Baidoun, Firas

Abstract Secondary central nervous system (CNS) large B-cell lymphoma (SCNSL) occurs in the de novo setting, as a CNS-isolated relapse, or synchronous (concomitant CNS and systemic) relapse. SCNSL is a devastating event without therapeutic consensus. Thus, we aimed to evaluate treatment outcomes in an international cohort. Progression-free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR, estimated using competing-risk models) were reported. Prognostic factors were identified in a 6-month landmark multivariate analysis. Outcomes after thiotepa autologous stem cell transplant (ASCT) and chimeric antigen receptor (CAR) T-cell therapy (CAR-T) delivered at relapse were compared after propensity score matching (PSM). A total of 1139 patients were included in the analysis (de novo: 537; relapsed SCNSL: 602). Two-year PFS estimates were 40.4%, 43.9%, and 16.2% for de novo SCNSL, CNS-isolated relapse, and synchronous relapse, respectively. Patients with CNS-isolated relapse demonstrated low rates of systemic recurrence (24-month CIR, 6%). Thiotepa-ASCT correlated with longer survival in de novo SCNSL (PFS: hazard ratio [HR], 0.57; P = .005; and OS: HR, 0.62; P = .023) and CNS-isolated relapses (PFS: HR, 0.55; P = .002; and OS: HR, 0.39; P< .0001). ASCT (thiotepa or no thiotepa) also associated with improved survival in synchronous relapses (PFS: HR, 0.57; P = .023; and OS: HR, 0.48; P = .019). Higher survival with thiotepa-ASCT than CAR-T was observed after PSM (PFS: HR, 0.45; P = .005 and OS: HR, 0.41; P = .014). These data support thiotepa-ASCT in eligible patients, particularly de novo disease and CNS-isolated relapses. CNS-isolated relapse was infrequently associated with systemic recurrence, supporting treatment regimens adopted from primary CNS lymphoma.

Background Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women. Women with PCOS have androgen excess as a defining feature. They also have increased insulin resistance and obesity, which are also risk factors for non-alcoholic fatty liver disease (NAFLD). However, published data regarding PCOS as independent risk factor for NAFLD remain controversial. Therefore, we conducted this study to evaluate the association between PCOS and NAFLD using a large national database. Methods We identified adult female patients (≥18 years) with PCOS using the National Inpatient Sample database between 2002 and 2014. The control group included patients who did not have a diagnosis of PCOS. Multivariate logistic regression analysis was performed to study the association of NAFLD with PCOS. Results Out of a total of 50 785 354 women, 77 415 (0.15%) had PCOS. These patients were younger (32.7 vs 54.8; p<0.001) and more likely to be obese (29.4% vs 8.6%; p<0.001) compared with non-PCOS patients. However, the PCOS group had less hypertension (23.2% vs 39.8%), dyslipidaemia (12% vs 17.8%) and diabetes mellitus (18.1% vs 18.3%) (p<0.001 for all). Using multivariate logistic regression, patients with PCOS had significantly higher rate of NAFLD (OR 4.30, 95% CI 4.11 to 4.50, p<0.001). Conclusion Our study showed that patients with PCOS have four times higher risk of developing NAFLD compared with women without PCOS. Further studies are needed to assess if specific PCOS treatments can affect NAFLD progression.

e16662 Background: Cholangiocarcinoma (CCA) is a relatively rare malignancy accounting for 3% of gastrointestinal cancers in the US. While multiple risk factors for CCA are established and well-studied, other potential risk factors are still controversial and not well established. Herein, we used a large national database to investigate possible risk factors and associations. Methods: We used the National Inpatient Sample (NIS) database to review all admissions between 2011 and 2015. We grouped patients based on the presence and absence of CCA using the appropriate ICD-9 codes. We used multivariate logistic regression to assess the association between obesity, alcohol abuse, smoking, diabetes mellitus (DM), and non-alcoholic fatty liver disease (NAFLD). Results: We reviewed 30,955,295 admissions of which 20,030 had CCA. CCA Patients were older compared to the rest of the patients (mean age 67 years ±12.8 vs. 57±20.6, P < .001) and had less female patients (48% vs 59%, P < .001). Patients’ characteristics are shown in the table. After adjusting for viral hepatitis B (HBV), viral hepatitis C (HCV), liver cirrhosis, inflammatory bowel disease (IBD), primary sclerosing cholangitis (PSC), and bile duct stones, logistic regression showed DM to be proportionately associated with CCA (OR = 1.04, 95%CI[1.01-1.08], P < .001), whereas alcohol, smoking and obesity were all inversely associated with CCA; OR = 0.75, 95%CI [0.69-0.81], P < .001, OR = 0.75, 95%CI [0.71-0.79], P < .001 and OR = 0.71, 95%CI [0.67-0.75], P < .001, respectively. In addition, compared to whites, Hispanic and Asian/Pacific Islander races were proportionally associated with CCA; OR = 1.27, 95%CI [1.21-1.34], P < .001, and OR = 1.79, 95%CI, [1.67-1.92], P < .001, respectively, while black race was inversely associated with CCA (OR = 0.85, 95%CI [0.81-0.89], P < .001). Conclusions: In our large database study, we found that patients with diagnosis of DM or being from certain minority ethnic groups are associated with increased incidence of CCA. Other factors like alcohol and smoking were associated with decreased incidence of CCA, but those factors may be under reported. This raises the need for further evaluation for these factors and their effect on CCA incidence and outcomes in those specific groups. [Table: see text]

e16059 Background: Anal cancer is an uncommon malignancy accounting for less than 3% of gastrointestinal malignancies in the US. In this large database study, we aimed to re-evaluate the difference in the incidence and mortality trend in both genders. Methods: We used SEER 18 database to study anal cancer cases in the US during 2000-2016. Incidence and mortality rates of anal cancer were calculated by gender and were expressed by 1,000,000 person-years. Annual percent change (APC) was calculated using join point regression software. Results: We reviewed 25,418 patients with anal cancer, of which 61.4% were females. Incidence of anal cancers was 14.375 and 19.427 per 1,000,000 person-years, in males and females, respectively. Incidence rates of anal cancer significantly increased over the study period, but this increase was sharper in females (APC = 2.220%, 95%CI [1.924-2.517], P < .001) when compared to males (APC = 0.915%, 95%CI [0.303-1.531], P = .006). Mortality rates from anal cancer over the study period were 7.425 and 7.532 per 1,000,000 person-years, in males and females, respectively. Overall anal cancer mortality rates did not change between 2000-2009 but started to decrease starting from 2010 and this decrease became sharpest between 2014-2016; APC = -44.905%, 95%CI [-57.572- -28.457], P = .001). Mortality rates followed the same trend in both genders. Conclusions: Anal cancer incidence is increasing with significant increase in the incidence trend is noticed in females compared to males which is a change from the previous trend that was seen from 1973-2000. On the other hand, anal cancer mortality has started to decrease for the first time starting from 2010 with no difference in the mortality trend between males and females. This improvement in mortality rate can be explained by the improvement in early detection rate and possibly improvement in the treatment approach for these high-risk patients.

Abstract Background: MDS is a clonal bone marrow disorder characterized by ineffective hematopoiesis with peripheral blood cytopenias and an increased risk for transformation to acute leukemia. Patients with MDS who have a history of prior exposure to chemotherapy and/or radiotherapy are called therapy-related MDS (t-MDS). We hereby describe our experience with this entity and compare it to our experience with de novo MDS patients. Aim: To study the differences of clinical outcome between t-MDS and de novo MDS patients. Method: A retrospective single institution study chart review of cases with MDS at Mayo Clinic Rochester between 1993- 2011 was performed. De novo MDS, t-MDS and leukemic transformation (LT) were defined according to the World Health Organization (WHO) classification (Swerdlow et al 2008). Prior exposures to chemotherapy, radiotherapy and/ or both were defined as t-MDS; while lack of any as de novo MDS. Appropriate IRB approval was obtained in accordance with the Helsinki declaration. Comparison between group medians was done using Wilcoxon test, comparison between values was done using contingency and One-way analyses (Means/Anova/Pooled t), while survival estimates were calculated using Kaplan-Meier curves JMP V10 Results: Out of 827 patients with MDS, 153 (19%) patients were t-MDS (group (Gr) 1) versus 674 (81%) (rest of patients, Gr 2). Out of the t-MDS, 79 (52%) pts had CTX, and 42 (27%) had XRT, and 32 (21%) pts had both CTX/XRT). Upon comparison between Gr 1 vs 2, statistical significant difference was seen in median age 69 vs 72 (p=0.01), Platelets 68 vs 114 x109(<p0.0001), and WBC 3.2 vs 3.6 x109(0.02), respectively. No significant statistical difference was found in median Hg 9.6 vs 9.7 gm/dL (p 0.6), peripheral blood (PB) blasts 0% in both groups, and bone marrow (BM) blasts 2% in both groups. IPSS was low, int-1, int-2, high in 16%, 40%, 34%, 9%in Gr 1 and 32%, 46%, 18%, 4% in Gr 2. IPSS-R was very low, low, int, high, very high in 9%, 24%, 18%, 20%, 28% in Gr 1 vs 18%, 36%, 20%, 16%, 10% in Gr 2. AML transformation (LT) was identical in both groups at 12%. Upon comparison between Gr 1 and 2, median time to AML transformation was 7.9 vs 13 months (p=0.08). Median overall survival (mOS) was shorter in Gr 1 vs 2 at 16 vs 34 months (P<0.0001). When analysis was limited to diploid cytogenetics, median OS was 63 vs 50 months, respectively (p=0.9). Both IPSS and IPSS-R were prognostic of mOS in t-MDS (p<0.0001). On multivariate analysis; age (<0.0001), IPSS-R (p<0.0001) and previous CTX and/ or XRT (P=0.02) were the only variables that affected mOS. Conclusion: T-MDS comprises a small portion of all MDS cases (19%). Median overall survival in the de novo MDS group was longer than t-MDS group; however this difference was not maintained in patients with diploid cytogenetics. Similarly, time to AML was longer in de novo MDS compared to t-MDS (although similar rates of incidence). All of age, IPSS-R and t-MDS did affect median OS on multivariate analysis. Disclosures Al-Kali: Celgene: Research Funding.

