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Background Racial/ethnic disparities in the utilization of hematopoietic cell transplantation (HCT) have been reported for patients with hematologic malignancies, but population‐based data are lacking for lymphoma patients. The objective of this study was to determine whether racial and ethnic disparities exist in the utilization of autologous HCT for lymphoma in the United States. Method We used Surveillance, Epidemiology, and End Results data linked to Medicare fee‐for‐service claims. We included Medicare beneficiaries aged 66+ years with Hodgkin or Non‐Hodgkin lymphomas diagnosed between 2008 and 2015. The primary outcome was time‐to‐autologous HCT. We used Cox proportional hazards models to estimate racial/ethnic differences in utilization. Missing data were handled using multiple imputation with chained equations. Results We included 40,605 individuals with lymphoma. A total of 452 autologous transplants were performed. In the unadjusted model, Non‐Hispanic Black patients were 51% less likely to receive a transplant than Non‐Hispanic White patients (95% CI, 0.26–0.96; p = 0.04). After adjusting for age at diagnosis and sex, Non‐Hispanic Black patients were 61% less likely to receive a transplant (95% CI, 0.20–0.76; p = 0.01). However, observed differences attenuated and became non‐significant after adjustment for socioeconomic factors (adjusted hazard ratio [aHR], 0.62; 95% CI, 0.32–1.21; p = 0.16) and disease‐specific factors (aHR, 0.58; 95% CI, 0.30–1.12; p = 0.11), separately. In the fully adjusted model, we also did not observe a statistically significant association between Non‐Hispanic Black race/ethnicity and receipt of transplant (aHR, 0.54; 95% CI, 0.28–1.05; p = 0.07). Conclusion In this population‐based cohort study of lymphoma patients, Non‐Hispanic Black patients were less likely to receive autologous HCT compared to Non‐Hispanic White patients, but this difference was partially explained by socioeconomic and disease‐specific factors., Non‐Hispanic Black patients diagnosed with lymphoma between 2008 and 2015 were 51% less likely to receive an autologous transplant compared to Non‐Hispanic White patients. This difference was partially explained by socioeconomic and disease‐specific factors.

There is a paucity of data regarding racial disparities in the survival of patients with indolent non-Hodgkin lymphomas (iNHL) in the contemporary time-period. Hence, we sought to determine whether racial disparities exist in the survival of patients with iNHLs in the US. We included 68,059 adult patients with follicular lymphoma (FL, n=41,943), marginal zone lymphoma (MZL, n=22,485), and lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM, n=3,631) who were diagnosed in the US between 2000-2017. Race was categorized as White, Black, Asian/Pacific Islander, or American Indian/Alaska Native (API/AI). The primary outcome was relative survival (RS), which was estimated using flexible parametric survival models. RS estimates varied according to race and disease histology but were consistently lower for racial minorities, including those diagnosed during the most recent 5-year time-period of 2012-2017. On multivariable analysis for RS, Black patients with FL had a 32% higher excess mortality rate compared to White patients [adjusted excess hazard ratio (aEHR), 1.32; 95% CI, 1.15-1.51; P

PURPOSESARS-CoV-2 (COVID-19) is a systemic infection. Patients with cancer are immunocompromised and may be vulnerable to COVID-related morbidity and mortality. The objectives of this study were to determine if patients with cancer have worse outcomes compared with patients without cancer and to identify demographic and clinical predictors of morbidity and mortality among patients with cancer.METHODSWe used data from adult patients who tested positive for COVID-19 and were admitted to two New York–Presbyterian hospitals between March 3 and May 15, 2020. Patients with cancer were matched 1:4 to controls without cancer in terms of age, sex, and number of comorbidities. Using Kaplan-Meier curves and the log-rank test, we compared morbidity (intensive care unit admission and intubation) and mortality outcomes between patients with cancer and controls. Among those with cancer, we identified demographic and clinical predictors of worse outcomes using Cox proportional hazard models.RESULTSWe included 585 patients who were COVID-19 positive, of whom 117 had active malignancy, defined as those receiving cancer-directed therapy or under active surveillance within 6 months of admission. Presenting symptoms and in-hospital complications were similar between the cancer and noncancer groups. Nearly one half of patients with cancer were receiving therapy, and 45% of patients received cytotoxic or immunosuppressive treatment within 90 days of admission. There were no statistically significant differences in morbidity or mortality ( P = .894) between patients with and without cancer.CONCLUSIONWe observed that patients with COVID-19 and cancer had similar outcomes compared with matched patients without cancer. This finding suggests that a diagnosis of active cancer alone and recent anticancer therapy do not predict worse COVID-19 outcomes and therefore, recommendations to limit cancer-directed therapy must be considered carefully in relation to cancer-specific outcomes and death.

