Genetic landscape and clinical outcomes of patients with <i>BCOR</i> mutated myeloid neoplasms

The BCL6-corepressor (BCOR) is a tumor-suppressor gene located on the short arm of chromosome X. Data are limited regarding factors predicting survival in BCOR-mutated (mBCOR) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We evaluated 138 patients with mBCOR myeloid disorders, of which 36 (26.1%) had AML and 63 (45.6%) had MDS. Sixty-six (47.8%) patients had a normal karyotype while 18 (13%) patients had complex karyotype. BCOR-mutated MDS/AML were highly associated with RUNX1 and U2AF1 co-mutations. In contrast, TP53 mutation was infrequently seen with mBCOR MDS. Patients with an isolated BCOR mutation had similar survival compared to those with high-risk co-mutations by European LeukemiaNet (ELN) 2022 criteria (median OS 1.16 vs. 1.27 years, P=0.46). Complex karyotype adversely impacted survival among mBCOR AML/MDS (HR 4.12, P<0.001), while allogeneic stem cell transplant (alloSCT) improved survival (HR 0.38, P=0.04). However, RUNX1 co-mutation was associated with an increased risk of post-alloSCT relapse (HR 88.0, P=0.02), whereas melphalan-based conditioning was associated with a decreased relapse risk (HR 0.02, P=0.01). We conclude that mBCOR is a high-risk feature across MDS/AML, and that alloSCT improves survival in this population

Quality and Value-Focused Decision Making in Heparin-Induced Thrombocytopenia: The Impact of the American Society of Hematology's Choosing Wisely Initiative

Abstract Introduction: For patients admitted to hospital, the use of heparin and its analogs is very common. Heparin administration can result in heparin-induced thrombocytopenia (HIT). Development of HIT is independent of the dose of heparin administration. Presence of HIT is determined by platelet antibody assays and confirmed by serotonin release assay. However, hospitalized patients have many comorbidities and are on several medications, both of which may be responsible for thrombocytopenia. The 4T scoring system was developed in 2006 to determine the pretest probability of HIT. Scores of 0-3, 4-5, and 6-8 are considered to correspond to a low, intermediate, and high probability of HIT, respectively. The 4T score was validated by a meta-analysis published in 2012 which reported that the negative predictive value of a low 4T score is close to 100% (Blood 2012;120(20):4160-4167). Inappropriate testing for thrombocytopenia can lead to inadvertent use of the platelet factor 4 assays, halting heparin administration unnecessarily and the over-treatment of patients with alternative anticoagulants. The American Society of Hematology (ASH) highlighted this in its 2014 Choosing Wisely guidelines (Blood 2014;124(24):3524-3528). The Choosing Wisely recommendations include using the 4T scoring system to assess the pretest probability of HIT. ASH recommends against testing and treating patients who have low pretest probability of HIT. We wanted to assess the impact of ASH Choosing Wisely recommendations on the appropriateness of checking for HIT. Methods: All the patients, admitted between January 2013 to March 2016, who had a HIT test done (CPT code 86022), were extracted from the hospital database. Of these patients, 140 were randomly selected before and after the publication of ASH Choosing Wisely guidelines. The immediately previous platelet count before ordering a HIT test was used to calculate the platelet nadir. The percentage in platelet count fall was determined by the difference between the immediately previous platelet count before ordering HIT test and the maximum platelet count documented on current admission. Timing of platelet count fall was determined as the number of days from HIT testing ordered to when patient received the first dose of heparin, or from the date of the immediately previous platelet count before ordering HIT test to the maximum platelet count, whichever is less. Patients were considered to have suspected thrombosis if an ultrasound doppler lower extremity or CT chest was ordered, but the results were not available at the time of ordering the HIT test. 4T scores were calculated for the first HIT test ordered to determine if the patients were a low-risk or intermediate- to high-risk for HIT. We did a chi-square test without Yate's correction to check if there has been a proportionate increase in HIT testing for patients with 4T score greater than 3, after the Choosing Wisely recommendations were published in 2014. Student's t-test was used to determine if there has been a decrease in the number of HIT tests ordered per patient after the release of Choosing Wisely guidelines. Patients who were not fit to be calculated for 4T score were excluded. Results: A total of 280 patient charts were reviewed. 23 patients were excluded as they received recent heparin and had platelet count fall within less than 4 days. Of the 129 patients admitted in 2013-2014, 31 (24%) were considered high/intermediate risk 4T score category. Of the 128 patients admitted from January 2015 to March 2016, 26 (20.3%) were considered high/intermediate risk 4T score category. The chi-square test did not show any difference between the two groups (chi-score 0.515 with 1 degrees of freedom, P = 0.47). However, the Student's t-test showed that the number of HIT tests ordered per patient declined significantly after the release of the Choosing Wisely guidelines (t = 2.09, P = 0.038). Conclusions: Physician adherence to 4T scoring system has not yet changed after the release of ASH Choosing Wisely guidelines. However, repeated testing for HIT has declined significantly after the guideline release. More efforts need to be taken to improve the quality of care in this population. Disclosures Baranwal: MacNeal Hospital: Employment. </jats:sec

