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Background: Extracorporeal membrane oxygenation (ECMO) is increasingly used in acute myocardial infarction (AMI); however, there are limited large-scale national data. Methods: Using the National Inpatient Sample database from 2000 to 2014, a retrospective cohort of AMI utilizing ECMO was identified. Use of percutaneous coronary intervention, intra-aortic balloon pump, and percutaneous left ventricular assist device (LVAD) was also identified in this population. Outcomes of interest included temporal trends in utilization of ECMO alone and with concomitant procedures (percutaneous coronary intervention, intra-aortic balloon pump, and percutaneous LVAD), in-hospital mortality, and resource utilization. Results: In ≈9 million AMI admissions, ECMO was used in 2962 (<0.01%) and implanted a median of 1 day after admission. ECMO was used in 0.5% and 0.3% AMI admissions complicated by cardiogenic shock and cardiac arrest, respectively. ECMO was used more commonly in admissions that were younger, nonwhite, and with less comorbidity. ECMO use was 11× higher in 2014 as compared with 2000 (odds ratio, 11.37 [95% CI, 7.20–17.97]). Same-day percutaneous coronary intervention was performed in 23.1%; intra-aortic balloon pump/percutaneous LVAD was used in 57.9%, of which 30.3% were placed concomitantly. In-hospital mortality with ECMO was 59.2% overall but decreased from 100% (2000) to 45.1% (2014). Durable LVAD and cardiac transplantation were performed in 11.7% as an exit strategy. Of the hospital survivors, 40.8% were discharged to skilled nursing facilities. Older age, male sex, nonwhite race, and lower socioeconomic status were independently associated with higher in-hospital mortality with ECMO use. Conclusions: In AMI admissions, a steady increase was noted in the utilization of ECMO alone and with concomitant procedures (percutaneous coronary intervention, intra-aortic balloon pump, and percutaneous LVAD). In-hospital mortality remained high in AMI admissions treated with ECMO.

BACKGROUND: Prolonged sitting has been shown to increase mortality and obesity. OBJECTIVE: We sought to determine whether physicians would use a treadmill desk, increase their daily physical activity and lose weight. PARTICIPANTS: 20 overweight and obese physicians aged 25 to 70 with Body Mass Index > 25. METHODS: Participants used a treadmill desk, a triaxial accelerometer, and received exercise counseling in a randomized, cross-over trial over 24 weeks. Group 1 received exercise counseling, accelerometer feedback, and a treadmill desk for 12 weeks and then accelerometer only for 12 weeks. Group 2 received an accelerometer without feedback for 12 weeks followed by exercise counseling, accelerometer feedback, and the treadmill desk for 12 weeks. RESULTS: Daily physical activity increased while using the treadmill desk compared to not using the desk by 197 kcal per day (p=0.003). The difference in weight during the two 12 week periods was 1.85 kg (p=0.03). Percent body fat was 1.9% lower while using the treadmill desk (p=0.02). There were no differences in metabolic or well-being measures. CONCLUSIONS: This study suggests that physicians will use a treadmill desk, that it does increase their activity, and that it may help with weight loss. Further studies are warranted.

Abstract INTRODUCTION: mTOR inhibitors have been associated with responses in Mantle cell lymphoma and other lymphomas (J Clin Oncol23; 5347, 2005). Phase I and II trials with the oral everolimus (RAD001, Novartis Pharmaceuticals) have demonstrated a favorable side effect profile. This phase II study tested everolimus in patients with relapsed/refractory Waldenstrom Macroglobulinemia (WM). METHODS: Patients who had at least one previous therapy for WM and who had relapsed or refractory disease were eligible. Other eligibility criteria included symptomatic disease, > 2 weeks from last therapeutic agent used, >10% involvement with lymphoplasmacytic cells in the bone marrow, IgM paraprotein > 2x upper limit of normal, absolute neutrophil count >1000/mm3 and platelet count >75,000/mm3, serum creatinine of < 2 x upper limit of normal. NCI CTCAE v3.0 was used for toxicity assessment. Response was assessed by criteria established at the second consensus panel for WM. All patients received 10mg RAD001 daily for 28 days per cycle for 6 cycles; response was assessed after 2 cycles. RESULTS: 10pts (8 men and 2 women, median age is 62 years, range 52–71) have been treated to date. The median number of lines of prior treatment was 3 (range 1 – 5). The median IgM at baseline was 3970 mg/dL (range 3120– 7410); median M-spike at baseline was 2.07 gm/dL (range 1.41 – 4.02); and median hemoglobin was 11.3 g/dL (9.4–13.3). The median follow up was 4 months (range 1 – 7 months). Prior therapy included rituximab, nucleoside analogues (fludarabine and 2-CDA), combination chemotherapy (e.g CHOP, CVP), chlorambucil. and bortezomib. Seven patients are currently evaluable for response. The best response to single agent RAD001 after 2 cycles is presented in Table 1. Median duration of response has not been reached. Patients tolerated RAD001 well without significant toxicities. The main toxicities observed were apthous ulcers in 4 patients. One patient required dose reduction due to mucositis. One patient stopped therapy within the first month of treatment and went on to hospice care before succumbing to his disease after one month. Attributable toxicities otherwise proved manageable with appropriate supportive care and RAD001 was generally well tolerated, with no peripheral neuropathy. CONCLUSIONS: Oral RAD001 as monotherapy has been well tolerated and demonstrates exciting activity achieving PR + MR in 57%, and/or stabilization of disease in 43% of evaluable patients with relapsed WM. Accrual of a total of 30 patients is rapidly ongoing. Updated data will be presented at the meeting. Table 1 Response N=7; ORR (CR+PR+MR)= 57% Median time to best response (months) Partial Response 1 (14%) 5 Minimal Response 3 (43%) 4 (3–6) Stable Disease (SD) 3 (43%) NA Progressive Disease 0

AbstractBackgroundThere are limited data on the use of intravascular ultrasound (IVUS), optical coherence tomography (OCT), and fractional flow reserve (FFR) during acute myocardial infarction (AMI).ObjectivesTo assess the temporal trends of IVUS, OCT, and FFR use in AMI.MethodsA retrospective cohort study from the National Inpatient Sample (2004–2014) was designed to include AMI admissions that received coronary angiography. Administrative codes were used to identify percutaneous coronary intervention (PCI), IVUS, OCT, and FFR. Outcomes included temporal trends, inhospital mortality and resource utilization stratified by IVUS, OCT, or FFR use.ResultsIn 4,419,973 AMI admissions, IVUS, OCT, and FFR were used in 2.6%, 0.1%, and 0.6%, respectively. There was a 22‐fold, 118‐fold, and 33‐fold adjusted increase in IVUS, OCT, and FFR use, respectively, in 2014 compared to the first year of use. Non‐ST‐elevation AMI presentation, male sex, private insurance coverage, admission to a large urban hospital, and absence of cardiac arrest and cardiogenic shock were associated with higher IVUS, OCT, or FFR use. PCI was performed in 83.2% of the IVUS, OCT, or FFR cohort compared to 64.2% of the control group (p < .001). The cohort with IVUS/OCT/FFR use had lower inhospital mortality (adjusted odds ratio 0.53 [95% confidence interval 0.50–0.56]), more frequent discharges to home (83.7% vs. 76.8%), shorter hospital stays (4.3 ± 4.4 vs. 5.0 ± 5.5 days) and higher hospitalization costs ($90,683 ± 74,093 vs. $74,671 ± 75,841).ConclusionsIn AMI, the use of IVUS, OCT, and FFR has increased during 2004–2014. Significant patient and hospital‐level disparities exist in the use of these technologies.

Abstract Prompted by the activity of lenalidomide (Revlimid®) in pts with chronic idiopathic myelofibrosis (CIMF), we sought to evaluate the safety and efficacy of the combination of lenalidomide and prednisone in a phase II study for pts with CIMF. The rationale for this combination is that the anti-angiogenic and anti-TNFa effects of lenalidomide may be potentiated by the effects of prednisone to reduce marrow fibrosis and improve hematopoiesis in CIMF. Initial therapy consisted of lenalidomide 10 mg/d (dose level [DL] 0) on days 1–21 of a 28–day cycle for 6 cycles, in combination with prednisone 30 mg/d orally during cycle 1, 15 mg/d orally during cycle 2, and 15 mg/d every other day during cycle 3. The lenalidomide dose could be reduced to 5 mg/d (DL -1) or to 5 mg/d every other day (DL -2), or increased to 15 mg/d (DL +1) or 20 mg/d (DL +2) depending upon toxicity or lack of response, respectively. A total of 40 pts (23 male, 17 female) have been enrolled. The median age was 62 years (range, 41–86), time from CIMF diagnosis to the study treatment 10 months (range, 0–269), WBC count 87x109/L (range, 1.1–89), hemoglobin 9.8 g/dL (range, 7.8–17.3), platelets 137x109/L (range, 8–1183). Pts had received a median of 1 prior therapy (range 0–4): hydroxyurea (HU; n=14), anagrelide (AG; n=4), azacitidine (n=6), steroids (n=5), thalidomide (n=4), and interferon (n=3). Ten (25%) pts had not received any prior therapy. JAK2 V617F mutation was detected in 18 (50%) of 36 tested pts and 20 (50%) of 40 had abnormal cytogenetics. A total of 260 cycles have been administered. All 40 pts are evaluable for response and toxicity. Responses have been observed in 12 (30%) pts, including complete response (CR) in 2 (normal blood counts and <5% bone marrow blasts, off HU, AG, growth factors, and no transfusions); partial response (PR) in 7 (at least 2 of the following: Hb increase by ≥2 g/dL, 50% increase in platelets, decrease of bone marrow blasts or organomegaly by ≥50%, normalization of WBC count without blasts, or reduction in bone marrow fibrosis; off HU, AG, growth factors, and transfusion independence); and hematologic improvement (HI) in 3 (at least 2 of the following: decrease by ≥25% of pretreatment leukocytosis, splenomegaly, or marrow blasts, or increase of Hb by ≥1g/dl without growth factor or transfusion support or platelets by ≥25%; off HU, AG, growth factors). Median time to response was 12 weeks (range, 2–32). Responses have been sustained for a median of 15 wks (range, 5–36) and are ongoing in all 12 responders. Overall, 21 (53%) pts experienced grade 3–4 toxicity, being the most frequent neutropenia, anemia, musculoskeletal pain, and fatigue. Twenty-four (60%) pts have required dose reduction to DL -1, of which 5 (12.5%) further reduced to DL -2. One (2.5%) pt dose-escalated to DL +1, while 15 (25%) remained at DL 0. Twenty-one (53%) pts discontinued lenalidomide due to: lack of response (n=8), pt’s decision (n=7), grade 3–4 toxicity (n=5), and poor compliance (n=1). No deaths or transformation to acute myeloid leukemia occurred. In summary, the combination of lenalidomide and prednisone is an active and generally well-tolerated regimen for pts with CIMF. Longer follow-up is warranted to evaluate the durability of ongoing responses. Updated results will be presented at the meeting.

Abstract Abstract 630 Introduction: Medical treatment options for myelofibrosis (MF) are palliative in nature. Short of allogeneic stem cell transplantation, no therapies are available that are curative or confer a survival benefit. Panobinostat (PAN; LBH589) is a potent pan-deacetylase inhibitor that belongs to a structurally novel cinnamic hydroxamic acid class of compounds. Preclinical studies demonstrated that treatment with PAN alone depletes the levels of JAK2V617F (JAK2) and signaling downstream through STAT3 and 5, AKT, and c-RAF/MAPK in human MPN progenitor cells, including those from patients (pts) with MF (Blood 2009; 114:5024). In a prior phase IA/II study of PAN in pts with advanced hematologic malignancies, among 12 pts with MF evaluable for response, 4 pts demonstrated durable clinical improvement. Methods: In this phase II trial, approximately 50 adult pts with primary MF, post essential thrombocythemia, or post polycythemia vera MF who have an International Prognostic Scoring System -MF score of 2 or 3 along with either symptomatic splenomegaly (>10 cm below the costal margin [BCM]) or anemia, enrolled. Initial PAN dose is 40 mg three times a week until disease progression or unacceptable toxicity with dose adjustments as required. Response is assessed using the International Working Group criteria. Peripheral blood samples are collected for correlative science studies at 7 time points during treatment; pre-dose on the first day of the study, 6 and 24 hours after the first dose, pre-dose on the first day of cycles 2, 4 and 6, and at the end of the study. The correlative studies include the determination of JAK2V617F allelic burden, immunoblot analyses of the protein expression of p-STAT3, p-STAT5, p-AKT, p-ERK1/2, p-PIM, as well as of their un-phosphorylated counterparts. Also, protein levels of HSP70 and acetylated (Ac)-α-tubulin, as well as the mRNA expression of JAK2 and PRV-1 genes were determined. Results: As of August 12, 2010, 31 pts (24 JAK2 mutated, 7 JAK2 wild type) have been enrolled in the trial. The majority of pts required dose reduction. Adverse events observed are consistent with the known safety profile of PAN. Correlative studies have been performed on MPN cells from19 patients. As compared to the pre-treatment levels, treatment with PAN (for 6 and/or 24 hours) resulted in varying levels of depletion of p-STAT3, p-STAT5, p-AKT, p-ERK1/2 and p-PIM protein. A decline in JAK2 and PRV1 mRNA levels (20 to 80%) was also observed. Conversely, PAN treatment induced Ac-α-tubulin and HSP70 levels, consistent with HDAC6 and HSP90 inhibition. This was associated with decline in the protein levels of AKT, PIM1 and STAT3. PAN treatment also reduced MCL-1 and Bcl-xL, while inducing BIML levels. Notably, of the 10 patients in whom it has been determined, PAN treatment depleted the allelic burden of JAK2V617F by an amount ranging between 10 to 90%. Conclusions: Consistent with its role as a pan-deacetylase inhibitor, PAN exerts in vivo anti-MPN cell activity, as was highlighted by the decrease in the allelic burden of JAK2V617F. Further patient enrollment is ensuing, and more mature clinical toxicity and efficacy data will be presented. Disclosures: DeAngelo: Novartis: Membership on an entity's Board of Directors or advisory committees. Off Label Use: Panobinostat is an investigational agent currently being evaluated for the treatment of hematologic and solid malignancies. Paley:Novartis: Employment. Snyder:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees. Ondovik:Novartis: Employment. Rine:Novartis: Employment.

Abstract Abstract 2702 Introduction/Background Tumor Lysis Syndrome (TLS) is a potentially life-threatening metabolic syndrome that frequently complicates the management of newly diagnosed mature B-NHL in children and adults (Cairo et al., BJH 2010). We have demonstrated rasburicase to be superior to allopurinol in the rapid reduction of uric acid (UA). (Goldman/Cairo et al, Blood 2001) In the previous FAB/LMB/96 international mature B-NHL trial, variables associated with a significant inferior EFS included advanced stage, elevated LDH, primary mediastinal involvement (PMBL) and combined BM/CNS disease (Cairo et al, JCO, 2011). We have previously reported the pharmacokinetics and safety of the addition of rituximab to a modified FAB/LMB/96 backbone in children and adolescents with advanced stage mature de-novo B-NHL. (Cairo et al., ASCO, 2010) Here we focus on outcome in those specific high-risk sub-categories of advanced childhood mature B-NHL following the incorporation of a recombinant urate oxidase (Rasburicase) and targeted immunotherapy (Rituximab) to the FAB/LMB/96 chemotherapy backbones. Material and Methods Children with newly diagnosed stage III/IV or high-risk (BM+±CNS+) de-novo mature B-NHL were prospectively treated with cyclophosphamide, vincristine, and prednisone (COP) reduction therapy preceded by 4–24 hours of non-alkaline hydration and rasburicase (0.2mg/kg) (generously supplied by Sanofi-Aventis). Laboratory and clinical TLS (LTLS and CTLS) was prospectively monitored as previously defined (Cairo & Bishop, BJH, 2004). Immunochemotherapy consisted of FAB B4 or C1 therapy (adriamycin 1 hr infusion) as we have previously described (Patte et al and Cairo et al, Blood, 2007) with the addition of rituximab 375 mg/m2/dose (generously supplied by Genentech) with 2 doses administered in each induction cycle and 1 dose in each consolidation cycle. Results With respect to LTLS and CTLS, 78 patients were evaluable: group B (stage III/IV) with NL-LDH (<2X ULN, n=23), Group B with HI-LDH (≥ 2X ULN, n=18), and Group C (n=37). The mean initial UA levels (mg/dl +/− SD) were 4.7±2, 8.7±4.6, and 7.1±4.6, respectively. At presentation, 31% of patients (all groups) had an elevated (> 8mg/dl) UA, and 47% received elective doses of rasburicase in the days prior to the first day of chemotherapy. The incidence of LTLS prior to rasburicase in Group B NL-LDH, Group B HI-LDH, and Group C, was 4.3%, 5.5%, and 16.6%, respectively. The incidence of CTLS prior to rasburicase was 0%, 11%, and 8.6%, respectively. Following the administration of rasburicase, the incidence of new onset LTLS and CTLS for the entire cohort was 13% (2.6% with hyperuricemia) and 4% (1% with hyperuricemia), respectively. Furthermore, there was a significant improvement in the estimated GFR in those with renal impairment from day -1 prior to rasbursicase to day+7 post R-COP (55 ± 29 ml/min1.73 m2 to 136 ± 29 respectively; p<0.0007; Figure 1). Following combined FAB 96 chemotherapy (with 1 hour Adriamycin) and rituximab, the 3- year EFS (95% CI) for pilot patients (6 doses of rituximab) with Stage III/IV and Group C BM/CNS patients were 95% (80–99%) (Figure 2) and 89% (73–98%), respectively. Interestingly, two of four patients with centrally reviewed mediastinal primaries developed recurrent disease, while none of the 19 stage III/IV patients with LDH < 2X ULN developed recurrent disease or toxic deaths. Conclusions Rasburicase and non-alkaline hydration largely prevented (94% of the time) new onset TLS with hyperuricemia safely during COP reduction therapy in children with advanced stages of de-novo mature B-NHL. For patients with mediastinal primaries, the high failure rate with group B4 therapy + rituximab suggests it would be appropriate to investigate new treatment strategies. Excluding this histology, combined modified FAB/LMB 96 chemotherapy and rituximab resulted in only 5 deaths (2 toxic deaths, 3 disease related deaths) among our cohort of 62 with advanced mature B-NHL. In comparing these current results from the previous FAB/LMB 96 trial without rituximab, the stage III/IV patients had a 95% vs. 84% and patients with CNS+ disease a 93% vs. 72% 3 year EFS. (Patte et al., Cairo et al. Blood, 2007) Future efforts to intensify chemotherapy in patients with CNS involvement should proceed only with careful toxicity monitoring, as preliminarily these patients seem to have excellent outcome with this immunochemotherapy approach. Disclosures: Gross: Pfizer Oncology: Consultancy; Roche/Genentech: Consultancy; Eli Lilly: Consultancy.

Lineage-specific growth factors mobilize peripheral blood progenitor cells (PBPC) and accelerate hematopoietic recovery after high-dose chemotherapy. Recombinant human thrombopoietin (rhTPO) may further increase the progenitor-cell content and regenerating potential of PBPC products. We evaluated the safety and activity of rhTPO as a PBPC mobilizer in combination with granulocyte colony-stimulating factor (G-CSF) in 29 breast cancer patients treated with high-dose chemotherapy followed by PBPC reinfusion. Initially, patients received escalating single doses of rhTPO intravenously (IV) at 0.6, 1.2, or 2.4 μg/kg, on day 1. Subsequent patients received rhTPO 0.6 or 0.3 μg/kg on days −3, −1, and 1, or 0.6 μg/kg on days −1 and 1. G-CSF, 5 μg/kg IV or subcutaneously (SC) twice daily, was started on day 3 and continued through aphereses. Twenty comparable, concurrently and identically treated patients (who were eligible and would have been treated on protocol but for the lack of study opening) mobilized with G-CSF alone served as comparisons. CD34+ cell yields were substantially higher with the first apheresis following rhTPO and G-CSF versus G-CSF alone: 4.1 × 106/kg (range, 1.3 to 17.6) versus 0.8 × 106/ kg (range, 0.3 to 4.2), P = .0003. The targeted minimum yield of 3 × 106CD34+ cells/kg was procured following a single apheresis procedure in 61% of the rhTPO and G-CSF–mobilized group versus 10% of G-CSF–mobilized patients (P = .001). In rhTPO and G-CSF mobilized patients, granulocyte (day 8 v 9, P= .0001) and platelet recovery (day 9 v 10, P= .07) were accelerated, and fewer erythrocyte (3 v 4,P = .02) and platelet (4 v 5, P = .02) transfusions were needed compared with G-CSF–mobilized patients. Peripheral blood platelet counts, following rhTPO and G-CSF, were increased by greater than 100% and the platelet content of PBPC products by 60% to 110% on the first and second days of aphereses (P < .0001) with the greatest effect seen with repeated dosing of rhTPO at 0.6 μg/kg. rhTPO is safe and well tolerated as a mobilizing agent before PBPC collection. Mobilization with rhTPO and G-CSF, in comparison to a comparable, nonrandomized G-CSF–mobilized group of patients, decreases the number of apheresis procedures required, may accelerate hematopoietic recovery, and may reduce the number of transfusions required following high-dose chemotherapy for breast cancer.