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Abstract Abstract 1940 Background: Chronic graft-versus-host disease (GVHD) is a significant source of morbidity, mortality, impaired patient-reported quality of life (QOL), greater symptom burden, and prolonged duration of immune suppressive therapy following allogeneic hematopoietic cell transplantation (HCT). While available data support the adverse prognosis of overlap subtype of chronic GVHD, the relative importance of site of gastrointestinal (GI) and type of hepatic involvement is not known. Methods: We analyzed prospectively acquired observational cohort data to examine whether the site of GI involvement (esophageal, upper GI, lower GI) and type of hepatic laboratory test abnormality (bilirubin, alkaline phosphatase (AP), alanine aminotransferase (ALT) elevation over the upper limit of normal based on study site-specific laboratory reference ranges) among chronic GVHD-affected patients are associated with overall survival (OS) and non-relapse mortality (NRM), symptoms (Lee Symptom Scale), and quality of life (QOL) per SF-36 and FACT-BMT instruments. Results: This analysis included 567 individual subjects with baseline and 1548 follow up visits. The majority were incident cases (59%), adults (98%), and predominantly White/Non-Hispanic. Median time from HCT to cohort enrollment was 11.9 months (range 3–294 months). Overall NIH chronic GVHD severity was mild in 10%, moderate in 52%, and severe in 38% at enrollment. Prior acute GVHD was noted in 66%, KPS < 80% in 17%, and platelet count at chronic GVHD onset of < 100 K/uL in 23%. At enrollment, GI involvement was seen in 40% (upper GI 20%, esophagus 16%, lower GI 13%), and liver involvement was seen in 52% (AP 38%, ALT 38%, bilirubin 10%). Time from transplant to cGVHD onset was not different for patients with or without GI involvement or hepatic involvement. In multivariate analysis utilizing data from enrollment visits only and adjusting for patient and transplant variables, lower GI involvement (HR 1.7, p=0.03) and elevated bilirubin (HR 2.36, p=0.001) were associated with OS; both were also associated with NRM. In multivariable analysis using all visits (time-dependent covariates), GI score greater than zero (HR 1.7, p=0.01) and elevated bilirubin (HR 3.7, p<0.001) were associated with OS; results were similar for NRM. Separate models were constructed to examine the relationship of severity of GI and hepatic involvement (0–3 severity score per NIH consensus) and mortality: Increasing lower GI severity at enrollment was significantly associated with non-relapse mortality, with progressively increasing HR for greater severity levels (lower GI score 2/3 vs. 0: HR 5.5, 95% CI 2.3–13.1, p = 0.0001). Increasing bilirubin was also associated with NRM (bilirubin score 2/3 vs. 0: HR 3.3, 95% CI 1.3–8.4, p=0.01). A similar association was observed for bilirubin elevation and NRM in the time-dependent model (bilirubin 2/3 vs. 0: HR 8.9, 95% CI 3.3–24, p < 0.0001). When analyzing all visits, any esophageal involvement and GI score greater than zero were associated with both symptoms and QOL while elevated bilirubin was associated with QOL. We found no consistent evidence that upper GI involvement, AP, ALT, or NIH liver score add prognostic value for survival, overall symptom burden, or quality of life. Conclusion: These data support important differences in patient-reported outcomes according to GI and hepatic involvement among chronic GVHD affected patients, and identify those with elevated bilirubin or higher GI score at any time, or lower GI involvement at cohort enrollment, as patients at greater risk for mortality under current treatment approaches. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 3925 Introduction: CLL patients (pts) who relapse following purine-analog or bendamustine-based treatments have a poor prognosis. These pts have limited therapeutic options and novel agents with alternative mechanisms of action are needed. Several phase 1 and 2 trials in rel/ref CLL showed promising activity with escalating dose regimens of lenalidomide (LEN). In other phase II studies improved clinical responses to lenalidomide appeared to correlate with dose levels > 5mg/day. This phase 2 trial investigates the safety of LEN initiated at 3 different starting doses followed by a step-wise dose escalation as tolerated in rel/ref CLL. Methods: In this ongoing trial, eligible pts with rel/ref CLL who