Common Sense Recommendations for the Application of Tax Law to Digital Assets

In response to the Joint Committee on Taxation’s July 2023 request for comments on application of various Internal Revenue Code sections on digital assets, we propose a consistent set of rules to apply current law to digital assets. We highlight that the underlying economics and characteristics of transactions should be the primary concern for the application of rules and the valuation of digital assets. We believe any digital asset rules should (1) treat classes of digital assets with unique characteristics differently based on their economics, (2) minimize incentives for users to engage in tax-motivated structuring of transactions, and (3) allow the Internal Revenue Service authority to react to and regulate new classes of digital assets as they are created. We do not believe that the unique features of digital assets are a challenge to applying current law or warrant special tax preferred treatment

Racial/Ethnic Disparities in Cancer-Associated Thrombosis: A Population-Based Study

Introduction Risk factors for cancer-associated venous thromboembolism (CAT) include tumor type, stage at diagnosis, age, and patient comorbidities. In the general population, race/ethnicity has been identified as a risk factor for venous thromboembolism (VTE), with an increased risk of VTE in African Americans (AA) and a lower risk in Asians/Pacific Islanders (API) and Hispanics compared to non-Hispanic Whites (NHW) after adjustment for confounders such as demographic characteristics and patient comorbidities. However, the impact of race/ethnicity on the incidence of CAT has not been as well-studied. Methods We performed an observational cohort study using data from the California Cancer Registry linked to the California Patient Discharge Dataset and Emergency Department Utilization database. We identified a cohort of patients of all ages with first primary diagnosis of the 13 most common cancers in California between 2005-2014, including breast, prostate, lung, colorectal, bladder, uterine, kidney, pancreatic, stomach, ovarian, and brain cancer, Non-Hodgkin lymphoma, and multiple myeloma, and followed them for a diagnosis of VTE using specific ICD-9-CM codes. The 12-month cumulative incidences of VTE [pulmonary embolism (PE) alone, PE + lower extremity deep venous thrombosis (LE DVT), proximal LE DVT alone, and isolated distal DVT (iDDVT)] were determined by race/ethnicity, adjusted for the competing risk of death. Multivariable Cox proportional hazards regression models were performed to determine the effect of race/ethnicity on the risk of CAT adjusted for age, sex, cancer stage, type of initial therapy (surgery, chemotherapy, radiation therapy), neighborhood socioeconomic status, insurance type, and comorbidities. Patients with VTE prior to cancer diagnosis were excluded. Results A total of 736,292 cancer patients were included in the analysis cohort, of which 38,431 (5.2%) developed CAT within 12 months of diagnosis. When comparing the overall cancer cohort to those that developed VTE, AA (7.2 vs 10.5%) and NHW (61.9 vs 64.3%) appear to be over-represented, and API (11.6 vs 7.6%) under-represented in VTE cohort (Figure 1). The greatest disparities in incidence by race/ethnicity were seen in PE. AA had the highest and API had the lowest 12-month cumulative incidences for all cancer types except for brain cancer (Figure 2). These racial/ethnic differences were also seen among cumulative incidences of proximal LE DVT. For iDDVT, AA again had the highest cumulative incidence compared to the other racial groups among all cancer types except for myeloma. Racial differences were not as prominent when examining cumulative incidence of all VTE (PE+DVT). In adjusted multivariable models of overall CAT, compared to NHW, AA had the highest risk of CAT across all cancer types except for brain cancer and myeloma. API had significantly lower risk of CAT than NHW for all cancer types. When examining PE only in multivariable models, AA had significantly higher risk of PE compared to NHW in all cancer types except for kidney, stomach, brain cancer, and myeloma (Hazard Ratio (HR) ranging from 1.36 to 2.09). API had significantly lower risk of PE in all cancer types except uterine, kidney, and ovarian cancer (HR ranging from 0.45 to 0.87). Hispanics had lower risk of PE than NHW in breast, prostate, colorectal, bladder, pancreatic cancer, and myeloma (HR ranging from 0.64 to 0.87). [Figure 3] Conclusion In this large, diverse, population-based cohort of cancer patients, race/ethnicity was associated with risk of CAT even after adjusting for cancer stage, type of treatment, sociodemographic factors, and comorbidities. Overall, AA had a significantly higher incidence and API had a significantly lower incidence of CAT than NHW. These racial/ethnic differences were especially prominent when examining PE only, and PE appears to be the main driver for the racial differences observed in overall rates of CAT. Current risk prediction models for CAT do not include race/ethnicity as a parameter. Future studies might examine if incorporation of race/ethnicity into risk prediction models for CAT may improve their predictive value, as this may have important implications for thromboprophylaxis in this high-risk population. Disclosures Wun: Glycomimetics, Inc.: Consultancy