Tumor Lysis Syndrome in a Patient With Gastric Adenocarcinoma

Tumor lysis syndrome (TLS) is a severe metabolic complication that usually occurs in patients with aggressive tumors who undergo treatment with chemotherapy. Traditionally, it was mainly associated with hematologic malignancies. However, over the past 4 decades, there have been increasing reports of TLS in solid tumors. We report a case of TLS in a patient with gastric cancer, as a complication of FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) chemotherapy. Our patient was a 48-year-old man with metastatic gastric adenocarcinoma who presented with altered mental status and slurred speech. On examination, he was confused and disoriented, but the rest of his examination, including vitals, was unremarkable. Laboratory findings on admission were significant for an elevated uric acid of 14.5 mg/dL, creatinine of 4.1 mg/dL, and phosphorus of 6.9 mg/dL. He had received his first cycle of FOLFOX chemotherapy 4 days prior to admission. The constellation of electrolyte abnormalities and the temporal relationship to chemotherapy led to the diagnosis of chemotherapy-induced TLS. He was treated with aggressive fluid repletion and rasburicase, following which the electrolyte derangements resolved, and he improved clinically. This case highlights the importance of early recognition of TLS in patients with gastric cancer. Initiation of early treatment can reduce the high morbidity and mortality associated with this oncologic emergency. </jats:p

Tumor Lysis Syndrome in a Patient With Gastric Adenocarcinoma.

Tumor lysis syndrome (TLS) is a severe metabolic complication that usually occurs in patients with aggressive tumors who undergo treatment with chemotherapy. Traditionally, it was mainly associated with hematologic malignancies. However, over the past 4 decades, there have been increasing reports of TLS in solid tumors. We report a case of TLS in a patient with gastric cancer, as a complication of FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) chemotherapy. Our patient was a 48-year-old man with metastatic gastric adenocarcinoma who presented with altered mental status and slurred speech. On examination, he was confused and disoriented, but the rest of his examination, including vitals, was unremarkable. Laboratory findings on admission were significant for an elevated uric acid of 14.5 mg/dL, creatinine of 4.1 mg/dL, and phosphorus of 6.9 mg/dL. He had received his first cycle of FOLFOX chemotherapy 4 days prior to admission. The constellation of electrolyte abnormalities and the temporal relationship to chemotherapy led to the diagnosis of chemotherapy-induced TLS. He was treated with aggressive fluid repletion and rasburicase, following which the electrolyte derangements resolved, and he improved clinically. This case highlights the importance of early recognition of TLS in patients with gastric cancer. Initiation of early treatment can reduce the high morbidity and mortality associated with this oncologic emergency

Health care utilization and outcomes of sepsis in HIV versus non-HIV patients with Burkitt Lymphoma: A nationwide analysis.