have received ≥ 1 prior treatment regimen containing purine-analog or bendamustine are being enrolled. The objectives of this study are to evaluate primarily the safety and secondarily the efficacy of different LEN dose regimens. Pts are randomized 1:1:1 to receive a double-blinded starting dose of 5 mg, 10 mg, or 15 mg oral LEN on days 1–28 of each 28-day cycle. In all 3 treatment arms, the dose is escalated by 5 mg increments every 28 days to reach a maximum dose of 25 mg/d, depending on tolerability. In instances of poor tolerability, dose reductions also occur in 5 mg steps. Pts are stratified by relapsed versus refractory status to their last purine-analog or bendamustine-based treatment regimen and according to age (< 65 vs ≥ 65 years). Tumor lysis syndrome (TLS) prophylaxis comprises of oral hydration and allopurinol 300 mg/day and is initiated ≥ 3 days prior to starting study drug and for a minimum of the first 3 treatment cycles. A total of 105 pts are planned for enrollment to the study. Per protocol, unblinded interim analyses were conducted by the independent Data Monitoring Committee (DMC) after 18 subjects completed 1 cycle and continue at 13-week intervals. Results: To date, 95 pts are enrolled at a median age of 64 years (range 32–81). Enrolled pts are primarily male (67%) and Caucasian (92%). Cytogenetic data are available for 73 pts; 21% have del(17p), 55% have del(13q), 25% have del(11q), and of 72 patients evaluable for trisomy 12, 11 patients (15%) tested positive. IGVH is unmutated in 77% of 77 evaluable pts and 44% of 84 evaluable pts are ZAP70-positive. Based on the Binet and Rai staging systems 9 (10%), 25 (26%) and 24 (25%) of subjects are stage A, B and C, respectively; 7 (7%), 12 (13%) and 16 (17%) subjects are low, intermediate or high-risk disease, respectively. For 2 (2%) subjects the Binet/Rai staging is currently unknown. Overall, 19 pts (20%) received prior bendamustine-containing treatment and 71 pts (75%) received prior fludarabine-based treatment. The median number of prior therapies was 3 (range 1–10). Most common hematological grade ≥ 3 AEs include neutropenia (62%) and thrombocytopenia (34%). At baseline, 19% of pts presented with grade 1–2 neutropenia. The most common non-hematological ≥ grade 3 AEs include pneumonia (13%), tumor flare (13%), and fatigue (11%). TLS was reported in 3 pts (3%): grade 1, 3, and 4. In total, 8 grade 5 events were reported, 3 of which were suspected to be related to LEN: 2 cases of pneumonia and 1 death for unknown cause. At the time of the cut-off, 59 pts (62%) have discontinued treatment. Most common reasons for treatment discontinuation include disease progression (n = 20) and AEs (n = 20). To date, 47 pts (49%) have dose escalated above their starting dose levels of which 12 patients escalated to the highest dose level (25 mg daily). 18 subjects have had no dose level reduction or escalations and 1 patient is still in the first cycle of the study. Average duration of treatment is 6.5 cycles, and median number of cycles is 4. Efficacy evaluations are completed monthly after 3 months of study drug treatment. At time of the data reporting, 5 pts were on study drug but did not reach the first assessment at cycle. For the 90 pts evaluable for response, the investigator's assessment indicates 2 pts (2%) reached CR, 36 (40%) achieved PR, 33 (37%) patients had SD, and 19 (21%) pts progressed. Conclusion: The independent DMC, as of 14 June, 2012 (N=95), recommended that accrual into all three treatment arms should continue as planned, suggesting all three starting doses were well tolerated. To date, the ORR is 42% and 49% of pts were dose escalated at least once. In this rel/ref CLL population LEN appears active, and completion of accrual will clarify the appropriate dose at which to initiate therapy. Disclosures: Wendtner: Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Mundipharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: use of lenalidomie in relapsed/refractory CLL. Hallek:Celgene Corporation: Consultancy, Honoraria, Research Funding. Hillmen:Celgene Corporation: Honoraria. Gregory:Celgene Corporation: Honoraria, Research Funding. Stilgenbauer:Celgene Corporation: Honoraria, Research Funding, Speakers Bureau. Kipps:Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Purse:Celgene Corporation: Employment, Equity Ownership. Zhang:Celgene Corporation: Employment, Equity Ownership. Mei:Celgene Corporation: Employment.

