mortality rate of COVID-19 positive pregnant/PP patients was 0%, which was not significantly different compared to the mortality rate of 3.06% in hospitalized COVID-19 women of childbearing age (P = .25). Further, VTE incidence of 0% in hospitalized COVID-19 positive pregnant/PP patients was not significantly different from the 0.1% incidence of VTE in the non COVID-19 pregnant population in the United States (P=.84). Lastly, the 0% mortality rate in COVID-19 positive pregnant/PP patients at our institution was no different than the 0.0169% mortality rate of pregnant women without COVID-19 infections in the United States (P = .93). Conclusion Our study demonstrates no significant difference in incidence of thrombosis and mortality rate between hospitalized COVID-19 positive pregnant/PP patients and hospitalized COVID-19 positive women of childbearing age. There was also no difference in VTE incidence between hospitalized COVID-19 positive pregnant/PP patients and non COVID-19 pregnant women in the United States. The lack of significant difference in both thrombosis incidence and mortality rate in patients who are both COVID-19 positive and pregnant/PP is reassuring and may imply that pregnancy might play a role in decreasing the inflammatory response of COVID-19. During certain phases of pregnancy a high number of macrophages, natural killer cells, and T regulator cells in the decidua have been identified, which could indicate an overall increased systemic immune response, potentially decreasing the dysregulation of the cytokine storm seen in critically ill COVID-19 patients. However, the systemic immunologic changes in pregnancy and the postpartum period remain largely unknown and prospective studies are needed to further investigate the effects of COVID-19 on pregnant patients. Disclosures No relevant conflicts of interest to declare.

Background Sickle cell disease (SCD) is a hemoglobinopathy which manifests clinically as hemolytic anemia and recurrent episodes of pain caused by vaso-occlusion, among other symptoms. Vaso-occlusive crises (VOCs) account for an overwhelming majority of visits to the emergency room (ER) and hospitalizations for patients with SCD (Shah et al. PLoS One 2019). Upregulation of P-selectin, a cellular adhesion protein expressed on activated platelets and endothelial cells, contributes to the pathophysiology of VOCs. Crizanlizumab is a monoclonal antibody administered intravenously that inhibits the interaction of P-selectin with its ligand; it was approved by the Food and Drug Administration (FDA) as a treatment for SCD patients in 2019. In the Phase II SUSTAIN trial, crizanlizumab therapy resulted in a significantly lower rate of sickle cell-related pain crises than placebo (Ataga et al. N Engl J Med 2017). Due to their high-risk status for COVID-19, the pandemic has posed significant challenges for SCD patients to readily access healthcare, including novel therapies such as crizanlizumab. This study aimed to investigate the utility of telemedicine in facilitating access to crizanlizumab as well as compare acute medical care utilization for patients on crizanlizumab six months before initiating therapy and up to six months after their final dose in 2020. Methods All patients (≥18 years of age as of January 1, 2020) with SCD who received crizanlizumab between January 1, 2020 and December 31, 2020 at Rush University Medical Center (RUMC) were included in the final analysis. Demographic features as well as the type of visit when the patient and healthcare provider discussed crizanlizumab treatment was documented. Paired t-tests and Wilcoxon matched-pairs signed rank tests were utilized to compare acute medical care utilization - defined by the number of ER visits, urgent care visits, and hospitalizations - six months prior to initiating therapy and six months after completing the specified therapy regimen for 2020. Simple linear regression models and multiple regression models were conducted to control for sex, BMI, age, insurance, duration of treatment, and type of visit. Results A total of ten patients were included in the final analysis. Five (50%) patients first agreed to proceed with crizanlizumab therapy during a telehealth video visit with their provider, one (10%) made the decision during a telehealth phone visit, and the other four (40%) did so during a traditional office visit. 9 (90%) patients were still on crizanlizumab after June 1, 2020, the date that RUMC urgent care started seeing patients with SCD. The mean number of visits to the ER in the period before initiating therapy was 2.8 (SD=4.26) compared to 2.5 (SD=2.76) after last dose in 2020, however this finding did not achieve statistical significance (p>0.9999). Visits to the urgent care clinic, on average, increased significantly from 1.7 (SD=2.87) in the six months before initiating therapy to 8.2 (SD=11.02) in the six months after ending therapy for 2020 (p=0.0234). The mean number of hospitalizations in the period before initiating therapy was 6.6 (SD=5.19) compared to 4.6 (SD=3.44) in the period after last dose in 2020, however this was also not statistically significant (p=0.2309). None of the covariates had a significant effect on differences in acute care utilization in the period before and after therapy in 2020. Conclusion This study suggests that administration of crizanlizumab therapy did reduce hospitalization and ED visits, but the results could not achieve statistical significance due to our small sample size and short study duration. The number of urgent care visits for these patients, however, did differ significantly from the period before initiating therapy to the six months after the last dose in 2020. This finding can be attributed to the fact that due to the COVID-19 pandemic, urgent care services were made increasingly available to SCD patients beginning on June 1, 2020 to avoid admissions to the ER and hospital. Additionally, our study suggests that during the COVID-19 pandemic, telemedicine played an important role in providing health services to patients with SCD, and it could continue to improve care accessibility for SCD patients after the pandemic. Continued collection and analysis of real-world data is needed to further understand the effect of crizanlizumab therapy on utilization of acute medical care. Figure 1 Figure 1. Disclosures Jain: DOVA: Other: advisory board; Sanofi: Other: advisory board; Argenx: Other: advisory board; Novartis: Speakers Bureau; GBT: Speakers Bureau.

