ALBERT

Description: Introduction: Thrombotic events are a frequent complication in patients with malignancy due to increased tissue factor expression and activation of hemostatic mechanisms by both host cells and cancer tissues. Patients with acute myeloid leukemia (AML) are at risk of venous thromboembolism (VTE) not only because of their malignancy but also because of prolonged hospitalizations, immobility, and the need for central venous access. Profound thrombocytopenia is an expected complication, due to myelosuppressive chemotherapy as well as from underlying marrow-infiltrative disease. This results in difficult prophylactic and treatment decisions where providers must carefully balance the risk of thrombosis and bleeding. There are no published consensus guidelines regarding appropriate use of prophylaxis in patients with leukemia. Methods: A retrospective chart review was completed on AML patients receiving induction or consolidation chemotherapy or treatment for relapsed disease admitted to the University of Virginia from October 2011 through September 2017. Patients with acute promyelocytic leukemia were excluded. Clinical data from 142 patients over a total of 667 hospital admissions were reviewed. The following data was collected: demographics (including age, sex, and race), clotting events, clot location, type of line placed, treatment of clot, and bleeding events. Bleeding events were defined according to International Thrombosis and Hemostasis criteria. χ2 analysis was performed to compare categorical values. Results: Twenty-nine of 142 (20.4%) AML patients were diagnosed with VTE. None of the patients had a prior history of clot or diagnosis of clotting disorder. Thrombosis occurred more commonly during induction therapy, 13 of the 29 events (45%), compared to other stages in their treatment (p value=0.37). Of the thromboses occurring during induction, 14 clotting events (48%) were central line associated, 4% (5/125) of thrombosis occurred in peripherally inserted central lines, 10% (5/51) in temporary internal jugular central lines and 2% (4/165) in tunneled central lines (p value=0.99). The average platelet count at the time of clot was 61 K/µl. Most patients were not on prophylaxis at the time of their clotting event (93.1% vs 6.9%; p value=

Description: Background: High dose methotrexate (MTX) is an important agent in the prevention and treatment of cancer in the central nervous system. Administration of this drug requires alkalization of the urine, which traditionally includes the use of intravenous (IV) sodium bicarbonate (bicarb). In May 2017, IV bicarb was on national shortage; at the University of Virginia, pharmacists and physicians designed an oral (PO) regimen using bicarb and acetazolamide to ensure patients could continue receiving MTX. As there are limited published data, we aimed to assess the safety and the impact on time to start of MTX. Methods: Retrospective chart review was done 5/2016-4/2017 to establish a baseline time to methotrexate. In a prospective analysis, data was collected from May 2017 to May 2018 on all patients who received MTX. For patients receiving the PO regimen, bicarb 2,600 mg PO 6 times daily and acetazolamide 250 mg PO every 6 hours were the initial doses and titrated to maintain a urine pH greater than or equal to 7. The primary endpoint was time to MTX for patients with planned admissions who start MTX upon meeting urine pH and output parameters. Secondary endpoints included incidence of acute kidney injury (AKI) and delayed methotrexate clearance for all patient encounters. AKI was defined using Kidney Disease Improving Global Outcomes criteria. Delayed MTX clearance was defined based on failure to meet goal levels based on published chemotherapy protocols. χ2 analysis was completed on categorical variables. A statistical process control chart (p-chart) depicted time to MTX. Results: A total of 162 patient encounters were included in the analysis. The median age of patients receiving oral bicarb was 51 years (range 21-69) and was 51 years (range 21-63) for patients receiving IV bicarb. Eighty-six encounters were planned admissions that started MTX when urine parameters were met and received either IV (n=32) or PO bicarb (n=54). In these patients median time from admission to MTX was 8.4 vs 7.9 hours, respectively. Figure 1 shows consecutive patients receiving MTX prior to, during, and after resolution of the IV bicarb shortage; there is less variability and fewer outliers in the MTX start time when exclusively administering the PO regimen during the shortage. For the secondary analysis an additional 76 encounters with either unplanned admissions or predetermined MTX start time on subsequent day to admission were analyzed for safety outcomes. The rate of AKI was 14.5% vs 8.9% in the PO vs IV groups, respectively (p=0.28). There was no difference in incidence of delayed methotrexate clearance with 26.5% of patients in PO group vs 25.3% patients in IV group (p=0.87). Length of stay was slightly increased in patients who received PO vs IV alkalization (3.78 vs 3.15 days). Conclusion: Our alternative oral bicarb and acetazolamide urine alkalization regimen appears safe in patients receiving MTX and allowed for continued treatment of patients during a national IV bicarb shortage. Time to start of MTX was decreased with implementation of PO regimen, and there appeared to be a more predictable start time for MTX. While not significant, the higher incidence of AKI in PO group warrants further analysis. Future efforts include using oral outpatient alkalization prior to inpatient admission to work towards improving length of stay. Disclosures No relevant conflicts of interest to declare.

