The cornea is the outermost layer of the eye and is a vital component of focusing incoming light on the retina. Central corneal thickness (CCT) is now recognized to have a significant role in ocular health and is a risk factor for various ocular diseases, such as keratoconus and primary open angle glaucoma. Most previous genetic studies utilized European and Asian subjects to identify genetic loci associated with CCT. Minority populations, such as Latinos, may aid in identifying additional loci and improve our understanding of the genetic architecture of CCT. In this study, we conducted a genome-wide association study (GWAS) in Latinos, a traditionally understudied population in genetic research, to further identify loci contributing to CCT. Study participants were genotyped using either the Illumina OmniExpress BeadChip (~730K markers) or the Illumina Hispanic/SOL BeadChip (~2.5 million markers). All study participants were 40 years of age and older. We assessed the association between individual single nucleotide polymorphisms (SNPs) and CCT using linear regression, adjusting for age, gender, and principal components of genetic ancestry. To expand genomic coverage and to interrogate additional SNPs, we imputed SNPs from the 1000 Genomes Project reference panels. We identified a novel SNP, rs10453441 (P = 6.01E-09), in an intron of WNT7B that is associated with CCT. Furthermore, WNT7B is expressed in the human cornea. We also replicated 11 previously reported loci, including IBTK, RXRA-COL5A1, COL5A1, FOXO1, LRRK1, and ZNF469 (P < 1.25E-3). These findings provide further insight into the genetic architecture of CCT and illustrate that the use of minority groups in GWAS will help identify additional loci.3

Background: The myelodysplastic syndromes (MDS) represent heterogeneous disorders with varied clinical courses. The major prognostic tool in MDS is the IPSS-R, which helps estimate survival outcome and estimate risk for AML transformation. In low or intermediate risk pts, the IPSS-R has shortcomings; in these pts, the development of transfusion dependent anemia is the major disease associated complication, and this is not addressed by IPSS-R stratification. Previous studies have indicated that aberrancies detected by flow cytometry can risk stratify pts with MDS. The purpose of this study was to determine whether detection of neoplastic-specific blast aberrancies in pts diagnosed with low or intermediate risk MDS can identify pts at higher risk for transfusion dependent anemia after MDS diagnosis. Methods: We performed a retrospective chart review on MDS patients initially diagnosed at our institution between 1/2010 and 12/31/2017. Patients with low/intermediate risk by IPSS-R were identified. Flow cytometry findings on initial diagnostic BM biopsies performed at our institution only were reviewed. Flow cytometry (4- and 8-color) was performed on bone marrow aspirates for the following antigens: CD3, CD7, CD11b, CD13, CD14, CD15, CD19, CD20, CD33, CD34, CD36, CD38, CD45, CD56, CD64, CD117, and HLA-DR using FACS Calibur or FACSCanto II flow cytometers. Myeloblasts were identified by cluster analysis, as previously described (Am J Clin Pathol. 2010 Nov; 134(5):749-61), and compared to 20 control cases. Blast aberrancies were defined as an immunophenotypic difference of > ¼ log compared to the blasts in the controls. Neoplasia-specific blast aberrancies were defined as: expression of CD7, CD11b, CD15, and/or CD56 and/or under expression of CD38 and CD45. We estimated probability of transfusion dependent anemia using Kaplan Meier product limit method and compared survival curves using log-rank test. Analyses were performed using Stata v12.0. Results: A total of 63 patients were identified, with median age of 68 years (range 31-89 years). Median hemoglobin (Hg) at diagnosis was 9.8 (range 5.2-15.3). Cytogenetic risk categories were very good, good, intermediate and poor in 3%, 71% 16%, and 10% respectively. IPSS-R category was very low or low in 70% (44 pts), and intermediate in 30% (19 pts). The presence of blast aberrancies was similar in proportion among low risk patients (61%, n=27) compared to intermediate risk patients (68%, n=13). Overall, the presence of only one blast aberrancy, whether neoplasia-specific or not, did not significantly segregate patients at greater risk for transfusion dependence. However, the presence of 2 or more aberrancies statistically defined two populations. Those possessing 0-1 blast aberrancy did not reach a median time to transfusion dependence, whereas those possessing 2+ aberrancies had a median time to transfusion dependence of 1.2 years (p=0.02). Additionally, when looking at neoplasia-specific blast aberrancies, pts with 0-1 aberrancy had a median time to transfusion of 4.7 years, compared to 2+ aberrancies, at 0.8 years (p=0.02). Figure 1 illustrates this finding. Conclusion: The determination of blast aberrancies by flow at time of MDS diagnosis may provide prognostic information in low/intermediate risk MDS patient and could help predict risk for early red blood cell transfusion dependence. Upfront risk stratification would be valuable information to plan follow-up for these patients, as well as treatment decision making including early initiation of ESAs. Disclosures Michaelis: Novartis: Consultancy; Celgene: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; JAZZ: Other: Data Safety Monitoring Board, uncompensated, Research Funding; BMS: Research Funding; Bioline: Research Funding; ASTEX: Research Funding; Janssen: Research Funding; Millenium: Research Funding; Macrogeneics: Research Funding; Pfizer: Equity Ownership, Research Funding; Incyte: Consultancy, Research Funding. Runaas:Agios: Honoraria; Blueprint Medicine: Honoraria. Atallah:Takeda: Consultancy, Research Funding; Pfizer: Consultancy; Jazz: Consultancy; Helsinn: Consultancy; Jazz: Consultancy; Novartis: Consultancy; Helsinn: Consultancy. Abedin:Actinium Pharmaceuticals: Research Funding; Pfizer Inc: Research Funding; Helsinn Healthcare: Research Funding; Agios: Honoraria; Jazz Pharmaceuticals: Honoraria.

