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The addition of high-dose cytarabine to rituximab/bendamustine (RB) induction could improve outcomes for transplant-eligible patients with mantle cell lymphoma (MCL). We conducted a pooled analysis of 2 phase 2 trials and an off-trial cohort each testing 3 cycles of RB and 3 cycles of rituximab/high-dose cytarabine (RC) followed by autologous stem cell transplantation (ASCT) among untreated, transplant-eligible patients with MCL. Dana-Farber Cancer Institute (DFCI) and Washington University in St. Louis (WUSTL) led separate phase 2 trials testing sequential and alternating cycles of RB/RC, respectively. Patients treated at DFCI with sequential RB/RC off trial were retrospectively identified. Minimal residual disease (MRD) was assessed in the DFCI trial. A total of 88 patients (23 DFCI trial, 18 WUSTL trial, and 47 off trial) received RB/RC; 92% of patients completed induction, and 84% underwent planned consolidative ASCT. Grade 3 or 4 adverse events among trial patients included lymphopenia (88%), thrombocytopenia (85%), neutropenia (83%), and febrile neutropenia (15%). There were no treatment-related deaths during induction and 2 following ASCT. Among 87 response-evaluable patients, the end-of-induction overall and complete response rates were 97% and 90%, respectively. After a median follow-up of 33 months, 3-year progression-free survival and overall survival were 83% and 92%, respectively. Patients undergoing MRD testing experienced prolonged MRD negativity after ASCT with emergence of MRD occurring in only 1 patient who subsequently relapsed. RB/RC followed by ASCT achieves high rates of durable remissions in transplant-eligible patients with MCL. These trials were registered at www.clinicaltrials.gov as #NCT01661881 (DFCI trial) and #NCT02728531 (WUSTL trial).

Mantle cell lymphoma is an incurable, moderately aggressive B cell lymphoma. While a small proportion of patients with indolent disease can be managed expectantly, most patients require treatment. The therapeutic approach is driven by physician recommendation, patient choice, age, fitness and comorbidities. Young, fit patients often receive combination chemoimmunotherapy, including high dose cytarabine, with autologous stem cell transplant. Recent data has indicated benefit from maintenance rituximab following autologous stem cell transplant. Ongoing trials are investigating combinations of chemotherapy and targeted agents as well as the role of minimal residual disease guided therapy. Older, less fit patients often receive bendamustine and rituximab or anthracycline based regimens. Maintenance rituximab is typically administered in older MCL patients after anthracycline based chemotherapy although its use after bendamustine based therapy is not supported by current data. Current trials focus on refining this regimen with the addition of targeted agents. In the relapsed and refractory setting, novel agents have demonstrated activity although durability of responses remains unsatisfactory.

Background: Myelodysplastic syndromes (MDS) represent a heterogeneous group of malignancies that are characterized by aberrant hematopoiesis and consequently abnormal blood counts. Patients with MDS have an increased likelihood of developing acute myeloid leukemia (AML). Next generation sequencing (NGS) is currently being used to study the genetic landscapes of diverse cancer types in finer detail than has previously been possible, owing to its ease-of-use and widespread availability. Crucially, the accuracy and broad breadth of genomic coverage provided by NGS approaches may permit the study of mutations that are rare in MDS patients, yet well studied in AML or other cancer types. Based on the fact that much less is known about particular rare somatic mutations in MDS, we decided to investigate 6 genes. IDH1 and IDH2 are targetable in patients with AML. Mutations in JAK2 are found in high proportions in patients with myeloproliferative neoplasms (MPNs) or MDS/MPN overlap neoplasms. Finally, other mutations in genes such as BCOR, BCORL1, and MUTYH also occur in MDS patients with appreciable-but generally low-frequencies such that their overall impact on MDS patients is largely unknown. Methods: We utilized the Tempus LENS platform to retrospectively characterize 236 MDS patients who underwent genomic-testing with the Tempus|xT assay (DNA-seq of 595-648 genes at 500x coverage; full transcriptome RNA-seq; data accessed on 06/28/2021). The patient population was 28% female, with a median age of 71.6 years. Mutations identified included germline and/or somatic single nucleotide variants (though we only considered somatic variants in this study), insertions/deletions and copy number variations (gains defined as ≥8 copies). For a subset of patients processed at Rush University Medical Center (RUMC), we additionally performed a curated clinical investigation into laboratory variables, prognostic data, treatment history and outcomes data. Results: Within the Tempus MDS dataset, we observed a range of mutation frequencies. In total, 58 patients had mutations in at least one of either: JAK2, BCOR, IDH2, IDH1, BCORL1, and MUTYH. When comparing the observed frequencies against values that have previously been reported, mutations in these 6 genes occurred with higher frequency in our dataset while most other mutations were in accordance with the relative frequencies reported by other sources (Table 1). We observed the largest deviation from expectation for BCOR. Whereas prior reports list this mutation as occurring with a frequency of Conclusions: We identified a higher frequency of BCOR/BCORL1 mutations among patients with MDS than has been previously reported. At the same time, most other mutation frequencies were in relative accordance with existing reports. We observed complex cytogenetic abnormalities in 75% of patients for which we had extensive clinical information. Our data suggest an association between BCOR/BCORL1 mutations and complex karyotypes, a finding that may establish a prognostic role of BCOR/BCORL1 and have potential therapeutic implications. This hypothesis is, however, subject to further investigation and will require larger sample sizes that are likely to become available with the rapidly increasing utilization of next generation sequencing techniques and availability of high-quality, curated clinical information. Figure 1 Figure 1. Disclosures Hockenberry: Tempus Labs, Inc: Current Employment, Current holder of stock options in a privately-held company. Okeke: Tempus Labs, Inc: Current Employment. Mahon: Tempus Labs, Inc: Current Employment. Hassane: Tempus Labs, Inc: Current Employment. Enschede: Tempus Labs, Inc: Current Employment, Current holder of stock options in a privately-held company. Shammo: Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Astra zeneca: Research Funding; CTI pharma: Research Funding; Stemline therapeutics: Research Funding; Kartos Pharma: Research Funding; Takeda: Consultancy, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company, Honoraria, Research Funding; Abbvie: Current holder of individual stocks in a privately-held company, Research Funding; Baxter: Current holder of stock options in a privately-held company; sanofi: Consultancy, Honoraria, Speakers Bureau; NS Pharma: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Apellis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Alexion: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Background Due to paucity of psychiatrists in India, psychiatric patients often present to other doctors. We aimed to study nonpsychiatric residents' attitude and stigma toward psychiatric patients. Methods A total of 57 postgraduate trainees participated in a cross-sectional study in a tertiary hospital in New Delhi. Attitudes to psychiatric patients were assessed using the attitude to mental illness questionnaire (AMIQ) and the perceived stigma questionnaire. This was correlated with sociodemographic information. Results Over 70% residents accepted mentally ill patients as friends and felt they were equally employable. However, AMIQ demonstrated a negative attitude towards patients with schizophrenia. Perceived competence in dealing with psychiatric patients was associated with adequate undergraduate exposure (Chi-square = 7.270, P = 0.026) and correlated with positive attitudes (t-test, P = 0.0008). Conclusions While the questionnaires revealed some prejudice toward psychiatric patients with schizophrenia, the postgraduate trainees who felt competent to deal with the mentally ill had the most positive attitudes toward them.