Description: Background Febrile neutropenia (FN) is an oncologic emergency associated with high morbidity and mortality, particularly in patients (pts) with hematologic malignancies. Delays in antibiotic administration, which can occur in busy emergency departments (EDs), lead to worse outcomes. We instituted a FN pathway (FNP) in the Cleveland Clinic (CC) ED to reduce antibiotic delays. Methods This prospective study comparing patients from 06/12 - 06/13 to historical pts from 02/10 - 05/12, represented a collaboration among cancer center, ED, infectious disease, pharmacy, and electronic medical record representatives. Fever was defined as temperature 〉38°C either at home or in the ED, while neutropenia as absolute neutrophil count

Description: Introduction: Higher risk MDS is a serious disease associated with poor survival with hypomethylating agents (HMAs) the standard of care in patients ineligible for stem cell transplantation. Unfortunately, HMAs are only effective in 30-40% of patients with duration of response typically shorter than 1.5 years (Fenaux, Lancet Oncol 2009) leading to evaluation of combination therapies to improve outcomes in higher risk MDS. Inhibition of both histone deacetylation and DNA hypermethylation has been shown to induce re-expression of silenced genes in myeloid malignancies in a synergistic fashion. Studies have evaluated HMAs in combination with HDACi but the results have been disappointing due to increased toxicity and early discontinuations. Pracinostat, a potent oral Class I, II, IV HDAC inhibitor, has been studied in combination with standard dose azacitidine in a prior Phase 2 study in 102 patients with untreated IPSS intermediate-2/high risk MDS (Garcia-Manero, Cancer 2017). Pracinostat was administered at 60 mg/day on 3 alternate days/week for 3 weeks/month, with step down dose to 45 mg in case of poor tolerability. Toxicity, primarily cytopenias, nausea, vomiting and fatigue resulted in early discontinuations and insufficient treatment exposure, potentially leading to diminished efficacy and no observed benefit of the pracinostat/azacitidine combination. This follow-up study is evaluating a lower dose of pracinostat (25% reduction) in combination with standard dose azacitidine with the goal of reducing toxicity, decreasing early discontinuations, and improving outcomes. Methods: The primary objective of this Phase 2, two-stage study at 24 sites is to determine the safety/tolerability and efficacy of the pracinostat/azacitidine combination in patients with IPSS-R high-/very high-risk MDS previously untreated with HMAs. Up to 40 subjects were to enroll in Stage 1, treated with pracinostat at 45 mg, 3 days each week for 3 consecutive weeks, followed by 1 week of rest, along with azacitidine at the standard dose of 75 mg/m2 for 7 days of each 28-day cycle. Study drugs are to be administered until disease progression or intolerable toxicity, avoiding early discontinuation (1 week follow-up were decreased neutrophil count (33%), anemia (30%), febrile neutropenia (27%), and dyspnea (12%). Non-hematologic AEs of fatigue and gastrointestinal events were reduced in this initial group of patients relative to that seen in the prior study. Conclusions: The interim analysis of this study evaluating the efficacy and safety of pracinostat + azacitidine in patients with IPSS-R high-/very high-risk MDS revealed a discontinuation rate and an efficacy response rate meeting the predefined thresholds to allow for expansion of the study. These findings suggest that a reduced dose of pracinostat may allow patients to remain on treatment longer, thus increasing the likelihood of a treatment response. Based on these data, the study IDMC approved expansion of this study to enroll 60 evaluable patients. Updated data, including 6 months efficacy data on the initial cohort, will be presented. Disclosures Khaled: Alexion: Consultancy, Speakers Bureau; Daiichi: Consultancy; Juno: Other: Travel Funding. Ramies:MEI Pharma, Inc: Employment. Mappa:Helsinn Healthcare: Employment. Atallah:Jazz: Consultancy; BMS: Consultancy; Abbvie: Consultancy; Pfizer: Consultancy; Novartis: Consultancy.

Description: Introduction: A dangerous consequence of chemotherapy used to treat patients with hematologic malignancy is the breakdown of intestinal and oral mucosa known as MBI (mucosal barrier injury). In the setting of neutropenia, this can lead to life-threatening laboratory confirmed blood stream infections (LCBI) from translocation of bacteria. This results in increased length of stay, ICU admissions, and decreased quality of life for patients. Sparse evidence exists to guide clinicians on interventions to help prevent and treat MBI and reduce its complications. Methods: In an attempt to reduce MBI-LCBI events, a multidisciplinary team including oncology physicians, nurses, and pharmacists was assembled. A retrospective chart review from 1/2015 to 12/2015 was completed to establish a baseline for MBI-LCBI rate. This rate was calculated by dividing the number of MBI-LCBI events by total number of patients on the malignant hematology wards receiving inpatient chemotherapy treatment. The average MBI-LCBI rate was 0.01. While there is no published national average MBI-LCBI rate, we aimed to decrease this rate by 75%. LEAN principles were applied to approach the problem. A statistical process chart (p-chart) was used to depict rates of MBI-LCBI in baseline cohort and intervention groups. Results: The baseline MBI-LCBI rate was found to be 0.01. Through LEAN methodology with analysis of an A3 and outlining "5 whys," a number of root causes leading to increased MBIs were identified. These included: accessibility of necessary supplies needed for compliance with standard work, availability of the oral care kits, importance of on-going education related to appropriate care and maintenance practices. The multidisciplinary team focused on 2 main interventions to improve MBI-LCBI rate. One Plan Study Do Act (PDSA) cycle was completed and post intervention data was analyzed. In March of 2016 the first intervention implemented was a robust education plan for nursing, including instructions for grading mucositis based on WHO criteria and completing through oral assessments marking the first PDSA cycle. Through further analysis of an A3, oral care was identified as a potential intervention in decreasing MBIs. A second intervention of oral care bundle, consisting of sodium bicarbonate mouth wash, artificial saliva, scheduled nursing oral assessments and teeth brushing, was implemented on May of 2016. After one year of implementation of PDSA cycle 1 the MBI rate (0.003 MBI-LCBIs per month) was reduced by 70% from baseline (Figure 1). This was not sustainable and ultimately after completion of first cycle in March of 2018 the average MBI-LCBI rate was found to be 0.009 which was still reduced from the baseline event rate of 0.01 MBI-LCBI per month. Conclusions: Through a multidisciplinary effort, the rate of MBI-LCBIs were able to be reduced through interventions in both education of nursing and physician staff and focus on oral care in patients. While there was initially significant success, it is apparent towards the end of PDSA cycle 1 there was difficulty with sustainability. There was a reduction in the number of oral care bundle ordered and therefore currently a second PDSA cycle is underway with a nurse driven oral care order set. Further focus in prevention, sustainability support structures (nurse driven protocol implementation) and reducing MBI rate is important in decreasing morbidity and mortality in this patient population. Disclosures No relevant conflicts of interest to declare.

Description: Background: Patients (pts) with MDS or AML who relapse after allogeneic transplantation (allo-HCT) have a very poor prognosis. Hypomethylating agents (HMA) and checkpoint blockade with the anti-CTLA4 blocking antibody ipilimumab (IPI) have each induced responses with acceptable toxicity in AML pts who relapse after allo-HCT. We hypothesized that adding decitabine (DAC) would improve response compared with IPI alone by activating and promoting T cell-mediated anti-leukemic immune reactivity. We are conducting a multicenter phase I study (CTEP 10026) of DAC plus IPI in pts with R/R MDS/AML in both post allo-HCT and transplant-naïve settings to assess safety and estimate efficacy. Methods: The primary objective is to determine the maximum tolerated dose (MTD) or RP2D of combination DAC + IPI in pts with R/R MDS/AML who are post allo-HCT (Arm A) or transplant-naïve (Arm B). Cohorts of 3-6 are sequentially enrolled in 3 dose levels (DL) of IPI using a 3+3 design with expansion in each arm; DLs 0-2 are 3, 5 and 10 mg/kg, respectively. Eligibility for both arms: relapsed AML (extramedullary or ≥ 5% blasts) or R/R MDS (≥ 5% blasts) or unfit elderly AML; Arm A only: ≥ 2 wks off systemic immunosuppressive (IS) therapy, T cell chimerism ≥ 20%, and no prior acute GVHD ≥ gr III. DLT is defined as ≥ gr 3 non-heme, ≥ gr 3 acute GVHD or ≥ gr 3 steroid-refractory immune-related adverse events (AEs) occurring within 8 weeks from first IPI dose. Epigenetic priming with DAC lead-in cycle 0 was followed by combination cycles of DAC + IPI. DAC is given at 20 mg/m2 days 1-5 q 28 days. IPI is given on day 1 of cycles 1-4 and every other cycle in cycles 5-12. Pts who discontinued study either in cycle 0 or DLT period without IPI-toxicity were replaced. Arm A opened after safety was confirmed at DL0 in Arm B. Results: As of June 9, 2019, 26 pts (15M, 11 F) have enrolled in this on-going trial. Of the 12 pts (11 AML and 1 MDS) enrolled in Arm A (post allo-HCT), median age was 66.5 (range 29-74) and 9 had previously received HMA. 7 of 8 pts in DL0 (1 progressed in cycle 0) and 3 of 4 pts in DL1 (1 died from pneumonia in cycle 0) received DAC + IPI. DL0 was expanded to 6 to confirm safety without DLT. Median treatment duration after first IPI dose was 5 cycles (range 1-7); 4 pts continue on trial. Common AEs were gr 1-2 dyspnea (n=4), gr 1-3 fatigue (n=4), and gr 1-2 fever (n=4). Gr 3 AEs were febrile neutropenia (n=2), pneumonia (n=1), and candidemia (n=1). Gr 1 immune-related dermatitis (n=1) reversed with steroids. Acute GVHD was not observed. Moderate-severe chronic GVHD was noted in 2 pts mainly involving skin, which was responsive to photopheresis and oral IS. Though 1 CR and 1 marrow CR have been observed at DL0, dose-escalation up to DL2 is on-going to determine MTD. Of the 14 pts (11 AML and 3 MDS) enrolled in Arm B (transplant naïve), median age was 75.5 (range 34-82) and 9 had previously received HMA. 4 of 6 pts in DL0 (1 progressed and 1 withdrew in cycle 0), 3 of 5 pts in DL1 (2 withdrew in cycle 0) and 3 of 3 pts in DL2 received DAC + IPI. Median treatment duration after first IPI dose was 4 cycles (range 1-8); 3 pts remain on study. Common AEs were gr 1-3 fatigue (n=9), gr 1-2 anorexia (n=5), and gr 3 febrile neutropenia (n=8). Immune-related gr 2 colitis (n=1) and gr 2/3 (n=4) dermatitis were all steroid-responsive. Of the 10 pts who received at least one IPI dose, 5 (50%) achieved an objective response including 3 CR, 1 CRi and 1 PR. All responses were observed in AML pts, including 1 with only skin involved. Expansion to confirm MTD is underway. No treatment-related deaths or DLTs were observed in either Arm. Reasons for discontinuation after IPI: progression (n=9), proceeding to allo-HCT or DLI (n=2), withdrawal (n=1), stroke due to underlying atrial fibrillation (n=1) and disseminated nocardiosis (n=1). In both Arms, multiplex immunofluorescence (MIF) staining of BM biopsies revealed a higher density of CD3+CD4+ cells after 4 cycles of DAC + IPI in 4 responders (R) compared to 4 non-responders (NR) (p=0.0433). Longitudinal MIF IHC in an Arm B responder identified the increasing presence of a tumor immune infiltrate composed of CD3+CD8+GZMB+ T cells prior to achieving CR (Fig 1). Conclusions: Combination DAC + IPI is tolerable and has encouraging clinical activity in post allo-HCT and transplant naïve pts with R/R MDS/AML. Ongoing studies focus on comparing the immunologic and genetic characteristics of the tumor immune infiltrate in each cohort to understand the contribution of alloimmunity to treatment response. Disclosures Garcia: Abbvie: Research Funding; Genentech: Research Funding. Keng:agios: Membership on an entity's Board of Directors or advisory committees. Brunner:Jazz Pharma: Membership on an entity's Board of Directors or advisory committees; Forty Seven Inc: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Research Funding. Khaled:Omeros: Consultancy; Alexion: Consultancy, Speakers Bureau; Daiichi Sankyo: Other: Travel support. Steensma:H3 Biosciences: Other: Research funding to institution, not investigator.; Arrowhead: Equity Ownership; Onconova: Consultancy; Stemline: Consultancy; Aprea: Research Funding; Pfizer: Consultancy; Summer Road: Consultancy; Astex: Consultancy. Winer:Jazz Pharmaceuticals, Pfizer: Consultancy. Cutler:Omeros: Consultancy; Kadmon: Consultancy; BiolineRx: Other: DSMB; Cellect: Other: DSMB; Kalytera: Other: DSMB; ElsaLys: Consultancy; Genentech: Consultancy; Pharmacyclics: Consultancy; Fate Therapeutics: Consultancy; Incyte: Consultancy; Jazz: Consultancy; BMS: Consultancy. Ho:Omeros Corporation: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Consultancy. Neuberg:Madrigal Pharmaceuticals: Equity Ownership; Pharmacyclics: Research Funding; Celgene: Research Funding. Lindsley:Takeda Pharmaceuticals: Consultancy; Jazz Pharmaceuticals: Research Funding; Medlmmune: Research Funding. Galinsky:ABIM: Other: Member of specialty oncology board; Merus Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; AbbVie Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pfizer Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Ritz:TScan Therapeutics: Consultancy; LifeVault Bio: Consultancy; Kite Pharma: Research Funding; Talaris Therapeutics: Consultancy; Draper Labs: Consultancy; Avrobio: Consultancy; Celgene: Consultancy; Merck: Research Funding; Equillium: Research Funding; Aleta Biotherapeutics: Consultancy. Davids:AbbVie, Acerta Pharma, Adaptive, Biotechnologies, Astra-Zeneca, Genentech, Gilead Sciences, Janssen, Pharmacyclics, TG therapeutics: Membership on an entity's Board of Directors or advisory committees; AbbVie, Astra-Zeneca, Genentech, Janssen, MEI, Pharmacyclics, Syros Pharmaceuticals, Verastem: Consultancy; Acerta Pharma, Ascentage Pharma, Genentech, MEI pharma, Pharmacyclics, Surface Oncology, TG Therapeutics, Verastem: Research Funding; Research to Practice: Honoraria. Wu:Pharmacyclics: Research Funding; Neon Therapeutics: Other: Member, Advisory Board. Stone:AbbVie, Actinium, Agios, Argenx, Arog, Astellas, AstraZeneca, Biolinerx, Celgene, Cornerstone Biopharma, Fujifilm, Jazz Pharmaceuticals, Amgen, Ono, Orsenix, Otsuka, Merck, Novartis, Pfizer, Sumitomo, Trovagene: Consultancy; Argenx, Celgene, Takeda Oncology: Other: Data and Safety Monitoring Board/Committee: ; Novartis, Agios, Arog: Research Funding. DeAngelo:Blueprint: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Abbvie: Research Funding; Glycomimetics: Research Funding; Amgen, Autolus, Celgene, Forty-seven, Incyte, Jazzs, Pfizer, Shire, Takeda: Consultancy. Soiffer:Jazz: Consultancy; Gilead, Mana therapeutic, Cugene, Jazz: Consultancy; Juno, kiadis: Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Kiadis: Other: supervisory board; Mana therapeutic: Consultancy; Cugene: Consultancy. OffLabel Disclosure: Combination of ipilimumab and decitabine for MDS/AML treatment for patients who are post-transplant or transplant naive

Description: Abstract 1487 The presence of VRE bacteremia in hematopoietic stem cell transplant recipients portends a worsening clinical course and poor overall survival (Avery et al; BMT, 2005). The impact of VRE bacteremia on outcome in AML patients (pts) receiving induction chemotherapy (IC) has not been established. We conducted an IRB-approved retrospective study of AML pts who received cytarabine-based IC at Cleveland Clinic between 2000–2008 to determine VRE rates and effect on complete remission (CR) and overall survival (OS). Data on age at AML diagnosis (dx), gender, diabetes, smoking history, history of antecedent hematological disorder, pathologic classification, hematologic parameters at dx and at VRE occurrence, metaphase cytogenetics (per CALGB/Alliance 8461), precedingnon-VRE bacteremias, invasive fungal infection (IFI), time from dx and induction to VRE and number of VRE infections, complete remission (CR) and overall survival (OS) were collected from our AML database. The association of these factors with VRE bacteremia was assessed using Fisher's exact test, the Cochran-Armitage trend test and Wilcoxon rank sum test. The impact of VRE bacteremia on OS was assessed using a 2:1 matched-pairs analysis based on gender and year of dx (+ 3 years), and factors known to influence outcome: age at dx (+ 5 years), etiology, and cytogenetic risk. The timing of VRE was also accounted for in the matching. Frailty models, which included a term for WBC at dx, were use to assess the impact of VRE bacteremia while taking into account both the impact of WBC and the paired nature of the data. Of 350 pts evaluable for analysis, the median age at dx was 57 years (range 19–88); 192 (55%) were male; 114 (33%) had secondary AML; median baseline WBC was 10.4K/mL (range, 0.48–550); cytogenetic risk distribution was favorable (14%), intermediate (54%), and unfavorable (32%); 45% were current or former smokers; 17% had a history of diabetes; and 7% had IFI. With the exception of IFI (16% in pts with VRE versus 6% in non-VRE pts, p=.04) there were no significant differences in these factors between the two groups (all p〉.08). Of 37 pts (9.8%) who had documented VRE bacteremias during IC, the median interval from the start of IC to VRE infection was 17 days (range, 9–58). The majority (89%) of VRE bacteremias occurred in pts receiving IC between 2005 and 2008 (infection rate of 22%, 33/152) while only 4 infections occurred in 198 pts treated between 2000 and 2004 (infection rate of 2%). One plausible explanation for this epidemiologic shift could be the frequent use of fluoroquinolone prohylaxis to prevent neutropenic fever, which became routine in 2004. The overall CR rate for the cohort was 73%; 70% in VRE pts and 73% in non-VRE pts (p=0.7). Median follow-up was 72.2 months (range 1.1–145.4). Unadjusted median OS for the entire cohort was 12.8 months (95% C.I. 10.6–15.9); 7.1 months (95% C.I. 3.9–16.5) for VRE pts and 13.1 months (95% C.I. 11.2–16.3) for non-VRE pts (p=0.13, Figure 1A). Using the 2:1 matching to adjust for the impact of age, etiology, and cytogenetics, VRE pts had a significantly inferior OS compared to non-VRE pts even after adjusting for WBC at dx (p=0.04 and.80, respectively, Figure 1B). Mutivariableanalyses confirmed this association. In conclusion, VRE bacteremia in pts undergoing IC for AML is an independent risk factor for worse OS. The routine use of fluoroquinoloneprophylaxis is likely contributing to the increased prevalence of VRE bacteremia. Consideration should therefore be given to escalating VRE appropriate antibiotic care in these patients sooner and in the post-remission setting. Figure 1. Survival from Diagnosis A. All patients B. VRE cases and matched controls Figure 1. Survival from Diagnosis . / A. All patients . / B. VRE cases and matched controls Disclosures: Saunthararajah: Cleveland Clinic Innovation: patent application for oral THU-decitabine., patent application for oral THU-decitabine. Patents & Royalties. Advani:Genzyme: Honoraria, Research Funding; Immunomedics: Research Funding. Maciejewski:NIH: Research Funding; Aplastic Anemia&MDS International Foundation: Research Funding.

Description: BACKGROUND: Invasive fungal infections (IFI) occur in 5% to 40% of patients with hematologic malignancies, most commonly in patients with acute myeloid leukemia (AML). Historically, at the University of Virginia (UVA), antifungal prophylaxis was not routinely used in patient undergoing induction chemotherapy for AML. With an antifungal treatment naïve patient cohort, this study had the unique opportunity to examine if specific patient characteristics, comorbidities, or diagnostic criteria were predictive for the development of an IFI. METHODS: A retrospective chart review of 126 consecutive patients undergoing induction or re-induction chemotherapy for AML at UVA from July 2011 to December 2015 was conducted. The primary endpoint was to determine the rate of probable or biopsy proven IFIs within ninety days of chemotherapy initiation as characterized by the European Organization for Research and Treatment of Cancer/Invasive Fungal Cooperative Group and the National Institute of Allergy and Infectious Disease Mycoses Study Group criteria. Secondary endpoints include patient comorbidity and disease specific indices associated with IFI. Each induction or re-induction regimen was counted as a distinct event. Statistical methods include pairwise Wilcoxon tests, univariate analyses, and Kruskal-Wallis tests. Statistical significance was defined as a p-value

Description: BACKGROUND: Clostridium difficile infection (CDI) is the most important cause of nosocomial infectious diarrhea and has been not well studied in patients with neutropenia who have hematologic malignancies in the United States. Previous studies suggest patients undergoing induction chemotherapy for acute myeloid leukemia (AML) are at a high risk of contracting CDI, but these patient's clinical and disease characteristics are not described. This study reports CDI rates and disease characteristics in AML patients at the University of Virginia (UVA). METHODS: A retrospective chart review of 126 consecutive patients undergoing induction or re-induction chemotherapy for AML at UVA from July 2011 to December 2015 was conducted. The primary endpoint was to determine the rate of CDI within ninety days of chemotherapy initiation. CDI was defined by a Clostridium difficile positive PCR in the presence of diarrhea. Secondary endpoints include patient characteristics, comorbidities, risk factors, and disease specific indices associated with CDI. Statistical methods include nonparametric Wilcoxon test, Fisher's exact test, and Holm's sequential Bonferroni procedure as appropriate. Statistical significance was defined as p-value

Description: Background The International Prognostic Scoring System (IPSS) has been the most widely used risk assessment tool to predict clinical outcome in MDS. Recently, the revised IPSS (IPSS-R) was introduced to allow a greater discriminating capacity in assessing cytogenetic abnormalities and cytopenias and further refines prognostication. However, like the IPSS, the IPSS-R was developed in pts with primary MDS and its utility in pts with secondary (s)MDS is unclear. Material and Methods We conducted an IRB-approved analysis of 765 pts diagnosed with MDS (per 2008 WHO criteria) and evaluated at the Cleveland Clinic between 9/1998 and 1/2013. IPSS-R was calculated as described previously (Greenberg et al, Blood 2012). Cytogenetic risk subgroups were per IPSS-R. Overall survival (OS) was measured from the time of diagnosis to time of death or last follow up. Time-to-event analyses were performed by the Kaplan-Meier method, and curves were compared with the 2-tailed log rank test. Differences among variables were evaluated by the chi-square test and Mann-Whitney U test for categorical and continuous variables, respectively. Results We identified 56 pts (7%) with sMDS: 14 (25%) pts had prior antecedent hematologic disorder, 32 (57%) had prior radiation therapy, and 10 (18%) received prior chemotherapies. Eleven pts (20%) were untreated and 45 pts (80%) received treatment: 17 (30%) with single agent 5-azacitidine, 12 (21%) with supportive measures, 9 (16%) with hematopoietic stem cell transplant (HSCT), and 7 (11%) with other therapies. For all pts, the median age was 66 years (range, 24-81). Median white blood cell count at diagnosis was 3.8 k/mL (range, 0.9-179.7), median absolute neutrophil count (ANC) was 2.2 k/mL (range, 0.1-145.6), median hemoglobin was 9.6 g/dL (range, 0.4-14), median platelet count was 65 X 103/mL (range, 4-460), and median bone marrow blasts was 5% (range, 0-26). The distribution of cytogenetic categories based on IPSS-R criteria was similar in pts with sMDS [2 (4%) very good, 28 (50%) good, 8 (14%) intermediate, 10 (18%) poor and 8 (14%) very poor] compared to primary MDS [28 (4%) very good, 351 (50%) good, 109 (15%) intermediate, 84 (12%) poor and 137 (19%) very poor]. IPSS-R risk categories in pts with sMDS [3 (5%) very low, 15 (27%) low, 11 (20%) intermediate, 15 (27%) high, and 12 (21%) very high] compared to primary MDS [75 (11%) very low (P = 0.15), 221 (31%) low (P = 0.3), 162 (23%) intermediate (P = 0.3), 145 (20%) high (P = 0.1), and 106 (15%) very high (P = 0.1)] were also similar. With a median follow up of 18.4 months (m, range, 1.8-104.6), the median OS for sMDS pts was not reached for very low risk pts, 31.6 m for low risk, 13.7 m for intermediate risk, 27.3 m for poor risk and 39 m for very poor risk (P = 0.15, Figure 1). Conclusion Although pts with sMDS had similar cytogenetic and IPSS-R risk categories compared to those with primary MDS, the IPSS-R did not predict for OS in sMDS pts. The lack of predictability of IPSS-R could be because that most of our pts with sMDS received therapy including HSCT. A new prognostic module to predict the outcome of pts with sMDS who are receiving treatment is needed. Disclosures: No relevant conflicts of interest to declare.