Racial/Ethnic Disparities in Cancer-Associated Thrombosis: A Population-Based Study

Introduction Risk factors for cancer-associated venous thromboembolism (CAT) include tumor type, stage at diagnosis, age, and patient comorbidities. In the general population, race/ethnicity has been identified as a risk factor for venous thromboembolism (VTE), with an increased risk of VTE in African Americans (AA) and a lower risk in Asians/Pacific Islanders (API) and Hispanics compared to non-Hispanic Whites (NHW) after adjustment for confounders such as demographic characteristics and patient comorbidities. However, the impact of race/ethnicity on the incidence of CAT has not been as well-studied. Methods We performed an observational cohort study using data from the California Cancer Registry linked to the California Patient Discharge Dataset and Emergency Department Utilization database. We identified a cohort of patients of all ages with first primary diagnosis of the 13 most common cancers in California between 2005-2014, including breast, prostate, lung, colorectal, bladder, uterine, kidney, pancreatic, stomach, ovarian, and brain cancer, Non-Hodgkin lymphoma, and multiple myeloma, and followed them for a diagnosis of VTE using specific ICD-9-CM codes. The 12-month cumulative incidences of VTE [pulmonary embolism (PE) alone, PE + lower extremity deep venous thrombosis (LE DVT), proximal LE DVT alone, and isolated distal DVT (iDDVT)] were determined by race/ethnicity, adjusted for the competing risk of death. Multivariable Cox proportional hazards regression models were performed to determine the effect of race/ethnicity on the risk of CAT adjusted for age, sex, cancer stage, type of initial therapy (surgery, chemotherapy, radiation therapy), neighborhood socioeconomic status, insurance type, and comorbidities. Patients with VTE prior to cancer diagnosis were excluded. Results A total of 736,292 cancer patients were included in the analysis cohort, of which 38,431 (5.2%) developed CAT within 12 months of diagnosis. When comparing the overall cancer cohort to those that developed VTE, AA (7.2 vs 10.5%) and NHW (61.9 vs 64.3%) appear to be over-represented, and API (11.6 vs 7.6%) under-represented in VTE cohort (Figure 1). The greatest disparities in incidence by race/ethnicity were seen in PE. AA had the highest and API had the lowest 12-month cumulative incidences for all cancer types except for brain cancer (Figure 2). These racial/ethnic differences were also seen among cumulative incidences of proximal LE DVT. For iDDVT, AA again had the highest cumulative incidence compared to the other racial groups among all cancer types except for myeloma. Racial differences were not as prominent when examining cumulative incidence of all VTE (PE+DVT). In adjusted multivariable models of overall CAT, compared to NHW, AA had the highest risk of CAT across all cancer types except for brain cancer and myeloma. API had significantly lower risk of CAT than NHW for all cancer types. When examining PE only in multivariable models, AA had significantly higher risk of PE compared to NHW in all cancer types except for kidney, stomach, brain cancer, and myeloma (Hazard Ratio (HR) ranging from 1.36 to 2.09). API had significantly lower risk of PE in all cancer types except uterine, kidney, and ovarian cancer (HR ranging from 0.45 to 0.87). Hispanics had lower risk of PE than NHW in breast, prostate, colorectal, bladder, pancreatic cancer, and myeloma (HR ranging from 0.64 to 0.87). [Figure 3] Conclusion In this large, diverse, population-based cohort of cancer patients, race/ethnicity was associated with risk of CAT even after adjusting for cancer stage, type of treatment, sociodemographic factors, and comorbidities. Overall, AA had a significantly higher incidence and API had a significantly lower incidence of CAT than NHW. These racial/ethnic differences were especially prominent when examining PE only, and PE appears to be the main driver for the racial differences observed in overall rates of CAT. Current risk prediction models for CAT do not include race/ethnicity as a parameter. Future studies might examine if incorporation of race/ethnicity into risk prediction models for CAT may improve their predictive value, as this may have important implications for thromboprophylaxis in this high-risk population. Disclosures Wun: Glycomimetics, Inc.: Consultancy