Increasing evidence suggests that asymptomatic carriers are an important source of healthcare-associated Clostridium difficile infection. However, it is not known which test for the detection of C. difficile colonization is most sensitive in patients with haematological malignancies. We performed a prospective cohort study of 101 patients with haematological malignancies who had been admitted to the hospital for scheduled chemotherapy or haematopoietic cell transplantation. Each patient provided a formed stool sample. We compared the performance of five different commercially available assays, using toxigenic culture as the reference method. The prevalence of toxigenic C. difficile colonization as determined by toxigenic culture was 14/101 (14 %). The Cepheid Xpert PCR C. difficile/Epi was the most sensitive test for the detection of toxigenic C. difficile colonization, with 93 % sensitivity and 99 % negative predictive value. Our findings suggest that the Xpert PCR C. difficile/Epi could be used to rule out toxigenic C. difficile colonization in this population.

Background Population‐based studies previously showed an improvement in overall survival (OS) for patients with diffuse large B‐cell lymphoma (DLBCL) who received chemoimmunotherapy with rituximab. However, there is limited data (especially at the population level) that show a similar trend in OS improvement, in the most recent time period. We hypothesized that survival for DLBCL patients diagnosed in the United States has continued to improve in recent years and intended to measure outcome improvements. Methods Using the SEER‐18 registries, we compared the incidence and relative survival rates (RSRs) of DLBCL patients between 2002‐2007 and 2008‐2013 (availability of novel agents, broader use of autologous hematopoietic cell transplantation and improvement in supportive care). Multivariable Cox regression models were used to assess associations between the year of diagnosis and OS while controlling for age, gender, stage, and ethnicity. Results There were a total of 53 439 patients with DLBCL who were diagnosed between 2002 and 2013. Of these, 25 810 were diagnosed during time period‐1 and 27 629 diagnosed during time period‐2. There was a slight decline in incidence of DLBCL (time period‐1 vs time period‐2), 7.75 (95% CI = 7.66‐7.84) vs 7.43 (95% CI = 7.34‐7.52) cases per 100 000 persons, respectively (P, There is a paucity of data at the population level on the overall survival trend in DLBCL patients in the contemporaneous time period. We show that although there has been a continuous improvement in the outcomes of DLBCL patients over the past decade, the magnitude of improvement is small, reflecting the modest progress made beyond rituximab in the treatment of DLBCL.

Acute leukemia is a family of clonal hematopoietic disorders characterized by genetic and epigenetic alterations leading to a block in differentiation and accumulation of leukemic blasts in blood a...

Introduction: Splenic marginal zone lymphoma (SMZL) is an indolent B-cell non-Hodgkin lymphoma that usually presents in elderly patients with splenomegaly, lymphocytosis, and cytopenias (either due to hypersplenism or autoimmune phenomena). Treatment of SMZL has advanced over the past decade including identification of better tolerable chemotherapy regimens (such as rituximab and bendamustine) and the advent of novel agents (such as ibrutinib and lenalidomide). We sought to determine whether advances in treatment and supportive care over the past decade have translated to decreased lymphoma-specific mortality among patients with SMZL. Method: We used the population-based Surveillance, Epidemiology, and End Results (SEER)-18 database. We included adult patients with SMZL diagnosed between 2000-2017 who were 18-84 years old at the time of diagnosis. We excluded patients with a history of malignancy prior to SMZL, those with missing survival times and those with central nervous system involvement. Patients were divided into two cohorts based on period of diagnosis (era-1: 2000-2008, and era-2: 2009-2017). Five-year relative survival (RS) was estimated using the Pohar-Perme method. Differences between RS distributions was tested with a log-rank-type test. The risk of SMZL-specific death was estimated by calculating the cumulative incidence function (CIF). The difference between CIF distributions was tested with the Pepe-Mori test. The competing risks of SMZL-specific death and death from other causes were modeled using Fine and Gray regression. All tests of differences were performed at a two-sided alpha of 0.05. Results: We included 1,548 patients with SMZL. Table 1 shows the baseline characteristics. The median age at diagnosis was 66 years (IQR = 57-74) years. Most patients were non-Hispanic White (81%) with advanced stage at diagnosis (stage III-IV, 70%). Five-year RS was 84% (95% CI = 80-87%) during era-1 and 89% (95% CI = 85-92%) during era-2 (p = 0.21. The CIF distributions for SMZL-specific death and death from other causes are shown in Figure 1A and Figure 1B, respectively (Pepe-Mori p = 0.02). In our multivariable competing risks model, the period of diagnosis, age, and stage at diagnosis were significant predictors of SMZL-specific death (Table 2). Patients in era-2 had significantly lower risk of SMZL-specific death [subhazard ratio (SHR) = 0.30, 95% CI = 0.22-0.41), while the cumulative incidence of mortality significantly increased with age (SHR = 1.39 per decade, 95% CI = 1.24-1.56) and advanced stage (SHR = 1.55, 95% CI= 1.04-2.13). Conclusion: There has been a significant reduction in the risk of SMZL-specific death for patients with SMZL in the most recent era possibly due to advances in therapy. This reduction in mortality persists even after accounting for competing risks of mortality from other causes. Disclosures Olszewski: Spectrum Pharmaceuticals: Research Funding; Adaptive Biotechnologies: Research Funding; TG Therapeutics: Research Funding; Genentech, Inc.: Research Funding. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria.