e19561 Background: Burkitt lymphoma (BL) is an aggressive AIDS-defining malignancy, the incidence of which has not declined over the last 2 decades despite use of antiretroviral therapy. HIV-BL is more advanced at diagnosis compared to non-HIV-BL with increased risks of immunosuppressive chemotherapy (Lancet Hematology 2020;7(8):e594-e600). We attempted to explore and quantify the prevalence, outcomes and healthcare utilization of HIV-BL vs non-HIV-BL patients admitted with sepsis. Methods: Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS) database was queried to identify all adult HIV and non-HIV admissions with BL between 2016–2018 with a primary diagnosis of sepsis. The groups were compared for demographic differences, inpatient mortality, length of stay (LOS) and hospital charges. Secondary outcomes studied included rates of septic shock (SS), acidosis, acute kidney injury (AKI), tumor lysis syndrome (TLS), pancytopenia, anemia, neutropenia, protein energy malnutrition (PEM) and history of bone-marrow/stem-cell transplant. Statistics were performed using the t-test, z-test and chi-square test. Results: A total of 2310 HIV-BL admissions comprising 205 (8.9%) with sepsis and 11,950 non-HIV-BL admissions with 865 (7.2%) with sepsis (p = 0.006) were identified. Compared to non-HIV cohort, HIV-BL patients were significantly younger (mean age 43.6 versus 55.3 years, p = 0.001) with few over 65 years old (2.4% vs 36%, p = 0.001). Both groups had similar gender ratio, but a higher number of HIV-BL admissions were African American (AA) (51.4% vs 4.9%, p = 0.001), on Medicaid (31.7% vs 15.6%, p &lt; 0.0001), from lowest quartile income zip codes (p &lt; 0.0001) and more likely to be treated at teaching hospitals (73.2% vs 54.9%, p &lt; 0.0001). The overall inpatient mortality was 21.9% in HIV-BL vs 15.6% in non-HIV-BL (p = 0.02). HIV-BL reported increased mean LOS (9 vs 8 days, p = NS) and average $39,599 more in hospital charges for each HIV-BL admission compared to non-HIV-BL with sepsis (amounting to over$8 million over 3 years). The rates of anemia, neutropenia, TLS, AKI, SS, TLS and PEM were similar (p = NS) between the groups. Conclusions: Nationwide, HIV-BL patients had significantly higher rates of sepsis despite being significantly younger. They were also more likely to be AA from lower socioeconomic zip codes and more likely to be on Medicaid. The mean inpatient LOS and hospital charges, although not statistically significant, were higher in HIV-BL compared to their non-HIV counterparts. Also, the difference in total charges for all HIV-BL admissions amounted to over $8 million extra compared to non-HIV-BL in 3 years. These trends need to be evaluated in prospective studies to help identify interventions to improve clinical outcomes and healthcare utilization. </jats:p

Four-Fold Increased Mortality from Sars-Cov-2 Infection in Patients with Hematologic Versus Non-Hematologic Malignancies Treated at the Largest Tertiary COVID-19 Center in Chicago/Rush University Medical Center (March 1, 2020-December 31,2020)

