ALBERT

Description: TRM, drug toxicities, life-threatening infections, poor quality of life, and graft versus host disease (GVHD) are significant risks of hematopoietic cell transplantation (HCT). In addition to the risks of HCT, existence of pre-transplant comorbidities can have significant impact on transplant outcomes. A comparison of CCI and the HCT-CI revealed that HCT-CI was prognostic and better at predicting TRM and overall survival (OS). However, the HCT-CI and CCI results have been inconsistent in predicting the TRM and OS in validation studies. In subgroup analyses of a large retrospective trial, HCT-CI did not predict TRM or OS for UCB recipients. Patient heterogeneity in age, disease, disease-risk, comorbidities, and conditioning regimens may have limited validation in these UCB recipients. The design of this research was to explore whether or not the HCT-CI and/or CCI can accurately predict post-transplant outcomes in young patients with high risk hematologic malignancies undergoing uniform RIC UCB transplantation. A retrospective chart review was performed on 52 consecutive young (age 〈 55) UCB transplant recipients receiving the RIC regimen fludarabine, cyclophosphamide, ATG, and 200 cGy TBI. All patients had received cyclosporine and mycophenolate mofetil for GVHD prophylaxis. Information on pre-transplant comorbidities was obtained from the CIBMTR pre-TED form for each patient and retrospective chart reviews. Demographic information, ECOG performance status (PS), identification of comorbidities, and post-transplant outcomes were obtained. Between 2005 and 2011, 52 patients age 19 – 54 (median 38) years, 30 males (58%) and 22 females (42%), underwent RIC UCB transplantation with the above regimen. Most patients had advanced stage or high risk hematologic malignancies; 28 patients had MDS/AML (54%), 8 patients had ALL (15%), while 16 patients had other hematologic malignancies. 39 patients had a PS = 0, while 13 had a PS = 1. Half of the patients were in CR 〉 2, with the same number receiving more than 2 prior therapies. 8 patients had received a prior autologous HCT, 8 a prior allo-HCT, and one patient had failed a previous UCD transplantation. 11 patients did not achieve engraftment. Median time to neutrophil engraftment was 26 days (95% CI: 24 – 28 d) and median time to platelets engraftment was 38 days (95% CI: 31 – 45 d). No patient developed grade 4 acute GVHD. Grade 3 acute GVHD was seen in 12 / 52 patients (23%). Chronic GVHD was seen in likewise seen in 12 patients (23%). To date 16 patients (30%) have relapsed. OS was 42% and PS was 37% at one year. Median PFS and median OS were 5 months and 7 months, respectively (PFS 95% CI: 1 – 11 months, OS 95% CI: 1 – 13 months). Neither CCI, nor HCT-CI were significant predictors of OS and PFS, however the ECOG PS was significantly associated with an improved OS and PFS (Table).OSPFSN1 yr2 yrs4 yrsp1 yr2 yrs4 yrspECOG PS03946%36%21%0.02644%36%21%0.0311331%0015%00CCI≤ 23944%26%10%0.2238%26%10%0.2〉 21338%31%31%38%31%31%HCT-CI02236%31%5%0.3632%32%5%0.3211443%14%14%29%14%14%≥21643%31%31%44%31%31%TRM occurred in 18 patients (35%). Neither comorbidity indices, nor the performance status were correlated to TRM (p 〉 0.05). For ECOG PS, OR 1.6 p = 0.49, CI 0.42 - 5.93; CCI OR = 2.4, p = 0.09, CI 0.86 - 6.59, HCT-CI OR = 0.6, p = 0.46, CI 0.19 - 2.08. In a previous presentation our group concluded that CCI performs better than HCT-CI in elderly patients undergoing UCB transplant. When tested in a population younger than 55 years old though, we were unable to validate the generally accepted prognostic indices. It is unclear whether this is due to a selection bias: it appears most of the patients were essentially health from a non-hematological stand-point, and as such the “classic” cardiac or pulmonary risk factors were underrepresented. The excess TRM is likely due to the severity of their underlying disease, and the majority were in CR ≥ 2 and had received multiple previous courses of antineoplastic chemotherapy. As umbilical cord transplants become more utilized, a new prognostic index needs to be developed, more fitting to the patients 〈 55 years old. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 2019 High-dose chemotherapy (HDC) followed by autologous hematopoietic cell transplantation (AHCT) has been shown to result in better outcomes than conventional salvage chemotherapy for treatment of relapsed Hodgkin (Lancet 2002;359:2065–71) and non – Hodgkin lymphoma patients (N Engl J Med 1995;333:1540–5). The relative efficacy of different conditioning regimens is still uncertain. Our center has had extensive experience with BEP, consisting of BCNU (600mg/m2), etoposide (2400mg/m2) and cisplatin (200mg/m2) (Lazarus HM, J Clin Oncol 1992;10:1682–9) with more than 150 patients transplanted using this conditioning regimen. We have observed it to be efficacious and associated with a low incidence of transplant-related mortality (Biol Blood Marrow Transplant 2005;11:13–22). The purpose of this analysis is to compare the outcomes of patients transplanted with BEP with a contemporaneous cohort of patients transplanted with BEAM (BCNU 300mg/m2, etoposide 800mg/m2, cytarabine 1600mg/m2, melphalan 140 mg/m2). We performed a retrospective analysis of 55 consecutive relapsed lymphoma patients who had either BEAM or BEP preparative therapy for AHCT between 2005 and 2010 at our institution. Given the potential for nephrotoxicity and ototoxicity of cisplatin, patients were selected to receive BEAM if they had previous renal dysfunction (any elevation of serum creatinine) or had previous hearing loss. All patients received corticosteroids for prophylaxis of BCNU – induced pneumonitis. The Mann – Whitney test was used for analysis of continuous variables, Fisher's exact test for categorical data, while survival analysis was performed with the Kaplan – Meier method. Twenty-four patients received BEAM and 31 received BEP. The median age was higher in BEAM-treated patients (51 vs. 43 years, p = 0.0392). Other baseline characteristics were comparable between both cohorts: gender (male 54 vs. 58%, p = 0.791); diagnosis (NHL 75 vs. 77.4%, p = 1.000); status of disease at transplant (partial remission or worse 33.3 vs. 35.5%, p = 1.000); median number of previous therapies (2 in both groups, p = 0.51). The rate of non-renal comorbidities was higher in the BEAM cohort, but the difference was not statistically significant (45.8 vs. 32.3%, p = 0.403). The median CD34 cell dose was similar in both groups (6.252 x106 vs. 6.475 x106 CD34 cells/μL, p = 0.842). The rate of complications, including bacteremia, other infections, mucositis, diarrhea and renal dysfunction were not statistically different (Table 1). The small sample size may have prevented us from observing a statistical difference in cardiac toxicity.Table 1.Complications observed after BEAM or BEP conditioning for Autologous Hematopoietic CellBEAM (%)BEP (%)Bacteremia45.835.5p = 0.580Non – bacteremic infections37.541.9p = 0.787Mucositis54.258.1p = 0.791Diarrhea79.164.5p = 0.370Increase in serum creatinine 〉 50%12.516.1p = 1.000Cardiac complications16.73.2p = 0.153BCNU pneumonitis4.26.4p = 1.000 The median follow up time for the whole cohort was 31 months (28 vs. 34 months, p 0.267). Relapse free survival (RFS) after 36 months was 81.1% and 82.9% for BEAM and BEP, respectively (p = 0.693) (Figure 1). Overall survival at 24 months was 89.6% for BEAM and 90.8% for BEP (p = 0.371) (Figure 2). Among patients transplanted in partial response or worse, the median RFS was 57 months after BEAM and 66 months after BEP (p = 0.3173). There were no deaths in the first 