This phase 1 study sought to characterize the safety, tolerability, and pharmacokinetic behavior of VLX1570, a small molecule inhibitor of the deubiquitinases (DUBs) that remove sterically bulky ubiquitin chains from proteins during processing in the19S regulatory subunit of the proteasome, in patients with relapsed and refractory multiple myeloma (MM). Fourteen patients were treated with escalating doses of VLX1570 ranging from 0.05 to 1.2 mg/kg as a brief intravenous (IV) infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Due to its poor aqueous solubility, VLX1570 was formulated in polyethylene glycol, polyoxyethylated castor oil, and polysorbate 80 and administered as a brief intravenous (IV) infusion via a central venous catheter. Anti-myeloma effects were noted at doses at or above 0.6 mg/kg, however, two patients treated at the 1.2 mg/kg dose level experienced severe, abrupt, and progressive respiratory insufficiency, which was associated with diffuse pulmonary infiltrates on imaging studies, similar to those rarely noted with bortezomib and other inhibitors of the 20S proteasome, culminating in death. Although the contribution of VLX1570s formulation to the pulmonary toxicity could not be ruled out, the severity and precipitous nature of the toxicity and the steep relationship between dose and toxicity, the study was discontinued. Despite the severe pulmonary toxicity noted with VLX1570, efforts directed at identifying DUB inhibitors with greater therapeutic indices appear warranted based on the unique mechanism of action, robustness of preclinical antitumor activity, and activity of the DUB inhibitors in MM resistant to PIs targeting the 20S proteasome subunit. Funding Agencies|Uppsala University; Vivolux, AB

A 60-year-old woman was diagnosed with isolated mucosa-associated lymphoid tissue (MALT) lymphoma of the ocular adnexa and treated with two years of weekly rituximab for eight doses followed by rituximab maintenance. After nearly two years of maintenance therapy, she developed a tender, indurated mass on the left neck. Biopsy results were consistent with primary cutaneous classical Hodgkin lymphoma (PCCHL).