Abstract Background Polycythemia vera (PV) is a clonal myeloproliferative disorder characterized by erythrocytosis, splenomegaly and a frequently burdensome symptom profile. Despite current guidelines of aspirin, phlebotomy, and selective cytoreduction, many patients have inadequately controlled PV-related symptoms and/or disease features. We performed a comparison of PV symptom burden/disease feature phenotypes to understand unmet needs in current medical management. Methods Data was collected prospectively amongst an international cohort of PV patients including symptom burden, demographics, and disease features. Subgroups were identified who had previously failed hydroxyurea (PV-HU), required ongoing phlebotomy (PV-P), had palpable splenomegaly (PV-S), or had all 3 features (PV-HUPS). Control groups were derived from the remaining PV patients lacking the specified subgroup trait; patients in whom the trait status was unknown were excluded from each respective control group. All participants completed the MPN specific symptom burden questionnaire (MPN-SAF TSS (MPN-10 – Table 1)) and had no prior history of splenectomy. Surveyed symptoms on the MPN-10 included the patient's perceptions of common MPN-related symptoms and overall quality of life (QOL) on a 0 (absent) to 10 (worst imaginable) scale. PV risk scores were calculated using the 2013 criteria (Leukemia 2013). Comparison of symptoms between groups employed t-tests. Results Patient Demographics and Disease Features Between Phenotypic Groups A total of 1334 PV patients completed the MPN-10, and were assigned to categories of PV-HU (499 [37%]), PV-P (646 [48%]), PV-S (369, [28%]), and PV-HUPS (148 [12%]). The demographics between these groups were similar (comparable age (median range 60-63), PV risk scores (mean risk range: Low 16.4-23.7%; Intermediate 31.4%-36.6%; High 42.8%-47%). Mean hemoglobin was similar among PV subgroups (range 14.4-14.9); PV-HUPS had a higher mean WBC count (20.3 g/dL vs. 8.8-11.8 g/dL) and platelet count (703.5 x 10(9)/L vs. 327.5-462.8 x 10(9)/L), and disease duration (11.5 years vs. 6.4-8.8 years). Prior thrombosis was most common in PV-S patients (28.5% vs. 21.8-25.2%) and prior hemorrhage was most common in PV-HUPS patients (23.8% vs. 13.7-15.8%). Symptom Burden The MPN-10 scores of each problematic PV phenotype (HU, P, S, HUPS) were compared to the remainder of the PV cohort lacking the trait (PV-control; Table 1). Both individual symptom scores and TSS were highest for PV-HUPS patients (mean TSS 32.5 vs. 27.7-29.2). All problematic PV subgroups demonstrated significant differences for individual symptoms and TSS compared to PV-control. Comparing "problematic" subgroup responses, PV-HU patients described more inactivity whereas PV-S patients described more early satiety and pruritus. No statistical differences were noted in PV-HU, PV-P and PV-HUPS patient responses to MPN-10 items of "fever" and "weight loss". Discussion PV patients who have either failed HU, are undergoing phlebotomy and/or have splenomegaly exhibit moderate to severe symptomatology and demonstrate unmet medical need for management. As evidenced in this study, considerable overlap in symptomatology exists in PV-HU, PV-P, PV-S and PV-HUPS. Current randomized trials of JAK inhibitors have demonstrated benefits in a PV-HUPS phenotype. This data suggests that PV patients with any evidence of inadequate control (PV-HU, P, or S) have similarly unmet needs and may be candidates for clinical trials, intensification of medical therapy or perhaps JAK inhibitor therapy. Disclosures Kiladjian: Shire Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zweegman:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Research Funding. Besses:Shire Pharmaceuticals: honoraria for educational lectures Other. Birgegard:Shire Pharmaceuticals: Consultancy, Honoraria, Research Funding. Etienne:Novartis, BMS, Pfizer, Ariad: Honoraria. Roy:Merck: Peg-Interferon provided for academic clinical trial in CML Other. te Boekhorst:Novartis: Consultancy. Griesshammer:Novartis: Honoraria; Shire: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; Roche: Honoraria. Mesa:Incyte Corporation, CTI, NPS Pharma, Inc., Gilead Science Inc., Celgene: Research Funding.

Abstract Abstract 1614 Poster Board I-640 Background Cytogenetic abnormalities in B-cell CLL are important prognostic indicators for predicting disease progression and treatment response. Until recently, only interphase cytogenetics has been readily applicable to clinical use in CLL due to the inability of traditional mitogens to promote effective metaphase cytogenetic identification. Recently, cytokine or CpG oligonucleotide stimulation has been utilized to promote efficient metaphase analysis. One concern with this approach is the actual clonality and reproducibility of such clones when examined by different cytogenetic laboratories. The CLL Research Consortium (CRC) conducted a prospective trial to test (1) whether CpG would enhance detection of abnormal clones and (2) whether the CRC cytogenetic laboratories would achieve similar results when testing the same patient samples. Methods Initially, one laboratory compared stimulation of CLL cells using CpG versus pokeweed mitogen (PWM) + 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in the same samples. To test the reproducibility of CpG stimulation, fresh blood samples from 1 normal control and 12 CLL patients were collected at one site and distributed (blinded to phenotype and prior cytogenetic results) to 5 CRC cytogenetic laboratories where they were cultured for 3 days using CpG stimulation, harvested, banded and analyzed utilizing standard laboratory procedures. When possible, each laboratory analyzed 20 metaphases per case. Interphase FISH analysis for CLL (including probes for chromosomes 6q, 11q, 12, 13q, 17p, and IGH/CCND1) was also done on each sample. Results In the PWM+TPA versus CpG comparison, more cases were found to have clonal abnormalities with CpG stimulation (147 of 229, 64%) than with PWM+TPA (110 of 229, 48%; P=0.0005). All clonal abnormalities detected in the PWM+TPA cultures were also observed in the CpG cultures. In the 5-laboratory CpG comparison, the results were compiled and compared to the concurrent FISH results. The CpG karyotypes were concordant with the FISH results. The control case had a normal CpG-stimulated karyotype in all 5 laboratories. Three cases exhibited a complex karyotype; one of these also exhibited 11q-, one had 17p-, and one had neither. The cytogenetic descriptions varied modestly among labs, but all identified the complex clones. Every case including the control exhibited some nonclonal abnormal cells, but no pattern was detected among the 5 labs. When an abnormal clone was found by only 1 or 2 labs, it was present in only a very small number of cells. A small 13q- clone was observed in 2 cases in 1 and 2 labs (3 of 20 and 5 of 50 cells, respectively), and was confirmed by interphase FISH. A single lab found 2 of 30 cells with a t(12;15) in one case. Conclusions Abnormal clones in CLL are more readily detected with CpG stimulation than with traditional B-cell mitogens. The clonal abnormalities revealed by CpG stimulation are consistent with the “gold standard” interphase FISH results, and are reproducible among different cytogenetic laboratories. We have no evidence that CpG oligonucleotides create new clonal B-cell populations in vitro during 3 days of cell culture. CpG stimulation in vitro reveals clonal cytogenetic abnormalities and complexity in CLL that should be evaluated as potential independent prognostic parameters. Disclosures Kay: Biogenc-Idec, Celgene, Genentech, genmab: Membership on an entity's Board of Directors or advisory committees; Genentech, Celgene, Hospira, Polyphenon Pharma, Sanofi-Aventis: Research Funding.