100 days after transplant for both cohorts. There were no differences in the median number of days from hematopoietic cell infusion to discharge (12.5 vs. 12.0 days, p = 0.600) or achievement of ANC 〉500/μL (10 days for both cohorts, p = 0.415). In conclusion, BEP conditioning achieved comparable engraftment, toxicity and survival outcomes to those achieved by BEAM for treatment of relapsed lymphoma patients. BEP is therefore a valid alternative for treatment of this patient population. The BCNU dose in BEP is twice that in BEAM, but we continue to observe limited rates of BCNU – induced pneumonitis. BEP may be preferable over BEAM in patients with underlying cardiac comorbidity. Longer follow up and prospective trials will help in identifying variables that aid in the selection of patients for the most appropriate conditioning regimen. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4536 Introduction: Allogeneic hematopoietic cell transplant (AHCT) is a potentially curative modality for various benign and malignant hematological disorders. Despite advances in supportive care, graft-versus-host disease (GVHD) remains the leading cause of morbidity and mortality following AHCT. In vivo T-cell depletion (TCD) with alemtuzumab or anti-thymocyte globulin (ATG) is commonly employed to prevent graft rejection and GVHD following AHCT. Published (albeit controversial) data suggest possible benefit with TCD in setting of unrelated donor (URD), HLA-mismatched and peripheral blood AHCT. We report here AHCT outcomes for patients who received alemtuzumab or ATG with transplant conditioning (TCD group) and compare them with patients who received T-cell replete allografts (non-TCD group). Methods: The study cohort consists of 150 consecutive patients who underwent AHCT between January 2003 through December 2009. All patients received peripheral blood allografts from matched sibling or URDs. T-cell depletion consisted of alemtuzumab 40mg in two divided doses on days -4 and -1 (n=39) or Thymoglobulin at a total dose of 6 mg/kg for ablative and reduced intensity conditioning (RIC) transplants and 7.5 mg/kg total dose for non myeloablative allografts (n=51). 4 patients received Atgam at 30mg/kg on days -5 to -3. Results: Of the 150 patients, 62.7% (n=94) were males. Median age was 49yrs (range 17–69). Baseline diagnosis included acute leukemias/myelodysplastic syndrome (n=88; 58.6%), chronic myeloid leukemia (n=19; 12.7%), non-Hodgkin lymphoma (n=27; 18%) and others (10.7%). There were 95 patients (63.3%) in the TCD group and 55 (36.7%) in the non-TCD group. The baseline characteristics of the TCD group and non-TCD group where well matched except for significantly more patients in the TCD group who had high risk disease (86.3% vs. 61.8%, p 〈 0.05) and received AHCT from URD (62.1% vs. 29.1%, p0.05). Relapse rate in the TCD group was 32.6% (n=31) and in the non-TCD group 40% (n=22) (p = 0.22). The overall survival at 3 years was 39.2% in the TCD group and 39.3% in the non-TCD group, (p = 0.93). The 3 year progression free survival in the TCD and non-TCD groups were 34.8% and 27.2% respectively (p=0.85). Non relapse mortality at 100 days similarly were 12.8% and 16% and at 3 years were 40% and 41% in the 2 groups (p〉0.05). CONCLUSION: Our limited, single institution experience in a cohort of 150 consecutive patients (transplanted within the last decade) suggests no significant benefit with routine use of in vivo TCD with AHCT. These results highlight the need to develop novel and more effective strategies for preventing and treating GVHD and for improving transplantation outcomes. Disclosures: Abraham: Genentech: Membership on an entity's Board of Directors or advisory committees. Hamadani:Celgene corporation: Honoraria, Speakers Bureau; Otsuka Pharmaceutical: Research Funding, Speakers Bureau.