4529 Background: Oncology patients experience more severe disease outcomes from COVID-19 infection than the general population. BCG is a live bovine tuberculosis bacillus with immunotherapeutic effects in urothelial cancers; it is also used as vaccination against Mycobacterium tuberculosis in parts of the world. As BCG vaccination has been associated with broad protection against viral pathogens, BCG exposure through vaccination or intravesical therapy may modulate host immunity and reduce the severity of COVID-19 infection. We report the effect of BCG exposure on COVID-19 severity in oncology patients from the CCC19 registry. Methods: The CCC19 registry (NCT04354701) was used to identify patients with prior BCG exposure. Cohort A received intravesical treatment for bladder carcinoma, and cohort B received prior BCG vaccination. Each cohort was matched 3:1 to non-BCG-exposed controls by age, sex, race, primary cancer type, cancer status, ECOG performance status (PS) and calendar time of COVID-19 infection. The primary endpoint was COVID-19 severity reported on an ordinal scale (uncomplicated, hospitalized, admitted to ICU +/- ventilated, died within 30 days) of patients exposed to prior BCG compared to matched non-exposed controls. 2-sided Wilcoxon rank-sum tests were used. Results: As of 6-Feb-2021 we included 124 patients with BCG exposure, 68 patients with bladder carcinoma who had received intravesical BCG (Cohort A), and 64 cancer patients with prior BCG vaccination (Cohort B). Median age was 76 years, IQR 69-83 (Cohort A) and 67 years, IQR 62-74 (Cohort B). Bladder cancer pts were predominately male (78%) vs 55% for Cohort B. Patients with PS 2+ were uncommon, 18% in Cohort A and 16% in Cohort B. COVID-19 illness severity was no different in patients exposed to prior intravesicular BCG (p=0.87). COVID-19 illness severity was no different in patients exposed to prior intradermal BCG vaccination (p=0.60). Conclusions: Despite this being the largest such cohort reported to date, we failed to demonstrate an association of prior BCG exposure with modulation of severity of COVID-19 illness. Prospective trials evaluating the protective effect of BCG vaccination are ongoing and will add further insight into the effect of BCG on COVID-19 illness.[Table: see text]

BACKGROUND: Allogeneic hematopoietic stem-cell transplantation is the only curative treatment for patients with myelodysplastic syndrome (MDS). The molecular predictors of disease progression after transplantation are unclear. METHODS: We sequenced bone marrow and skin samples from 90 adults with MDS who underwent allogeneic hematopoietic stem-cell transplantation after a myeloablative or reduced-intensity conditioning regimen. We detected mutations before transplantation using enhanced exome sequencing, and we evaluated mutation clearance by using error-corrected sequencing to genotype mutations in bone marrow samples obtained 30 days after transplantation. In this exploratory study, we evaluated the association of a mutation detected after transplantation with disease progression and survival. RESULTS: Sequencing identified at least one validated somatic mutation before transplantation in 86 of 90 patients (96%); 32 of these patients (37%) had at least one mutation with a maximum variant allele frequency of at least 0.5% (equivalent to 1 heterozygous mutant cell in 100 cells) 30 days after transplantation. Patients with disease progression had mutations with a higher maximum variant allele frequency at 30 days than those who did not (median maximum variant allele frequency, 0.9% vs. 0%; P

Introduction Treatment of metastatic castration-resistant prostate cancer (mCRPC) has evolved significantly during the past decade, and the preferred combination and/or sequence of these treatments remains controversial. In this retrospective study, we explored clinical and pathologic factors that could predict response to consecutive treatment with enzalutamide (ENZA) after disease progression (PD) on abiraterone acetate and prednisone (AA/P). Patients and Methods Data were collected from 40 consecutive patients with mCRPC who were treated with ENZA without other interim therapy after progression on AA/P. Results The median time from prostate cancer initial diagnosis to AA/P treatment was 6.2 (range, 0.9-16.3) years. The median prostate-specific antigen (PSA) progression-free survival (PSA-PFS) from treatment initiation was 8.5 months (95% confidence interval [CI], 7.1-10.1 months) and 2.3 months (95% CI, 1.8-3.4 months) on AA/P and ENZA, respectively. The median time to PD from treatment initiation was 9.7 months (95% CI, 7.1-12.4 months) and 3 months (95% CI, 2.3-4.1 months) on AA/P and ENZA, respectively. The correlations were weak between the best percent change in PSA on ENZA and time from diagnosis to AA/P initiation, best absolute or percentage change in PSA on AA/P, time to PSA progression or PD on AA/P. Patients with longer than the median duration of treatment with AA/P (11.73 months) had longer PSA-PFS on ENZA (median 2.8 vs. 1.9 months; P = .035). Conclusions In this retrospective analysis, we did not find any clinical or pathologic factors associated with response to ENZA administered consecutively after AA/P. Patients with longer than median AA/P treatment duration had longer PSA-PFS on ENZA. Further evaluations and validation are greatly needed.

The use of drugs to enhance cognitive function and academic performance is clearly a global phenomenon, with the reported prevalence of stimulant use among medical students ranging from 15-20%. A multi-institution study from the USA reported a 6.9% lifetime prevalence of non-prescription use of cognitive enhancers among college students. A comprehensive systematic review indicates a 16-29% use of non-prescribed stimulants among all students for reasons that include increasing concentration and alertness. While mental health professionals and guidance counsellors anecdotally recall requests for pharmacological cognitive enhancement from otherwise healthy students, the exact magnitude of this problem in the Indian context is not clear.

Background: Induction chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) is a standard of care for transplant eligible (TE) patients (pts) with untreated mantle cell lymphoma (uMCL); however, there is no consensus on the optimal induction regimen. The addition of rituximab + high-dose cytarabine (RC) to an RCHOP-like regimen is associated with better outcomes. In addition, two randomized trials have demonstrated superior efficacy and tolerability for rituximab/bendamustine (RB) compared to RCHOP for uMCL. Based on this, we conducted a phase 2 trial of 3 cycles of RB followed by 3 cycles of RC in 23 TE pts with uMCL, with encouraging preliminary results (Armand, BJH 2016). Pts continued to be followed for relapse and survival. Meanwhile, RB/RC became the standard frontline regimen at Dana-Farber Cancer Institute (DFCI). Simultaneously, investigators at Washington University in St. Louis (WUSTL) initiated a similar study of alternating cycles of RB/RC for uMCL. Herein, we report the results of both phase 2 trials as well as the off-trial experience. Methods: In the DFCI trial, TE pts (age 18-69) with uMCL were treated with 3 cycles of RB (R 375 mg/m2 d1, B 90 mg/m2 d1-2) followed by 3 cycles of RC (R 375 mg/m2 d1, C 3gm/m2 BID d1-2 with dose reductions for age, renal dysfunction, or pre-existing neurotoxicity). Off-trial pts treated with RB/RC at DFCI or in consulting community practices were retrospectively identified using clinical and pharmacy databases. In the WUSTL trial, TE pts (age 18-65) received alternating cycles of RB (cycles 1, 3, 5) and RC (cycles 2, 4, 6) (same dosing as above). Response assessments were made using CT scans for the DFCI trial and PET/CT for the WUSTL trial and DFCI off-trial pts. Results: In total, 86 pts (23 DFCI trial, 49 DFCI off-trial, 14 WUSTL trial) were treated with RB/RC. The median age was 57 (range 30-72). Pts in the WUSTL cohort were more likely to be male, have a high MIPI score, and have blastoid variant (Table). 94% of pts completed 6 cycles of RB/RC therapy. Off-trial pts were more likely to receive a lower starting dose (≤ 2gm/m2) of cytarabine (76%) compared to trial pts (38%). At the EOI, the overall response rate and CRR were 98% and 92%, respectively, with similar response rates across cohorts (Table). 73 pts (85%) subsequently underwent ASCT and 4 additional pts (5%) have ASCTs planned. 9 pts did not undergo ASCT because of persistent or PD (n=3), prolonged cytopenias (n=3), an incidentally identified ASXL1 mutation without cytopenias (n=1), pt preference (n=1), and inadequate stem cell collection (n=1). Delayed platelet engraftment after ASCT was seen for pts receiving alternating cycles of RB/RC compared to sequential RB/RC at day 30 (plts 2gm/m2 was also associated with reduced 30-day platelet count (plts Median follow-up was 32m (range 4-69m) among survivors overall (54m for DFCI trial, 28m for DFCI off-trial, 19m for WUSTL trial). The 24m and 48m PFS for the entire cohort were 88% (95CI 77-93) and 80% (95CI 66-89), respectively (Figure, panel A); the 24m and 48m OS were 96% (95CI 89-99) and 92% (95CI 81-97), respectively. PFS and OS were similar across cohorts with a trend towards inferior PFS in the higher-risk WUSTL cohort (Figure, panel B). PFS was similar among non-trial pts treated at DFCI (n=32) and in community centers (n=17). In univariate analyses, a higher cytarabine dose (>2gm/m2) was not associated with improved PFS, while blastoid or pleomorphic variant (HR 4.5, p=0.016) and high-risk MIPI score (HR 4.0, p=0.034) were both associated with inferior PFS. Conclusions: Induction therapy with RB/RC followed by ASCT achieved high rates of durable remissions in two phase 2 clinical trials. Similarly favorable outcomes were observed with off-trial use of this regimen both at an academic center and in community practices. RB/RC is therefore an excellent choice of induction therapy for TE pts with uMCL, and could be further tested in comparative prospective trials. Sequential, rather than alternating, RB/RC cycles and lower dose cytarabine may reduce the risk of prolonged thrombocytopenia post-ASCT. Figure 1. Figure 1. Disclosures Kahl: Juno: Consultancy; Seattle Genetics: Consultancy; Celgene: Consultancy; Abbvie: Consultancy; AstraZeneca: Consultancy; Genentech: Consultancy; Acerta: Consultancy; ADC Therapeutics: Consultancy; CTI: Consultancy; Gilead: Consultancy. LaCasce:Research to Practice: Speakers Bureau; Bristol-Myers Squibb: Other: Data safety and monitoring board; Seattle Genetics: Consultancy, Honoraria; Humanigen: Consultancy, Honoraria. Jacobson:Bayer: Consultancy; Novartis: Consultancy; Precision Bioscience: Consultancy; Humanigen: Consultancy; Kite: Consultancy; Pfizer: Consultancy. Davids:Gilead: Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Consultancy, Research Funding; Surface Oncology: Research Funding; Merck: Consultancy; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Brown:Sun Pharmaceutical Industries: Research Funding; Roche/Genentech: Consultancy; Pharmacyclics: Consultancy; Morphosys: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Invectys: Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Research Funding; Genentech: Consultancy; Celgene: Consultancy; Boehringer: Consultancy; Beigene: Membership on an entity's Board of Directors or advisory committees; Acerta / Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Verastem: Consultancy, Research Funding; Loxo: Consultancy; TG Therapeutics: Consultancy; Sunesis: Consultancy. Bartlett:Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Celgene: Research Funding; Forty Seven: Research Funding; Pharmacyclics: Research Funding; Merck & Co: Research Funding; Affimed: Research Funding; Novartis: Research Funding; ImaginAB: Research Funding; Astra Zeneca: Research Funding; Bristol-Meyers Squibb: Research Funding; Immune Design: Research Funding; Genentech: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Research Funding; Novartis: Research Funding; Millennium: Research Funding. Armand:Merck: Consultancy, Research Funding; Adaptive: Research Funding; Otsuka: Research Funding; Affimed: Consultancy, Research Funding; Pfizer: Consultancy; Infinity: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Roche: Research Funding; Tensha: Research Funding. Jacobsen:Seattle Genetics: Consultancy; Merck: Consultancy.

Background Venous thromboembolism (VTE) is a complication of glioblastoma. Anticoagulating patients with glioblastoma carries a theoretical risk of intracranial hemorrhage (ICH). Methods We performed a retrospective cohort study of consecutive glioblastoma patients (2007–2013) diagnosed with VTE. Results The study population comprised of 523 glioblastoma patients of whom 173 (33%) had VTE events. Seventeen (10%) had ICH: 6 (35%) subdural hematomas and 11 (65%) intratumoral hemorrhages. In total, 4 patients with ICH required neurosurgical intervention. Enhancement in the area of subsequent intratumoral hemorrhage was noted in 9 of 10 with available pre-ICH scans. Multivariable regression did not show associations between ICH and tumor enhancement diameter or use of vascular-endothelial-growth-factor inhibitor. Fifteen (16%) patients receiving anticoagulation had ICH compared with 2 (2.6%) not receiving anticoagulation (P = .005). The method of anticoagulation was not associated with development of ICH. Median survival times from nondistal VTE diagnosis to death were 8.0 and 3.5 months (P = .05) in patients receiving anticoagulation and those not on anticoagulation, respectively. Conclusion Patients with glioblastoma and VTE on anticoagulation have increased incidence of ICH. However, development of ICH was not associated with lower median survival from time of VTE. Intratumoral hemorrhage occurred within the enhancing portion of tumor; however, no relationship was identified between the development of ICH and (i) the median diameter of enhancement or (ii) type of anticoagulant used. However, patients with absence of enhancing tumor did not have intratumoral bleed, suggesting gross total resection may limit this adverse outcome. It is appropriate to initiate anticoagulation in glioblastoma patients with VTEs.

Patients with glioblastoma (GBM) are at increased risk of initial and recurrent venous thromboembolism (VTE) but rates of recurrence and real-world treatment choices are incompletely understood.We aim to describe the treatment of incident VTE, report incidence and risk factors for recurrence.We conducted a retrospective cohort study of consecutive Cleveland Clinic patients with GBM presenting with objectively diagnosed deep vein thrombosis (DVT) or pulmonary embolism (PE) from 2007 to 2013 with at least 6-month follow-up. We collected information on patient demographics, VTE incidence, treatment and recurrence. Data were analyzed using multivariate logistic regression analysis.Of 450 patients with GBM, 145 (32.2%) developed VTE and comprised the study population. Of these, 11 (7.6%) experienced PE, 117 (80.7%) had DVT and 16 (11%) had DVT as well as PE. Fifty five (37.9%) VTE events occurred in the first 30 post-operative days and 56 (38.6%) during chemotherapy. Thirty one (21.4%) patients were untreated. Treatments included enoxaparin (N=36, 24.8%), warfarin (15, 10.3%) or vena cava filters either alone (N=39, 26.9%) or in combination with anticoagulation (N=21, 14.5%). Recurrent VTE occurred in 39 patients (26.9%).In multivariate analysis, lack of long term anticoagulation (HR 11.2, CI 1.5-86.3, p0.05) and the presence of second primary malignancy (HR 3.69, CI 1.2-11.1, p0.05) were significantly associated with recurrent VTE.VTE and recurrent VTE are highly prevalent throughout the disease course among patients with GBM. Long term anticoagulation is associated with reduced risk of recurrent VTE but is often not utilized.

BACKGROUND: Venous thromboembolism (VTE) is a complication of glioblastoma. Anticoagulating patients with glioblastoma carries a theoretical risk of intracranial hemorrhage (ICH). METHODS: We performed a retrospective review of consecutive glioblastoma patients (2007-2013) diagnosed with VTE, with documentation of historical, clinical, and radiologic findings. RESULTS: 173 (33%) of 523 glioblastoma patients had VTE events. Seventeen (9.8%) had ICH: 6 (35%) subdural hematomas and 11 (65%) intratumoral hemorrhage. Enhancement in the area of subsequent intratumoral hemorrhage was noted in 9 of 10 with available pre-ICH scans. Multivariable regression did not show associations between ICH and tumor enhancement diameter or VEGF-inhibitor use. Fifteen (16%) patients receiving anticoagulation had ICH compared to 2 (2.6%) not receiving anticoagulation (p = 0.005). The type of anticoagulant used was not associated with development of ICH. Median survival from VTE diagnosis to death was 7.2 months in ICH group, compared to 6.2 months in non-ICH individuals (p = 0.4). Median survival from VTE diagnosis to death were 7.9 and 4.7 months (p = 0.07) in patients receiving anticoagulation and those not on anticoagulation, respectively; percentage of patients with KPS scores ≥ 70 was not statistically significant between the groups (p = 0.14). Of fifty-one patients with perioperative VTEs, 38 (74%) were not treated with anticoagulation, while 13 (26%) did receive anticoagulation post-VTE diagnosis (p < 0.0001). CONCLUSION: Patients with glioblastoma and VTE on anticoagulation have increased incidence of ICH. However, ICH was not associated with lower median survival from time of VTE. Additionally, patients receiving anticoagulation trended towards longer survival from time of VTE. Intratumoral hemorrhage typically occurs within the enhancing portion of tumor; however, no relationship was identified between the development of ICH and (i)the diameter of enhancement or (ii)type of anticoagulant used. It is appropriate to initiate anticoagulation in glioblastoma patients with VTEs and, in the case of peri-operative VTEs, start anticoagulation during post-operative outpatient visits.

Background Compared to the general population, patients with multiple myeloma (MM) have a 9-fold increased risk of developing venous thromboembolism (VTE). VTE is a preventable disease that causes death and morbidity. Thromboprophylaxis is a safe and effective way to decrease VTE in other high-risk populations (i.e. atrial fibrillation). Current guidelines recommend pharmacologic thromboprophylaxis in patients with MM receiving an immunomodulatory agent in the presence of additional VTE risk factors. However, putative risk factors vary across guidelines and lack validation. Recently, an attempt to validate the International Myeloma Working Group 2014 guidelines for thromboprophylaxis found current risk factors to be inadequate. Identification of risk factors for VTE in MM can allow for effective risk-stratification to clarify thromboprophylaxis in the MM population. We sought to identify risk factors for VTE in patients with MM. Methods We identified patients diagnosed with MM within the Veterans Administration Central Cancer Registry from September 1, 1999 and December 31, 2013 and followed them through October 2014. We excluded patients who did not receive MM-directed therapy within 6 months of diagnosis. Using a previously validated algorithm, (Thromb Res, 2015), we identified patients diagnosed with VTE after MM diagnosis by a combination of ICD-9 code for VTE plus pharmacologic treatment for VTE or IVC filter placement. We obtained information on baseline patient demographics, medical comorbidities, laboratory data, MM-directed therapy, and use of aspirin and/or warfarin. Univariate analyses identified the association between individual variables and VTE in the cohort. Clinically meaningful and significant associations were included in the multivariate model. Multivariate analysis was done using competing risks regression modeling. The study was approved by the Saint Louis VHA Medical Center and Washington University institutional review boards. Results A total of 3,384 patients comprised the final cohort of whom 414 developed a VTE. Patients who developed VTE were more likely to be younger (66.2 vs 68.5, p < .001), have a body mass index (BMI) ≥ 25 (p < .001), be diagnosed with MM prior to 2007 (p < .001), have a VTE before MM diagnosis (p < .001), have a lower comorbidities (p < .001), have received autologous stem cell transplant (ASCT) (p < .001), have received lenalidomide, thalidomide, or bortezomib (p < .001), and less likely to have received warfarin (p < .001). Among predefined risk factors, age (Hazard Ratio (HR) 0.99, 95% Confidence Interval (CI) 0.98-1.00, p = 0.02), VTE before MM diagnosis (HR 4.13, 95% CI 2.81-6.05, p < .001), heart failure (HR 0.70, 95% CI 0.51-0.96, p = 0.03), treatment with thalidomide (HR 2.02, 95% CI 1.63-2.50, p < 0.001), BMI ≥ 30 (HR 1.34, 95% CI 1.03-1.74, p = 0.03), and diabetes mellitus (HR 0.79, 95% CI 0.63-0.99, p = 0.04) were associated with VTE. After inclusion into multivariate analysis and adjusting for warfarin/aspirin use; age, BMI, year of MM diagnosis, VTE before MM, thalidomide, warfarin, and aspirin were all associated with VTE in MM (Table 1). Conclusion We identified several risk factors associated with VTE in MM. Incorporation of these risk factors into a MM-specific risk model has the potential to reduce risk of VTE in MM. Disclosures Sanfilippo: National Heart, Lung, and Blood Institute: Research Funding. Gage:National Heart, Lung, and Blood Institute: Research Funding. Carson:American Cancer Society: Research Funding.

Introduction: While 65-70 years is the median age of presentation for AML, outcomes continue to be suboptimal in patients 60 years of age or greater. This population tends to have adverse cytogenetic and molecular profiles while their medical management is often complicated by multiple co-morbidities. There is paucity of literature on the outcomes in AML patients greater than 60 years of age undergoing allogeneic hematopoietic cell transplant (allo-HCT), particularly for patients beyond complete remission 1(CR1). <> Methods: <> We retrospectively identified all patients at Washington University School of Medicine undergoing allo-HCT for AML between January 2006 and December 2012. Patients were then classified as CR1 or beyond CR1 (>CR1). The primary study endpoint was overall survival (OS). Secondary endpoints included leukemia free survival (LFS), cumulative incidence of relapse and non-relapse mortality (NRM). Patient, disease and treatment-related variables for the study groups were compared using the chi-square statistic or Fishers Exact test for categorical variables and the Kruskal-Wallis test for continuous variables. Cumulative incidence plots were generated by SAS macro %CIF and Gray's test was utilized to test equality of cumulative incidence function between study groups. Kaplan-Meier (KM) curves for OS were generated and provide unadjusted survival estimates between study groups. Differences between study groups were determined by log-rank tests. Cox proportional hazard model was used in multivariate analysis for OS and LFS. All statistical tests were two-sided using an alpha level of significance of 0.05. SAS Version 9.3 (Cary, NC) was used to perform all statistical analyses. Results: We identified 114 patients who met inclusion criteria. The patient characteristics are described in Table 1. Of these, 62 patients were beyond CR1 (24 in CR2, 17 with persistent cytogenetic abnormalities (CP) and 21 with active disease). The remaining 52 patients transplanted in CR1 were included as a control cohort. Patient characteristics in the two cohorts are described in Table 1. Three-year OS was 35.0% (95% CI 22-48) for individuals transplanted in CR1, while it was 26.6% (95% CI 16-38) in >CR1 (p=0.0504, Figure 1a). Relapse Incidence (RI) at 3-years was 43.3% (95% CI 29-57) in CR1, and 50.8% (95% CI 37-63) in >CR1 (Figure 1b). Three-year NRM in CR1 was 27.2% (95% CI 16-40) and 24.7% (95% CI 15-36) in >CR1 (Figure 1c). aGVHD (acute graft versus host disease) at 3-years of follow up in CR1 group was 50.9% (95% CI 36-64) and 41.0% (95% CI 28-53) in >CR1. cGVHD (chronic graft versus host disease) in CR1 group at 3-years of follow up was 23.8% (95% CI 13-36) and 10.6% (95% CI 4-20) in >CR1. On multivariate analysis, active disease at the time of transplant was associated with poor OS (p Conclusions: Given these findings, allo-HCT is a viable treatment option with acceptable long-term survival in AML patients 60 years of age or greater. Overall, there is a trend towards worse survival in patients transplanted beyond CR1. Specifically, active disease at transplant is associated with poor outcomes. These results underscore an unmet need to develop novel protocols associated with improved survival in these patients. Disclosures DiPersio: Incyte Corporation: Research Funding. Schroeder:Incyte Corporation: Honoraria, Research Funding.

Background Patients with multiple myeloma (MM) have a 9-fold increased risk of developing venous thromboembolism (VTE). Current guidelines recommend pharmacologic thromboprophylaxis in patients with MM receiving an immunomodulatory agent in the presence of additional VTE risk factors (NCCN 2015, ASCO 2014, ACCP 2012). However, putative risk factors vary across guidelines and no validated VTE risk tool exists for MM. Khorana et al. developed a VTE risk score in patients with solid organ malignancies and lymphoma (Blood, 2008). We sought to apply the Khorana et al. score in a population with MM. Methods We identified patients diagnosed with MM within the Veterans Health Administration (VHA) between September 1, 1999 and December 31, 2009 using the International Classification of Diseases (ICD)-03 code 9732/3. We followed the cohort through October 2014. To eliminate patients with monoclonal gammopathy of undetermined significance and smoldering myeloma, we excluded patients who did not receive MM-directed therapy within 6 months of diagnosis. We also excluded patients who did not have data for hemoglobin (HGB), platelet (PLT) count, white blood count (WBC), height and weight, as these are all variables included in the Khorana et al. risk model. Height and weight were assessed within one month of diagnosis and used to calculate body mass index (BMI). We measured HGB, PLT count, and WBC count prior to treatment initiation: within two months of MM diagnosis. A previously validated algorithm, using a combination of ICD-9 code for VTE plus pharmacologic treatment for VTE or IVC filter placement, identified patients with incident VTE after MM diagnosis (Thromb Res, 2015). The study was approved by the Saint Louis VHA Medical Center and Washington University School of Medicine institutional review boards. We calculated VTE risk using the Khorana et al. score: We assigned 1 point each for: PLT ≥ 350,000/μl, HGB < 10 g/dl, WBC > 11,000/μl, and BMI ≥ 35 kg/m2. Patients with 0 points were at low-risk, 1-2 points were considered intermediate-risk and ≥3 points were termed high-risk for VTE. We assessed the relationship between risk-group and development of VTE using logistic regression at 3- and 6-months. We tested model discrimination using the area under the receiver operating characteristic curve (concordance statistic, c) with a c-statistic range of 0.5 (no discriminative ability) to 1.0 (perfect discriminative ability). Results We identified 1,520 patients with MM: 16 were high-risk, 802 intermediate-risk, and 702 low-risk for VTE using the scoring system in the Khorana et al. score. At 3-months of follow-up, a total of 76 patients developed VTE: 27 in the low-risk group, 48 in the intermediate-risk group, and 1 in the high-risk group. At 6-months of follow-up there were 103 incident VTEs: 41 in the low-risk group, 61 in the intermediate-risk group, and 1 in the high-risk group. There was no significant difference between risk of VTE in the high- or intermediate-risk groups versus the low-risk group (Table 1). The c-statistic was 0.56 at 3-months and 0.53 at 6-months (Figure 1). Conclusion Previously, the Khorana score was developed and validated to predict VTE in patients with solid tumors. It was not a strong predictor of VTE risk in MM. There is a need for development of a risk prediction model in patients with MM. Figure 1. Figure 1. Disclosures Carson: American Cancer Society: Research Funding. Gage:National Heart, Lung and Blood Institute: Research Funding. Kuderer:Janssen Scientific Affairs, LLC: Consultancy, Honoraria. Sanfilippo:National Heart, Lung and Blood Institute: Research Funding.

294 Background: Efficacy data of E immediately after AP failure in castrate resistant prostate cancer (CRPC) is limited. Although clinical cross-resistant has been observed, the optimal sequence of these agents is not defined. Specific patient pt) characteristics on AP could be useful in selecting appropriate pts for subsequent therapy with E. Methods: We retrospectively reviewed records of 40 pts with CRPC treated at the Cleveland Clinic with E immediately after disease progression on AP. We evaluated clinical / pathological features that could predict subsequent response or lack thereof to E. For this exploratory analysis, best % change in PSA (%Ch-PSA) was used as indicator of treatment response. Results: Median age at E initiation was 69 (58-81), median time from diagnosis to AP initiation was 6.1 years (0.9-16.3). Median PSA was 30.9ng/mL (1.5-1680) at the time of AP initiation and 66.9ng/mL (2.52-3130) at E initiation. 30/40 and 35/40 pts had bone metastasis at AP and E initiation, respectively. Prior treatments to AP included Ketoconazole (45%), Docetaxel (35%). Median time to PSA progression on AP was 9.6 m (0.5-49.6) and 2.3 m (1.8-3.1) on subsequent E. 26/39 pts on AP achieved PSA decline >25%; among these 20 had >50% PSA decline. Similarly, 13 and 8 pts receiving subsequent E achieved >25% and >50% PSA decline, respectively. 10/40 pts did not have PSA response with either agent. 4 pts had PSA decline > 50% on both agents. There was no significant correlation between %Ch-PSA on E and %Ch-PSA on AP, pre-E PSA, time to PSA progression on AP, or time from diagnosis to AP. Longer interval between AP and E initiation was associated with better outcome on E (p=.03). Prior treatment to AP did not predict subsequent response to E. Conclusions: Except for the association between longer interval between AP and E initiation with PSA response on subsequent E, other clinicopathological factors did not predict response to consecutive E in this cohort of pts. Identifying clinical and/or molecular factors predictive of response to AP and E in this setting is of critical importance. Ongoing randomized prospective studies will help determine the optimal treatment sequencing in men with CRPC.

e13027 Background: Venous thromboembolism (VTE) is a common complication of glioblastoma (GBM). Impact of VTE on mortality and risk factors for VTE in GBM are incompletely understood. Methods: We c...

Background: Laboratory criteria for antiphospholipid antibody syndrome (APS) include lupus anticoagulant (LAC), anti cardiolipin antibodies, and anti-β2 glycoprotein antibodies. International Society of Thrombosis and Hemostasis (ISTH) criteria for the diagnosis of LAC include a positive screening test, positive mixing study, phospholipid dependence and absence of a co-existing factor inhibitor or anti-coagulant drug effect. Patients with test results that fulfill some but not all of the above criteria are considered to have indeterminate LAC. While a positive LAC is an established risk factor for thrombosis, there are limited data about the significance of indeterminate LAC test results. Objective: Our study aimed at determining the prevalence of venous and arterial thrombotic events in patients with indeterminate LAC. Results: We reviewed the clinical course of 500 patients that underwent LAC testing at Cleveland Clinic from 1/11/2008 to 12/28/2010; 346 had indeterminate results. Patients with indeterminate results while on warfarin (n=52) and enoxaparin (n=4) were excluded. Patients treated with heparin at the time of testing (n=50) were included, as heparin in the plasma was neutralized prior to testing. Multivariate logistic regression modeling was performed using XLSTAT software to study the value of various thrombotic risk factors as predictive factors for venous and arterial thrombosis. Associations between categorical variables were tested using the χ2 test or Fisher's exact test. Differences were considered statistically significant at an alpha level of 0.05. In our final cohort of 281 patients with indeterminate results, there were 110 males (39.1%) and 171 females (60.8%), with a median age of 52.5 yrs. Thrombotic manifestations of patients with indeterminate LAC are summarized in Table 1. There were a total of 170 venous thrombotic events in 119 patients (42.5%). Seventy-nine patients had one or more (≥1) instances of deep vein thrombosis (DVT); 45 patients had pulmonary embolism. There were 17 patients with porto-mesenteric thrombosis and 6 patients with other venous thrombotic events. Forty-five patients had concurrent malignancy (16 %) and 22 (8%) had other prothrombotic risk factors including factor V Leiden (n=14), prothrombin G20210A mutation (n=6), elevated homocysteine (n=1), and protein S deficiency (n=1). On multivariate analysis, a relationship was confirmed between the presence of associated prothrombotic disorders and venous thrombosis (OR = 3.36, 95% CI: 1.31- 8.61, P=0.012) (Table 2). Arterial thrombosis was noted in 63 patients, with stroke, myocardial infarction and acute limb ischemia being most common (Table 1). On multivariate analysis, taking into account atherosclerotic risk factors, co-existing hypertension, hyperlipidemia and smoking history were associated with arterial thrombosis (Table 2). Conclusion: Indeterminate results are common among patients referred for LAC testing. In this retrospective cohort, patients with indeterminate LAC had significant rates of venous and arterial thrombosis. Close observation, analysis of other prothrombotic risk factors, and repeat testing of these individuals at a later date should be considered. Disclosures No relevant conflicts of interest to declare.

Background: The presence of the lupus anticoagulant (LA) is an established risk factor for thrombosis especially in the post operative setting. The risk of thrombosis among patients testing indeterminate for lupus anticoagulant is unknown. In our study we aim to estimate the incidence of postoperative thrombosis in this population and determine risk factors. Methods: We studied adult patients undergoing LA testing within 3 months of major surgery at the Cleveland Clinic between 2008 and 2013. The International Society for Thrombosis and Hemostasis (ISTH) defines the following criteria for a positive lupus anticoagulant: 1) a prolonged phospholipid dependent screening test, 2) an inhibitor demonstrated on a mixing study with normal plasma, 3) evidence that the inhibitor is phospholipid dependent, and 4) absence of a coexisting factor inhibitor, direct thrombin inhibitor or heparin. Patients fulfilling some but not all of the ISTH criteria were considered to be LA indeterminate. Patients with previous venous thromboembolism (VTE) and hypercoagulable states were excluded. We collected data on patient demographics, surgery and VTE in the first 30 postoperative days. Patients were divided into different groups based upon the presence of concomitant malignant or rheumatological disease, types of surgery and the utilization of thromboprophylaxis. Associations between categorical variables were determined using Fisher’s exact test. Multivariate logistic regression was performed; variables included age, type of surgery and utilization of pharmacologic thromboprophylaxis. Results: Of 791patients undergoing perioperative lupus anticoagulant testing, 176 were diagnosed LA indeterminate. The median age was 55 years with males comprising 52.3% of the population. Twenty six (14.7%) patients had a concomitant malignancy. Eighteen patients (10.2%) were diagnosed with a rheumatological illness. Seventy four (42.1%) patients underwent cardiac and vascular surgical procedures. General surgery including gastrointestinal surgery accounted for 53 (30.1%) patients. Neurosurgical patients (20) comprised 11.4% of the population studied. Fifteen (8.5%) patients underwent orthopedic surgery and fourteen (8%) patients had urologic procedures. Thirty eight (21.6%,CI 16.1-28.3%) patients developed VTE in the first 30 postoperative days. Of the patients with VTE, 16 (42.1%) had isolated deep vein thrombosis (DVT). Six patients had DVT associated with internal jugular vein (IJV) thrombosis (15.8%). Five patients (13.2%) patients had DVT associated with PE. Two patients (5.2%)had IJV DVT and PE in combination. Thrombosis was also reported at the sites of arteriovenous grafts, portal vein and in the central retinal vein. Twelve (31.5%) clots were related to the presence of indwelling central venous catheters. No significant association between presence of cancer or rheumatological disease and incident thrombosis was identified. Of those tested for beta 2 glycoprotein antibodies and anticardiolipin antibodies, no significant association was observed between presence of post-operative thrombosis and the presence of antibodies. While only 70 patients (39.8%) received any form of pharmacological prophylaxis against VTE, there was significant reduction in the incidence of VTE in patients that received prophylaxis as compared to those that did not. A statistically significant increased odds of thrombosis was observed in the neurosurgical population as compared to the patients undergoing other surgical procedures. On multivariate logistic regression analysis, neurosurgical patients had 3.4 fold increased risk of post operative thrombosis (CI 1.3-9.3) when compared to the rest of the surgical population studied, irrespective of the utilization of thromboprophylaxis. Conclusion: The incidence of thrombosis for patients with an incidental finding of LA indeterminate is 21.6%, comparable to that seen in the general population of patients undergoing similar procedures. This implies that standard guidelines should be used in choosing appropriate post-operative thromboprophylaxis in patients with this laboratory finding. More aggressive anticoagulant regimens do not appear to be necessary, although this remains to be confirmed in a controlled randomized study. Disclosures No relevant conflicts of interest to declare.

2068 Background: Patients with glioblastoma (GBM) are at increased risk of venous thromboembolism (VTE) as well as intracranial bleeding and clinicians are reluctant to use anticoagulants. The natu...