Background Periodic wellness assessments can provide an estimate of a person’s relative risks for major diseases, but wellness visits are underused. Our suggestion is to use a comprehensive device during a single visit. Objective The goal of this pilot study was to evaluate the feasibility of a novel one-stop wellness device (Preventiometer; iPEx5 GmbH, Greifswald, Germany) for performing multiple tests and providing a comprehensive wellness assessment in a short period. Methods A Preventiometer was used to provide wellness assessments for 10 healthy volunteers who then answered a 25-question survey to rate their satisfaction with the testing and their overall impression. Results All volunteers agreed or strongly agreed with the following: The assessment reports were easy to understand, the Preventiometer met their satisfaction, the participants were comfortable during the assessment, and all measurements and testing were well coordinated. Participants liked the instant test result feature. Most (90%) agreed that the machine was useful for a quick health assessment for busy people, and 70% felt that it was time efficient. Conclusion In this feasibility pilot study, the Preventiometer performed multiple tasks and provided a comprehensive wellness assessment in a short period. Participants reported remarkably high satisfaction with the tests. A larger study is needed to prove that this is a pragmatic approach to help individuals improve their health.

INTRODUCTION: Primary lung cancers infrequently metastasize to the gastrointestinal tract. We describe one case of isolated colonic metastasis identified at diagnosis of the primary lung malignancy and the associated immunohistochemical pattern. CASE DESCRIPTION/METHODS: An 80-year-old man presented for evaluation of subacute onset shortness of breath. CT imaging showed a spiculated mass with associated ipsilateral intrathoracic lymphadenopathy. PET-CT was performed for staging and revealed a hypermetabolic focus in the left colon with recommendation for follow up colonoscopy. No other significant lesions or evidence of distant metastatic disease were seen and subsequent biopsy of a subcarinal lymph node demonstrated primary pulmonary adenocarcinoma. The colonoscopy visualized a sessile 12 mm polyp in the recto-sigmoid colon (Figure 1). Prior colonoscopy within 5 years of presentation was normal. Colon polyp morphology showed moderately differentiated adenocarcinoma. Immunohistochemical staining of resected polyp was positive for TTF-1 and negative for CDX2. Oncology recommended tyrosine kinase inhibitor therapy for Stage IV disease and alectinib was initiated with good response at 6 month follow up. DISCUSSION: Non-small cell lung cancer metastatic to the colon is uncommon but can present as a spectrum from asymptomatic mucosal involvement to bulky obstructive disease. Autopsy series and published case reports suggest broad estimates of asymptomatic involvement in between 1-10% of lung primaries, with symptomatic gastrointestinal involvement in <1% of cases. 1 Endoscopic presentation of metastatic disease to the gastrointestinal tract is often non-characteristic and differentiating adenocarcinoma tissue of origin is aided by immunohistochemical staining. TTF-1 staining has been shown to be highly specific to pulmonary adenocarcinomas. 2 CDX2 expression is an important intestine-specific transcription factor, and CDX2 negativity suggests adenocarcinoma of non-GI origin. 3 Used in conjunction, distant metastatic disease to the GI tract can be identified.

INTRODUCTION: Rates of musculoskeletal (MSK) injury among gastroenterologists are estimated to be as high as 75%, exceeding rates of 35% among non-proceduralists. Specific ergonomic/procedural factors influencing these injuries have yet to be defined. We sought to characterize potential risk factors for MSK injury by analyzing the physical traits and technical procedural data of a cohort of endoscopists. METHODS: The QuickDASH (Disabilities of Arm, Shoulder, and Hand) survey was sent to all gastroenterologists across a large tertiary care system. Added questions assessed injury characteristics, glove size, and other demographic data. Endpoints defining affected vs. unaffected groups include self-reported function-limiting upper extremity or back pain, injury necessitating limiting/stopping endoscopy, and trends toward higher QuickDash, Work Impairment, or Sport/Instrument Disability scores. A procedural database capturing all endoscopic activities of each respondent from 2011 to 2018 was queried to gather procedural types, volumes, durations, and insertion times; scope types; and polyp detection rates. RESULTS: 64 surveys were completed (28.1% female, mean age 44.4 ±10.8 yrs). The average time in practice was 18.9 (±10.8) years. 51% (n = 33) of respondents reported significant activity-limiting pain, including hand/wrist (n = 31), arm/elbow (n = 12), shoulder (n = 19), and back (n = 24) pain. Characteristics between affected and non-affected groups are detailed in Table 1 with further exploratory analyses found in Table 2. Those needing to limit/stop endoscopy due to pain more frequently used pediatric scopes (31% vs. 19%, P = 0.037), took longer to perform colonoscopy (25.3 vs. 22.1 minutes, P = 0.035) and had lower yearly procedural volumes (532 vs. 807, P = 0.009). Those with hand/wrist pain had longer colonoscopy insertion times (9.35 vs. 8.21 minutes, P = 0.03) and less colonoscopy hands-on scope hours per year (81.2 vs. 111.7 hours, P = 0.039). Females had more severe shoulder pain ( P = 0.04), but there were no other associations with sex or small glove size. CONCLUSION: Activity-limiting MSK injuries affect over 50% of endoscopists. MSK symptoms were associated with longer procedure times and higher EGD or push enteroscopy volumes. Symptomatic subjects were more likely to use pediatric colonoscopes. Hand/wrist pain is the most common and (presumably) the most limiting type of injury. Further prospective monitoring is warranted to better elucidate which variables are causative versus compensatory responses to injury.