Abstract N.K.Y., P.C., &amp; P.R.Y. contributed equally to this study Introduction: Many studies have concluded that active cancer patients infected with SARS-CoV-2 have a more complicated infection course and worse outcomes compared to the general patient population hospitalized with COVID-19. However, little evidence exists whether having a history of cancer plays a significant role in these observations. Patients with hematologic malignancy (HM) might have worse prognosis among all cancer patients but the reason remains unclear. Our objective is to evaluate outcomes and severity of COVID-19 in patients with Hematological Malignancy (HM) versus Solid-tumors (ST) in different clinical settings and also compare these outcomes within the group of patients with hematological malignancies. Methods: This retrospective study examines risk factors and outcomes of COVID-19 in patients with a history of cancer and laboratory-confirmed COVID-19 diagnosis between March 1 st, 2020, and December 31 st, 2020, at Rush University Medical Center, one of the largest COVID-19 tertiary care hospitals in Chicago. Baseline characteristics, malignancy type and types of cancer treatment within the last 30 days were recorded. Measures of COVID-19 severity included hospital admission versus outpatient care, use of oxygen, intensive care unit (ICU) admission, and mechanical ventilation. The primary outcome was death. Statistical analysis was conducted using optimal discriminant analysis, a non-parametric exact machine-learning algorithm which identifies the relationship between independent and dependent variables that maximizes model predictive accuracy adjusted to remove the effect of chance. Analysis was performed separately for each attribute using the entire sample ("training" analysis), then one-sample jackknife analysis was conducted to estimate cross-generalizability of findings using the model to classify an independent random sample. Results: 378 total patients with a history of cancer tested positive for COVID-19 within the time frame of the study. Of these, 294 (78%) patients had ST malignancy and 84 (22%) patients had HM. Characteristics and outcomes are summarized in Table 1. ST patients were marginally older than HM patients (p&amp;lt;0.025). A significantly greater proportion of HM patients were male (p&amp;lt;0.0023). HM and ST patients did not differ with respect to percentage receiving active cancer treatment (p&amp;lt;0.81). Compared to ST patients, more HM patients had received corticosteroids in the 30 days prior to COVID-19 diagnosis (p&amp;lt;0.017), had higher rates of hospitalization (p&amp;lt;0.0013) and ICU requirement (p&amp;lt;0.0001) with a significantly longer length of ICU stay (p&amp;lt;0.0036). Compared to ST patients, HM patients also required oxygen (p&amp;lt;0.002) and mechanical ventilation (p&amp;lt;0.0005) more often and had a 3.88-fold statistically higher death rate (OR 3.88 [95% CI 1.62-9.29] p&amp;lt;0.003). Patients with HM are categorized by disease subtype and summarized in Table 2. The case fatality rate from COVID-19 was 33.3% for patients with myeloproliferative neoplasms/myelodysplastic syndromes (MPN/MDS), 21.4% for patients with chronic lymphocytic leukemia (CLL), 13.6% for patients with non-Hodgkin lymphoma, 10.5% for patients with plasma cell neoplasms, and 4.5% for patients with acute leukemia. When looking at outcomes, CLL had the highest percentage of patients requiring hospital admission, oxygen, and ICU admission, and MPN/MDS had the highest percentage of patients requiring mechanical ventilation. Conclusions: Patients with hematologic malignancies had more severe COVID-19 illness and hospitalization rates and a 3.88-fold higher rate of death than patients with solid tumors. The comparable proportion of patients on anti-cancer therapy despite differences in survival suggests that being on anti-cancer therapy is less important than the underlying diagnosis of HM versus ST as a determinant of poor outcomes. Clinicians should closely monitor and initiate early COVID-19 treatments for all patients with HM and COVID-19. Because HM are highly heterogenous group of cancers, it is important to look at subtypes in greater detail. Numerous patient-level, disease-specific, and therapy-related factors may impact outcomes of COVID-19 among patients with HM, and we are currently analyzing additional data to better understand the factors which make this disease group more susceptible to severe infection. Figure 1 Figure 1. Disclosures Kuzel: Sanofi-Genzyme Genomic Health Tempus laboratories Bristol Meyers Squibb: Honoraria; Genomic Health: Membership on an entity's Board of Directors or advisory committees; Exelixis: Membership on an entity's Board of Directors or advisory committees; Cardinal Health: Membership on an entity's Board of Directors or advisory committees; Abbvie: Other; Curio Science: Membership on an entity's Board of Directors or advisory committees; AmerisourceBergen Corp: Membership on an entity's Board of Directors or advisory committees; CVS: Membership on an entity's Board of Directors or advisory committees; Tempus Laboratories: Membership on an entity's Board of Directors or advisory committees; Bristol Meyers Squibb: Membership on an entity's Board of Directors or advisory committees; Merck: Other: Data Monitoring Committee Membership; Amgen: Other: Data Monitoring Committee Membership; SeaGen: Other: Data Monitoring Committee Membership; Medpace: Other: Data Monitoring Committee Membership. </jats:sec