Description: Abstract 4367 Introduction: Clofarabine is a purine nucleoside analogue which is approved for pediatric patients with relapsed or refractory acute lymphoblastic leukemia. A number of small phase I and II studies have shown activity in adult patients with newly diagnosed and relapsed/refractory acute myeloid leukemia (AML). Promising activity of clofarabine in combination with cyclophosphamide and etoposide has been reported in the pediatric setting (Hijiya et al., Leukemia 2009; Locatelli et al., Br J Haematol 2009). This combination has limited data in adult patients. We present a series of five cases in which clofarabine was combined with cyclophosphamide in adult patients with relapsed or refractory acute leukemia. Methods: We retrospectively reviewed patient charts of five patients treated with clofarabine in combination with cyclophosphamide. Results: Three patients received clofarabine 30mg/m2 + cyclophosphamide 340mg/m2, both on Days 1–5. Two patients received clofarabine 40mg/m2 + cyclophosphamide 440mg/m2 + Etoposide 100mg/m2, each drug on Days 1–5. Median age was 21 (range: 17 – 54). Patients had received 2 to 4 prior induction regimens (median of 3). Three patients were AML, one ALL, and one biphenotypical acute leukemia. Two patients were primary refractory and the other three were relapsed disease. Two out of the five patients achieved a morphologic complete remission (CR), one patient had a morphologic complete remission with incomplete blood count recovery (CRi) and the other 2 patients had treatment failure per Cheson criteria. Three patients went on to receive allogeneic transplants after clofarabine salvage therapy. Two patients that received allogeneic transplant had achieved complete remission (CR) after clofarabine/cyclophosphamide. The third patient was transplanted with a hypocellular marrow 38 days after clofarabine therapy. This patient ultimately achieved CR that was documented post-transplant, making it difficult to determine if the clofarabine regimen or allogeneic transplant achieved the remission status. Event-free survival ranged from 5 to 265+ days (median: 82 days). Treatment was complicated by neutropenic fever (n=5), grade III-IV mucositis (n=4), prolonged aplasia 〉30 days (n=4). One patient died of sepsis before completing the regimen. Conclusion: Clofarabine in combination with a cyclophosphamide-containing regimen appears to have anti-leukemic potential in adult patients. This regimen might be used to achieve cytoreduction before considering allograft transplant with refractory disease, in selected patients. More studies with this combination in adults are warranted. Disclosures: Hamadani: Celgene: Honoraria, Speakers Bureau; Otsuka: Research Funding, Speakers Bureau.

Description: Background: Myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET), are chronic MPNs associated with a broad array of symptoms that may negatively impact patients’ quality of life (QoL). To enhance patient care, it is important to have a current and clear understanding of how MPNs affect the overall health and daily lives of patients. The MPN LANDMARK SURVEY was developed to examine patients’ perceptions of these MPNs related to disease burden, QoL, productivity, and activities of daily living (ADLs). Methods: Eligible patients diagnosed with an MPN were recruited to participate in an online survey conducted from May–July 2014in the US. Patients were asked about the overall burden of disease and impact of symptoms on their QoL, productivity, and ADLs. Descriptive analyses were conducted to assess these outcomes and examined by calculated (not reported) prognostic risk score (MF - DIPSS: Passamonti, Blood 2010; PV: Tefferi, Leuk 2013; ET - IPSET: Passamonti, Blood 2012) and symptom severity quartiles, which were determined