Upper Extremity Deep Vein Thrombosis in Acute Leukemia and Non-Hodgkin's Lymphoma: Analysis of the California Cancer Registry

Background Venous thromboembolism (VTE) is a known complication in patients with acute myeloid leukemia (AML), acute lymphoid leukemia (ALL) and non-Hodgkin's lymphoma (NHL). However, the cumulative incidence, risk factors, rate of subsequent VTE and impact on mortality of upper extremity deep vein thrombosis (UE DVT) in these diseases is not well-described. Methods Using the California Cancer Registry, we identified patients with a first primary diagnosis of AML, ALL and NHL from 2005-2014 and linked these patients with the statewide hospitalization and emergency department databases to identify an incident UE DVT event using specific ICD-9-CM codes. Patients with VTE prior to or at the time of malignancy diagnosis or who were not treated with chemotherapy were excluded. We determined the cumulative incidence of first UE DVT, adjusted for the competing risk of death. We also examined the cumulative incidence of subsequent VTE (UE DVT, lower extremity deep vein thrombosis (LE DVT) and pulmonary embolism (PE)) and major bleeding after incident UE DVT. Using Cox proportional hazards regression models, stratified by tumor type and adjusted for other prognostic covariates including sex, race/ethnicity, age at diagnosis, neighborhood, sociodemographic status and central venous catheter (CVC) placement, we identified risk factors for development of incident UE DVT, the effect of incident UE DVT on PE and/or LE DVT development, and impact of incident UE DVT on cancer specific survival. The association of CVC placement with incident UE DVT was not assessed in acute leukemia patients, as all who undergo treatment were assumed to have a CVC. Results are presented as adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results Among 37,282 patients included in this analysis, 6,213 had AML, 3,730 had ALL and 27,339 had NHL. The 3- and 12-month cumulative incidence of UE DVT was 2.6% and 3.6% for AML, 2.1% and 3% for ALL and 1.0% and 1.6% for NHL respectively (Figure 1A). Most (56-64%) incident UE DVT events occurred within the first 3 months of malignancy diagnosis. African Americans (HR 1.66; CI 1.22-2.28) and Hispanics (HR 1.35; CI 1.10-1.66) with NHL had an increased risk of incident UE DVT compared to non-Hispanics Whites. NHL patients with a CVC had over a 2-fold increased risk of incident UE DVT (HR 2.05; CI 1.68-2.51) compared to those without a CVC. UE DVT was a risk factor for development of PE or LE DVT in ALL (HR 2.53; CI 1.29-4.95) and NHL (HR 1.63; CI 1.11-2.39) but not in AML. The 12-month cumulative incidence of subsequent VTE after an incident UE DVT diagnosis was 6.4% for AML, 12.0% for ALL and 7.6% for NHL. 46-58% of subsequent VTEs occurred within the first 3 months of incident UE DVT diagnosis. The majority of subsequent VTEs were UE DVT which had a 12-month cumulative incidence of 4.6% for AML, 6.6% for ALL and 4.0% for NHL (Figure 1B). The 12-month cumulative incidence of subsequent LE DVT was 1.3% for AML, 1.6% for ALL and 1.9% for NHL (Figure 1C). The 12-month cumulative incidence of subsequent PE was 0.4% for AML, 4.1% for ALL and 1.8% for NHL (Figure 1D). The 12-month cumulative incidence of major bleeding after an UE DVT diagnosis was 29% for AML, 29% for ALL and 20% for NHL. Common major bleeding events included gastrointestinal (GI) bleeds, epistaxis and intracranial hemorrhage. GI bleeding was the most common major bleeding event among all three malignancies (14.2% in AML, 9.6% in ALL and 12.4% in NHL). The rate of intracranial hemorrhage was 6% in AML, 3.5% in ALL and 1.7% in NHL. A diagnosis of incident UE DVT was associated with an increased risk of cancer-specific mortality in all three malignancies (HR 1.38; CI 1.16-1.65 in AML, HR 2.16; CI 1.66-2.82 in ALL, HR 2.38; CI 2.06-2.75 in NHL). Conclusions UE DVT is an important complication among patients with AML, ALL and NHL, with the majority of UE DVT events occurring within the first 3 months of diagnosis. The most common VTE event after an index UE DVT was another UE DVT, although patients also had subsequent PE and LE DVT. UE DVT was a risk factor for development of PE or LE DVT in ALL and NHL, but not in AML. Major bleeding after an UE DVT was high in all three malignancies (>20%), with GI bleeds being the most common. UE DVT in patients with AML, ALL and NHL is associated with increased risk of mortality. Disclosures Wun: Janssen: Other: Steering committee; Pfizer: Other: Steering committee

