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Background and objective Immune-mediated diarrhea and colitis (IMDC) is a common adverse event in cancer patients receiving immune checkpoint inhibitors (ICIs). Gastrointestinal (GI) infections can co-occur with IMDC, and its impact on the course and outcome of IMDC remains unclear. Patients and methods We retrospectively reviewed cancer patients who received ICIs and developed IMDC between January 2015 and September 2019. GI multiplex panel is used to assess GI infection. The study group included patients with positive infection except those who are only positive for Clostridioides difficile or cytomegalovirus. The control group is IMDC patients with negative infection using frequency matching. Patients' disease course and outcome were compared between groups. Results A total of 72 patients with IMDC were included: 22 in the study group and 50 as control. Escherichia coli of different pathotypes was observed in 17 patients. Five patients had viral infections, for example, adenovirus, norovirus, and sapovirus. Patients with GI infections more frequently had grade 3 or 4 colitis (43% vs. 18%, P=0.041). Overall, GI infections were not associated with different risks of IMDC recurrence or overall survival. Antibiotics treatment did not affect the requirement for infliximab or vedolizumab but relate to a higher risk of IMDC recurrence (50.0% vs. 0.0%, P=0.015). Conclusions In our study, concomitant GI infections are associated with more severe symptoms in IMDC patients. Antimicrobial treatment did not circumvent the need for immunosuppressive therapy for IMDC or improve the clinical outcome. Concomitant GI infection was not associated with a higher risk of IMDC recurrence or poor overall survival.

Gains or amplification (amp) of chromosome 1q21/CKS1B are reported to be a high-risk factor in myeloma. In this retrospective study, we analyzed the impact of CKS1B gain/amp on overall survival in the context of other genetic aberrations, such as TP53 deletion, FGFR3-IGH, IGH-MAF, MYEOV/CCND1-IGH, and RB1, as well as karyotype. The cohort included 132 myeloma patients with CKS1B gain/amp detected by fluorescence in-situ hybridization. There were 72 men and 60 women with a median age of 65 years (range 39–88 years). A normal, simple, or complex karyotype was observed in 39.5%, 5.4%, and 55% of patients, respectively. “Double hit,” defined as CKS1B gain/amp coexisting with TP53 deletion, or “triple hit,” defined as double hit plus t(4;14)FGFR3-IGH or t(14;16)IGH-MAF, were identified in 25 patients (18.9%) and five patients (3.8%), respectively. Double and triple hit were highly associated with a complex karyotype (p = 0.02). Ninety-nine patients (99/128, 77.3%) received stem cell transplantation. The median follow-up time was 48.2 months (range 2–104 months); 68 patients (51.5%) died, with a median overall survival of 58.8 months. Multivariate analysis (Cox model) showed that double hit with TP53 deletion (p = 0.0031), triple hit (p = 0.01), and complex karyotype (p = 0.0009) were each independently associated with poorer overall survival. Stem cell transplantation was associated with better overall survival, mainly in patients with a double or triple hit and complex karyotype (p = 0.003). These findings indicate that the inferior outcome of myeloma patients with CKS1B gain/amp is attributable to the high number of high-risk patients in this group. The prognostic impact of CKS1B gain/amp depends on the background karyotype and TP53 status.

INTRODUCTION Small cell prostate cancer (SCPC) is a rare histologic subtype of prostate cancer, for which the optimal staging strategy remains unclear. METHOD The Surveillance, Epidemiology, and End Results database was used to analyze the incidence and outcomes of SCPC between the years 2004 through 2016. Limited-stage SCPC (LS-SCPC) was defined as SCPC without any metastasis regardless of local invasion. Extensive stage SCPC (ES-SCPC) was defined as any metastasis to lymph nodes and/or to distant organs. RESULT A total of 403 SCPC patients were included in the study cohort, accounting for 0.056% of all prostate cancer cases (n=719,655). Of the 358 patients with known metastasis status, 275 (76.8%) patients had ES-SCPC, whereas 83 (23.2%) patients had LS-SCPC. LS-SCPC was associated with better overall survival (17 vs. 9 mo, P

Background: Immune checkpoint inhibitor (ICI) therapy has significantly improved outcomes across a range of malignancies. While infections are a well-known contributor to morbidity and mortality amongst patients receiving systemic chemotherapy regimens, little is known about the impact of infections on patients receiving ICI therapy. This study aims to assess incidence, risk factors, and outcomes in patients who develop infections while on pembrolizumab-based therapies for non-small cell lung cancer (NSCLC). Methods: Patients receiving pembrolizumab for stage III/IV NSCLC from 1/1/2017-8/1/2021 across seven hospitals were identified. Incidence and type of infection were characterized. Covariates including baseline demographics, treatment information, treatment toxicities, and immunosuppressive use were collected and compared between infected and non-infected patients. Outcomes included the rate of infections, all-cause hospital admissions, median number of treatment cycles, overall survival (OS), and progression free survival (PFS). Univariable and multivariable analysis with reported odds ratio (OR) and 95% confidence intervals (CI) were utilized to evaluate infection risks. OS and PFS were analyzed by Kaplan–Meier analysis and tested by log-rank test. p-value < 0.05 was considered statistically significant. Results: There were 243 NSCLC patients that met the inclusion criteria. Of these, 111 (45.7%) had one documented infection, and 36 (14.8%) had two or more. Compared to non-infected patients, infected patients had significantly more all-cause Emergency Department (ED) [37 (33.3%) vs. 26 (19.7%), p = 0.016], hospital [87 (78.4%) vs. 53 (40.1%), p < 0.001], and ICU visits [26 (23.4%) vs. 5 (3.8%), p < 0.001], and had poorer median OS (11.53 [95% CI 6.4–16.7] vs. 21.03 [95% CI: 14.7–24.2] months, p = 0.033). On multivariable analysis, anti-infective therapy (OR 3.32, [95% CI: 1.26–8.76], p = 0.015) and ECOG of >1 (OR 5.79, [95% CI 1.72–19.47], p = 0.005) at ICI initiation conferred an increased risk for infections. At last evaluation, 74 (66.7%) infected and 70 (53.0%) non-infected patients died (p = 0.041). Conclusion: Infections occurred in nearly half of patients receiving pembrolizumab-based therapies for NSCLC. Infected patients had frequent hospitalizations, treatment delays, and poorer survival. ECOG status and anti-infective use at ICI initiation conferred a higher infection risk. Infection prevention and control strategies are needed to ameliorate the risk for infections in patients receiving ICIs.