Background The virus SARS-CoV-2, which causes COVID-19 has rapidly spread into a global pandemic. In critically ill patients with the disease, common symptoms include sepsis, severe pneumonia with acute respiratory distress syndrome (ARDS), and complications such as coagulopathy and thrombosis. Many patients with COVID-19 have sequelae such as venous thromboembolism (VTE) including pulmonary embolism (PE) and deep vein thrombosis (DVT) as well as arterial thromboembolism (ATE) including stroke. COVID-19 induced inflammation can induce a prothrombotic state by activating the coagulation cascade; coupled with the immobility of severe and critically ill patients in ICU, making thrombosis common in this patient population. Different blood types in patients include A, B, AB, and O. ABO carbohydrate moieties are genetically inherited and have been linked to predisposing patients to cardiovascular diseases, cancers, and even susceptibility of COVID-19. Blood type positivity and negativity are determined by the Rhesus (Rh) factor, which is a protein found on the surface of red blood cells and is also genetically inherited and linked to higher incidence of certain diseases such as diabetes. Studies have shown a relationship between blood types and increased severity of infection from COVID-19 including increased risk of thrombosis. Blood type A has been shown to have higher severity of disease with O blood type having a lower risk of infection or mortality. This study was done to evaluate if patients with different blood types have increased risk for thrombosis or higher mortality rates with COVID-19 infection. Methods A retrospective analysis was performed on COVID-19 positive hospitalized patients between March 1, 2020 and June 26, 2020 at our institution with reported blood typing. Patients who had a thromboembolism (VTE, DVT, PE, ATE, or stroke) verified by imaging were extracted from this cohort and included in the analysis. The prevalence of different blood types in COVID-19 patients was compared to the general population without COVID-19. The incidence of thrombosis and mortality rate based on blood type was analyzed to understand severity of COVID-19 disease. Statistical analysis was performed using chi-squared testing. Results Among 1265 COVID-19 positive patients during our time frame, 138 patients were identified to have a thrombosis. Of those, 102 patients with thrombosis and 402 without thrombosis had reported blood types that were used for analysis. There was no significant difference in prevalence of blood types in COVID-19 patients (A 34.3%, AB 2.9%, B 16.7%, O 46.1%) to the general nonCOVID-19 population (A32.7%, AB 4.2%, B 14.9%, O 48.1%) (p=0.8572). There was no significant difference in incidence of thrombosis between blood types: A (23.3%), AB (15%), B (20.7%), and O (18.7%) (p=0.6513). When stratifying by Rh factor, there was also no significant difference in incidence of thrombosis by blood types: A- (11.1%), A+ (24.1%), AB- (0%), AB+ (15.8%), B- (25%), B+ (20.3%), O- (18.2%), O+ (18.7%) (p=0.9054). There was also no significant difference in mortality rate between COVID-19 patients based on blood types in our cohort: A (20.7%), AB (15%), B (13.4%), and O (21.8%) (p=0.3747). Conclusion Our study demonstrates that there is no increased prevalence of one blood type over another between COVID-19 patients compared to the general population, showing that patients are not at higher risk for COVID-19 infection based on blood type. There was also no difference between blood types based on incidence of thrombosis. When further stratifying with Rh factor, there was also no difference in incidence of thrombosis based on blood types. This shows that regardless of Rh positivity or negativity, there is no increased risk for thrombosis in COVID-19 patients based on blood type. There is also no difference in mortality in COVID-19 patients based on blood type. Since COVID-19 patients who are critically ill and have more severe disease have higher incidence of thrombosis and higher mortality rates, our study suggests that patients are not at higher risk for severe COVID-19 disease based on blood type. However, this study is also limited due to small sample size, and prospective studies are needed to better understand the relationship between blood type and severity of disease in COVID-19+ patients. Disclosures No relevant conflicts of interest to declare.

Specific cytokine signatures correlate with genetic aberrations in CLL/SLL, reflecting a pattern of Th1/Th2/Treg dysregulation that may predict aggressive disease, and a need for therapy. Early treatment of CLL/SLL does not impact survival-reflecting limitations in detecting progression early and identifying asymptomatic patients likely to benefit from early treatment. Improved understanding of CLL/SLL biology would identify better prognostic/predictive markers. This study attempts to address these issues by determining the relationship between cytokine aberrations and poor clinical outcomes in CLL/SLL in the context of a genetic–based prognostic model. Fifty-nine serum cytokines/chemokines were measured in 28 untreated CLL/SLL patients. Patients were stratified as GR or int/PR using cytogenetics. Comparison of CLL/SLL with 28 HCs revealed increased expression of Th2 cytokines (IL-10, IL-5, sIL-2Rα; P≤0.01) and decreased levels of Th1 cytokines (IL-17, IL-23, IFN-γ; P≤0.003). In a multivariate analysis of GR versus int/PR groups, differential expression of sIL-2Rα maintained significance with increased expression in int/PR CLL/SLL. With median follow-up of 54.3 months after diagnosis, four patients incurred disease progression, with an IL-17/sIL-2Rα model predicting need for treatment in all cases. In summary, specific cytokine signatures are associated with genetically defined aggressive disease and predict need for therapy. This suggests utility in detecting disease progression early, identifying those likely to incur a survival advantage with early treatment, and directing future therapy.

Achieving improvements in survival and reducing relapse remains a challenge in acute myelogenous leukemia (AML) patients. This study evaluated thein vitroefficacy of the active form of novel agent sapacitabine, CNDAC, compared to current chemotherapeutic drugs Ara-C and mitoxantrone using two AML cell lines, HL-60 (promyelocytic) and THP-1 (monocytic), as well as bone marrow (BM) and peripheral blood (PB) cells collected from AML patients. Cell lines were exposed to compound for 3–6 days and primary cells for 4 days. The viability of primary cells was additionally evaluated 3, 7, and 31 days after removal of tested compound to determine the durability of the response. Our studies indicate that CNDAC and mitoxantrone have a greater impact on viability than ara-C in primary AML cells and AML cell lines. CNDAC is more effective at reducing viability and inducing apoptosis than ara-C at equivalent concentrations in the THP-1 cell line, which is defined as displaying resistance to ara-C. As sapacitabine has shownin vivoactivity at clinically achievable doses, future studies are warranted to assess the potential for combining it with ara-C and/or mitoxantrone, with an emphasis on cells and patients insensitive to ara-C treatment.