Fragmentation of Care for Young Adults with Sickle Cell Disease in California

Background: Sickle Cell Disease (SCD) predominantly affects people of African ancestry, causing significant morbidity and mortality. In high-income countries children, who are more likely to receive comprehensive care than adults, have better health care outcomes. Young adults (YA) are in a period of transition from pediatric to adult models of care and the effect of receiving care at multiple medical facilities (fragmentation) during this time on outcomes has not been well-described. In this study we sought to examine fragmentation of care for YA SCD patients and the association of fragmentation on mortality. Methods: Using a previously published definition, longitudinal records from the California Patient Discharge, Emergency Department, and Ambulatory Surgery datasets were used to identify SCD patients from 1991-2016. SCD patients were placed into three different age cohorts: children (10-17), YA (18-25) and adults (26-33). Each patient required the full 7 year follow up time in each age category; patients could be in multiple age cohorts. Patients with no inpatient admissions were excluded. The number of inpatient admissions during each age group period was used as a measure of disease severity (<10, 10-19, 20-29, ≥30). SCD specialty care centers (SCD SC) were determined using all SCD inpatient admissions; facilities in the top 5% based on number of unique SCD patients seen were considered SCD SC. Patients were classified as always, sometimes and never seen at SCD SC facilities in each age group. We classified care fragmentation by the number of facilities an individual received inpatient care (1, 2, 3-4 or ≥5 unique facilities) during their time in each age group. Descriptive statistics were used to describe patients' characteristics by age group. Multivariable Poisson regression was used to identify risk factors associated with fragmented care. Multivariable Cox regression was used to determine the impact of fragmented care, disease severity and care at SCD SC on all-cause mortality, conditional on surviving to 26 years of age for the YA group. Results We identified a cohort of 6,977 unique SCD patients: 1,019 children, 1,122 YAs and 1,015 adults. The YA cohort consisted of predominately African Americans (91.3%) with 43.9% male and 56.1% female. Forty-two % YAs had Medi-Cal followed by 26.7% with private insurance as first reported health insurance. Forty-four % (494) had <10, 20.1% (226) had 10-19, 11.1% (125) had 20-29 and 24.7% (277) had ≥30 inpatient admissions while in the YA age period. Twenty-two % (248) YAs were seen at 1, 25.8% (290) were seen at 2, 30.2% (339) were seen at 3-4, and 21.8% (245) were seen at > 5 inpatient facilities. YAs and older adults were seen at a similar number of facilities while children were seen at less (Figure 1). In multivariable regression models among YAs, those with private insurance (vs. Medi-Cal) were at lower risk of fragmentation (Incident Rate Ratio (IRR)=0.85, CI 0.78-0.93, p=0.0002), while those without insurance were at a higher risk (IRR 1.45, CI 1.22-1.72, p<0.0001). Patients with more admissions (vs. <10) were at higher risk of fragmentation (IRR for 10-19 =1.42, CI 1.29-1.57; IRR for 20-29 1.49, CI 1.33-1.67, IRR for >30 admissions 2.13, CI 1.98-2.43 p<0.0001). Patients who were sometimes admitted to an SCD SC (IRR=2.19, CI 1.98-2.43, p<0.0001) or never (IRR=1.15, CI 1.15-1.46, p<0.0001) were at increased risk of fragmented care compared to those who were always admitted to an SCD SC. In the multivariable mortality model, YAs with increasing number of admissions, regardless of location, were at increased risk of death (10-19 HR 2.36, CI 1.13-4.91 p=0.022; 20-29 HR 4.25, CI 2.03-8.92, p=0.0001; > 30 admissions HR 7.79, CI 4.09-14.83, p<0.0001). Fragmentation of care and always or sometimes being admitted to an SCD SC were not associated with mortality. Conclusion Most young adult SCD patients (78%) received inpatient care at >1 facility. Of all age groups, children were most likely to be seen at only 1 facility, suggesting that fragmentation of care begins in early adulthood. Young adults without insurance, patients with more frequent admissions and those who did not always receive care at an SCD SC were at higher risk for fragmented care. Young adults with more frequent admissions were also at an increased risk of mortality. The effect of specialty centers and more consistent location of care on health-related outcomes for patients with SCD requires further study. Disclosures Wun: Janssen: Other: Steering committee; Pfizer: Other: Steering committee