using the MPN Symptom Assessment Form (MPN-SAF) total symptom scores. Results: 813 patients (MF=207; PV=380; ET=226) responded to the survey. A majority of patients were female (MF, 54%; PV, 62%; ET, 72%), approximately half were aged 60–74 years (MF, 55%; PV, 51%; ET, 46%), and most were covered by health insurance (〉98%). Nearly half (48%) were diagnosed within the last 5 years and average time to diagnosis from first symptoms was 〉2 years. A high proportion of patients had intermediate to high prognostic risk scores (MF, 94%; PV, 87%; ET, 44%). The majority of patients reported feeling anxious or worried about their MPN (MF, 91%; PV, 78%; ET, 74%). Among all groups, fatigue was the most severe symptom reported (mean MPN-SAF score=6.0–6.4 on a scale of 0–10). A subset of patients in each group described their symptoms as very severe (severity score ≥7 on a scale of 0–10; MF: fatigue [59%], problems with sexual desire [49%], inactivity [46%]; PV: inactivity [48%], fatigue [49%], problems with sexual desire [49%]; and ET: problems with sexual desire [49%], fatigue [50%], headaches [40%]). The majority of patients reported that MPN-related symptoms reduced their QoL (MF, 81%; PV, 66%; ET, 57%); this was reported in all risk groups but more frequently by patients with a high risk score vs a low risk score in MF and ET (MF, 89% vs 69%; PV, 63% vs 65%; ET, 71% vs 59%). A more substantial QoL impact was reported by patients in high vs low symptom quartiles (MF, 95% vs 51%; PV, 94% vs 33%; ET, 93% vs 15%). Similarly, MPNs also had a marked negative impact on reduced work hours, sick days, voluntary job termination, receipt of medical disability, early retirement, and ADLs (Table 1). For example, among patients employed, approximately one fourth reported missing ≥1 day of work (MF, 29%; PV, 19%; ET, 23%) in the last 30 days before the survey. Even patients with low prognostic risk scores often reported missing ≥1 day of work (MF, 33%; PV, 23%; ET, 22%) or cancelling ≥1 day of planned activities (MF, 46%; PV, 35%; ET, 34%). Patients in the high vs low symptom quartiles were more likely to call in sick to work (MF, 48% vs 0%; PV, 52% vs 4%; ET, 38% vs 0%) or cancel ≥1 day of planned activities (MF, 77% vs 5%; PV, 56% vs 7%; ET, 67% vs 3%). Conclusion: The findings from this large, first-of-its-kind survey demonstrate a marked burden of disease across all 3 MPNs that is not limited to symptoms but extends to QoL, productivity, and ADLs. Although high prognostic risk scores have long been associated with a significant burden of disease, in this study, patients with a low risk score also reported significant burden. The symptom burden reported is consistent with previous studies, thus validating the present dataset. MPN treatment considerations should include reducing the symptom burden and improving QoL and productivity to enhance the overall health and lives of MPN patients. Disclosures Mesa: Incyte Corporation: Research Funding; CTI: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Eli Lilly: Research Funding; Promedior: Research Funding; NS Pharma: Research Funding; Sanofi: Research Funding; Celgene: Research Funding. Miller:Incyte Corporation: Honoraria, Research Funding. Thyne:Incyte Corporation: Speakers Bureau. Mangan:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Goldberger:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Fazal:Incyte Corporation: Consultancy, Research Funding, Speakers Bureau; Gilead: Research Funding, Speakers Bureau. Ma:Incyte Corporation: Consultancy. Wilson:Incyte Corporation: Honoraria. Dubinski:Incyte Corporation: Employment, Equity Ownership. Boyle:ICF International: Employment, Equity Ownership. Mascarenhas:Incyte Corporation: Consultancy, Research Funding; Novartis Pharmaceuticals Corporation: Research Funding.

