Coakley, Maria

Background: As the United States medical system transitions to value-based reimbursement, interested parties will increase scrutiny in testing that may not alter management or outcomes. We investigated whether transesophageal echocardiography (TEE) provokes treatment alteration across age strata in hospitalized patients undergoing a TIA/stroke work-up. Methods: Consecutive patients admitted to the Mayo Clinic Arizona healthcare system between 1/1/2010 and 2/9/2015 were evaluated. A total of 832 patients were identified of which 314 were excluded primarily due to the fact that the TEE was performed as an outpatient. Therefore, 518 subjects (mean age = 68.2 +/- 14.1 y, 42.5% female) were included. A change in treatment was defined a priori as: anticoagulation (AC) initiated for atrial fibrillation found on TEE only (i.e. not identified on telemetry), complex proximal aortic arch plaque, left atrial or left atrial appendage thrombus, intracardiac mass, intracardiac shunt (atrial septal defect (ASD)/ patent foramen ovale (PFO)) ; PFO closure; cardiac mass removal; valve replacement for endocarditis; antibiotics for endocarditis. Results: See Tables A & B Conclusion: TEE in the evaluation of hospitalized patients with TIA/stroke resulted in a change in treatment in approximately 7% of patients regardless of age. Many of the decisions to change treatment were judgment-based and therefore adoption of the routine use of TEE in all patients with TIA/stroke is dependent on institutional practice standards.

Abstract Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). In this large multicenter retrospective study, overall survival (OS) in MF patients treated with allogeneic HCT (551 patients) and without HCT (non-HCT) (1377 patients) was analyzed with Cox proportional hazards model. Survival analysis stratified by the Dynamic International Prognostic Scoring System (DIPSS) revealed that the first year of treatment arm assignment, due to upfront risk of transplant-related mortality (TRM), HCT was associated with inferior OS compared with non-HCT (non-HCT vs HCT: DIPSS intermediate 1 [Int-1]: hazard ratio [HR] = 0.26, P < .0001; DIPSS-Int-2 and higher: HR, 0.39, P < .0001). Similarly, in the DIPSS low-risk MF group, due to upfront TRM risk, OS was superior with non-HCT therapies compared with HCT in the first-year post treatment arm assignment (HR, 0.16, P = .006). However, after 1 year, OS was not significantly different (HR, 1.38, P = .451). Beyond 1 year of treatment arm assignment, an OS advantage with HCT therapy in Int-1 and higher DIPSS score patients was observed (non-HCT vs HCT: DIPSS-Int-1: HR, 2.64, P < .0001; DIPSS-Int-2 and higher: HR, 2.55, P < .0001). In conclusion, long-term OS advantage with HCT was observed for patients with Int-1 or higher risk MF, but at the cost of early TRM. The magnitude of OS benefit with HCT increased as DIPSS risk score increased and became apparent with longer follow-up.

Abstract Introduction: Allogeneic hematopoietic stem cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). Consideration of HCT is recommended by international working groups and national guidelines for MF patients (pts) age <70 with intermediate-1 with adverse indicators, intermediate-2 or high-risk disease by the Dynamic International Prognostic Scoring System (DIPSS) for MF- a recommendation made in the absence of clear data indicating the optimal timing of HCT for MF. In this large multicenter retrospective study, we analyze overall survival in MF pts treated with and without HCT. Methods: Disease characteristics, treatments, and outcome data from MF pts receiving non-transplant therapy at 14 US academic medical centers between 2000-2014 were retrospectively collected. MF pts who underwent HCT were identified from the Center for International Blood and Marrow Transplant Research (CIBMTR). The Cox proportional hazards model was used. The reference time point (time zero) was time of referral for the non-transplant (non-HCT) arm and the time of transplant for the HCT arm. The main effect variable (HCT vs. non-HCT) violated the proportionality assumption where comparing to non-HCT, mortality was higher with HCT in early time period from time zero but then was lower in late time period; therefore, the comparison is presented as early time period and late time period. The Cox model identified 14 months from time zero as the ideal cut point to define early and late time periods. The proportionality assumption is satisfied within each of these two periods. Results: A total of 1377 and 551 pts were included in the non-HCT and HCT arms, respectively (Table 1). In the overall cohort, survival was higher with non-HCT vs. HCT in early time period (relative risk [RR]: 0.34, P< .0001, Figure 1D), but in late time period survival was lower with non-HCT vs. HCT (RR: 2.37, P< 0.001) (Table 2). In the DIPSS low-risk MF group, while survival was higher with non-HCT vs. HCT in the early time period (RR: 0.19, P=0.007, Figure 1A), survival was lower with non-HCT in the late time period, but the latter did not reach statistical significance (RR: 1.45, P=0.39). In the DIPSS intermediate-1 risk group, a survival advantage was present with non-HCT treatments vs. HCT in the early time period (RR: 0.27, P < .0001, Figure 1B), however survival was lower with non-HCT in the late time period (RR: 3.13, P < .0001). Similarly, in those with DIPSS intermediate-2 and high-risk MF, survival advantage was observed with non-HCT in the early time period (RR: 0.41, P< .0001, Figure IC), but survival was lower with non-HCT in the late time period (RR: 2.82, P < .0001). Conclusion: A long-term survival advantage with transplant was observed for pts with intermediate-1 or higher risk MF, but at the cost of potential early mortality. The magnitude of benefit increased as DIPSS risk score increased. Although this retrospective study has limitations, the results have an impact on clinical practice by suggesting that transplantation could be considered earlier in the disease course and supports the recommendation for consideration of HCT in the setting of intermediate-1 risk MF. Disclosures Gowin: Incyte: Consultancy, Other: Scientific Advisory Board, Speakers Bureau. Verstovsek:Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Consultancy; Italfarmaco: Membership on an entity's Board of Directors or advisory committees. Ali:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Gupta:Novartis: Consultancy, Honoraria, Research Funding; Incyte: Research Funding. Gerds:Celgene: Consultancy; Apexx Oncology: Consultancy; CTI Biopharma: Consultancy; Incyte: Consultancy.

Abstract Background: Post polycythemia vera (PV) and essential thrombocytosis (ET) myelofibrosis (MF), like primary MF (PMF), are heralded by splenomegaly, cytopenias, heavy symptom burden, and decreased overall survival. Risk prognostication tools, including the dynamic international prognostic scoring system (DIPSS) and the Passamonti risk score for post-PV MF (Passamonti et al. Blood 2010, 2008), are helpful to estimate survival and guide therapeutic decision-making. For Post-PV/ET MF, it is unknown if DIPSS correlates with the Passamonti risk score. Here we evaluate the correlation between the two available risk prognostication tools in post-PV/ET MF. Methods: Retrospective chart review conducted for patients with post-PV/ET MF seen between 2000-2012. Descriptive statistics were used to describe patient demographic and clinical variables in post PV/ET patients. DIPSS Score: calculated at time of last follow up: 1 point for age >65, 2 points for hemoglobin <10g/dL, 1 point for leukocytes >25 x 109, 1 point for circulating blasts 1% and 1 point for constitutional symptoms. Risk group was assigned: low-risk (0 adverse points), intermediate-1 risk (1 adverse point), intermediate-2 risk (2-3 adverse points) and high-risk (4-6 adverse points). Passamonti Risk Scores: calculated at time of last follow up: with 1 point assigned for hemoglobin level less than 100 g/L (10 g/dL), platelet count less than 100 x10 (9)/L, and/or leukocyte count more than 30x10(9)/L. Cross-tabulation of DIPSS score versus Passamonti risk score at time of last follow-up was conducted and the percent agreement was described. Spearman correlation coefficient between DIPSS score at follow-up with Passamonti score was conducted. Results: Patients: Sixty-one (58%) post-ET and 44 (42%) post-PV patients were identified, total N=105. Male to Female ratio was 1:1. Median age was 65 (range 25-87). JAK2 V617Fpresent in 68 (65.4%). Median hemoglobin was 10.9 g/dL (range 5.3-17.0), median platelet count 287 x 109 (range 20-1864), and median WBC was 11.1x 109 (range 1.1-165). Risk prognostication: When DIPSS risk scores were applied 11 patients were low, 48 patients were Intermediate-1, 31 patients were Intermediate-2, and 10 patients were high. When Passamonti risk scores were applied 57 patients received score of 0, 31 patients scored 1, 9 patients scored 2, and 3 patients scored 3. DIPSS and Passamonti risk score agreement: The overall agreement between DIPSS and Passamonti risk scores was low, with 24% of cases in agreement. Spearman correlation: Rho=0.451; p<0.001. See Table #1 with agreement seen in highlighted cells. Table 1. DIPSS and Passamonti Agreement Passamonti Risk Score DIPSS 0 1 2 3 Total Low 9 (75%) 3 (25%) 0 0 12 Int-1 31 (77.5%) 8 (20%) 1 (2.5%) 0 40 Int-2 17 (43.6%) 14 (35.9%) 6 (15.4%) 2 (5.1%) 39 High 0 6 (75%) 1 (12.5%) 1 (12.5%) 8 Total 57 (57.6%) 31 (31.3%) 8 (8%) 3 (3%) 100 Conclusion: Post PV/ET MF represents a unique clinical entity and risk prognostication schemes developed for PMF, such as DIPSS, may not represent accurate prognosis estimation in this subgroup of MF. When DIPSS and Passamonti risk scores were applied to same post PV/ET group, agreement was poor at 24%. Additionally, DIPSS was more likely to assign patients to high-risk category than Passamonti. Further studies are needed to evaluate the DIPSS and Passamonti prognostic risk score application to the post PV/ET MF population. Disclosures Mesa: Incyte Corporation: Research Funding; Pfizer: Research Funding; NS Pharma: Research Funding; Promedior: Research Funding; Incyte Corporation: Research Funding; Gilead: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Genentech: Research Funding; Promedior: Research Funding; CTI Biopharma: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; CTI Biopharma: Research Funding; Genentech: Research Funding; Gilead: Research Funding; Pfizer: Research Funding; NS Pharma: Research Funding.