Abstract Background:The 2008 World Health Organization (WHO) developed a new classification system for Myelodysplastic Syndrome (MDS). The well-defined categories are refractory anaemia with excess blasts (type 1 or 2 based on the marrow blast count being below or above 10%), refractory anaemia with or without ringed sideroblasts, refractory cytopenias with multilineage dysplasia and myelodysplastic syndromes with isolated deleted 5q. MDS cases that do not meet the diagnostic criteria of the above categories are classified myelodysplastic syndrome (MDS-U). However, few reports in the literature exist in terms of natural progression and clinical outcome of patients with MDS-U. Aim: To study the clinical outcome of patients with MDS-U. Method: A retrospective, IRB-approved, single-institution study through chart review of cases with MDS at Mayo Clinic Rochester between 1993 and 2014 was performed. Patients diagnosed with MDS based on WHO classification were included. MDS classification was based on routine Mayo Clinic pathology reports. Central independent hematopathology review for bone marrow biopsy was performed for cases diagnosed with MDS-U or simply generic MDS. Comparison between groups’ medians was done using Wilcoxon test, while survival estimates were calculated using Kaplan-Meier curves using JMP V10. Result: A total of 802 patients, who met WHO criteria for MDS, were studied. Median age was 71 years (range, 18-99), 69% were males. Median white blood cell (WBC) 3.6 x109, hemoglobin (Hbg) 9.6 g/dl, platelets (PLT) 105 x109, peripheral blood (PB) blasts 0% and bone marrow (BM) blasts 2%. Median overall survival (OS) was 28 months. One hundred nine (14%) cases transformed to AML. Out of the 802 patients, 90 (11%) patients were initially classified as MDS-U according to 2008 WHO criteria, 69% were males with median age 71 years. Upon pathology review, only 42/90 cases (47%) were confirmed to be MDS-U (group 1). Among 47 cases not meeting MDS-U, 40% were best classified as RARS, 17% refractory anemia, and 9% as 5Q del Syndrome, while 2 cases did not have any myeloid neoplasm. Group 1 had median WBC 3 x109, Hbg 9.9g/dL, PLT 71 x109, PB blasts 0% and BM blasts 0%. IPSS grouping was low, intermediate-1, intermediate-2 and high in 27%, 52%, 21% and 0%, respectively. R-IPSS grouping was very low, low, intermediate, high and very high in 15%, 42%, 15%, 21% and 6%, respectively. Median OS in group 1 was 68, 37, 13 and 0 months per IPSS (p=0.04), and 101, 44, 14, 11, 13 months per IPSS-R (p=0.005), respectively. Of the 43 patients with MDS-U, 39 had follow-up; 21 patients (54%) of which progressed. MDS-U became 42% RAEB, 24% RCMD, 14% CMML, 5% RARS, 10% MDS/MPN, and 5% atypical. Group 2 (MDS other than MDS-U) 759 patients had median age 71 years, 69% were males. They had WBC 3.6 x109, Hbg 9.6g/dL, PLT 107 x109(p=0.01), PB blasts 0% and BM blasts 0%. IPSS grouping was low, intermediate-1, intermediate-2 and high in 29%, 44%, 22% and 5% respectively. R-IPSS grouping was very low, low, intermediate, high and very high in 17%, 32%, 20%, 17% and 14% respectively. On comparison between Group 1 vs 2, mOS was 27 vs 29 months (p=0.7), and percentage transformed to AML 14% in both groups. On multivariate analysis for mOS only age, IPSS-R and IPSS but not MDS-U nor gender were statistically significant. Conclusion: MDS-Uis a small subset of MDS. With independent pathology review, half of the MDS-U cases were subclassified into other MDS groups. In follow-up more than half of the cases were subclassified into other MDS groups and some were non-MDS. IPSS and IPSS-R are helpful tools for survival assessment in MDS-U. High risk MDS was infrequent in MDS-U per IPSS. We found no significant difference in mOS nor AML transformation when comparing MDS-U to other groups. Disclosures No relevant conflicts of interest to declare.