Introduction We compared the safety and efficacy of Xa-inhibitors to LMWH for treatment of venous thromboembolism in mixed and gastrointestinal cancer cohorts (CA-VTE). Methods A systematic search identified RCTs and non-randomized studies (NRS) comparing Xa-inhibitors to LMWH for treating CA-VTE. Relative risks were computed. Certainty was assessed using the GRADE approach. Results Xa-inhibitors reduced the risk of recurrent VTE (RR0.64;0.49-0.84) and NRS (RR0.74;0.60-0.92;Moderate-Low Certainty). There was no significant difference in recurrent PE in RCTs (RR0.72;0.50-1.02) and NRS (1.43;0.65-3.12;Low-Very Low Certainty). Xa-inhibitors increased the risk of overall bleeding events in RCTs (RR1.45;1.05-2.01) and NRS (RR1.72;1.42-2.08;Moderate-Low Certainty), and the risk of major bleeding events in NRS (RR1.56;1.17-2.07), but not in RCTs (RR1.33;0.94-1.89; Low-Very Low Certainty). Similar results were detected in gastrointestinal cancer patients. Conclusion Xa-inhibitors may reduce the risk of recurrent VTE, but not recurrent PE compared to LMWH. A higher overall bleeding risk, and a questionably higher major bleeding risk was found with Xa-inhibitor use.

BACKGROUND Current therapeutic techniques for pancreatic pseudocyst include surgical management with a laparoscopic approach or an open surgical procedure, percutaneous catheter drainage and endoscopic drainage. Yet it remains controversial whether different treatment approaches affect inpatient outcome. AIM To investigate inpatient outcome of different treatment approaches in treating pancreatic pseudocyst. METHODS Here we conducted a retrospective analysis of pancreatic pseudocyst-associated hospitalizations using the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample. International Classification of Diseases 10 clinical modification and procedure codes are used. RESULTS A total of 7060 patients meeting the above criteria were identified. Our study revealed laparoscopic approach associated with the lowest rate of red blood cell transfusion (P < 0.001), and it had lower short-term complications including acute renal failure (P = 0.01), urinary tract infection (P = 0.01), sepsis (P < 0.001) and acute respiratory failure (P = 0.01). Laparoscopic surgical approach associated with the shortest mean length of stay (P = 0.009), and it had the lowest total charge (P = 0.03). All three modalities have similar inpatient mortality (P = 0.28). The study also revealed that percutaneous drainage associated with more emergent admission (P < 0.001), rural hospital performs the most open surgical drainage (P < 0.001) and patients who received laparoscopic drainage are more likely to be discharged home (P < 0.001). CONCLUSION Laparoscopic drainage of pancreatic pseudocysts associated with the least short-term complications and had better outcomes comparing to percutaneous and open surgical drainage from 2016 National Inpatient Sample database.

4573 Background: Over the past decade, studies have shown the benefit of immune checkpoint inhibitors (IO) in patients with advanced urothelial cancer. These agents work by reconditioning the adaptive anti-cancer immune response within the tumor microenvironment. Immune-related adverse events have been well documented, but there is limited data evaluating infections in patients treated with IO. We performed a retrospective analysis to assess the incidence of infection and its effect on morbidity and mortality in patients treated with pembrolizumab for advanced urothelial cancer. Methods: Data was collected from a network of 7 hospitals for patients who received pembrolizumab for advanced urothelial cancer from 1/1/2017-8/1/2021. Date of last follow up was 12/1/2021. Covariates compared among infected and non-infected cohorts included age, gender, race, comorbidities, ECOG, anti-infective therapy at IO initiation, and line of therapy (1L, 2L, > 2L). Univariable analysis with reported odds ratio (OR) and 95% confidence interval (CI) was used to assess risk factors for infection. Outcome measures included all-cause emergency department (ED) visits, inpatient and intensive care unit (ICU) admissions, median number of IO cycles, and overall survival (OS). OS was evaluated using the Kaplan-Meier model. All analyses were deemed statistically significant if the p-value was < 0.05. Results: A total of 51 patients were identified. Of these, 34 (66.7%) had at least one documented infection and 17 (33.3%) had no reported infections. Baseline characteristics were similar across cohorts. Compared to non-infected patients, infected patients received fewer cycles of IO (median 4 vs 8, p = 0.016). At last follow-up, 20 (58.8%) patients in the infected cohort and 4 (23.5%) in the non-infected cohort died (p = 0.017). Median OS was 7.4 months (95% CI: 3.4-24.9) among patients with infection while not reached in those without infection (p = 0.014). ED visits (p = 1.00), inpatient admissions (p = 0.21), and ICU admissions (p = 0.17) did not significantly differ between cohorts. Univariable analysis did not identify significant risks among covariates. Conclusions: The incidence of infection in patients treated with pembrolizumab for advanced urothelial cancer is high and associated with fewer cycles of IO therapy and shorter OS. Further study of infectious process prevention is of value to maximize immunotherapy benefit.