Upper Extremity Deep Vein Thrombosis in Acute Leukemia and Non-Hodgkin's Lymphoma: Analysis of the California Cancer Registry

Background Venous thromboembolism (VTE) is a known complication in patients with acute myeloid leukemia (AML), acute lymphoid leukemia (ALL) and non-Hodgkin's lymphoma (NHL). However, the cumulative incidence, risk factors, rate of subsequent VTE and impact on mortality of upper extremity deep vein thrombosis (UE DVT) in these diseases is not well-described. Methods Using the California Cancer Registry, we identified patients with a first primary diagnosis of AML, ALL and NHL from 2005-2014 and linked these patients with the statewide hospitalization and emergency department databases to identify an incident UE DVT event using specific ICD-9-CM codes. Patients with VTE prior to or at the time of malignancy diagnosis or who were not treated with chemotherapy were excluded. We determined the cumulative incidence of first UE DVT, adjusted for the competing risk of death. We also examined the cumulative incidence of subsequent VTE (UE DVT, lower extremity deep vein thrombosis (LE DVT) and pulmonary embolism (PE)) and major bleeding after incident UE DVT. Using Cox proportional hazards regression models, stratified by tumor type and adjusted for other prognostic covariates including sex, race/ethnicity, age at diagnosis, neighborhood, sociodemographic status and central venous catheter (CVC) placement, we identified risk factors for development of incident UE DVT, the effect of incident UE DVT on PE and/or LE DVT development, and impact of incident UE DVT on cancer specific survival. The association of CVC placement with incident UE DVT was not assessed in acute leukemia patients, as all who undergo treatment were assumed to have a CVC. Results are presented as adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results Among 37,282 patients included in this analysis, 6,213 had AML, 3,730 had ALL and 27,339 had NHL. The 3- and 12-month cumulative incidence of UE DVT was 2.6% and 3.6% for AML, 2.1% and 3% for ALL and 1.0% and 1.6% for NHL respectively (Figure 1A). Most (56-64%) incident UE DVT events occurred within the first 3 months of malignancy diagnosis. African Americans (HR 1.66; CI 1.22-2.28) and Hispanics (HR 1.35; CI 1.10-1.66) with NHL had an increased risk of incident UE DVT compared to non-Hispanics Whites. NHL patients with a CVC had over a 2-fold increased risk of incident UE DVT (HR 2.05; CI 1.68-2.51) compared to those without a CVC. UE DVT was a risk factor for development of PE or LE DVT in ALL (HR 2.53; CI 1.29-4.95) and NHL (HR 1.63; CI 1.11-2.39) but not in AML. The 12-month cumulative incidence of subsequent VTE after an incident UE DVT diagnosis was 6.4% for AML, 12.0% for ALL and 7.6% for NHL. 46-58% of subsequent VTEs occurred within the first 3 months of incident UE DVT diagnosis. The majority of subsequent VTEs were UE DVT which had a 12-month cumulative incidence of 4.6% for AML, 6.6% for ALL and 4.0% for NHL (Figure 1B). The 12-month cumulative incidence of subsequent LE DVT was 1.3% for AML, 1.6% for ALL and 1.9% for NHL (Figure 1C). The 12-month cumulative incidence of subsequent PE was 0.4% for AML, 4.1% for ALL and 1.8% for NHL (Figure 1D). The 12-month cumulative incidence of major bleeding after an UE DVT diagnosis was 29% for AML, 29% for ALL and 20% for NHL. Common major bleeding events included gastrointestinal (GI) bleeds, epistaxis and intracranial hemorrhage. GI bleeding was the most common major bleeding event among all three malignancies (14.2% in AML, 9.6% in ALL and 12.4% in NHL). The rate of intracranial hemorrhage was 6% in AML, 3.5% in ALL and 1.7% in NHL. A diagnosis of incident UE DVT was associated with an increased risk of cancer-specific mortality in all three malignancies (HR 1.38; CI 1.16-1.65 in AML, HR 2.16; CI 1.66-2.82 in ALL, HR 2.38; CI 2.06-2.75 in NHL). Conclusions UE DVT is an important complication among patients with AML, ALL and NHL, with the majority of UE DVT events occurring within the first 3 months of diagnosis. The most common VTE event after an index UE DVT was another UE DVT, although patients also had subsequent PE and LE DVT. UE DVT was a risk factor for development of PE or LE DVT in ALL and NHL, but not in AML. Major bleeding after an UE DVT was high in all three malignancies (>20%), with GI bleeds being the most common. UE DVT in patients with AML, ALL and NHL is associated with increased risk of mortality. Disclosures Wun: Janssen: Other: Steering committee; Pfizer: Other: Steering committee