Abstract Background Capsule endoscopy (CE) is frequently hindered by intra-luminal debris. Our aim was to determine whether a combination bowel preparation would improve small-bowel visualization, diagnostic yield, and the completion rate of CE. Methods Single-blind, prospective randomized–controlled study of outpatients scheduled for CE. Bowel-preparation subjects ingested 2 L of polyethylene glycol solution the night prior to CE, 5 mL simethicone and 5 mg metoclopramide 20 minutes prior to CE and laid in the right lateral position 30 minutes after swallowing CE. Controls had no solid food after 7 p.m. the night prior to CE and no liquids 4 hours prior to CE. Participants completed a satisfaction survey. Capsule readers completed a small-bowel-visualization assessment. Results Fifty patients were prospectively enrolled (56% female) with a median age of 54.4 years and 44 completed the study (23 patients in the control group and 21 in the preparation group). There was no significant difference between groups on quartile-based small-bowel visualization (all P &gt; 0.05). There was no significant difference between groups in diagnostic yield (P = 0.69), mean gastric (P = 0.10) or small-bowel transit time (P = 0.89). The small-bowel completion rate was significantly higher in the preparation group (100% vs 78%; P = 0.02). Bowel-preparation subjects reported significantly more discomfort than controls (62% vs 17%; P = 0.01). Conclusions Combined bowel preparation did not improve small-bowel visualization but did significantly increase patient discomfort. The CE completion rate improved in the preparation group but the diagnostic yield was unaffected. Based on our findings, a bowel preparation prior to CE does not appear to improve CE performance and results in decreased patient satisfaction (ClinicalTrials.gov, No. NCT01243736).

Abstract Background: Cancer incidence rates for American Indian and Alaska Native (AI/AN) populations vary by geographic region in the United States. The purpose of this study is to examine cancer incidence rates and trends in the AI/AN population compared with the non-Hispanic white population in the United States for the years 2010 to 2015. Methods: Cases diagnosed during 2010 to 2015 were identified from population-based cancer registries and linked with the Indian Health Service (IHS) patient registration databases to describe cancer incidence rates in non-Hispanic AI/AN persons compared with non-Hispanic whites (whites) living in IHS purchased/referred care delivery area counties. Age-adjusted rates were calculated for the 15 most common cancer sites, expressed per 100,000 per year. Incidence rates are presented overall as well as by region. Trends were estimated using joinpoint regression analyses. Results: Lung and colorectal cancer incidence rates were nearly 20% to 2.5 times higher in AI/AN males and nearly 20% to nearly 3 times higher in AI/AN females compared with whites in the Northern Plains, Southern Plains, Pacific Coast, and Alaska. Cancers of the liver, kidney, and stomach were significantly higher in the AI/AN compared with the white population in all regions. We observed more significant decreases in cancer incidence rates in the white population compared with the AI/AN population. Conclusions: Findings demonstrate the importance of examining cancer disparities between AI/AN and white populations. Disparities have widened for lung, female breast, and liver cancers. Impact: These findings highlight opportunities for targeted public health interventions to reduce AI/AN cancer incidence.