No abstract

No abstract

Introduction: Patients with hematologic malignancies frequently require lumbar punctures (LPs) for administration of intrathecal chemotherapy. With myelosuppressive chemotherapy, thrombocytopenia is common and patients often require platelet transfusions in order to reduce the risk of bleeding during invasive procedures. However, there is a dearth of evidence supporting a platelet threshold required for LPs. Guidelines from the American Association of Blood Banks recommend a minimum platelet count of 50 x 103/µL, but this is based largely on expert opinion. Platelet transfusion is associated with risk of transfusion reaction and alloimmunization, cost, and procedural delays. Given these risks, we instituted a reduction in platelet threshold to 40 x 103/µL for lumbar puncture. We retrospectively reviewed patient outcomes to assess the safety and efficacy of this approach. Methods: In November 2017, a platelet count threshold for LPs was introduced for adult oncology patients in both the inpatient and outpatient settings at Froedtert and the Medical College of Wisconsin. Previous guidelines recommended a platelet count of 50 x 103/µL in order to undergo a lumbar puncture. This threshold was decreased to 40 x 103/µL for oncology patients. Guidelines were agreed upon and implemented in all procedure settings: the inpatient procedure team, the outpatient procedure suite, and the radiology department (for fluoroscopy-guided lumbar puncture). Data regarding the pre-procedure platelet count, number of platelet transfusions given per procedure, CSF RBCs, and occurrence of post-procedure spinal hematomas were collected through the electronic medical record. Results: From November 1, 2016 to May 1, 2018 267 oncology patients underwent a lumbar puncture. Oncologic diagnosis was NHL, ALL, AML, solid malignancy, or other hematologic malignancy/disorder in 26%, 23%, 18%, 16%, and 17%, respectively. 42% of were female. A total of 845 LPs were performed under fluoroscopy, with ultrasound guidance, and by an experienced provider in 26%, 58%, and 16% of cases respectively. 534 LPs (63%) were performed with a platelet transfusion threshold of 50 x 103/µL (Plt≥50) and 311 LPs (37%) were performed with a platelet transfusion threshold of 40 x 103/µL (Plt≥40). The average pre-LP platelet count was 152.8 x 103/µL in the Plt≥50 group and 138.4 x 103/µL in the Plt≥40 group. 79 patients in the Plt≥50 group and 42 patients in the Plt≥40 group had a recorded platelet count between 40-49 x 103/µL within 24 hours prior to the procedure. After institution of the new guidelines, 40 LPs were performed with a platelet count < 50 x 103/µL. The average number of units of platelets transfused per procedure significantly decreased from 0.58 to 0.39 after lowering the transfusion threshold (p < 0.05). One lumbar epidural hematoma occurred post-intervention and one lumbar subarachnoid hematoma occurred pre-intervention, both in patients whose pre-procedure platelet counts were > 100 x 103/µL. No traumatic hematomas were observed in patients whose pre-procedure platelet count was < 50 x 103/µL. The incidence of traumatic taps (identified as CSF red blood cells > 10/µL) was significantly higher in patients whose pre-procedure platelet count was < 50 x 103/µL (64% vs. 46%, p <0.05). Conclusion: Decreasing the LP platelet transfusion threshold from 50 x 103/µL to 40 x 103/µL significantly reduced platelet transfusions. This was not associated with an increased risk of complications. However, the incidence of traumatic taps was significantly higher in patients with a platelet count < 50 x 103/µL. Given that the average cost of one unit of platelets is approximately $500 and 40 procedures were performed with a platelet count < 50 x 103/µL, decreasing the platelet transfusion threshold resulted in a cost savings of approximately $20,000 over the course of 6 months, not including administrative costs. Overall, this data suggests that lowering the platelet transfusion threshold for lumbar punctures to 40 x 103/µL is both safe and cost effective for oncology patients. Disclosures Atallah: Abbvie: Consultancy; Jazz: Consultancy; Novartis: Consultancy; BMS: Consultancy; Pfizer: Consultancy.