Immune-mediated diarrhea and colitis (IMDC) is among the most common immune-related adverse events in patients with cancer treated with immune checkpoint inhibitors (ICIs). Many factors will affect the risk of IMDC, including the type of ICI used, the type of underlying cancer, and patient characteristics. A recent study showed that preexisting inflammatory bowel disease significantly increases the risk of diarrhea and colitis with ICI treatment. In terms of management, early endoscopic evaluation improves clinical outcome by identifying high-risk patients who will benefit from early add-on immunosuppressants. Inflammatory markers, including fecal lactoferrin and calprotectin, are good screening tools to predict which patients are at risk for colitis. Calprotectin especially is associated with colitis outcome and can be used as a surrogate marker to follow treatment response. Corticosteroids remain the first-line medical treatment of IMDC management, and add-on therapy with vedolizumab or infliximab should be considered in selected patients. Fecal microbiota transplantation may be considered in refractory cases. The decision to resume ICI should be decided by balancing the risk of recurrent IMDC and the likelihood of benefiting from further ICI treatment. There is no clear evidence about whether the use of immunosuppressants will result in a worse cancer outcome. With emerging evidence, our understanding and management strategies are likely to evolve in the future.

Background The diagnosis of chronic myeloid leukemia (CML) is based on characteristic clinical and laboratory findings and the presence of BCR/ABL1 in the blood and/or bone marrow (BM). The utility of BM core biopsy in the workup of patients with CML has been questioned. Methods The potential added value of BM biopsy versus aspiration in the workup of a single-institution series of 508 patients with CML at their initial presentation was systematically assessed. BM biopsy was considered essential when it was needed to establish the disease phase, often because blast counts derived from aspirate smears were misleading because the biopsy specimen was more representative of the disease. BM biopsy was considered helpful if it was needed for other nonessential reasons. Results In 127 patients (25%), BM biopsy was either essential (109 patients) or helpful (18 patients). Patients with accelerated-phase (AP) or blast-phase (BP) disease often required a biopsy related to essential reasons. High-grade myelofibrosis (MF) was more frequent in patients with AP/BP disease than patients with chronic-phase disease (P = .0005), and the identification of BP disease required a BM biopsy assessment in 75% of the patients (P = .001). A follow-up BM evaluation more often yielded inadequate aspirates in patients with inadequate BM aspirates at the time of their initial diagnosis. Conclusions BM core biopsy remains valuable in the workup of 25% of patients with CML because it facilitates identification of the disease phase or MF. The initial grade of MF is associated with the disease stage and outcome after therapy. BM biopsy is, therefore, indicated for patients with CML who have AP/BP disease or other findings suggestive of progressive disease.

Introduction- Chromosome 1 abnormalities in multiple myeloma (MM) are increasingly recognized as high risk defined features. While there is robust data on 1q21 gain and amplification (amp), the clinical characteristics and outcome of patients with del 1p is less defined. Novel agents are incorporated into a backbone of multi-agent chemotherapy and tandem autologous stem cell transplantation (ASCT) in successive Total Therapy (TT) protocols for MM patients. We hereby report the prognostic value of del 1p by FISH at enrollment in subjects treated on TT protocols. Methods: (FISH was performed on bone marrow obtained at the time of first visit to our institution or initial diagnosis. FISH probes were generated from specific BAC DNA clones for AHCYL1 gene locus (1p13.3) and CKS1B locus (1q21). MM cells were identified post-hybridization using isotype specific antibody conjugated with 7-amino-4-methylcoumarin-3-acetic acid (AMCA) to stain Ig-Kappa or Ig-Lambda light chain in cytoplasm (cIg) of myeloma tumor cells. The FISH signals in 100 myeloma cells were recorded. For this analysis, 3 copies of 1q21 are considered as 1q21 gain and ≥ 4 copies as 1q21 amp. A 20% cutoff point was used for detection of significant abnormalities, i.e. del 1p and 1q21 gain and amp. A multivariable logistic regression model was used to examine the combined effects of clinical variables on progression free (PFS) and overall survival (OS). Results- A total of 1133 patients were included in this analysis. The median age was 60 (range 30.2-75), 434 (38.3%) patients were female and 106 (9.4%) were African Americans. ISS stage III disease accounted for 287 (25.3%). GEP70 high-risk was noted in 160/1133 (14.1%) of all patients. Of all patients, 1084 (95.7%) had at least one ASCT and 812 (71.7%) had tandem upfront ASCT. Metaphase cytogenetic abnormalities were noted in 548 (48.4%). While del 1p was detected in 220 (19.4%) patients, 1q21 gain or amplification were observed in 300 (26.5%) and 150 (13.2%) patients, respectively. Isolated 1q21 gain and amplification without del 1p were seen in 235 (20.7%) and 121 (10.7%) patients. Overall, there was enrichment of high-risk features such as ISS stage III disease (5.7% vs 10.9% p=0.049), GEP70 high-risk (8.4% vs 36.8%), GEP 70 subtypes such as MF (4.6% vs 8.2%), MS (10.5% vs 13.6%) and PR (11.3% vs 22.7%) and abnormal cytogenetic abnormalities (45.7% vs 59.5% p= Conclusion: Deletion of short arm of chromosome 1p was observed in 19% of MM patients. Concomitant del 1p with 1q21 gain and /or amp was present in 8% of patients. The PFS and OS of patients with combined del1p/1q21gain abnormalities was significantly worse compared to del 1p alone and 1q21 gain alone and thus identifies a subset of patients with poor clinical outcome. Figure 1 Figure 1. Disclosures Mohan: Medical College of Wisconsin: Current Employment.