Second primary malignancy risk after Hodgkin lymphoma treatment among HIV-uninfected and HIV-infected survivors

We compared secondary primary malignancy risk (SPM) in HIV-uninfected and HIV-infected Hodgkin lymphoma (HL) survivors. We used data from the California Cancer Registry on patients diagnosed with HL from 1990 to 2015 (all ages included), and standardized incidence ratios (SIRs) and multivariable competing risk models for analyses. Of 19,667 survivors, 735 were HIV-infected. Compared with the general population, the risk of SPM was increased by 2.66-fold in HIV-infected and 1.92-fold in HIV-uninfected survivors. Among HIV-infected survivors, median time to development of SPM was shorter (5.4 years) than in HIV-uninfected patients (8.1 years). Additionally, the highest risk of SPM was observed <2 years after diagnosis in HIV-infected survivors (SIR = 4.47), whereas risk was highest ≥20 years after diagnosis (SIR = 2.39) in HIV-uninfected survivors. The risk of SPMs persisted for decades and was higher among HIV-infected survivors, suggesting that these patients should benefit from long-term surveillance and cancer prevention practices

Drowning the pain: Intimate partner violence, and drinking to cope prospectively predict problem drinking

The present study examined the longitudinal association among drinking problems, drinking to cope, and degree of intimate partner violence (IPV). Two competing models were tested; the first model posited that drinking to cope leads to greater drinking problems and this subsequently leads to more violence in the relationship (an intoxication-violence model). The second model speculated that violence in the relationship leads to drinking to cope, which in turn leads to greater drinking problems (a self-medication model). Eight hundred and eighteen undergraduate students at a large north-western university participated in the study over a two year period, completing assessments of IPV, alcohol related problems and drinking to cope at five time points over a two year period as part of a larger social norms intervention study. Analyses examined two competing models; Analyses indicated there was support for the self-mediation model, whereby people who have experienced violence have more drinking problems later, and this association is temporally mediated by drinking to cope

Second Primary Malignancy Risk Among HIV-Uninfected and HIV-Infected Survivors of Hodgkin Lymphoma: A 30-Year Follow-up Population-Based Study