Introduction: Racial and ethnic disparities have been described for patients with aggressive non-Hodgkin lymphomas (NHLs), but few studies have investigated racial disparities in patients with indolent NHLs. Indolent NHLs are a large group of lymphoid neoplasms that include follicular lymphoma (FL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and Waldenstrom macroglobulinemia (WM). Differences in biologic factors (e.g., metabolism of drugs), health disparities (e.g., enrollment in clinical trials), individual factors (e.g., comorbid conditions), and structural barriers (e.g., access to novel therapies) may lead to racial and ethnic disparities in these patients. We aimed to determine whether racial and ethnic disparities exist in the survival of patients with indolent NHLs in the United States. Method: We used the population-based Surveillance, Epidemiology, and End Results (SEER)-18 database. We included adult patients with FL, MZL, MCL, and WM diagnosed between 2000-2017 who were 18-84 years old at the time of diagnosis. We excluded patients with a history of prior malignancies, missing survival times, central nervous system involvement, and unknown race/ethnicity. Race/ethnicity were categorized as Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Hispanic, Asian/Pacific Islander, and American Indian/Alaska Native. Marginal relative survival (RS) was estimated using the Pohar-Perme method, which estimates net survival within a relative survival framework. Expected survival was determined by matching patients to individuals in the general population by age, sex, race/ethnicity, and year. RS was modeled using Poisson regression where the effect of follow-up time was included as restricted cubic spline with 5 knots. The primary exposure variable in our model was race/ethnicity. Interactions between the main effect and significant covariates were examined (in particular disease histology). All tests of differences were performed at a two-sided alpha of 0.05. Results: There were a total of 63,855 patients included in our study. Among these patients, 35,466 had FL, 18,188 had MZL, 7,005 had MCL, and 3,196 had WM. Table 1 shows the baseline characteristics stratified based on the race/ethnicity. The median age for all patients was 63 years (IQR = 54-72 years). The majority of patients were NHW (75%). Median length of follow-up was 5.4 years (IQR = 2.2-9.7 years). As shown in Figure 1, RS (unadjusted) for patients with indolent NHL varied according to race and ethnicity. American Indians/Alaska Natives had the lowest survival at 10 years. Estimated 10-year RS (95% CI) was 78% (77-79%) for NHW, 76% (73-79%) for NHB, 79% (77-81%) for Hispanics, 79% (76-81%) for Asians/Pacific Islanders, and 69% (59-76%) for American Indians/Alaska Natives. On multivariable Poisson regression after adjusting for differences in age, sex, stage, median household income, and disease histology, racial/ethnic minorities had significantly increased hazard for excess mortality (NHB=1.37, Hispanic=1.14, Asians/Pacific Islanders=1.20, American Indians/Alaska Natives=1.75) compared to NHW patients (Table 2). There was no significant interaction between race and disease histology (likelihood ratio test p=0.21). Conclusion: In this large population-based analysis of patients with indolent NHL in the US, we found that racial and ethnic minorities had inferior survival over the past two decades after adjusting for other confounding variables. American Indians and Alaska Natives had the highest mortality followed by NHB, Asians/Pacific Islanders, and Hispanics. One of the plausible explanations for this trend could be related to decreased access to healthcare. Our study emphasizes the need for additional research into racial/ethnic disparities for lymphoma patients. Disclosures Epperla: Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria.

Introduction: Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL) is the most common subtype of MZL. EMZL can affect multiple organs throughout the body, and the management depends on the primary site of involvement and extent of disease. The most common primary site is the stomach, but other sites can be involved including the breasts, eyes, lungs, salivary glands, and skin. The last population-based survival analysis of EZML included follow-up through 2009 (Olszewski and Castillo, 2013). Given the paucity of population-based analyses of EMZL in the contemporary time-period, we sought to provide an updated analysis of disease-specific mortality and site-associated mortality using the Surveillance, Epidemiology, and End Results (SEER)-18 database. Method: We included adult patients with EMZL diagnosed between 2000-2017 who were 18-84 years old at the time of diagnosis. We excluded patients with a history of malignancy prior to EMZL, those with missing survival times and those with central nervous system involvement. Patients were divided into two cohorts based on period of diagnosis (era-1: 2000-2008, and era-2: 2009-2017). Five-year relative survival (RS) was estimated using the Pohar-Perme method. The risk of EMZL-specific death was estimated by calculating the cumulative incidence function (CIF). The difference between CIF distributions was tested with the Pepe-Mori test. The competing risks of EMZL-specific death and death from other causes were modeled using Fine and Gray regression. All tests of differences were performed at a two-sided alpha of 0.05. Results: We included a total of 11,597 patients with EMZL. Table 1 shows the baseline characteristics. Among the entire cohort, the median age at diagnosis was 63 years (IQR = 53-72). There was a slight female predominance (55%), and most patients were Non-Hispanic White (65%). Five-year RS was 95% (95% CI = 94-96%) during era-1 and 96% (95-97%) during era-2. There was a significant reduction in the cumulative incidence of EMZL-specific death between era-1 and era-2 (p < 0.001, Figure 1A) but not death from other causes (p = 0.35, Figure 1B). The cumulative incidence of EMZL-specific death varied according to EMZL subtype (Figure 2). In our multivariable competing risks model after adjusting for confounders (Table 2), EZMLs arising from the genitourinary (GU) tract had the worst prognosis [subhazard ratio (SHR) = 2.06, 95% CI=1.30-3.27, p=0.002], whereas EZMLs arising from the skin and connective tissue had the best prognosis [SHR = 0.66, 95% CI = 0.48 - 0.91, p = 0.01]. Conclusion: In this updated population-based analysis of EZML that includes patients treated in the contemporaneous time-period, we found that patients diagnosed with EZML in the most recent era had a significantly better prognosis. Additionally, we noted that the outcomes varied depending on primary site of involvement. Patients with EZMLs involving the GU tract had the worst prognosis, whereas patients with primary sites in the skin and connective tissue had the best prognosis. It is important to study the biology of EMZL involving the GU tract to design better therapeutic options to improve the outcomes. Disclosures Epperla: Pharmacyclics: Honoraria; Verastem Oncology: Speakers Bureau.

Introduction Racial disparities have been documented in hematopoietic cell transplantation (HCT), a complex and expensive therapeutic modality for hematologic malignancies. Prior work suggests that racial minorities in the US have lower rates of utilization of HCT compared to White patients. However, the available literature on racial disparities in HCT is limited, particularly with regard to lymphoma patients. Objectives The objective of this study was to determine if racial differences exist in utilization of HCT for lymphoma by comparing transplant activity to disease incidence rates between 2013-2016. Methods This was a retrospective cohort study using publicly available data from the Center for International Blood and Marrow Transplant Research; Surveillance, Epidemiology, End Results program; and US Census Bureau. All patients in the US who underwent HCT for Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL) between 2013-2016 were included. Patients with unknown race or multiple races were excluded. We assessed transplant utilization by calculating the transplant utilization rate (TUR) for each disease, separately. Rates were operationalized as the number of transplants performed per 100 new cases of the disease diagnosed in the US during the same time period. Results There were a total of 18,569 transplants for HL and NHL included. Table 1 shows patient characteristics by transplant type. During the same time period, age-adjusted incidence rates [95% confidence interval (CI)] for HL for Whites, Blacks, Asians/Pacific Islanders (API), and American Indians/Alaska Natives (AI) were 2.65 (2.59-2.71), 2.61 (2.46-2.77), 1.24 (1.14-1.36), and 1.00 (0.73-1.34) cases/100,000 persons at risk, respectively. Incidence rates were higher for NHL for the same racial groups at 20.22 (20.05-20.38), 14.44 (14.06-14.82), 13.53 (13.16-13.90), and 8.75 (7.82-9.75), respectively. Transplant and incidence data were consistent from 2013-2016. There were no significant differences in TURs for HL between racial groups. However, Whites with NHL had a higher TUR than Blacks [7.02 (95% CI 6.90-7.13) vs 4.75 (95% CI 4.49-5.02), p Conclusion Autologous HCT for NHL is underutilized for Black patients compared to White patients in the US. Additional research is needed to understand the reasons for this difference.

Introduction: The majority of patients with classical Hodgkin lymphoma (cHL) will be cured with anthracycline-containing chemotherapy regimens. However, 10-20% of patients with early-stage disease and 30-40% of patients with advanced-stage cHL will relapse. The standard treatment for patients with relapsed cHL is salvage chemoimmunotherapy followed by high-dose chemotherapy (HDT) and autologous hematopoietic cell transplantation (auto-HCT) in chemotherapy-sensitive patients. Patients with primary treatment failure (PTF), i.e. patients who have progressive disease while on therapy or who fail to achieve complete remission (CR) at the end of initial therapy, or experience early relapse after CR1 are expected to have a worse prognosis than patients with late relapse. Since 2011 newer treatments, namely Brentuximab vedotin and PD1/PDL1 blockers have been introduced for the treatment of relapsed and refractory cHL. It is unknown whether changes in disease monitoring and management, including the availability of new agents, impacted survival of patients with cHL and PTF. Methods: Fifteen US academic medical centers contributed cases to the ECLIPSE study (Evaluation of Classical Hodgkin Lymphoma patients wIth Primary treatment failure and analySis of outcomEs). ECLIPSE retrospectively captured patient, disease and treatment characteristics and treatment response as assessed by treating physicians. Eligible patients were ≥ 15 years diagnosed with cHL on or after 2005, who received treatment with curative intent with anthracycline-containing chemotherapy regimens, and developed one of the 3 patterns of PTF: detection of progressive disease during or within 6 weeks of completion of chemotherapy (PP cohort, primary progression), partial response (PR) or stable disease (SD) by functional imaging at completion of chemotherapy (PR/SD cohort), or disease progression detected within 12 months of completion of chemotherapy after prior documentation of CR (ER cohort, early relapse). Patients were divided into two "eras" based on year of diagnosis, 2005-2010 (era1) and 2011-2018 (era2), with the latter expected to reflect changes in salvage therapy for cHL. Results: Patient characteristics for the 553 cases are summarized in Table. Median follow up of survivors was 58.7 and 31.2 months for patients diagnosed in era1 and era2, respectively. ABVD was the upfront treatment for 97.6% of cases. Nearly all patients (98.5%) received salvage therapy after PTF and 60.9% underwent auto-HCT. Patients who relapsed or progressed post auto-HCT received a median of 1 (range 0 to 3) salvage regimens. Five-year overall survival (OS) from time of PTF was 70.3% (95% CI=63.4-77.2%) for patients diagnosed in era1, and 77.6% (95% CI=70.3-84.8%, p = 0.018) for patients diagnosed in era2 (Figure A). While there was no difference in OS among the PP, PR/SD and ER cohorts in the era1 (Figure B), the PR/SD and ER cohorts had better OS than PP cohort in era2 (Figure C). On comparing the OS for each of the 3 cohorts between era1 and era2, there was an improvement in OS in the PR/SD (Figure E) and ER cohorts (Figure F) but no improvement among the PP cohort (D). Multivariable analysis of patients in era 2 identified only age (HR 1.05, 95% CI=1.03-1.07, P Conclusions: Though there has been an improvement in survival among cHL cases with PTF treated in the most recent years, the outcome of patients with PP did not change significantly across eras. Patients with PP disease should be prioritized for clinical trials incorporating newer agents and innovative cellular therapy to current available effective treatments. Disclosures Epperla: Pharmacyclics: Honoraria; Verastem Oncology: Speakers Bureau. Costa:Abbvie: Consultancy; Karyopharm: Consultancy; Fujimoto Pharmaceutical Corporation Japan: Other: Advisor; Sanofi: Consultancy, Honoraria, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding. Cashen:Novartis: Other: Speaker's Bureau; Seattle Genetics: Other: Speaker's Bureau; Celgene: Other: Speaker's Bureau. Hamadani:Otsuka: Research Funding; Takeda: Research Funding; Pharmacyclics: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Merck: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Celgene: Consultancy; Janssen: Consultancy; Medimmune: Consultancy, Research Funding. Barta:Mundipharma: Honoraria; Celgene: Research Funding; Takeda: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Research Funding; Bayer: Consultancy, Research Funding; Mundipharma: Honoraria; Merck: Research Funding; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees. Reddy:Celgene: Consultancy; BMS: Consultancy, Research Funding; Genentech: Research Funding; Abbvie: Consultancy; KITE Pharma: Consultancy. Karmali:Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau; Takeda, BMS: Other: Research Funding to Institution; Astrazeneca: Speakers Bureau. Bello:Celgene: Speakers Bureau. Chavez:Novartis: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Svoboda:AstraZeneca: Consultancy; Celgene: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; Kyowa: Consultancy; Merck: Research Funding; BMS: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding. Glenn:BMS: Research Funding; Merck: Research Funding; Genentech: Research Funding. Cohen:Lymphoma Research Foundation: Research Funding; Seattle Genetics, Inc.: Consultancy, Research Funding; ASH: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; Bristol-Meyers Squibb Company: Research Funding; Genentech, Inc.: Consultancy, Research Funding; Janssen Pharmaceuticals: Consultancy; LAM Therapeutics: Research Funding; UNUM: Research Funding; Hutchison: Research Funding; Astra Zeneca: Research Funding.