Long non-coding RNAs (lncRNAs) are continuously transcribed and are involved in various cellular activities. However, their contributions to the occurrence and development of germinal center B-cell (GCB)-like diffuse large B-cell lymphoma (DLBCL) remain largely unknown. We applied microarray technology to profile the expression of lncRNAs in two different GCB-DLBCL cell lines (OCI-ly1 and OCI-ly19) and normal B lymphocytes. We demonstrated that 21,539 lncRNAs were expressed in all of the samples analyzed. This included 1,648 lncRNAs that showed a ≥2-fold upregulation and 2,671 lncRNAs that displayed a ≥2-fold downregulation in tumor cell lines (P

Gains or amplification (amp) of chromosome 1q21/CKS1B are reported to be a high-risk factor in myeloma. In this retrospective study, we analyzed the impact of CKS1B gain/amp on overall survival in the context of other genetic aberrations, such as TP53 deletion, FGFR3-IGH, IGH-MAF, MYEOV/CCND1-IGH, and RB1, as well as karyotype. The cohort included 132 myeloma patients with CKS1B gain/amp detected by fluorescence in-situ hybridization. There were 72 men and 60 women with a median age of 65 years (range 39-88 years). A normal, simple, or complex karyotype was observed in 39.5%, 5.4%, and 55% of patients, respectively. "Double hit," defined as CKS1B gain/amp coexisting with TP53 deletion, or "triple hit," defined as double hit plus t(4;14)FGFR3-IGH or t(14;16)IGH-MAF, were identified in 25 patients (18.9%) and five patients (3.8%), respectively. Double and triple hit were highly associated with a complex karyotype (p = 0.02). Ninety-nine patients (99/128, 77.3%) received stem cell transplantation. The median follow-up time was 48.2 months (range 2-104 months); 68 patients (51.5%) died, with a median overall survival of 58.8 months. Multivariate analysis (Cox model) showed that double hit with TP53 deletion (p = 0.0031), triple hit (p = 0.01), and complex karyotype (p = 0.0009) were each independently associated with poorer overall survival. Stem cell transplantation was associated with better overall survival, mainly in patients with a double or triple hit and complex karyotype (p = 0.003). These findings indicate that the inferior outcome of myeloma patients with CKS1B gain/amp is attributable to the high number of high-risk patients in this group. The prognostic impact of CKS1B gain/amp depends on the background karyotype and TP53 status.

Background Immune-mediated diarrhea and colitis (IMDC) can limit immune checkpoint inhibitors (ICIs) treatment, which is efficacious for advanced malignancies. Steroids and infliximab are commonly used to treat it. These agents induce systemic immunosuppression, with its associated morbidity. We assessed clinical outcomes of vedolizumab as an alternative treatment for IMDC. Methods We analyzed a retrospective case series of adults who had IMDC refractory to steroids and/or infliximab and received vedolizumab from 12/2016 through 04/2018. Results Twenty-eight patients were included. The median time from ICI therapy to IMDC onset was 10 weeks. Fifteen patients (54%) had grade 2 and 13 (46%) had grade 3 or 4 IMDC. Mucosal ulceration was present in 8 patients (29%), and nonulcerative inflammation was present in 13 (46%). All patients had features of active histologic inflammation; 14 (50%) had features of chronicity, and 10 (36%) had features of microscopic colitis concurrently. The mean duration of steroid therapy was 96 days (standard deviation 74 days). Nine patients received infliximab in addition to steroids and their IMDC was refractory to it. Among these, the duration of steroid use was 131 days compared with 85 days in patients who did not receive infliximab. Likewise, patients who failed infliximab before vedolizumab had a clinical success rate of 67% compared to 95% for patients that did not receive infliximab. The median number of vedolizumab infusions was 3 (interquartile range 1–4). The mean duration of follow-up was 15 months. Twenty-four patients (86%) achieved and sustained clinical remission. Repeat endoscopic evaluation was performed in 17 patients. Endoscopic remission was attained in 7 (54%) of the 13 patients who had abnormal endoscopic findings initially; 5/17 patients (29%) reached histologic remission as well. Conclusions Vedolizumab can be appropriate for the treatment of steroid-refractory IMDC, with favorable outcomes and a good safety profile. Electronic supplementary material The online version of this article (10.1186/s40425-018-0461-4) contains supplementary material, which is available to authorized users.

e19098 Background: Tumor lysis syndrome (TLS) is a life-threatening oncological emergency. Spontaneous TLS (STLS) in solid tumors occurring prior to initiation of therapy is a rarely reported entity and has poor outcomes. Little is known about the prognostic factors influencing STLS in solid tumors. Methods: A systematic search of Medline, PubMed, and Embase was conducted to identify reports of patients ≥18 years diagnosed with STLS in solid tumors. Individual case reports and case series were summarized, and descriptive statistics were employed to report clinical outcomes. Fischer exact t test was used for statistical analysis. Results: 63 patients from 61 case reports and one patient from our institution resulted in a total of 64 patients. 53.1% were males with a median age of 56.1 years. The most common solid tumors were of pulmonary origin. 85.9% patients had stage 4 malignancy, 75.0% had hepatic involvement. The most common presenting symptom was abdominal discomfort. The mean serum potassium, phosphorus, uric acid, calcium, lactate dehydrogenase, and creatinine upon presentation were 6.1 mmol/l, 7.5 mg/dl, 16.4 mg/dl, 7.5 mg/dl, 4421.2 IU/L and 3.7 mg/dl, respectively. In addition to intravenous hydration, allopurinol and rasburicase were administered in 48.4% and 42.2% patients. Urinary alkalization and sodium bicarbonate administration were reported in 6.3% and 15.6% patients. 43.8% patients required hemodialysis and 39 patients died (mortality of 60.9%). Patients who underwent hemodialysis had a similar mortality of 60.4%. We assessed liver involvement (primary hepatocellular carcinoma and hepatic metastasis) as a potential prognostic factor. Compared to patients without liver involvement, patients with liver involvement had a higher unadjusted all-cause mortality (70.83% vs 25%; OR 7.29 [95% CI 1.71 - 30.98]; p = 0.006). Conclusions: Hepatic involvement is a potential prognostic factor for STLS in solid tumors and is associated with a grave prognosis. Future large prospective studies are needed to probe into the role of early hemodialysis and to identify other prognostic factors of STLS in solid tumors.