Introduction Second primary malignancy (SPM) is one of the most devastating late complications following Hodgkin lymphoma (HL) treatment. Historically, the most common SPMs in patients treated for HL are solid tumors, which are largely related to radiation exposure during initial therapy. For the last three decades, efforts to address the risk of SPM after HL therapy have focused on reducing exposure to radiation, as well as refining the approach for patients where radiation is indicated. To date, few population-based studies in the United States have quantified the burden of SPMs and evaluated the potential effect of changes in therapeutic management over time. Additionally, to our knowledge, no study has compared SPM risk between human immunodeficiency virus (HIV)-infected and HIV-uninfected HL survivors. Methods We used data from the California Cancer Registry on 21,043 patients diagnosed with primary HL between 1988 and 2015 with follow-up through 2017. We calculated standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (CIs) and absolute excess risks (AERs) to compare SPM incidence in our HL cohort with the expected number of first primary cancer incidence in the general California population, based on patient's age at diagnosis (5-year categories), sex, calendar year (3-year intervals), cancer site, and race/ethnicity. SIRs are presented by HIV status, SPM latency, treatment era, and cancer type. P-values for trends were used to examine whether SPM risk changed over time. Findings Among 20,303 HIV-uninfected patients (median follow-up of 14.1 years), overall SPM risk was increased 1.95-fold compared with the general population (SIR=1.95, 95% CI 1.86-2.04). In 740 HIV-infected patients (median follow-up of 11.7 years), overall risk was increased 2.68-fold compared with the general population (SIR=2.68, 95% CI 2.0-3.40), translating to an 37% higher incidence of SPM in HIV-infected vs. HIV-uninfected patients. The AER (per 10,000 person-years) of SPM was 43.1 in HIV-uninfected and 76.5 in HIV-infected patients, resulting in a 33.4 excess SPM per 10,000 person-years in HL survivors with HIV. Malignancies that contributed the most to overall AER were non-Hodgkin lymphoma (NHL), female breast and lung cancers in HIV-uninfected patients; and Kaposi sarcoma, NHL, anorectal and head & neck (HNC) cancers in HIV-infected patients. Notably, among HIV-uninfected patients, the highest overall risk of SPM occurred ≥20 years after diagnosis (SIR= 2.27, 95% CI 1.99-2.58) (Figure). In contrast, the highest overall risk in HIV-infected patients was observed <2 years after diagnosis (SIR=4.42, 95% CI 2.53-7.19). Radiation used decreased from 46.9% in 1988-1996 to 29.5% in 2007-2015. Among HIV-uninfected patients, there was a trend towards decreased risk over time of overall and selected solid SPMs (lung, female breast, and gastrointestinal cancers) (Table). In an analysis restricted to HIV-uninfected patients who received radiation irrespective of chemotherapy, findings also suggested a declined risk of overall and selected solid SPMs over time: any solid (SIR=2.15 in 1988-1996 and SIR=1.30 in 2007-2015, p<0.0001), lung (SIR=3.69 in 1988-1996 and SIR=1.81 in 2007-2015, p=0.0031), and female breast (SIR=2.95 in 1988-1996 and SIR=0.63 in 2007-2015, p<0.0001). Conclusion Compared with the general population, the risk of developing a SPM following HL treatment was significantly higher among both HIV-uninfected and HIV-infected patients, with the absolute excess risk greater for those with HIV infection. There were different temporal patterns and types of SPM between HIV-uninfected and HIV-infected patients. These findings prompt the question on whether earlier and/or more intensive cancer screening should be pursued for HIV-infected survivors. The trend towards decreased risk for selected solid SPMs among HIV-uninfected patients, especially lung and female breast cancers, suggest that strategies to reduce radiation in HL survivors may be working. Despite promising trends in this group, the observation that SPM risk was highest ≥20 years after initial therapy further highlights the need for long-term surveillance and survivorship care in this at-risk population. Disclosures Rosenberg: Takeda: Speakers Bureau; Janssen: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Wun:Glycomimetics, Inc.: Consultancy

Pregnancy Outcomes in Women with Sickle Cell Disease in California: A Retrospective Cohort Study

Abstract Background: Women with sickle cell disease (SCD) are at high risk for obstetrical and SCD-related complications throughout pregnancy. Given the dearth of recent population-based studies on female reproductive health in SCD, we used hospitalization data from the socio-economically diverse state of California to describe peripartum outcomes in women with SCD. Methods: For our retrospective cohort study, we identified females with SCD who were either evaluated in the emergency department (ED) or hospitalized between the ages of 10-45 years from California's patient discharge dataset (1991-2016). We defined SCD severity by frequency of utilization with severe disease requiring an average of ≥ 3 hospitalizations and/or ED visits per year, and less severe with an annual rate of < 3 acute care visits. We used ICD-9/10-CM codes to identify all deliveries, and categorized pregnancy outcomes as either incomplete (hydatidiform mole, elective termination, miscarriage, and ectopic pregnancies) or delivery (live or stillbirths). We defined race/ethnicity as Black (or African American) vs. non-Black and quantified the total number of pregnancies for each patient. We described delivery age, mode (C-section vs. vaginal), outcome (live vs. stillbirth), median length of stay (LOS), and maternal mortality for the first in-hospital delivery. Results: Our cohort comprised 3,089 females with SCD of childbearing age, with a median follow-up of 11 years. Of the 1,108 (35.9%) women with at least one pregnancy, 1,000 (90.3%) were Black and 591 (53.3%) had severe SCD. Overall, we observed 2,330 pregnancies; of the 1,864 (80%) deliveries , 45% occurred via C-section (Figure 1). When we restricted our analysis to first deliveries only, 346 (36.0%) occurred in women ages 20-24 years; the next highest proportion of deliveries (23.4%) was in adolescents ages 15-19 years (Figure 2). Only 5.5% of deliveries occurred in women ≥ 35 years old. One hundred seventy-two (15.5%) first pregnancies were incomplete (Table 1), primarily due to miscarriage (59.3%). Of the women with incomplete first pregnancies, 69.2% had severe SCD; in contrast, 50.4% had severe SCD in the first delivered pregnancies' subset. Of the 936 first deliveries, 41.5% were by C-section with a median LOS of 5 days, compared with 3 days for those who delivered vaginally. Twenty-two first deliveries (2.4%) were stillbirth for a rate of 24.9 stillbirths per 1000 deliveries. Of the 862 live births, 5 women died, which resulted in an inpatient maternal mortality rate of 580.1 per 100,000 live births. Discussion Pregnant women with SCD first delivered in the hospital at a mean age of 24.1 years, which is younger than the US national mean of 26.8 years (all races) and 24.9 years (Black), based on 2017 maternal health data from the Centers for Disease Control and Prevention (CDC). We attribute this age difference to the higher proportion of first deliveries in adolescents with SCD coupled with the trend towards older age of first delivery in the general population. For first deliveries, 41.5% of women with SCD underwent a C-section, compared with a 2013 national average of 22.8% (all races) and 25.7% (Black) in primigravid women in the US. Stillbirths in our SCD cohort surpassed the 2014 national rates of 5.9 (all races) and 10.3 (Black) stillbirths per 1000 deliveries. Lastly, the inpatient maternal mortality rate in women with SCD, while based only on 5 deaths, far exceeds the 2014-2017 US maternal mortality rates of 17.3 (all races) and 41.7 (Black) deaths per 100,000 live births. Limitations include the lack of outpatient data, which likely resulted in an underestimation of the total number of pregnancies. Maternal mortality rates from the CDC cover death up to 12 months postpartum, so a comparable mortality rate for women with SCD might be higher. The striking disparities in outcomes in our study cohort, compared to national averages, suggests notable deficits in the optimal management of pregnancy in SCD. Analyses are ongoing to determine the effect of pregnancy on sickle-cell related complications, to evaluate the frequency of peripartum complications in women with SCD (e.g., venous thromboembolism, preeclampsia, and post-partum hemorrhage), and to compare rates of obstetrical complications in SCD vs non-SCD women, adjusted for social determinants of health. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare