Purpose Gliosarcoma is a histologic variant of glioblastoma (GBM), and like GBM carries a poor prognosis. Median survival is less than one (1) year with less than 5% of patients alive after 5 years. Although there is no cure, standard treatment includes surgery, radiation and chemotherapy. While very similar to GBM, gliosarcoma exhibits several distinct differences, morphologically and molecularly. Therefore, we report a comprehensive analysis of DNA copy number changes in gliosarcoma using a cytogenomic DNA copy number (CN) microarray (OncoScan ® ). Methods Cytogenomic DNA copy number microarray (OncoScan ® ) was performed on 18 cases of gliosarcoma. MetaCore™ enrichment was applied to the array results to detect associated molecular pathways. Results The most frequent alteration was copy number loss, comprising 57% of total copy number changes. The number of losses far exceeded the number of amplifications (***, < 0.001) and loss of heterozygosity events (***, < 0.001). Amplifications were infrequent (4.6%), particularly for EGFR . Chromosomes 9 and 10 had the highest number of losses; a large portion of which correlated to CDKN2A/B loss. Copy number gains were the second most common alteration (26.2%), with the majority occurring on chromosome 7. MetaCore™ enrichment detected notable pathways for copy number gains including: HOXA, Rho family of GTPases, and EGFR; copy number loss including: WNT, NF-kß, and CDKN2A; and copy number loss of heterozygosity including: WNT and p53. Conclusions The pathways and copy number alterations detected in this study may represent key drivers in gliosarcoma oncogenesis and may provide a starting point toward targeted oncologic analysis with therapeutic potential.

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Title:Outcomes of Elderly Patients Undergoing Allogeneic Transplantation for Acute Myeloid Leukemia with Fludarabine/Melphalan or Fludarabine/TBI Conditioning Regimen Intro:Acute myeloid leukemia (AML) is an aggressive hematological disorder that primarily occurs in the elderly with an average age of 68 at the time of diagnosis. Allogeneic transplantation provides the only chance for long term survival and several studies have shown that allogeneic transplantation in elderly patients using reduced intensity regimens are safe and well tolerated and lead to long term survival. Fludarabine/melphalan, a reduced intensity conditioning regimen, and fludarabine/total body irradiation (TBI) a non-myeloablative conditioning regimen, are two regimens that are often used for elderly patients. Fludarabine/TBI is considered to be a less intensive conditioning regimen than fludarabine/melphalan. We examined outcomes of allogeneic transplantation in elderly patients with AML that received fludarabine/melphalan or fludarabine/TBI as a conditioning regimen. Methods:Ninety-five (95) patients that had a diagnosis of an AML or secondary AML that were 60 or older and received an allogeneic transplantation between April 2008 and October 2017 at Winship Cancer Institute of Emory University were included in this retrospective analysis. Patients that had active disease relapse at the time of transplant were excluded. Patients were identified using the institutional transplant database and confirmed with our electronic medical record system. Results: Ninety-five patients (95) were included in our study with a median age at transplant of 66. Melphalan was given at a dose of 140mg/m2 in each patient. TBI was given at a dose between 200-300cGy in each patient. Seventy-seven patients (81%) received fludarabine/melphalan conditioning regimen. Twenty patients (21%) were 70 or older. Thirty-two patients (35.6%) patients had unfavorable cytogenetics. Patients that received conditioning regimen with fludarabine and melphalan had a longer 1 year overall survival rate than patients that received fludarabine/TBI (71.2% vs 50.0%, p=0.08). In multivariate analysis, only disease risk score was significantly associated with overall survival (p=0.039). Patients with higher co-morbidity index score (p=0.003) were more likely to receive fludarabine/TBI for conditioning, however the 1 year overall survival rate was higher in the fludarabine/melphalan than the fludarabine/TBI group (69% vs 43.8%, p=0.09). In sub-group analysis, patients between the ages of 60-64 and those with complete remission with incomplete hematological recovery derived the most benefit from fludarabine/melphalan rather than fludarabine/TBI with a 1 year survival rate of 74.3% vs 40.0% (p=0.06) and 61% vs 0%, (p=0.06), respectively. Relapse rates were similar between the two groups (p=.536). Treatment related mortality (TRM) was not significantly different between the two conditioning regimens, with a slightly higher TRM in fludarabine/TBI group (OR= 1.36, 95% CI=0.42-4.35, p=0.60). Conclusions: This retrospective analysis sought to examine the outcomes in elderly patients undergoing allogeneic transplantation for AML with either fludarabine/melphalan or fludarabine/TBI. Fludarabine/TBI is non-myeloablative regimen and considered to a be a less intense regimen than fludarabine/melphalan. There was a trend for better overall survival for the fludarabine/melphalan group in comparison to fludarabine/TBI, even in patients with higher comorbidity index and patients over the age of 70. Thus, fludarabine/melphalan is a reasonable regimen even in elderly and less fit patients that improves overall survival without unacceptable toxicities, including TRM. Disclosures Langston: Astellas Pharma: Other: Research Support; Incyte: Other: Research Support; Jazz Pharmaceuticals: Other: Research Support; Chimerix: Other: Research Support; Takeda: Other: Research Support; Kadmon Corporation: Other: Research Support; Novartis: Other: Research Support; Bristol Myers Squibb: Other: Research Support. Waller:Amgen: Consultancy; Cerus Corporation: Other: Stock, Patents & Royalties; Pharmacyclics: Other: Travel expenses, Research Funding; Cambium Oncology: Patents & Royalties: Patents, royalties or other intellectual property ; Chimerix: Other: Stock; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kalytera: Consultancy.

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