Background: Haploidentical hematopoietic cell transplantation (haplo-HCT) is an advancing and potentially curative therapy for patients with hematologic malignancies when the availability of HLA-matched donors are limited. The common source for haplo-HCT is donor bone marrow, but peripheral blood (PB) haplo-HCT is an emerging and less invasive option with similar survival outcomes. However, multiple series showed an increased incidence of culture negative fever early after haplo-HCT, which has been attributed to cytokine release syndrome (CRS) and more commonly observed with PB haplo-HCT. In this study, we investigated the incidence and impact of CRS on clinical outcomes and financial toxicity in PB haplo-HCT patients treated at a single center. Methods: A total of 40 patients who underwent PB haplo-HCT in the Ohio State University between Jan 2015 - Dec 2017 were included. CRS was defined and graded based on the criteria proposed by Lee, et al (Blood, 2014). Symptoms occurring before day +14 were included, patients with a documented infection (e.g. positive culture data) and clinical suspicion of sepsis were excluded. Overall survival (OS) was defined as the time from transplantation until death. Transplant-related mortality (TRM) was defined as death before day +28 from any cause and patients who died after day +28 with no evidence of disease. Results:. The median age at HCT was 53 years (range, 19 to 74), 63% were male. The most common diagnosis was acute myeloid leukemia (47.5%), followed by lymphoma (22.5%), acute lymphoblastic leukemia (7.5%) and myelodysplastic syndrome (7.5%). Two patients had undergone previous autologous HCT. At the time of haplo-HCT, 62% of patients were in complete remission, 38% had relapsed/refractory disease. Donor was the child in 58%, sibling in 24% and parent in 18% with an antigen match ratio of 5/10 in 50%, 6/10 in 30%, 7/10 in 12.5%, 8/10 in 7.5%. Mismatch for sex and ABO blood group were seen in 50% and 45%, respectively. Twenty percent of patients received myeloablative conditioning with fludarabine/busulfan/thiotepa, while 80% received reduced-intensity regimen with fludarabine/cyclophosphamide/total body irradiation. The incidence of CRS was 85%, including grade 1-2 CRS in 77.5% and grade 3-4 CRS in 7.5%. Time to the onset of CRS was Conclusions: CRS is commonly observed after PB haplo-HCT and usually manifests with fever within 48 hours of cell infusion. We observed favorable survival outcomes in patients who experienced mild CRS, which may suggest an association between mild CRS and graft-versus-leukemia effect. A minority of patients developed severe CRS requiring intensive care unit support, which was associated with poor OS, high TRM, prolonged hospital stay and increased financial toxicity. Further studies investigating biomarkers that can predict the development of severe CRS might enable the incorporation of CRS prophylaxis (e.g. with tocilizumab) into standard conditioning regimens for PB haplo-HCT. Disclosures Vasu: Boehringer Ingelheim Inc: Membership on an entity's Board of Directors or advisory committees. Mims:Novartis: Consultancy; Abbvie Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Devine:Kiadis Pharma: Consultancy. Jaglowski:Novartis Pharmaceuticals Corporation: Consultancy, Research Funding; Kite Pharma: Consultancy, Research Funding; Juno: Consultancy.

Phenomenon: Medical students commonly participate in patient care in a variety of different settings. However, a systematic review of patients' attitudes toward medical student participation across specialties has not been performed.The authors searched 7 databases (CINAHL, Cochrane Library, ERIC, MEDLINE, PsycINFO, Scopus, and Web of Science) between January 1, 1999, and August 5, 2014. Two authors independently screened the results and selected articles that were written in English, were published in a peer-reviewed journal, and used a structured or semistructured survey or interview to determine patients' attitudes toward medical student participation in their care. Study quality was assessed using the Medical Education Research Study Quality Instrument.Fifty-nine studies were included. Average study quality was low. Sixty-one unique evaluation instruments were used, and 34 instruments (56%) lacked validity data. Patient satisfaction was not significantly affected by medical student participation. However, patients' acceptance of medical student participation varied widely between studies and depended on the type of participation. The most common reason for acceptance was a desire to contribute to the education of others, and the most common reason for refusal was concerns about privacy. Minorities were more likely to refuse medical student participation. Patients preferred to be informed before medical students participated in their care. Insights: Patient satisfaction is not significantly affected by medical student participation. However, patient satisfaction may be a poor surrogate marker of patients' acceptance of medical students. Future research should employ validated evaluation instruments to further explore patients' attitudes toward medical student participation.

Sulindac is a long-acting nonsteroidal anti-inflammatory drug (NSAID) widely used for the management of osteoarthritis, rheumatoid arthritis, ankylosing sponydlitis, and acute gouty arthritis. Reports of sulindac toxicity in the literature are rare. We report the case of a 22-year old male with a history of bipolar disorder who was brought to the emergency department after ingesting approximately 15 g of sulindac in a suicide attempt. He was found to have acute kidney injury and hyperbilirubinemia. Despite aggressive fluid resuscitation, his renal function progressively worsened requiring the initiation of hemodialysis. Ten days following ingestion of sulindac, he began to develop ischemic skin changes with a gangrenous appearance in his hands and feet. He continued to receive supportive treatment, and his acute kidney injury, hyperbillirubinemia, and ischemic skin necrosis eventually resolved. Clinicians should be aware of this long-acting NSAID and its ability to cause prolonged multisystem organ dysfunction.

Factor Va, the cofactor of prothrombinase, is composed of heavy and light chains associated noncovalently in the presence of divalent metal ions. The COOH-terminal region of the heavy chain contains acidic amino acid clusters that are important for cofactor activity. In this work, we have investigated the role of amino acid region 659-663, which contains five consecutive acidic amino acid residues, by site-directed mutagenesis. We have generated factor V molecules in which all residues were mutated to either lysine (factor V(5K)) or alanine (factor V(5A)). We have also constructed a mutant molecule with this region deleted (factor V(Δ659-663)). The recombinant molecules along with wild-type factor V (factor V(WT)) were transiently expressed in mammalian cells, purified, and assessed for cofactor activity. Two-stage clotting assays revealed that the mutant molecules had reduced clotting activities compared to that of factor Va(WT). Kinetic analyses of prothrombinase assembled with the mutant molecules demonstrated diminished k(cat) values, while the affinity of all mutant molecules for factor Xa was similar to that for factor Va(WT). Gel electrophoresis analyses of plasma-derived and recombinant mutant prothrombin activation demonstrated delayed cleavage of prothrombin at both Arg(320) and Arg(271) by prothrombinase assembled with the mutant molecules, resulting in meizothrombin lingering throughout the activation process. These results were confirmed after analysis of the cleavage of FPR-meizothrombin. Our findings provide new insights into the structural contribution of the acidic COOH-terminal region of factor Va heavy chain to factor Xa activity within prothrombinase and demonstrate that amino acid region 659-663 from the heavy chain of the cofactor contributes to the regulation of the rate of cleavage of prothrombin by prothrombinase.

Abstract 4460 Introduction: Multiple myeloma patients after autologous hematopoietic stem cell transplant (HSCT) achieve a minimal residual disease state, providing an opportunity for immunomodulatory therapy – but the details of immune recovery after transplant are not clear. Early lymphocyte recovery is associated with improved overall survival (Porrata et al, 2003) which is thought to be related to NK cell recovery. Myeloma patients with long term disease control have recovered circulating B-cells, bone marrow dendritic cells and tissue macrophages similar to healthy adults, but have few circulating regulatory T-cells (Pessoa et al, Haematologica, 2012). Methods: This trial assessed immune function as measured by response to the conjugate vaccine to Streptococcus pneumoniae (Prevnar, PCV7), detailed peripheral blood lymphocyte subset analysis (including NK cell subsets and Tregs), as well as quality of life measures (Hospital Anxiety and Depression Scale, Brief Fatigue Inventory [BFI], Brief Pain Inventory [BPI], and the FACT-G) after autologous transplant for myeloma. Myeloma patients after either 140 or 200 mg/m2 melphalan HSCT were enrolled if they had ANC ≥1000/μL, platelet count ≥ 75,000/μL, and adequate hepatic function by the time Prevnar [serotypes 4, 9V, 14, 18C, 19F, 23F, and 6B] was administered on weeks 9 [month 2], 17 [month 4], and 25 [month 6] after autologous HSCT. Maintenance therapy was an exclusion criteria. Results: Thirty patients were enrolled – twelve with ISS stage 1 at diagnosis, six with ISS 2, five patients with ISS 3, and nine were unknown. Disease status pre-transplant revealed 34% CR and 78% ≥PR, at +60 days 44% CR and 94% ≥PR, but by +180 days the ≥PR was down to 76% due primarily to relapses from CR. With a median follow-up of 35 months since diagnosis and 28 months since transplant, median time to progression has not been reached. We used ELISA to assess antibody concentration against immunogenic antigens (14 & 18c) and the less immunogenic antigen 23F. Two months after each PCV7 injection [weeks 13, 25, and 33], an adequate response (>35 mcg/mL) was demonstrated for antigen 14 in 7% (2/29) at week 13, 16% (4/25) at week 25, and 19% (5/27) at week 33. For antigen 18C, 6.7% (2/30) at week 13, 8.3% (2/24) at week 25, and Z% (4/26) at week 33. At one year responses faded with only 10% (2/20) for antigen 14, 0% (0/24) for antigen 18C, and 0% (0/7) for antigen 23F. Quality of life analyses including BFI, FACT-G, BPI, and HADS showed no significant changes from weeks 9, 17, 25, and off study except for worsening anxiety and depression at one year post-transplant compared to study entry. Peripheral blood flow cytometry using Cox univariate analysis showed an association with overall survival with late activated T-cells (CD3+HLA-DR+, p Conclusions: In this pilot trial of 30 myeloma patients we have shown that the adaptive immune system is profoundly suppressed with a minority of patients reacting to the conjugate vaccine Prevnar. Depression and anxiety both worsen in the first year post transplant. Multivariate and grouped covariate analyses of peripheral blood lymphocyte subsets with both Prevnar response and time to progression will be presented at the meeting. Disclosures: No relevant conflicts of interest to declare.

Abstract 1127 The timely activation of prothrombin (II) to thrombin (IIa) by the prothrombinase (IIase) complex is required for the maintenance of hemostasis. The IIase complex is composed of the enzyme factor Xa (fXa) and the cofactor factor Va (fVa) assembled on a membrane surface in the presence of divalent ions. While fXa alone is capable of activating II, the incorporation of fVa into the IIase complex results in a 300,000-fold increase in the catalytic efficiency of fXa for IIa formation. FVa is generated following limited proteolysis of factor V (fV) by IIa at Arg709, Arg1018, and Arg1545, releasing a heavy chain (residues 1–709) and light chain (residues 1546–2196) that associate noncovalently through divalent ions. The A3 domain of the light chain of fVa has been implicated in the interaction of the cofactor with fXa. To determine the contribution of the A3 domain of fVa to IIase assembly and function, synthetic peptides representing residues 1546–1612 were screened for their ability to inhibit IIase. The peptide representing residues 1546–1558 strongly inhibited IIase with an IC50 of 50 μM. Additional fluorometric studies with overlapping pentapeptides from that region revealed that amino acids 1553–1558 were responsible for the observed inhibition. To verify the data from the overlapping pentapeptide studies, site-directed mutagenesis was used to generate a fVa mutant molecule with amino acids 1549–1558 deleted (fVaLCD1). FVaLCD1 demonstrated greatly reduced clotting activity in two-stage clotting assays. Gel electrophoresis of the IIase catalyzed activation of II using fVaLCD1 revealed a 50% reduction in the rate of prothrombin consumption. IIase assembled with fVaLCD1 exhibited a 5-fold increase in the apparent disassociation constant (Kdapp) for the enzyme-cofactor interaction and a 50% reduction in the turnover number (kcat) for the enzyme. To investigate the possibility that amino acids 1549–1558 are important for procofactor activation, the fVaLCD1 mutant was incubated with IIa and visualized with gel electrophoresis. The fVaLCD1 mutant exhibited a greatly reduced rate of IIa catalyzed activation. Additional recombinant fVa molecules with overlapping alanine mutations within the amino acid region 1548–1559 revealed that amino acids 1554–1555 were responsible for the observed effects in fVaLCD1. The recombinant fVa molecule with amino acids 1554–1555 mutated to alanines (fVaAA) demonstrated a greatly reduced clotting activity, an 8-fold increase in the Kdapp for the enzyme-cofactor interaction, and a 50% reduction in the kcat for the enzyme. To further investigate the mutational robustness of fVa against mutations in amino acids 1554–1555, a recombinant fVa molecule with both tyrosine residues in that region mutated conservatively to phenylalanines (fVaFF) was created. The more conservative fVaFF mutant, which differed from fVaWT only in the absence of side-chain hydroxyl moieties, exhibited normal clotting activity, kinetics, and procofactor activation. Altogether, the data demonstrate that amino acids 1554–1555 from the N-terminal region of the fVa light chain are important for IIase assembly and function because they constitute an interactive site for IIa and fXa. Disclosures: No relevant conflicts of interest to declare.

Introduction: Nodal marginal zone lymphoma (NMZL) is an indolent B-cell non-Hodgkin lymphoma (iNHL) that usually presents in elderly patients with painless lymphadenopathy. Patients often have advanced disease at diagnosis, and bone marrow involvement is common. Treatment of NZML involves radiation therapy for localized disease, and systemic therapy for advanced disease including single-agent rituximab, rituximab and chemotherapy (such as bendamustine, chlorambucil), or novel agents (especially in the relapsed setting such as ibrutinib, lenalidomide and PI3K inhibitors). The objective of this study was to determine whether advances in treatment and supportive care over the past decade have translated to improved relative survival at the population level in patients with NMZL in the United States. Method: We used the population-based Surveillance, Epidemiology, and End Results (SEER)-18 database. We included adult patients with NMZL diagnosed between 2000-2017 who were 18-84 years old at the time of diagnosis. We excluded patients with a history of malignancy prior to NMZL, those with missing survival times and those with central nervous system involvement. Patients were divided into two cohorts based on period of diagnosis (era-1: 2000-2008, and era-2: 2009-2017). Relative survival (RS) was estimated using the Pohar-Perme method, and the difference between RS distributions was tested using a log-rank-type test. Relative survival was modeled using Poisson regression where the effect of follow-up time was included as restricted cubic spline with 5 knots. All tests of differences were performed at a two-sided alpha of 0.05. Results: We included 5,355 patients with NMZL. Table 1 shows the baseline characteristics. The median age at diagnosis was 66 years (IQR = 56-74 years). Most patients were non-Hispanic White (73%) with advanced stage at diagnosis (stage III-IV, 63%). The 5-year RS (unadjusted) was 84% (95% CI = 82% - 86%) for patients diagnosed in era-1 and 86% (95% CI = 84% - 89%) for patients diagnosed in era-2 (log-rank-type p = 0.07). Figure 1A shows cumulative RS, and Figure 1B shows the trend in 5-year RS over the study period (including model-based and empirical estimates). In our multivariable Poisson regression model for RS, the period of diagnosis, age, sex, median household income, and stage at diagnosis were significant predictors of excess mortality (Table 2). Patients in era-2 had significantly lower excess mortality [excess hazard ratio (EHR) = 0.76, 95% CI=0.62-0.93], while excess mortality significantly increased with age over 65 years [EHR = 2.09, 95% CI=1.70-2.56], male sex [EHR = 1.38, 95% CI=1.13-1.68], and advanced stage at diagnosis [EHR = 1.96, 95% CI=1.47-2.63]. Conclusion: There has been a significant improvement in RS in the most recent era for patients with NMZL in the United States after adjusting for differences in age, sex, race/ethnicity, income, and stage at diagnosis. This improvement at the population level is likely reflective of the improvement in supportive care and advances in the NMZL treatment including identification of better tolerable chemotherapy regimens and novel agents. Disclosures Epperla: Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria.