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Abstract Background: Little data exists on the incidence rate of transfusion reactions and red cell antibody formation following allogeneic (allo) hematopoietic progenitor cell transplant (HPCT) recipients. Study Design and Methods: Consecutive related and unrelated Allogeneic HPCTs from 2006 to 2013 were retrospectively reviewed regardless of graft source. Allo HPCT recipients were analyzed as a whole as well as divided into ABO compatibility groups of identical, minor mismatch, and major/bidirectional mismatch. Transfusions, transfusion reactions and antibodies were analyzed for the first year post-transplant while survival was recorded throughout the available follow-up period. Results: During the study period, 573 patients ranging in age from 0.6 to 72 years underwent first allo HPCT for various malignant and non-malignant etiologies: 278 acute leukemias, 89 lymphomas, 40 multiple myelomas, 134 other hematologic malignancies, 32 non-neoplastic etiologies. Of these, 52% underwent myeloablative conditioning and 48% reduced intensity conditioning. Transfusion reactions were reported in 93 of the 573 allo HPCT recipients. The incidence rate of transfusion reactions per 10,000 transfusion episodes was 45.54 in the ABO identical, 61.28 in the minor mismatch, and 29.95 in the major mismatch groups (p=0.04). The most common reaction type reported in all groups was allergic followed by febrile non-hemolytic, transfusion associated circulatory overload, and delayed hemolytic or serologic reactions. No acute hemolytic, transfusion related acute lung injury (TRALI), post transfusion purpura, transfusion associated graft-versus-host disease, or transfusion associated sepsis reactions were reported. A total of 43 unique patients(7.5%) developed new antibodies post-transplant: 16 allo HPCT recipients developed clinically significant antibodies, 17 developed clinically insignificant antibodies, and 17 developed auto antibodies post-transplant. Including those patients with pre-transplant antibodies the overall prevalence of red blood cell antibodies was 14.5%. See Table 1 for incidence rate for forming new rbc antibodies post-transplant. Table 1. New RBC Antibody Formation Incidence Rate Post-Transplant ABO Compatibility Group Clinically Significant Antibody Incidence /10,000 RBC Transfusions Clinically Insignificant Antibody Incidence/ 10,000 RBC Transfusions, Auto Antibody Incidence/10,000 RBC Transfusions Total Antibody Incidence/10,000 RBC Transfusions Identical 39.33 16.85 39.33 95.51 Minor Mismatch 35.87 57.39 43.04 136.30 Major Mismatch 8.34 16.67 8.34 33.35 A statistically significant difference (p=0.001) was seen in total antibody incidence when comparing the ABO compatibility groups. The most common, clinically significant allo antibodies formed were Anti-E, Anti-Jka, Anti-A1, Anti-K, Anti-D, and Anti-C. Survival of allo HPCT recipients as a whole was not statistically different for those who formed new rbc antibodies post-transplant following adjustment for ABO compatibility, age at transplant, diagnosis, graft source, and pre-transplant rbc infusions (p=0.068). Allo HPCT recipients that formed new rbc antibodies were not shown to have prolonged engraftment. Engraftment, neutrophils (ANC) and platelets (PLT), were not statistically different (p=0.34 ANC; p=0.20 PLT) when comparing all allo HPCT recipients to those who formed a new rbc antibody. Conclusion: Transfusion reaction and rbc antibody incidence rates were higher in the ABO minor mismatch when compared to the ABO identical and ABO major mismatch groups. The reaction etiology (predominantly antibody mediated) and the formation of new antibodies indicates a surprisingly active humoral immune system. The overall prevalence of antibody formation is likely affected by high exposure to transfusions. Development of a new rbc antibody did not affect engraftment or survival outcomes. Disclosures No relevant conflicts of interest to declare.

Objective: The Pediatric Proton/Photon Consortium Registry (PPCR) is a comprehensive data registry composed of pediatric patients treated with radiation. It was established to expedite outcomes-based research. The attributes which allow the PPCR to be a successful collaboration are reviewed. Methods and materials: Current eligibility criteria are radiotherapy patients < 22 years treated at one of the 15 US participating institutions. Detailed health and treatment data are collected about the disease presentation and treatment exposures, and annually thereafter, in REDCap (Research Electronic Data Capture). DICOM (Digital Imaging and Communications in Medicine) imaging and radiation plans are collected through MIM/MIMcloud. An optional patient-reported quality-of-life (PedsQL) study is administered at 10 sites. Results: Accrual started October 2012 with 2,775 participants enrolled as of 25 July 2019. Most patients, 62.0%, were treated for central nervous system (CNS) tumors, the most common of which are medulloblastoma (n = 349), ependymoma (n = 309), and glial/astrocytoma tumors (n = 279). The most common non-CNS diagnoses are rhabdomyosarcoma (n = 284), Ewing’s sarcoma (n = 153), and neuroblastoma (n = 130). While the majority of participants are US residents, 18.7% come from 36 other countries. Over 685 patients participate in the PedsQL study. Conclusions: The PPCR is a valuable research platform capable of answering countless research questions that will ultimately improve patient care. Centers outside of the USA are invited to participate directly or may engage with the PPCR to align data collection strategies to facilitate large-scale international research. Advances in knowledge: For investigators looking to carry out research in a large pediatric oncology cohort or interested in registry work, this paper provides an updated overview of the PPCR.

Abstract Introduction: Our current understanding of CLL biology and optimal therapies is based on clinical trials that have largely enrolled White patient populations. Whether these findings are applicable to Hispanic or non-White patients is unknown but critical to evaluate given the growing numbers of minority patients in the U.S. While retrospective studies have suggested inferior outcomes in non-White patients, prospective data on these disparities are lacking. Patients and Methods: We utilized the Mayo Clinic CLL database to better understand variations in disease characteristics, molecular differences, and treatment selections between non-Hispanic White patients and those not in this category (referred to hereafter as “other race”). After excluding 49 patients with missing diagnosis date and another 490 patients with missing race and/or ethnicity, the remaining 4104 cases within the registry were included in the analysis. Comparisons by race were made using Chi-square or Wilcoxon rank sum tests for qualitative or quantitative variables, respectively. Overall survival (OS) was calculated from diagnosis until death or last known alive date; time to first treatment (TTFT) was calculated from diagnosis until treatment date or date last known to be untreated. OS and TTFT were displayed via Kaplan-Meier plots, and differences in OS and TTFT by race were calculated using log-rank statistics. Individuals who were enrolled in early intervention trials (n=61) were excluded from analyses involving treatment. Results: In total, 4104 CLL patients were identified: 4011 (97.7%) non-Hispanic Whites and 93 (2.3%) other races. Median age at CLL diagnosis was younger for other race patients (59 vs. 63 years; p=0.002), while gender and stage distributions were comparable between both groups. Serum β-2-microglobulin and absolute lymphocyte counts at diagnosis were similar but more other race patients had elevated LDH (29.5% vs. 16.1%; p=0.02). Cytogenetic data by FISH were available for 1884 non-Hispanic Whites and 46 other race patients; poor-risk cytogenetics (17p and/or 11q deletions) were present in 23.9% of other race and 13.5% of non-Hispanic White patients, respectively (p=0.04). No statistically significant differences were observed for CD38, ZAP-70, or IGHV by race TTFT was similar for both non-Hispanic Whites and other race patients (4.6 vs. 5.5 years, respectively; p=0.12). First-line treatment selection was similar for both groups (Table). . With a median follow-up of 12.1 years, median overall survival was 9.3 years for other race and 12.2 years in non-Hispanic White patients (P=0.15; Figure). Conclusions: This prospective data supports the notion that CLL might be biologically different between non-Hispanic White and other race patients with less favorable FISH present in the latter group. Despite the observation that TTFT and type of first therapy are similar between both groups, the trend towards shorter OS in other race patients argues that other factors might contribute to outcome differences, such as disease biology, access to care, co-morbidities, and socioeconomic considerations. Further studies with larger cohorts are warranted. Table: First-line treatment selection among treated individual by racial First-line Treatment Non-Hispanic Whites(n=1875) Other race(n=41) Chemoimmunotherapy Purine analogue-based Alkylator-based 675 (36.0) 495 (26.4) 180 (9.6) 15 (35.6) 9 (22.0) 6 (14.6) Purine analogue -monotherapy 157 (8.4) 4 (9.8) Alkylator monotherapy 610 (32.5) 9 (22.0) PA+Alkylator 41 (2.2) 1 (2.4) Antibody alone 190 (10.1) 6 (14.6) Other 202 (10.8) 6 (14.6) Figure: Overall survival in CLL cases stratified by race Figure:. Overall survival in CLL cases stratified by race Disclosures Nabhan: Genentech: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Speakers Bureau. Kay:Celgene: Research Funding. Shanafelt:Genentech: Research Funding; GlaxoSmithKline: Research Funding; Celegene: Research Funding; Cephalon: Research Funding; Pharmacyclics/Jannsen: Research Funding; Hospira: Research Funding; Polyphenon E Int'l: Research Funding.

Abstract Multiple myeloma (MM) is 2-3 times more common among African-Americans compared to non-Hispanic whites. The 2-3-fold increased risk among family members of cases suggests a genetic contribution to risk. Genome-wide association studies (GWAS) in populations of European ancestry have identified seven novel risk loci at 2p23.3 (rs6746082), 3q26.2 (rs10936599), 3p22.1 (rs1052501), 6p21.32 (rs2285803), 7p15.3 (rs4487645), 17p11.2 (rs4273077) and 22q13.1 (rs877529) (Broderick, et al. Nat Genet, 2011, Chubb, et al. Nat Genet, 2013), three of which were replicated in another European series (Martino et al., Br J Haematol, 2012). Here we examined the index signals and conducted fine-mapping for each locus in a case-control study of 1,049 multiple myeloma cases and 7,084 controls of African ancestry to identify better markers of risk and novel independent loci in seven previously reported regions in this high risk population. Incident cases were recruited from 10 clinical centers and SEER cancer registries from 2011 to 2013 and genotyped using the Illumina HumanCore GWAS array. Control data were obtained from previous genome-wide studies of breast and prostate cancer, genotyped using the Illumina 1M-Duo in 4425 male controls from the African Ancestry Prostate Cancer Consortium (consisting of 14 independent studies) and 2632 female controls from a breast cancer GWAS of African-American women (consisting of 9 independent studies). Imputation to 1000 Genomes (March 2012 release) was conducted for regions around six of the previously identified single nucleotide polymorphisms [SNPs] (the HLA region harboring rs2285803 is still being imputed, results will be presented). A case-control analysis of SNPs/indels >1% frequency within 250 kb of each index variant was conducted using unconditional multivariable logistic regression adjusting for age, sex and five leading principal components. Region-specific alpha levels were determined through permutation tests. The minimum alpha level across the six regions was α=0.002. All previously reported risk variants were common in African-Americans (minor allele frequency [MAF] >0.05). For five of the six SNPs, we had ≥94% power to detect the same effect observed in non-Hispanic whites, and 64% power for the less common variant rs10936599 (MAF=0.07). We observed directionally consistent effects (odds ratio [OR]>1) for the six risk variants tested, with three replicating at p≤0.05 (7p15.3, p=1.4x10-7; 17p11.2, p=0.05; 22q13.1, p=0.02). For three of the six regions, we observed better markers of risk in African-Americans that were correlated with the index SNP in Europeans (7p15.3, rs56333627, p=1.5x10-5, r2=0.89; 17p11.2, rs34562254, p=2.9x10-3, r2=0.90; 22q13.1, rs2092410, p=1.1x10-4 r2=.71). The missense variant identified in the 17p11.2 region (rs34562254, Pro251Leu) is located in TNFRSF13B, which encodes the protein TACI, a B cell surface receptor which plays a role in B cell maturation, apoptosis and antibody production by inducing activation of transcription factors including NFAT and NFκβ. In addition, there is evidence suggesting that TACI is involved in MM pathogenesis. Our results demonstrate that many of the risk loci for MM found in European ancestry populations are also risk loci in men and women of African ancestry and that by fine-mapping, we are able to identify variants that better capture risk in populations of African ancestry. Disclosures Terebelo: Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Lonial:Millennium: The Takeda Oncology Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Onyx Pharmaceuticals: Consultancy, Research Funding.

Abstract Background: The association of clinical trial participation with outcomes in cancer patients is controversial, with some studies reporting better outcomes for trial participants while others do not. It is possible that the difference in outcomes is due to differences in baseline characteristics of participants and non-participants. The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 trial was a large randomized, multi-center study comparing peripheral blood (PB) with bone marrow (BM) for hematopoietic cell transplantation (HCT) from HLA-matched or 1 allele mismatched unrelated donors (URD) in patients with acute leukemia, chronic myeloid leukemia and myelodysplastic syndromes. The trial reported no significant survival differences between PB and BM; there was decreased risk of graft failure but increased risk of chronic graft-versus-host disease (GVHD) with PB grafts (Anasetti et al NEJM 2012). Methods: We compared characteristics of BMT CTN 0201 study participants (n=494) with HCT recipients who did not participate on the trial (n=1384) but were potentially eligible by virtue of known characteristics. These patients received similar conditioning and GVHD prophylaxis as trial participants at 38 United States trial centers during the study time-period. Centers that had no eligible non-trial participants were excluded. Outcomes between patients on and off trial were compared using Cox proportional hazards regression models. Data were obtained from the Center for International Blood and Marrow Transplant Research (CIBMTR) that collects patient data on all trial and non-trial allogeneic HCT recipients through its registry function. Results: Approximately 29% [494/1878] of apparently eligible patients were randomized and analyzed as part of the trial. There were no significant differences between study participants and non-participants in age or sex distribution, disease types, HLA or sex matching, comorbidities, or interval from diagnosis to HCT. Higher proportions of non-participants were Hispanic, had a lower performance status and lower disease risk, and received myeloablative conditioning and antithymocyte globulin (ATG) or Campath than the study participants. PB was used more commonly as the graft source in the non-participants as compared to the study participants (65% vs. 50%, p<0.001). In multivariate models, overall mortality (HR 1.09, 95% CI 0.95-1.25, p=0.22), transplant-related mortality (HR 1.08, 95% CI 0.89-1.32, p=0.42) and risks of acute grade II-IV (HR 0.96, 95% CI 0.82-1.12, p=0.57) and chronic GVHD (HR 1.06, 95% CI 0.92-1.23, p=0.41) were comparable between study non-participants and participants. Non-participants were at higher risk for relapse than participants (HR 1.24, 95%CI 1.04-1.49, p=0.02) in the multivariate analysis adjusted for disease risk and other clinical variables. Center effect was examined and was not found to be significant (p=0.10). There was no significant interaction between graft source and trial participation (P=0.22) and the risk of mortality was comparable for BM (HR 0.99, 95% CI 0.80-1.22, p=0.90) and PB recipients (HR 1.17, 95% CI 0.97-1.41, p=0.09) whether on trial or off trial. (Figure) Conclusion: Approximately 29% of patients who appeared eligible and were treated with conditioning and GVHD prophylaxis regimens allowed on the trial were enrolled. Despite some differences in clinical characteristics, most of the outcomes of non-trial participants were comparable to trial participants, suggesting that there is no definitive evidence that the outcomes of patients in a clinical trial are superior to those of the non-participants treated in a similar fashion. The comparable outcomes also indicate that the results of this trial were not seriously affected by selection bias and are therefore representative of the larger population. Figure 1: Adjusted overall survival in BMT CTN 0201 trial participants and non-participants Figure 1:. Adjusted overall survival in BMT CTN 0201 trial participants and non-participants Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Abstract Introduction: Several B-cell malignancies, including chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), are known to have a familial component to disease risk. Although several common inherited genetic variants have been found to be associated with risk of these malignancies, a large proportion of the heritability remains unexplained. Here we set out to identify rare high-penetrance susceptibility variants for CLL and MM using the established Mayo Clinic family study of B-cell malignancies. Methods: We performed exome sequencing on germ line DNA of 106 families with either two or more members with CLL (n=93 families) or two or more members with MM or monoclonal gammopathy of undetermined significance (MGUS) (n=13 families) using Aglient capture kits. All samples were sequenced on an Illumina HiSeq2000. Bioinformatics analyses leveraged the following software packages: Novoalign, Picard, The Genome Analysis Toolkit (GATK), and the Biological Reference Repository (bioR). Quality control filters were implemented; subjects with mis-specified relationships were removed as were variants with <95% call rate or <20x coverage, and those variants identified as sequencing artifacts. To identify potentially functional single nucleotide variants, the following was required a) uncommon in public databases, b) cosegregating variants in multiple families, c) variants to be highly conserved and in coding regions, and d) functional prediction status of deleterious (SIFT score), damaging (PolyPhen score), and a moderate, or high variant impact (SNPEffect). The association of these variants with risk was then evaluated in large samples of cases and controls in genome-wide association studies (GWAS). Results: In the CLL familial cohort, there were 443 individuals (160 with CLL, 73 with monoclonal B cell lymphocytosis (MBL), and 210 relatives without CLL or MBL) sequenced; and in the MM cohort, there were 39 individuals (13 with MM, 13 with MGUS and 13 without MM or MGUS) sequenced. A total of 61,992 single nucleotide variants passed quality control filters in the CLL cohort and 39,456 single nucleotide variants in the MM cohort. From these, we identified 32 variants in the CLL cohort and 39 variants in the MM cohort that were cosegregating in multiple CLL or MM families, respectively, and were predicted to affect protein structure or function. Of these, one CLL variant was within 1 Mb of a known GWAS-discovered locus. Moreover, there were seven CLL and four MM variants that were within 1 Mb of single nucleotide polymorphisms (SNPs) that had statistical significance between p<10-4 and p<10-6 in GWAS. Finally, there were 3 variants found to be common between CLL and MM families (see Table). Conclusions: Through whole exome sequencing, we identified a number of rare, highly penetrant predisposition variants for CLL and MM. Several of these variants were common to both B-cell malignancies providing evidence of shared genetic components; one variant may be a functional driver of the GWAS-discovered loci. These identified variants provide a list for future validation studies. Table: Exome variants common in both Chronic Lymphocytic Leukemia and Multiple Myeloma SNP ID rs41314099 rs61754114 rs143025033 Chromosome 17 6 7 Gene WSCD1 BACH2 TNS3 Penetrance (CLL) 0.70 0.75 0.80 Penetrance (MM) 1.00 0.80 0.75 Allele Frequency (CLL) 0.015 0.025 0.017 Allele Frequency (MM) 0.077 0.077 0.058 1000 Genome Frequency (European) 0.010 0.020 0.010 SIFT Term Deleterious Deleterious Deleterious PolyPhen Term Probably Damaging Probably Damaging Probably Damaging SNP: Single Nucleotide Polymorphism; CLL: Chronic Lymphocytic Leukemia; MM: Multiple Myeloma; Penetrance is defined as proportion of individuals carrying the alternate allele that are also affected; SIFT: Sorting Intolerant From Tolerant, predicts whether an amino acid substitution affects protein function; PolyPhen: Polymorphism Phenotyping, predicts possible impact of an amino acid substitution on the structure of a human protein Disclosures No relevant conflicts of interest to declare.

Background Acute pancreatitis (AP) is a frequent disorder with considerable morbidity and mortality. Obesity has previously been reported to influence disease severity. Objective The aim of this study was to investigate the association of adipose and muscle parameters with the severity grade of AP. Methods In total 454 patients were recruited. The first contrast‐enhanced computed tomography of each patient was reviewed for adipose and muscle tissue parameters at L3 level. Associations with disease severity were analysed through logistic regression analysis. The predictive capacity of the parameters was investigated using receiver operating characteristic (ROC) curves. Results No distinct variation was found between the AP severity groups in either adipose tissue parameters (visceral adipose tissue and subcutaneous adipose tissue) or visceral muscle ratio. However, muscle mass and mean muscle attenuation differed significantly with p ‐values of 0.037 and 0.003 respectively. In multivariate analysis, low muscle attenuation was associated with severe AP with an odds ratio of 4.09 (95% confidence intervals: 1.61–10.36, p ‐value 0.003). No body parameter presented sufficient predictive capability in ROC‐curve analysis. Conclusions Our results demonstrate that a low muscle attenuation level is associated with an increased risk of severe AP. Future prospective studies will help identify the underlying mechanisms and characterise the influence of body composition parameters on AP.

INTRODUCTION: Increasing rates of obesity have led to increased numbers of bariatric surgeries performed world-wide. However, some patients do not achieve significant weight loss or develop weight regain following these procedures. Other than estimating the size of the gastric remnant at endoscopy or transaxial imaging, there are limited approaches to quantitate the function of the post-surgical stomach in order to evaluate the disparate weight patterns, or to develop strategy for future treatments, e.g., pharmacotherapy or endoscopic intervention. We hypothesize that altered gastric function in the pre- and post-surgical periods may offer an explanation. Studies performed thus far are difficult to interpret due to heterogeneity in approaches to diagnostic evaluation. The aims of this project were: to assess the feasibility of a new protocol for simultaneous evaluation of gastric accommodation and gastric emptying in the post-bariatric state; and to report normative values in healthy volunteers. METHODS: Methods: We utilized single photon emission computed tomography (SPECT) and gamma scintigraphy to concurrently study postprandial gastric accommodation responses and gastric emptying rates of a limited size meal designed for subsequent use in post-bariatric patients. The standard meal consisted of 1 egg and 1 extra egg yolk scrambled with 111 Indium-activated charcoal (∼130kcal, 9.5g fat) and 120mL 2% milk (130kcal, 4.4g fat). Gastric accommodation was measured using 99m Technetium-SPECT. SPECT imaging was obtained concomitant with gastric emptying of the 111 In-labeled meal. Anterior and posterior scans of the abdomen were obtained for estimating gastric emptying parameters every 15 minute until 90 minutes, and then in 30-minute intervals until 240 minutes or complete emptying. RESULTS: Data on 28/30 healthy volunteers (35.7% men; 67% Caucasian) with completed studies to date are shown in the Table 1 (data presented as mean ± standard deviation). Gastric emptying proportion at 1, 2, and 4 hours, T 1/2 , and gastric volumes including accommodation are graphically depicted in Figures 1 and 2, respectively. CONCLUSION: Discussion: This study has demonstrated feasibility of simultaneous measurement of gastric emptying and accommodation and provides normal values; this sets the stage for future baseline and post-operative scans on patients undergoing sleeve gastrectomy.

Distress is defined in the NCCN Guidelines for Distress Management as a multifactorial, unpleasant experience of a psychologic (ie, cognitive, behavioral, emotional), social, spiritual, and/or physical nature that may interfere with the ability to cope effectively with cancer, its physical symptoms, and its treatment. Early evaluation and screening for distress leads to early and timely management of psychologic distress, which in turn improves medical management. The panel for the Distress Management Guidelines recently added a new principles section including guidance on implementation of standards of psychosocial care for patients with cancer.

Abstract Background: Mild cognitive impairment (MCI) is an intermediate stage between the cognitive changes of normal aging and early dementia. Tai Chi (TC) may be particularly beneficial to patients with MCI due to its whole-body coordination characteristics. This systematic review protocol aims to outline the methods that will be used to assess the comparative effectiveness and safety of TC for MCI through a systematic review and meta-analysis. Methods: A systematic review will identify and evaluate randomized controlled trials (RCTs) that examined the effects and safety of TC compared to a placebo, conventional treatment, and no treatment on cognitive function in individuals with MCI. Studies from databases of MEDLINE, PubMed, Embase, Global Health, Cochrane Library, and Scopus from January 1990 to March 2019 reported in English will be searched. Two independent reviewers will screen the studies for inclusion with the eligibility criteria and extract data. Risk of bias of individual studies will be assessed in line with Cochrane risk of bias tool. The overall quality of cumulative evidence will be assessed using selected Grading of Recommendations, Assessment, Development, and Evaluations criteria. Statistics will be used for heterogeneity assessment, sensitivity analysis, data synthesis, generating funnel plots, and subgroup analysis. Meta-analysis will be performed, if sufficiently homogeneous studies are found. A narrative synthesis will be conducted, grouping studies by exposure and outcome definitions, and describing any differences by subgroups. Results: This study will provide practical and targeted evidence in investigating the impact of TC exercise for individuals with MCI. Conclusion: The findings of our study will provide updated evidence to determine whether TC is an effective intervention to patients with MCI. Trial registration number: International Prospective Register for Systematic Reviews (PROSPERO) number CRD42019125104.