bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Three Year Experience at An Inner City Safety-Net Hospital with Immune Thrombocytopenic Purpura (ITP)
Authors: Poola Harsha V , Gaddh Manila , Ofori Samuel N. , Shah Moushmi , Kassem Mohammed A. , Haidau Augustin , Catchatourian Rosalind , Telfer Margaret 
Published: October 2019

Abstract
Abstract 4684

Immune Thrombocytopenic Purpura or ITP remains a clinical diagnosis of exclusion. There are numerous treatments, attesting to the fallibility of each. A 3 year experience at an Inner City safety net hospital was analyzed. For inclusion in the study, the hematology service had to have excluded consumption disorders, prior chemotherapy, medication known to cause thrombocytopenia and Viral Infection- HIV and/Hepatitis. 93 patients met these criteria and had platelet counts below 50,000. The median age of the whole group was 49 yrs, with a range of 21 to 78 years. A few were ANA positive. The female preponderance reflects the literature.
All Patients were started on Prednisone at 1mg/kg. Three Patients also received IV IGG to hasten the response. There were no intracranial hemorrhages or bleeding described as major.
Patients from the Far East had to be excluded for Hepatitis Virus exposure.

Results
All who did not respond to steroids fully were treated with a second line Rx. i.e, Rituximab, Azathioprine, IV IGG or WIN Rho. One patient received high dose Dexamethasone and responded.

Conclusion:
Pending the use of TPO agonists, treatment of ITP in adults remains a chronic problem challenging the Hematologist to use as little corticosteroid as possible.

Disclosures:
No relevant conflicts of interest to declare.
Genome-Wide Analysis Reveals Frequent Inactivating Mutations of Acetyltransferase Genes In B-Cell Lymphoma
Authors: Pasqualucci Laura , Dominguez-Sola David , Chiarenza Annalisa , Fabbri Giulia , Grunn Adina , Trifonov Vladimir , Kasper Lawryn H. , Lerach Stephanie , Jing Ma , Rossi Davide , Mullighan Charles , Gaidano Gianluca , Rabadan Raul , Brindle Paul K. , Dalla-Favera Riccardo 
Published: October 2019

Abstract
Abstract 474
B cell non-Hodgkin lymphoma (B-NHL) comprises a variety of biologically and clinically distinct diseases whose pathogenesis is associated with largely unique genetic lesions affecting oncogenes and tumor suppressor genes. The identification of the complete set of genes and cellular pathways that are altered in the lymphoma cell is critical for a full understanding of the genesis and maintenance of these malignancies. Using genome-wide copy number analysis and high throughput whole exome sequencing, we have recently found that the two most common types of B-NHL, follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL), are associated with frequent structural alterations inactivating the genes that encode CREBBP and, in a smaller fraction of cases, EP300, two highly related histone and non-histone acetyltranferases (HAT) that act as transcriptional coactivators in multiple signaling pathways. Overall, ~29% (n=39/134) of DLBCL and 32% (n=15/47) of FL samples display genomic deletions and/or somatic point mutations that remove or inactivate the HAT domain of CREBBP. In 19 additional cases (15 DLBCL and 4 FL), mutations and deletions were found in the EP300 gene, also predicting its functional loss. With few exceptions, structural alterations of CREBBP and EP300 were mutually exclusive, suggesting that inactivation of these loci is at least in part functionally equivalent. Thus, in total ~36% of all DLBCL (n=49/134) and at least 40% of FL cases (n=19/47) display genetic aberrations targeting acetyltransferase genes. Interestingly, while these lesions were observed in both DLBCL phenotypic subtypes, their frequency appears to be significantly higher in germinal center B cell type DLBCL, where they account for ~46% of the cases (n=30/65) as compared to 27% in activated B cell type DLBCL (n=11/69; p<0.01). CREBBP and EP300 structural alterations commonly affect a single allele, suggesting that reduction in HAT dosage is important for lymphomagenesis. While the functional consequences of these lesions are likely to be broad on gene transcription, we demonstrate specific defects in the acetylation-mediated inactivation of the BCL6 onco-protein and activation of the p53 tumor suppressor, both of which contribute to transformation. These results identify CREBBP/EP300 alterations as a major pathogenetic mechanism shared by common forms of B-NHL, and have direct implications for the development of therapeutic regimens targeted to acetylation/deacetylation mechanisms.

Disclosures:
No relevant conflicts of interest to declare.
Cognitive Impairment In Adult De Novo Acute Leukemia Patients
Authors: Verleden Stijn , Audenaert Kurt , Noens Lucien 
Published: October 2019

Abstract
Abstract 4746

Introduction:
A significant percentage of cancer patients develop or have chemotherapy-induced cognitive impairment, during and even long after completion of aggressive treatment. Cognitive deficits are usually subtle and mild, and can occur in various cognitive domains. In AML/MDS patients, impaired cognitive functions, even prior to initiation of chemotherapy, have been described.

Objective:
To assess baseline cognitive functions and short-term cognitive evolution in de novo acute leukemia patients during induction treatment, and to compare our data with previous research.

Methods:
Current longitudinal-prospective study of adult de novo AML/ALL patients, treated with induction chemotherapy at the Hematology Department, UZ Ghent, Belgium. Eligible patients are enrolled and investigated with a comprehensive cognitive test battery, within on average five days after admission (pre-induction) and after completion of induction chemotherapy, on average after two months (pre-consolidation). Cognitive functions are assessed across various domains, including attention, executive functions, motor dexterity, and verbal/visual memory. Patients’ psychological functions and quality of life are assessed simultaneously.

Results:
Twenty adult patients were enrolled between 01/2009 and 06/2010. The median age was 43 years, 50% were male, 80% had AML (20% ALL), and median years of education was 12 years. Baseline hematological values were assessed, with WBC count (mean: 10,4 10E3/uL), RBC count (mean: 3,1 10E6/uL), and HgB (mean: 9,8 g/dL). Adult patients had normal cognitive functions (range: 1,0 SD below normative mean) in different cognitive domains, and mainly in attention and executive functions (COWA letter fluency & semantic fluency, and SCWT mental flexibility), except for mild cognitive deficits in verbal learning (AVLT A1-5), but especially in motor dexterity (PPT left and right hand). These functions were heterogeneous at baseline, ranging from severely impaired to good within a cognitive domain. At follow-up, attention, executive functions, motor dexterity, and verbal learning had all improved significantly (p<0.02).

Conclusion:
Adult de novo AML/ALL patients exhibit at baseline normal cognitive functions, except for verbal learning and motor dexterity. Cognitive deficits in attention, executive functions, and verbal learning were found similar to previous reported research in AML/MDS. However, our data showed less impaired motor dexterity. Moreover, cognitive functions improved at follow-up.

Disclosures:
No relevant conflicts of interest to declare.
Development of A Clinical Prediction Rule for Risk Stratification of Recurrent Venous Thromboembolism In Patients with Cancer-Associated Venous Thromboembolism
Authors: Louzada Martha L , Lazo-Langner Alejandro , Dao Vi , Zhang Jerry , Kovacs Michael J. , Carrier Marc , Rodger Marc , Wells Phil 
Published: October 2019

Abstract
Abstract 475

Background:
Current guidelines suggest that all cancer patients with venous thromboembolism be treated with long-term low molecular weight heparin (LMWH). However, whether treatment strategies should vary according to patient and malignancy characteristics, in particular whether patients with low risk of VTE recurrence can be identified, remains unknown.

Methods:
We performed a single centre retrospective cohort study conducted at the Thrombosis Unit of the Ottawa Hospital. The charts of patients with cancer and VTE followed from 2002 to 2004 and from 2007 to 2008 were reviewed to assess the feasibility of derivation of a clinical prediction rule that stratifies VTE recurrence risk in patients with cancer—associated venous thrombosis through identification and evaluation of characteristics of malignancy and other clinical characteristics. We analysed only the patients who had a recurrent VTE within the first 6 months of anticoagulation. A univariate analysis determined the strength of association between each potential predictor and VTE recurrence. All potential predictor variables (p<0.25) were evaluated in a logistic regression model.

Result:
Of 543 patients 55 (10.1%) presented with a VTE recurrence during the first 6 months of anticoagulation. At VTE recurrence 19 (9.5%) patients were using VKA and 36 (10.5%) patients were using LMWH. The relative risk for VTE recurrence was not significantly different between patients who used VKA or LMWH [RR= 1. 13 (95%CI, 0.743 – 1.711; p= 0.565)]. A multivariate analysis suggested that gender, primary tumour site, tumour stage and history of prior VTE were significant variables to include in the clinical prediction rule. The final model included female gender, lung cancer and prior history of VTE as increasing risk and breast cancer and stage I disease as lowering risk. Patients with a score equal or less than 0 have low risk (4.5%) for VTE recurrence and this represented 48% of our patients. Patients with a score equal or above 1 have high risk (> 19%) for VTE recurrence (Tables 1 and 2).

Conclusion:
We were able to derive a simple and easy scoring system that stratifies patients with cancer-associated thrombosis into low or high risk of recurrent VTE. Future prospective validation of the model is warranted and may be very relevant to better tailor anticoagulation treatment in this heterogeneous population.

Disclosure:
No relevant conflicts of interest to declare.
Polyploidization of Megakaryocyte Is Associated with the Proliferation Rate of Precursor Cell
Authors: Wang Jianhui , Nardi Michael A. , Li Zongdong 
Published: October 2019

Abstract
Abstract 4802
Endomitosis, the uncoupling of DNA replication with cytokinesis, occurs during the maturation of megakaryocytes (MK) and leads to the MK polyploidization (4N to 128N DNA content). The mechanism that controls the ploidy in MKs is not well understood. We investigated the correlation of cell proliferation rate with MK ploidy in several differentiating megakaryoblastic cell lines. Meg-01, CHRF-288, and K562 cells were treated with a Src kinase inhibitor (3 μm Su6656) for 4 days and the ploidy was assessed by propidium iodide. Proliferation rate was determined by the doubling time of synchronized cells cultured in 10% serum. We found a significant correlation between ploidy and proliferation rate in these cell lines, with the K562 line having both the highest proliferation rate and the percentage of ploidy cells. We then differentiated the megakaryocyte cell line L8057 cells by thrombopoietin using various concentrations of serum (5%, 10%, and 20%) to control proliferation. The proliferation rate of L8057 cells varied with serum concentration and was also highly correlated the percentage of ploidy cells (23%, 32.8%, and 40.9% respectively). Thus, our data suggest that factors control the cell proliferation rate may contribute to the polyploidization of megakaryocyte.

Disclosures:
No relevant conflicts of interest to declare.
The Value of Procalcitonin and Lipopolysaccharide Binding Protein to Differentiate the Fever In the Patients with Sickle Cell Anemia
Authors: Unal Selma , Arslankoylu Ali Ertug , Kuyucu Necdet , Aslan Gönül , Erdogan Semra 
Published: October 2019

Abstract
Abstract 4818

Objective:
Differentional diagnosis of fever is very important in patients with sickle cell anemia (SCA) in order to prevent inappropriate antibiotic use, drug resistance and to shorten the hospitalization period. A reliable marker to be used in the differentional diagnosis of fever in these patients has not been defined yet. We aimed to evaluate the values of C Rective Protein (CRP), procalcitonin (PCT), and lipopolysaccharide binding protein (LBP) levels in the differentional diagnosis of fever in patients with SCA.

Material and Methods:
86 children with SCA (40 males and 36 females, mean age of 9.6 ± 3.84, range: 1–18 years), (Group 1) and 49 healthy children as a control group (mean age: 8.8 ± 3.91, range: 1–18 years) (Group 2) were included in this study. Patients who had admitted to the emergency department for concurrently vasoocclusive crisis and fever (axillary temperature ≥38C°) were classified as Group 1A and who had vasoocclusive crisis but no fever were classified as Group 1B and the patients without fever and vasoocclusive crisis were classified as Group 1C. A detailed history was taken from every child, and a full physical examination was performed. The patients who had taken antibiotics in last one week were excluded. The type of vasoocclusive crisis were recorded in Group 1A and 1B patients. In Group 1A patients, the fever was evaluated with appropriate laboratory tests (WBC count, periferic blood smear, serum CRP level, urinary test, chest radiography, blood and urinary culture). No infection focus was identified in patient and conrol groups. The WBC count, serum CRP, PCT and LBP levels were evaluated in all the patient and control groups.

