bluuebunny/crossref_metadata_2025_split huggingface dataset:
MYC Translocations Are Associated with Poor Overall Survival in DLBCL Patients in Both the Chemotherapy and Immunochemotherapy Eras.
Authors: Dogan Ahmet , Maurer Matthew J , Macon William R , Inwards David J , Micallef Ivana N , Johnston Patrick L , Law Mark , Ristow Kay , Witzig Thomas E , Cerhan James R , Habermann Thomas M 
Published: October 2019

Abstract
Abstract 443

Background:
MYC translocations have been reported to have inferior outcome in aggressive non-Hodgkin lymphomas. Here we present MYC translocation prevalence and outcome from two cohorts of newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients treated in the chemotherapy (C) and immunochemotherapy (IC) eras.

Methods:
Tissue microarrays were created from 302 newly diagnosed DLBCL patients evaluated at the Mayo Clinic with availabel paraffin tissue. 233 DLBCL patients first diagnosed from March 1986-July 2001 were retrospectively identified based on a diagnosis of DLBCL and treatment with anthracycline-based chemotherapy. 69 DLBCL patients diagnosed from March 2002-October 2005 and treated with immunochemotherapy were prospectively enrolled in the University of Iowa / Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource. Central pathology review was performed on all samples to confirm the diagnosis of DLBCL. Interphase FISH was performed using a breakapart strategy for MYC and BCL6 gene regions and a dual fusion strategy for t(14;18)(IGH&/BCL2).

Results:
Chemotherapy (C) era patients were primarily treated with CHOP (88%); immunochemotherapy (IC) era patients were all treated with an R-CHOP based regimen. The median age at diagnosis was 65 years (range, 22-92) for C patients and 65 years (range, 20-82) for IC patients. Median follow-up for C patients was 11.3 years (range, 2.7-21.3) with 145 (62%) deaths; for IC patients, the median follow-up was 5.0 years (range, 2.1-6.4) with 17 deaths (25%). FISH was successful in 195 of 302 patients (65%). MYC translocations were identified in 6 of 141 C patients (4%) and 3 of 54 IC patients (6%). MYC translocations were associated with inferior overall survival in the C patients (p=0.001), the IC patients (p=0.04), and in the combined group (p≤0.001). Median survival of patients with MYC translocations was 19 months and 16 months for C and IC respectively, compared to 112 months (C) and unreached (IC) for DLBCL patients without MYC translocations. 4 of the 9 MYC translocation patients had a double hit (2 with both MYC and BCL2 translocations and 2 with translocations of MYC, BCL2, and BCL6). Associations of MYC and outcome remained significant in all patients after adjusting for treatment and IPI (p<0.05).

Conclusions:
MYC translocations are present in approximately 5% of DLBCL patients and are associated with poor outcome in patients treated with C or IC. New treatment approaches are needed for DLBCL patients with MYC translocations.

Disclosures:
No relevant conflicts of interest to declare.
Effect of YC-1, a HIF Inhibitor,On Apoptosis of Leukemia Cell.
Authors: Chen Bao-An , Wang Fei , Cheng Jian , Ding Jia-Hua , Xu Wen-Lin , Wang Xue-Mei , Gao Chong , Wang Jun , Zhao Gang , Bao Wen , Song Hui-Hui , Gao Feng , Zhang Wei , Xia Guo-Hua , Pei Xiao-Ping , Wu Wei-Wei , Chen Ning-Na 
Published: October 2019

Abstract
Abstract 4432

Object
This study was purposed to investigate the expression of HIF-1α and VEGF in leukemia cell lines and the effect of YC-1 on the regulation of HIF-1α and VEGF and the induction of apoptosis in U937 cell, exploring the mechanism of apoptosis after treatment of YC-1.

Methods
RT-PCR was used to determine the levels of HIF-1α mRNA and VEGF mRNA in K562,U937 and Jurkat cells. After treatment of U937 cell with 4μmol/L YC-1 for 0 hour, 8 hours,16 hours and 24 hours respectively, the changes of morphologic features were observed by DAPI staining under fluorescent microscope and the apoptotic rates were assayed by flow cytometry with Annexin V-FITC/PI staining; the levels of HIF-1α mRNA and VEGF mRNA were measured with RT-PCR ; the protein expression of HIF-1α, VEGF, Bax,Bcl-2 and Caspase-3 were measured by Western blot.