Description: Abstract 4924 Purpose: Radioimmunotherapy (RIT) delivers targeted radiation to tumor cells using cancer-specific monoclonal antibodies. Two agents, 90Y-ibritumomab tiuxetan (Zevalin®) and 131I-tositumomab (Bexxar) have been approved for the treatment of relapsed or refractory CD20 positive low-grade, follicular, or transformed NHL. With increasing use of RIT, it is important to elucidate short and long-term toxicities of treatment, particularly the development of therapy-related myelodysplastic syndrome and/or acute myelogenous leukemia (t-MDS/AML). We are reporting on the incidence and characteristics of t-MDS/AML in 149 patients with NHL treated at a single institution. Methods: We conducted a retrospective chart review of 149 patients with NHL treated with radioimmunotherapy at our institution. Incidences of t-MDS/AML, along with patient and disease characteristics were investigated. Results: 149 patients with NHL were included in this analysis: All patients had received at least one cytotoxic chemotherapy regimen prior to RIT. Regimens most commonly included purine analogues, anthracyclines, alkylating agents, and topoisomerase II inhibitors. Seven out of 149 patients developed t-MDS/AML with an estimated incidence of 4. 69%, (t-MDS: 5, t-AML: 2). Five patients had follicular lymphoma, 1 with mantle cell lymphoma, and 1 with diffuse large B-cell lymphoma. Three patients received 131I-tositumomab and 4 patients received 90Y-ibritumomab tiuxetan. The median age at RIT, and at diagnosis of t-MDS/AML, was 71. 3 and 73. 1 years respectively. The median time from RIT to diagnosis of t-MDS/AML was 1266 days (3. 47 years). The median time from initial NHL treatment to t-MDS/AML was 1680 days (4. 60 years). Two patients developed t-AML without a preceding t-MDS; one of whom had received topoisomerase II inhibitors. Six patients had cytogenetic abnormalities, with complex karyotype present in 4 patients. The majority of the karyotypic abnormalities involved chromosomes 5, 7, 11, and 20. The median time from diagnosis of t-MDS/AML to death was 278 days (0. 76 years). Conclusion: Therapy –related myeloid neoplasms develop after exposure to cytotoxic agents and carry a worse prognosis than de novo disease as is shown in our series. Incidence varies according to underlying disease, specific agents received, timing of exposure, and dose. The incidence rate of 4. 69% observed in this study is within the range previously described for NHL patients treated with conventional-dose chemotherapy (Armitage J. O. et al., 2003). Most patients received fludarabine, an agent linked to a high incidence of t-MDS/AML (Carney D. A. et al., 2010). Roboz et al., 2007, noted that the median time to t-MDS/AML after standard initial therapy is approximately 6 years, which is slightly longer than our study (4. 60 years). This difference may be attributed to differences in chemotherapeutic agents utilized in that analysis for NHL therapy. T-AML without antecedent t-MDS was likely related to etoposide as has been observed in previous studies (Ratain M. J. et al., 1987, 1992). Chromosome 5 and 7 abnormalities were seen with the greatest frequency, a finding typical of t-MDS/AML (Armitage J. O. et al., 2003). This study provides an estimate of 4. 69% for the development of t-MDS/AML after NHL therapy which included chemotherapy/RIT, and suggests that RIT may not contribute to an increased risk of developing t-MDS/AML beyond what is expected with chemotherapy alone. Longer follow-up of NHL patients treated with RIT alone is necessary to determine the precise role of RIT in the development of t-MDS/AML. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 1347 Introduction: High dose therapy and autologous hematopoietic cell transplantation (AHCT) is a standard therapy option for at least young (

Description: Background : Patients diagnosed with myeloproliferative neoplasms (MPNs), including myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET), experience disease burdens that can negatively affect their quality of life. Disconnects between patient and physician perceptions of disease burden or poor patient-physician communication may delay or prevent achievement of treatment goals. The MPN LANDMARK SURVEY is the first large US-based survey designed to evaluate disease burden and patient-physician communication in MPN disease settings. Methods : All eligible patients diagnosed with 1 of the 3 MPNs and physicians treating patients with MPNs that were recruited