Results:
The median CRP level of all patient groups was significantly higher than the control group (0.78 mg/L; range 0.21–70.0) (p<0.0001). The median CRP level in Group 1A (7.42 mg/L) and Group 1B (6.94 mg/L) were significantly higher than group 1C patients (2.24 mg/L). There were no significant difference between the SCA groups considering median serum PCT levels (Group 1A: 0.18 ng/ml, Group 1B: 0.11 ng/ml, Group 1C: 0.13 ng/ml, p>0.05). These values were significantly higher than control group (0.08 ng/ml) (p<0.0001). LBP level in Group 1A (median:11.5 μg/ml) was significantly higher than Group 1B (median: 8.9μg/ml), Group 1C (median: 7.7μg/ml) and control group (median:5.9μg/ml) (p<0.0001). Also serum LBP in both Group 1B and Group 1C were higher than control group (p<0.0001).

Conclusion:
PCT level is not affected from the acute inflamation originates from the vasoocclusive crisis. Thus, serum PCT level can be considered a good marker in the differentional diagnosis of fever in patients with SCA.

Disclosures:
No relevant conflicts of interest to declare.
The Separate Diagnosis of Hodgkin Lymphoma (HL) and Non-Hodgkin Lymphoma (NHL) In a Single Patient May Not Signify a Common Clonal Origin
Authors: Ganzel Chezi , Pogrebijsky Galina , Krichevsky Svetlana , Neuman Tzahi , Ben-Yehuda Dina 
Published: October 2019

Abstract
Abstract 4824

Background:
HL and NHL have traditionally been considered as two distinct entities. However, there have been reported rare cases of patients that over time develop both diseases. It is an unresolved issue whether the origin of the two diseases is from the same clone. The literature is replete with anecdotal reports but it has never been prospectively or retrospectively evaluated in consecutive patients from a large series. In this study we attempted to retrospectively investigate this phenomenon by reviewing the clinical and molecular aspects of a group of patients who developed both lymphomas. Although not absolutely definitive, a differing gene rearrangement (GR) pattern is currently thought to be highly suggestive of a different clonal origin.

Methods:
Study patients were all patients treated at the Hadassah University Medical Center, Jerusalem, Israel, who developed both kinds of lymphoma throughout their lives and were treated for at least one of the lymphomas during the period 1989–2010. The clinical and pathologic records of these patients were reviewed.
Archival, formalin fixed, paraffin embedded tissue samples from all the patients that had available samples from both diseases were obtained. The rearranged immunoglobulin heavy-chain variable region genes from both diagnoses were amplified by polymerase chain reaction (PCR) and were compared to each other.

Results:
There were 26 patients who presented with two diagnoses. Twelve had HL as the primary disorder and the majority of these (75%) presented with aggressive lymphoma as the second lymphoma. The mean survival from the second lymphoma was 4.06 years. Five patients are still alive. In contrast, in the 11 patients where NHL was the primary disorder, this was usually (82%) of low grade histology. The mean survival in this case was 2.16 years. Four patients are still alive. Three patients were diagnosed concurrently with both diseases.
For 11 patients there were available diagnostic samples for molecular analyses from both diagnoses of HL and NHL. In 6 of these 11 patients gene rearrangement studies were informative providing data for both diagnoses. The same GR was not found in any of the 6 patients.
DLBCL=Diffuse Large B Cell Lymphoma, CLL/SLL=Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, marginal=marginal zone lymphoma, low grade=low grade B cell lymphoma unspecified
Although the numbers are small, these data suggest that it is likely that in the case of two different lymphoproliferative disorders they are of separate clonal origin.

Conclusions:
The development of HL and NHL at different time points should be assumed to be a different biologic disease, until proven otherwise.

Disclosures:
No relevant conflicts of interest to declare.
STIM1 Deficiency Results In Impaired Platelet Procoagulant Activity and Protection From Arterial Thrombosis
Authors: Ahmad Firdos , Stefanini Lucia , Ouellette Timothy Daniel , Greene Teshell K , Feske Stefan , Bergmeier Wolfgang 
Published: October 2019

Abstract
Abstract 485
Platelet activation is a central event in thrombosis and hemostasis. We recently demonstrated that most aspects of platelet activation depend on synergistic signaling by two signaling modules: 1) Ca2+/CalDAG-GEFI/Rap1 and 2) PKC/P2Y12/Rap1. The intracellular Ca2+ concentration of platelets is regulated by Ca2+ release from the endoplasmic reticulum (ER) and store-operated calcium entry (SOCE) through the plasma membrane. Stromal interaction molecule 1 (STIM1) was recently identified as the ER Ca2+ sensor that couples Ca2+ store release to SOCE. In this study, we compared the activation response of platelets lacking STIM1−/− or CalDAG-GEFI−/−, both in vitro and in vivo. To specifically investigate Ca2+-dependent platelet activation, some of the experiments were performed in the presence of inhibitors to P2Y12. The murine Stim1 gene was deleted in the megakaryocyte/platelet lineage by breeding Stim flox/flox mice with PF4-Cre mice (STIM1fl/fl). STIM1fl/fl platelets showed markedly reduced SOCE in response to agonist stimulation. aIIbβ3 activation in STIM1fl/fl platelets was significantly reduced in the presence but not in the absence of the P2Y12 inhibitor, 2-MesAMP. In contrast, aIIbb3 activation was completely inhibited in 2-MesAMP-treated CalDAG-GEFI−/− platelets. Deficiency in STIM1, and to a lesser extent in CalDAG-GEFI, reduced phosphatidyl serine (PS) exposure in platelets stimulated under static conditions. PS exposure was completely abolished in both STIM1fl/fl and CalDAG-GEFI−/− platelets stimulated in the presence of 2-MesAMP. To test the ability of platelets to form thrombi under conditions of arterial shear stress, we performed flow chamber experiments with anticoagulated blood perfused over a collagen surface. Thrombus formation was abolished in CalDAG-GEFI−/− blood and WT blood treated with 2-MesAMP. In contrast, STIM1fl/fl platelets were indistinguishable from WT platelets in their ability to form thrombi. STIM1fl/fl platelets, however, were impaired in their ability to express PS when adhering to collagen under flow. Consistently, when subjected to a laser injury thrombosis model, STIM1fl/fl mice showed delayed and reduced fibrin generation, resulting in the formation of unstable thrombi. In conclusion, our studies indicate a critical role of STIM1 in SOCE and platelet procoagulant activity, but not in CalDAG-GEFI mediated activation of aIIbb3 integrin.

Disclosures:
No relevant conflicts of interest to declare.
A New Pathogenomic Mechanism In FPD/AML by a Constitutional T(16;21) Involving 16p13 ATF7IP2 and 21q22 RUNX1 Loci
Authors: Buijs Arjan , van der Crabben Saskia , van der Zwaag Bert , van Binsbergen Ellen , Poot Martin , de Weerdt Okke , van Gijn Marielle , Nieuwenhuis H. Karel 
Published: October 2019

Abstract
Abstract 4851
Familial platelet disorder with propensity to myeloid malignancy (FPD/AML) is an autosomal dominant disorder characterized by platelet abnormalities and a predisposition to acute myeloid leukemia (AML). FPD/AML is caused by inherited mutations in 21q22 RUNX1. Recent publications by us and others reported on RUNX1 copy number changes as a pathogenomic mechanism next to point mutations in diagnosing FPD/AML. Given the clinical heterogeneity of FPD/AML, the syndrome could be overlooked, and has resulted in the past in stem cell transplantation (SCT) of patients from affected siblings before detection of the inherited RUNX1 mutation.
Here we report on the identification of two novel missense mutations (G143R and Q235X), and a constitutional RUNX1 gene rearrangement as a result of a t(16;21)(p13;q22) as a novel pathogenomic mechanism in FPD/AML. The 16p13 breakpoint was confined to the ATF7IP2 (MCAF1) locus, a transcription factor associated with Sp1, which is involved in myeloid differentiation, and in proliferation in human cancer by epigenetic transcriptional control of Sp1-dependent maintenance of telomerase activity. This is the first report on genomic involvement of the ATF7IP2 locus in cancer. We will discuss ongoing studies to molecularly identify the breakpoints.
Our data indicate that in diagnosing FPD/AML FISH has to be performed for structural abnormalities along with sequencing and copy number analysis of RUNX1. Furthermore, this is the first report on a constitutional chromosome translocation with an oncogene rearrangement as a pathogenomic mechanism in a hematological malignancy.

Disclosures:
No relevant conflicts of interest to declare.