Results
HIF-1α mRNA and VEGF mRNA were expressed in all three leukemia cell lines. After treatment of U937 cell with 4μmol/L YC-1 for 0 hour,8 hours,16hours and 24hours respectively, the typical apoptotic morphologic features of U937 cells were observed under fluorescent microscope and the apoptotic rates were significantly increased in a time-dependent manner, they were (4.87±0.70)%, (27.27±2.00)%, (51.53±2.81) and (60.5±3.20)% respectively, the level of VEGF mRNA reduced, while the level of HIF-1α mRNA had no obviously changes. Furthermore, the expression of HIF-1α, VEGF and Bcl-2 decreased, while the expression of Bax and Caspase-3 increased in a time-dependent manner.

Conclusion
HIF-1α mRNA and VEGF mRNA are expressed in leukemia, YC-1 has significant effect of down-regulation the protein expression of HIF-1α and VEGF and induction of apoptosis in U937, its mechanisms may involve in up-regulating Bax/Bcl-2 ratio and expression of Caspase-3.

Disclosures:
No relevant conflicts of interest to declare.
A Clinical Significance of Helicobacter Pylori Infection in Hemophilic Children with Gastrointestinal Hemorrhage.
Authors: Kim Ji Yoon , Choi Yong-Mook , Lee Kun Soo 
Published: October 2019

Abstract
Abstract 4442

Purpose
For hemophiliacs gastrointestinal hemorrhage is a life-threatening complication and can be caused by the Helicobacter pylori infection. In this study, the prevalence of H. pylori infection among child hemophiliacs with gastrointestinal hemorrhage and the recurrence rate after eradication H. pylori treatment was investigated.

Patients and Methods
Seven children with hemophilia A with hematemesis (age, 5.3∼17.0 year) were evaluated for the causes of gastrointestinal hemorrhage and the detection of H. pylori. Gastroendoscopy was done to find the bleeding focus and for further evaluation including rapid urease test and mucosal biopsy.
Result: Four patients had dyspepsia and abdominal pain for several weeks or months prior to hematemesis. Three patients did not show any signs of bleeding. From gastroendoscopy, four patients were diagnosed as duodenal ulcer, one as H. pylori associated chronic gastritis and one as hemorrhagic gastritis. One patient showing a normal finding was diagnosed with adenoid hemorrhage after nasopharyngoscopy. H. pylori infection was found in four of six patients with GI bleeding (3, duodenal ulcer; 1, H. pylori associated chronic gastritis). The patients with H. pylori infection had an eradication treatment of triple therapy and no recurrence happened.

Conclusion
In child hemophiliacs, H. pylori should also be considered as an important cause of gastrointestinal hemorrhage. The recurrence of the infection and gastrointestinal hemorrhage can be prevented with eradication of H. pylori. Screening test for H. pylori would be needed in child hemophiliacs in endemic area.

Disclosures:
No relevant conflicts of interest to declare.
Rituximab Treatment in Childhood Chronic Immune Thrombocytopenic Purpura (ITP).
Authors: Kim Ji Yoon , Lee Kun Soo , Kang Hyoung Jin , Kook Hoon , Koo Hong Hoe , Kim Sun Young , Park Byung-Kiu , Park Hyeon Jin , Baek Hee-Jo , Seo Jong Jin , Sung Ki Woong , Shin Hee Young , Ahn Hyo Seop , Yoo Keon Hee , Lee Soo Hyun , Im Ho Joon , Choi Yong-Mook , Han Dong kyun , Hwang Tai Ju 
Published: October 2019

Abstract
Abstract 4461

Background
Immune thrombocytopenic purpura (ITP) is characterized by mucocutaneous purpura and thrombocytopenia caused by circulating anti-platelet auto-antibodies. ITP is usually self-limited in children, but around 20% of patients will develop chronic ITP. The conventional treatments for children chronic ITP include intravenous immunoglobulin (IVIG), corticosteroid therapy, anti-D immune globulin, or splenectomy. Some children with chronic ITP are refractory to these treatments and nowadays begun to try new treatment agents such as rituximab. Rituximab as a monoclonal antibody to CD-20, has shown promising reports to these patients with refractory chronic ITP in adults groups and a few children groups. We investigated this study to evaluate the efficacy of rituximab for childhood chronic ITP in Korea.

Methods
We reviewed the questionnaires and medical records about the clinical progresses and results in thirteen children from eight clinical institutes, retrospectively. Complete response (CR) was considered if the platelet count was > 100,000/uL.