were surveyed in the US during May-July 2014.The surveys included ≤67 questions (depending on the type of MPN and respondent) and required approximately 20–25 minutes to complete. Descriptive analyses were conducted to identify gaps in perceptions of disease burden and patient-physician communication. Results : The MPN LANDMARK SURVEY was completed by 813 patients (MF=207; PV=380; ET=226) and 457 physicians. Approximately half of the patients were 60–74 years of age (MF, 55%; PV, 51%; ET, 46%), the majority were female (MF, 54%; PV, 62%; ET, 72%) and had a degree from a 4-year college or postgraduate institution (MF, 65%; PV, 65%; ET, 58%), and 〉98% had health insurance. The majority of physicians graduated from medical school 5–24 years before the survey (67%) and practiced in outpatient settings (single specialty groups, 42%; academic hospitals, 31%). Patient-physician communication gaps were identified in several important areas: (1) Prognostic assessment: most patients did not recall receiving a prognostic risk score, but most physicians reported classifying patients by prognostic risk (Table 1). (2) Symptom assessment: physicians were more likely than patients to report that physicians ask about patients' most important disease-related symptoms or about a full and comprehensive list of symptoms (Table 1). (3) Treatment goals: the most important treatment goals were different in MF (patients: delay disease progression; physicians: improve symptoms) and PV (patients: delay disease progression; physicians: prevent vascular/thrombotic events) settings (Table 2). Patients and physicians in the ET setting both reported that prevention of vascular/thrombotic events was the most important treatment goal. Patients and physicians in the MF and PV settings reported fatigue as the most pressing disease manifestation that patients would like to resolve (MF: patients, 47%; physicians, 65%; PV: patients, 33%; physicians, 31%), whereas patients and physicians differed in the ET setting (patients: fatigue, 33%; physicians: stroke, 29%). Most patients reported a desire to be ≥50% responsible for their treatment decisions (MF, 72%; PV, 71%; ET, 75%). Physicians reported that most patients sometimes or often did not wish to comply with their primary treatment recommendation (MF, 77%; PV, 84%; ET, 79%). (4) Treatment satisfaction: overall, more than one third of patients were somewhat satisfied or dissatisfied with their physician's communication about their condition and treatment (MF, 34%; PV, 43%; ET, 45%) and with their physician's overall management of their disease (MF, 36%; PV, 40%; ET, 42%). Among patients who changed their MPN doctor (MF, 47%; PV, 46%; ET, 56%), dissatisfaction with prior care received was the most frequently reported reason for the change (MF, 40%; PV, 37%; ET, 33%). Approximately one fifth to one fourth of patients included their doctor's office among the most helpful sources of information about their diagnosis (MF, 27%; PV, 22%; ET, 20%), and most patients included the internet among the most helpful sources (MF, 90%; PV, 87%; ET, 89%). Conclusion : Important disconnects exist between patients' and physicians' perceptions in MPN disease settings. In addition, the majority of physicians report classifying patients by prognostic risk, including PV and ET settings, which do not have widely accepted prognostic risk scores. Although physicians generally appreciate the burden that MPNs have on patients, patient management may be enhanced with improved elucidation of patient symptoms and clear communication regarding the goals and potential benefits of interventions. Disclosures Mesa: Incyte Corporation: Research Funding; CTI: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Eli Lilly: Research Funding; Promedior: Research Funding; NS Pharma: Research Funding; Sanofi: Research Funding; Celgene: Research Funding. Miller:Incyte Corporation: Honoraria, Research Funding. Thyne:Incyte Corporation: Speakers Bureau. Mangan:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Goldberger:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Fazal:Incyte Corporation: Consultancy, Research Funding, Speakers Bureau; Gilead: Research Funding, Speakers Bureau. Ma:Incyte Corporation: Consultancy. Wilson:Incyte Corporation: Honoraria. Dubinski:Incyte Corporation: Employment, Equity Ownership. Boyle:ICF International: Employment, Equity Ownership. Mascarenhas:Novartis Pharmaceuticals: Research Funding; Incyte Corporation: Consultancy, Research Funding.

Description: TG02 is a potent cyclin-dependent kinase 9 (CDK9) inhibitor. It also inhibits CDK1, CDK2, ERK5 and JAK2 at clinically relevant doses. In vitro studies of TG02 have shown robust induction of apoptosis in both acute myeloid leukemia (AML) cell lines and primary cells (Goh et al Leukemia 2011). A phase I dose escalation trial enrolled relapsed/refractory AML patients 〉18 years of age or patients 〉65 years with newly diagnosed AML unable to undergo standard induction therapy. Leukemia stem cells (LSCs) comprise a largely quiescent, highly chemotherapy-resistant cell population that contributes to the initiation, propagation and relapse of disease. Thus, the effect of in vivo treatment with TG02 in LSCs was investigated. Peripheral blood (PB) and bone marrow (BM) samples were evaluated (n=16) for LSC percentages and cell cycle status using flow cytometry. Colony forming assays were also performed. TG02 was not found to have an effect on AML tumor burden; however, 8 patients were found to have an increase in immunophenotypically-defined LSCs in both BM and PB with increased colony formation, suggestive of LSC mobilization from marrow into the circulation (Guzman et al Blood 2013). Thus, we hypothesized that exposure to TG02 in vivomay result in mobilization of LSCs from marrow into the periphery, potentially allowing their sensitization to chemotherapeutic agents, such as cytarabine. We tested this hypothesis in vivo by xenotransplanting NOD/SCID mice with primary human AML samples. Mice were divided randomly into one of four groups which received either TG02, cytarabine, both drugs, or saline (control). TG02 was dosed orally at 50mg/kg twice weekly, and the combination group received two doses of TG02 prior to initiation of intraperitoneal cytarabine 10mg/kg days 1-5/week, and for its duration. The total treatment time for all groups was three weeks. Flow cytometry was used to assess the effects of these agents, individually and in combination, on LSCs. BM examination revealed significantly fewer human leukemia cells in mice receiving the combination of TG02 and cytarabine than in those receiving TG02 alone (p=0.027), and both groups had significantly fewer human leukemia cells compared to controls (p=0.018). Mice receiving TG02 alone had significantly higher numbers of leukemic cells in the peripheral blood than untreated controls (p=0.005), suggesting that the agent resulted in mobilization of leukemic cells from marrow. In the group of mice treated with TG02 combined with cytarabine, there were significantly fewer peripheral leukemia cells (p

Description: Background The availability of Computed Tomography Pulmonary Angiography (CTPA) has led to an increase in the number of investigations for Pulmonary Embolism (PE). With more widespread use of these high resolution scans, the frequency of identification of isolated Small Sub-segmental Emboli (SSPE) is also expected to increase. Current clinical practice guidelines do not make any treatment distinctions for SSPE, though the benefits of anticoagulation for SSPE have not been established. Aims To review the frequency of Pulmonary Embolism and Sub-segmental Pulmonary Embolism identified through CTPA as well as their management Methods Retrospective review of 2213 patient charts who underwent CTPA in three Hamilton teaching hospitals from 2009-2011. In depth chart review of patients with SSPE was undertaken to determine the frequency with which patients who received anticoagulation therapy for SSPE. The frequency of bleeding complications and recurrent thrombosis were also investigated in this detailed SSPE chart review. Results Our patient population (mean age 65) consisted of 1099 medical inpatients (50%), 702 surgical inpatients (32%) and 412 (18%) emergency department patients. PE was identified in 26 % of scans (n=576). Of these, SSPEs were the only identified thrombus in 82 patients (4% of total scans and 14% of identified PEs). In 55 of these 82 SSPEs, in addition to the SSPE, an alternative diagnosis that might explain the PE symptoms was found. Fifty-two percent (n=43) of the patients with an SSPE received therapeutic anticoagulation. In these life threatening bleeding occurred in 2 patients. There was no documented recurrent thrombosis or thrombosis-related deaths in three month follow-up among the 39 patients who did not receive anti-coagulation for SSPE. Of the 1,608 CTPAs that did not identify PE, an alternative diagnosis to account for the patient’s symptoms was identified on CT in 1078 (67%) and no alternative cause was found in 531 (33%). Summary/Conclusions Our study demonstrated a much lower frequency of pulmonary embolism in comparison to approximate 50 % pre-test probability of a positive scan seen in studies which validated CTPA for the diagnosis of PE. Isolated SSPEs accounted for 14% of all PEs found in our study population – and were present in 4% of all patients undergoing CTPA. A substantial proportion of patients were anti-coagulated SSPE (52%) and two developed life-threatening bleeding complications. No recurrent VTE was documented in patients who were not anticoagulated for PE, though follow-up was limited to hospital records. Randomized controlled trial data is needed to further investigate the risks and benefits of anticoagulation in patients with SSPE. Disclosures: No relevant conflicts of interest to declare.