The impact of atrial fibrillation (AF) in acute ischemic stroke patients treated with thrombolysis remains unclear, largely limited by confounding factors including age and comorbidities (anticoagulation (AC), antiplatelets, etc). We aim to investigate this with a large, population-based database.

Introduction: Portal vein thrombosis (PVT) is usually associated with intra-abdominal malignancies, particularly pancreatic cancer (PC). PVT prevalence rate and impact on outcome of PC patients are not well studied, especially on a large scale of cohort. We described the prevalence and mortality trends of PVT amongst PC patients and analyzed their demographic characteristics. We also studied the impact of PVT with PC on hospitalization outcomes. Methods: We queried the 1998-2016 National Inpatient Sample (NIS) database of the Agency of Healthcare Research and Quality (AHRQ). Hospitalized adult patients (age≥18 years) with diagnosis of PC as well as presence of PVT were identified by using ICD-9 or ICD-10 codes. Cost of hospitalization was adjusted for inflation in reference to 2016. Comorbidities were classified using the Elixhauser comorbidity index. We used linear regression models to analyze trends in prevalence and outcomes over time. Logistic regression models were generated to evaluate multivariate predictors of length of stay (LOS), total charges, mortality, and complications in PC patients with and without PVT. The regression model was adjusted for age, sex, primary expected payer, teaching status of the hospital, hospital location, comorbid conditions, and presence of venous thromboembolism (VTE). Results: Among a total of 1,488,543 hospitalized PC patients, 19,725 (1.3%) experienced PVT. Mean age was 68 years. Hispanic Americans, younger age, teaching hospital, urban hospital and metastatic disease were associated with higher PVT prevalence rate. Interestingly, VTE prevalence in PC patients with and without PVT were 11% and 6% respectively, P Conclusion: In retrospective analysis of the NIS cohort of hospitalized patients with PC and PVT from 1998-2016, the prevalence increased by 10 folds. However, in-hospital mortality decreased significantly. Compared to those without PVT, patients with PC with PVT had higher inpatient mortality, longer length of stay, higher hospital cost and higher degree of disability upon discharge. Further studies are warranted to reveal a certain subgroup of PC patients who may benefit from prophylactic anticoagulation. Figure Disclosures No relevant conflicts of interest to declare.

Introduction: Sickle cell disease (SCD) is one of the most common inherited hematological disorder in the United States. Sickle cell crisis is a common complication caused by excessive sickling of red blood cells, resulting in tissue ischemia. The frequency of such pain crisis, however, varies greatly among patients depending on disease control and other patient characteristics. Asthma is a common comorbidity in SCD patients which is associated with higher incidence of acute chest syndrome (ACS). However, the impact of asthma on short term outcome of acute sickle cell crisis remains unclear. Methods: We analyzed data from the National Inpatient Sample database. Data entries from year 2005 through 2014 were included. The presence of SCD, sickle cell crisis, ACS, asthma are identified using corresponding ICD codes. Data regarding demographic information, performed procedures, inpatient mortality, and length of stay are extracted and analyzed accordingly. Results: A total of 247,266 records were identified. The median age at admission was 26 years (interquartile range 18 - 37), with most patients being of African American origin (91.8%). A total of 16,828 (6.8%) patients presented with ACS, whereas 173,869 (70.3%) presented with non-ACS crisis. The remaining 56,569 (22.9%) patients were admitted for reasons other than sickle cell crisis, most commonly infection. Overall, 34,609 patients (14.0%) had asthma. Compared to patients without ACS, the incidence of asthma was significantly higher in patients with ACS (19.0% vs 13.6%, P Conclusion: Our study again demonstrated the association between asthma and ACS in SCD patients. Furthermore, asthma appears to be associated with superior outcome in both patients with ACS and non-ACS sickle cell crisis. Further studies are warranted to elucidate if asthma is associated with a milder form of sickle cell crisis which may correlate with the physiologic basis of these associations. Disclosures No relevant conflicts of interest to declare.

Introduction: Pancreatic cancer (PC) has a known association with venous thromboembolism (VTE), with incidence of approximately 17%. There is limited published data about trends and outcomes of PC patients with VTE. The purpose of this study was to describe the prevalence and mortality trends in PC with VTE and analyze VTE impact on hospitalized PC patients from 1998 to 2016. Methods: We analyzed data from the National Inpatient Sample (NIS) database of the Agency of Healthcare Research and Quality (AHRQ). Adults≥18 years with PC as well as presence of VTE were identified by using ICD-9 or ICD-10 codes. Cost of hospitalization was adjusted for inflation in reference to 2016. Comorbidities were classified using the Elixhauser comorbidity index. Demographic characteristics, trends and in-hospital outcomes between PC with and without VTE were compared. Multiple logistic regression was used to obtain risk-adjusted odds ratio (OR) to compare inpatient mortality, length of stay (LOS), total charges, and disability at discharge between PC patients with and without VTE. The regression model was adjusted for age, sex, primary expected payer, teaching status of the hospital, hospital location, and presence of comorbid conditions. Results: 96,777 (6.5%) of a total of 1,488,543 hospitalized PC patients had an accompanying diagnosis of VTE. Mean age of the study population was 67 years. African Americans, younger age, and metastatic disease are associated with higher VTE prevalence rate. After adjusting for potential confounders, compared with those without VTE, PC patients with VTE had significantly higher inpatient mortality (12.6% vs 9.7%; OR, 1.41 [confidence interval (CI), 1.34-1.49]; P Conclusion: In the NIS cohort of hospitalized patients with PC and VTE from 1998-2016, annual prevalence increased while mortality overall decreased. When compared to patients without VTE, PC patients with VTE had higher inpatient mortality, longer length of stay, higher hospital cost and higher degree of disability upon discharge. Consideration for anticoagulation and interventions to limit VTE in PC patients may improve in-hospital outcomes. Figure Disclosures No relevant conflicts of interest to declare.

Recently, O’Connor et al . reported the high activity of the combination of brentuximab vedotin (BV) and bendamustine in relapsed/refractory Hodgkin’s lymphoma (HL) patients (1). The study is notable for the heavily treated population and relatively large sample size.

The diagnosis of chronic myeloid leukemia (CML) is based on characteristic clinical and laboratory findings and the presence of BCR/ABL1 in the blood and/or bone marrow (BM). The utility of BM core biopsy in the workup of patients with CML has been questioned.The potential added value of BM biopsy versus aspiration in the workup of a single-institution series of 508 patients with CML at their initial presentation was systematically assessed. BM biopsy was considered essential when it was needed to establish the disease phase, often because blast counts derived from aspirate smears were misleading because the biopsy specimen was more representative of the disease. BM biopsy was considered helpful if it was needed for other nonessential reasons.In 127 patients (25%), BM biopsy was either essential (109 patients) or helpful (18 patients). Patients with accelerated-phase (AP) or blast-phase (BP) disease often required a biopsy related to essential reasons. High-grade myelofibrosis (MF) was more frequent in patients with AP/BP disease than patients with chronic-phase disease (P = .0005), and the identification of BP disease required a BM biopsy assessment in 75% of the patients (P = .001). A follow-up BM evaluation more often yielded inadequate aspirates in patients with inadequate BM aspirates at the time of their initial diagnosis.BM core biopsy remains valuable in the workup of 25% of patients with CML because it facilitates identification of the disease phase or MF. The initial grade of MF is associated with the disease stage and outcome after therapy. BM biopsy is, therefore, indicated for patients with CML who have AP/BP disease or other findings suggestive of progressive disease.

The Philadelphia chromosome resulting from t(9;22)(q34;q11.2) or its variants is a defining event in chronic myeloid leukemia. It is also observed in several types of de novo acute leukemia, commonly in B lymphoblastic leukemia, and rarely in acute myeloid leukemia, acute leukemia of ambiguous lineage, and T lymphoblastic leukemia. Acquisition of the Philadelphia chromosome during therapy of acute leukemia and myelodysplastic syndrome is rare. We reported 19 patients, including 11 men and 8 women with a median age of 53 years at initial diagnosis. The diagnoses at initial presentation were acute myeloid leukemia (n = 11), myelodysplastic syndrome (n = 5), B lymphoblastic leukemia (n = 2), and T lymphoblastic leukemia (n = 1); no cases carried the Philadelphia chromosome. The Philadelphia chromosome was detected subsequently at relapse, or at refractory stage of acute leukemia or myelodysplastic syndrome. Of 14 patients evaluated for the BCR-ABL1 transcript subtype, 12 had the e1a2 transcript. In 11 of 14 patients, the diseases before and after emergence of the Philadelphia chromosome were clonally related by karyotype or shared gene mutations. Of 15 patients with treatment information available, 7 received chemotherapy alone, 5 received chemotherapy plus tyrosine kinase inhibitors, 2 received tyrosine kinase inhibitors only, and 1 patient was not treated. Twelve patients had follow-up after acquisition of the Philadelphia chromosome; all had persistent/refractory acute leukemia. Thirteen of 15 patients died a median of 3 months after the emergence of the Philadelphia chromosome. In summary, secondary Philadelphia chromosome acquired during therapy is rare, and is associated with the e1a2 transcript subtype, terminal disease stage, and poor outcome.

Background Extranodal natural killer/T-cell lymphoma (ENKTL) usually presents as a localized disease in the nasal cavity; extension to the male genitourinary system is very rare and has been characterized only recently. Most cases present with predominantly extranodal involvement, advanced stage disease, highly aggressive course, and strong association with Epstein-Barr virus (EBV). While metastasis is common in ENKTLs, the penis is rarely involved in both nasal and non-nasal ENKTLs and only one report was published to date. Case presentation One patient with NK/T-cell lymphoma, presented initially with a penile mass, is reported. The 58-year-old man who presented with progressive painless penile swelling underwent penectomy for penile tumor. Histologically, the glans and foreskin revealed neoplastic infiltration of medium-sized lymphoma cells expressing CD56, CD3, granzyme-B, and labeled for EBV-encoded RNA in situ hybridization. Findings were consistent with NK/T-cell lymphoma. By detailed history, we learned that the patient had nasal obstruction for more than 10 years. Nasopharyngeal involvement was screened with PET-CT; ENKTL was diagnosed after a nasopharyngeal biopsy. The final diagnosis was primary nasal NK/T-cell lymphoma, with metastasis to the penis. Additional sites of disease appeared soon afterward (adrenal gland, liver, spleen and lymph nodes). The patient died within 4 months. Conclusion This study suggested that penile NK/T-cell lymphoma tends to disseminate early and pursues an aggressive course. It is imperative to distinguish nasal NK/T lymphoma from other types of tumors, because the prognosis and treatment differ significantly for secondary metastases.

The high fatality of patients with blast phase (BP) chronic myeloid leukemia (CML) necessitates identification of high-risk (HR) patients to prevent onset of BP. Here, we investigated the risk of BP based on additional chromosomal abnormality (ACA) profiles in a cohort of 2326 CML patients treated with tyrosine kinase inhibitors (TKIs). We examined the time intervals from initial diagnosis to ACA emergence (interval 1), from ACA emergence to onset of BP (interval 2), and survival after onset of BP (interval 3). Based on BP risk associated with each ACA, patients were stratified into intermediate-1, intermediate-2, and HR groups, with a median duration of interval 2 of unreached, 19.2 months, and 1.9 months, respectively. There was no difference in durations of intervals 1 or 3 among 3 groups. Including patients without ACAs who formed the standard-risk group, the overall 5-year cumulative probability of BP was 9.8%, 28.0%, 41.7%, and 67.4% for these 4 groups, respectively. The pre-BP disease course in those who developed BP was similar regardless of cytogenetic alterations, and 84.4% of BP patients developed BP within the first 5 years of diagnosis. In summary, interval 2 is the predominant determinant of BP risk and patient outcome. By prolonging the duration of interval 2, TKI therapy mitigates BP risk associated with low-risk ACAs or no ACAs but does not alter the natural course of CML with HR ACAs. Thus, we have identified a group of patients who have HR of BP and may benefit from timely alternative treatment to prevent onset of BP.

Introduction: Small cell prostate cancer (SCPC) is one of the most common extrapulmonary small cell cancers as well as one of the most common histology type among non-adenocarcinoma prostate cancers. While small cell lung cancer follows a limited-versus-extensive staging system which is different from the stage I to IV system used for non-small cell lung cancer, the prostate adenocarcinoma staging system is used in SCPC despite its distinct clinical feature and aggressive disease course. Limited by the rarity of SCPC, the optimal staging strategy for SCPC remains unknown. The present study aimed to investigate the prognostic value of limited-vs-extensive staging system in SCPC patients. Method: The Surveillance, Epidemiology, and End Results database was used to analyze the incidence and outcome of small cell prostate cancer. Patients diagnosed between the year 2004 through 2015 were included. Limited stage is defined as those without metastasis regardless of degree of local invasion. Extensive stage is defined as any metastasis to locoregional lymph node, to distant lymph node, or to distant organs. Result: A total of 364 SCPC patients are included in the study cohort, accounting for 0.05% of all prostate cancer cases (n=665,054). Age adjusted incidence of SCPC was 0.959 per 1,000,000 per year over the whole study period. The median age at diagnosis of SCPC is 71 years. The median overall survival is 9 months. In the 322 patients with known metastasis status, 243 (75.5%) patients are in extensive stage, whereas 79 patients are in limited stage. Patients in extensive stage are more likely to have PSA level greater than 20 than those in limited stage (26.3% vs 6%), but a similar proportion of patients in both groups have PSA level less than 4 (44.3% vs 40.0%). Compared to patients with extensive stage, those with limited stage disease had a significantly better overall survival (17 months vs 9 months, p Conclusion: SCPC patients can be staged to limited stage and extensive stage based on the absence versus presence of metastasis. T stage in limited stage patient and type of metastasis in extensive stage patient is not associated with different outcome. Citation Format: Salman Syed, Faisal Ali, Spyridon Basourakos, Zimu Gong. Limited-versus-extensive staging system for small cell prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4189.

e15749 Background: Pancreatic Adenocarcinoma (PA) is an aggressive malignancy with an estimated 5-year survival of 8.5%. PA was responsible for 7.3% of all cancer deaths in 2018 in the US. We aimed to evaluate the impact of pretreatment serum creatinine (SCr) level on Overall Survival (OS) in patients with PA. Methods: A retrospective review of electronic health records of patients with PA seen at our institution between 01/2014 and 01/2018 was done. We collected patients’ SCr at the time of diagnosis, and excluded patients with a glomerular filtration rate (GFR) below 60 mL/min per 1.73 m2 or SCr > 1.3 mg/dL. Patients were dichotomized around a SCr of 0.5 mg/dL. Kaplan-Meier survival estimate was performed to evaluate statistical significance. Results: A total of 83 patients, including 37 females and 46 males, with a median age at diagnosis of 67 years, were included. SCr of < 0.5 mg/dL was associated with a lower median OS as compared to a SCr of ≥0.5 mg/dL, (253 days versus 364 days; P = 0.035). There were more female patients in the low SCr group (71% vs 39%, P = 0.027). Patients with SCr of < 0.5 mg/dL had a lower mean BMI compared to patients with a SCr of ≥0.5 mg/dL, however this was not statistically significant (BMI = 22.45 versus 25.72; P = 0.49). Conclusions: Low SCr is predictive of a lower median OS in patients with PA. SCr has been suggested as a surrogate marker for muscle mass, which is closely associated with the degree of cancer cachexia. Our finding emphasizes the need for future larger studies to evaluate the utility of SCr as a prognostic indicator, as well as a cost-effective surrogate for measuring cancer cachexia. [Table: see text]

e14117 Background: Cytotoxic T-lymphocyte activator-4 immune checkpoint inhibitors (CTLA-4-ICPI) is believed to cause more toxicity than programmed cell death/Ligand-1 (PD-1/PD-L1) ICPIs. We conducted a meta-analysis to outline the gastrointestinal (GI), pancreatic, and hepatic toxicity of CTLA-4 ICPIs when used alone and in combination with PD-1/PD-L1 ICPIs (C-ICPI). Methods: Ovid MEDLINE, EMBASE, Cochrane Library, SCOPUS, Web of Science, ClinicalTrials.gov, and WHO ICTRP were queried from January 2007-October 2018. Clinical trials reporting ICPI associated adverse events (AEs) were included. Colitis was defined as the development of diarrhea or documented colitis of any grade. Pancreatitis was defined as an elevation of amylase or lipase. Hepatitis was defined as elevation of ALT, AST, or transaminitis of any grade. A meta-analysis of proportions was conducted to report pooled AEs rate with 95% confidence intervals (CI) using a random effects model. Results: Overall, 30 study arms (20 CTLA-4, 10 C-ICPI) enrolling 3721 patients were included. There were a total of 3944 and 3317 AEs with CTLA-4 and C-ICPI use, respectively, with a pooled incidence of high grade AEs (grade 3-5; HAEs) of 23% (95% CI 16-33%) with CTLA-4 use and 52% (95% CI 37-67%) with C-ICPI use ( Table). The incidence of high-grade colitis was higher among patients treated with CTLA-4 ICPI. The proportion of high-grade pancreatitis was higher among patient who received C-ICPI. Two GI perforations were reported with CTLA-4 use. Pooled incidence of treatment related mortality was 1% in both groups. Conclusions: Though the overall GI, hepatic and pancreatic safety profile of CTLA-4 is comparable to C-ICPI, a higher incidence of high-grade colitis was found with CTLA-4. Two GI perforations were reported with CTLA-4 and warrant further investigation. No difference in treatment related mortality was found among the two groups. [Table: see text]

e18185 Background: Tumor lysis syndrome (TLS) is a constellation of metabolic disturbances that can occur in virtually any malignancy, though it is more common in hematological malignancies given their high tumor burden and growth index. While TLS can occur in patients with solid tumors, the clinical behavior and outcome of solid tumor associated-TLS (STA-TLS) is not well characterized. Methods: We used the national inpatient sample to identify patients with STA-TLS (utilizing the ICD10 code E883; and ICD9 code 27788), from year 2010 through year 2016. Patients with both hematological malignancy and solid tumor, and patients without a cancer diagnosis were excluded. Results: A total of 11,733 patients were identified using the above criteria, of which 2117 (18.0%) had STA-TLS. The median age at admission was 63 years and 940 (44.4%) STA-TLS patients were females. The most common primary cancer sites were lung (26.8%), breast (4.2%), and colon (3.7%). Patients with STA-TLS were more likely to receive mechanical ventilation and less likely to receive red blood cell or platelet transfusion compared to those with hematological malignancies ( Table). STA-TLS was also associated with a significantly higher inpatient mortality rate and shorter length of stay than TLS in hematological malignancies ( P < 0.001). No statistically significant difference was found in the requirement of dialysis, transfusion of plasma, and cardiac arrest rates. Conclusions: STA-TLS is rare with an inferior outcome than TLS in hematological malignancies evident by a higher mechanical ventilation and mortality rate. Future studies should identify factors that impact management and outcome of STA-TLS. [Table: see text]

e14131 Background: The safety of programmed death receptor and ligand-1 (PD-1/PDL-1) inhibitors in hematologic cancers is not well-defined. We conducted a meta-analysis to investigate their safety. Methods: Pubmed & Cochrane databases were searched from 1968-2018. Full-text articles of clinical trials reporting treatment-related adverse events (AE) of PD-1/PDL-1 inhibitors in hematologic cancers were included. Incidences of all-grade and high-grade (≥grade 3) AEs were pooled and generated with a 95% confidence interval (CI) using a random effect model on STATA. Results: Eight studies (5 nivolumab & 3 pembrolizumab) were identified, with 703 patients and the median age of 34. Six studies were done in patients with relapsed/refractory (R/R) classical Hodgkin Lymphoma, one in R/R diffuse large B-cell lymphoma and one in combined hematologic cancers. There were 1092 total AEs, with a pooled high grade AEs rate of 13% (95% CI 9-17%). High-grade AEs (HAE) are summarized in the Table. Lipase elevation was the most common HAE for nivolumab (pooled incidence of 13%; 95% CI 6-23%), whereas leukopenia was the most common HAE reported with pembrolizumab use (pooled incidence of 36%; 95% CI 10-65%) There were 47 treatment discontinuation due to treatment-related AE. For Nivolumab, there was one treatment-related death (of a heavily pretreated patient) due to fatal pneumonitis. Conclusions: PD-1/PDL-1 inhibitors are well-tolerated in hematologic malignancies with a favorable risk of adverse events and very low treatment-related mortality. The HAE profile of Nivolumab differs from Pembrolizumab, and future studies should assess this heterogeneity further. [Table: see text]

Objectives The aim of this study was to assess whether outcomes of patients with metal allergy after coronary stent implantation differ from those of patients without metal allergy. Methods A meta-analysis was carried out to compare the outcome in patients who are allergic to the metal material of a stent with those who are nonallergic. A computer-based online retrieval of databases and manual searches were performed to identify articles that addressed the association between in-stent restenosis (ISR) and contact allergy to stent materials, without language restrictions. The meta-analysis was carried out with a fixed-effect model using STATA 11. Odds ratio (OR) was used as an effect size. Result Nine relevant articles, encompassing 1223 patients, were identified. Being allergic to stent material obviously increased the risk of ISR. With the fixed model, ORs for allergic patients and nonallergic patients were 2.65 (confidence interval 1.82-3.82). A subgroup analysis of race was carried out. OR in the Asian group was higher than that in the European group (3.71 vs. 2.25), which might suggest that Asians who are allergic to stent material have a higher risk of ISR than Europeans. Conclusion Allergy to stent material worsens the prognosis of patients with coronary stent implantation. New well-designed prospective clinical trials are required to confirm this relationship and to establish the indispensability of a skin patch test before coronary stent implantation.