Results
Thirteen patients with chronic thrombocytopenia who had been treated with rituximab were investigated. Two patients were lost to follow-up after rituximab. Finally eleven patients were evaluated including one patient with Evans syndrome. Median age was 6.5 year (range, 0.5 ∼ 15.4). Median platelet count at baseline was 13,700/uL (3,000∼46,000). All patients had been treated with conventional therapy including IVIG and steroids. One had done splenectomy. Median follow-up duration was 2.8 years (1.1-5.9). Among 11 patients, CR was achieved in 3 patients (27%). Their platelet count prior to rituximab were < 10,000/uL. They were treated as the regimen of 375 mg/m2/dose weekly for 4 doses. Time from the first rituximab dose to achievement of complete response was 3.9, 4.9 and 5.7 weeks respectively. One patient who was relapsed 6months after the first course of rituximab was received second course of rituximab using the same regimen and achieved a new CR at 9.3 weeks after. There were no reports about severe complication or interruption of medication.

Conclusions
Therefore, we suggest that rituximab is effective treatment choice in childhood refractory chronic ITP and well tolerated.

Disclosures:
No relevant conflicts of interest to declare.
Response to Anti D immunoglobulin in Adults with Chronic Immune Thrombocytopenic Purpura in a Minority Cohort with Long Term Follow up.
Authors: Sreenivasappa Shylendra B , Braik Tareq , Sandhu Sonia , Yim Barbara , Catchatourian Rosalind 
Published: October 2019

Abstract
Abstract 4465

Background
Immune Thrombocytopenic Purpura (ITP) is a common hematological disorder. We sort to characterize the risk profiles and efficacy of anti D immunoglobulin in chronic ITP in a largely minority cohort.

Methods
31 patients (pts) with chronic immune thrombocytopenic purpura treated 2003-2008 were studied as a retrospective cohort for clinical presentation, prognostic characteristics, time to next therapy and long term survival. Prognostic factors, time to relapse and overall survival was analyzed using fisher's exact test, logistic regression, Kaplan Meier survival analysis and Cox Proportional Hazards model.

Results
31 pts 19(61.3%) female and 12(38.7%) male. 11 (35.5%) African Americans, 12(38.7%) Hispanic, 5 (16.2%) Asians and 3 (7.8%) Caucasians. Median age at diagnosis was 44 yrs (21-66). 25 (80.5%) were HIV negative and 6 (19.5%) had HIV. 16 (51.6%) had O positive blood group, 9 (29.6%) had A positive and 4 (12.9%) had B positive. The median number of co-morbidities at diagnosis was 1(0-6). Median age at which anti D immunoglobulin was initiated was 45 yrs. Pt had received a median of 3 (2-6) therapies prior to anti D therapy. All patients had received steroids, 17 (54.8%) had immunoglobulin therapy, 2 (6.5%) had vincristine and 6(19.3%) had splenectomy prior to anti D therapy. The median duration to anti D therapy was 6 months (0-228). Anti D therapy was given in the dose of 50-75mcg/kg IV weekly. Median number of doses given was 2 (1-7) doses.
The response rate was 64.5%. Response was defined as Complete response, platelet count of > 100 × 109/L, Partial response >30 × 109/L. 17 (54.8%) achieved complete response, 3 (9.7%) achieved partial response. 11(35.5%) did not respond. Median time to relapse was 4 months (0-79). 9 (29%) achieved a complete response for over a year.
Pt with HIV (p=0.013), O blood group (p=0.030) had a significant poor response to anti D therapy on univariate analysis. Pt with HIV (p=0.035) had poor response to therapy on multivariate analysis. O blood group (p=0.001), HIV (p=0.016), > 2 lines of therapy (p=0.007), one dose of anti D (0.037) were associated with shorter time to progression on univariate analysis. On multivariate analysis prior immunoglobulin administration (p=0.039), >2 lines of therapy (p=0.004) and single dose of anti D immunoglobulin (p=0.039) were associated with shorter time to progression.

Conclusion
Anti D immunoglobulin had a response rate of 64.5% which is similar to other studies. About 29% of patients had a complete response for over a year. Pts who not received anti D immunoglobulin, HIV negative and early anti D administration had the best response and longer time to progression.

Disclosures:
No relevant conflicts of interest to declare.
Evaluation of Platelet Indices for Differential Diagnosis of Thrombocytosis by ADVIA 120.
Authors: Song YoungHee , Ahn Jeong-Yeal , Park Soon Ho , Kim Jung Eun , Seo Yiel Hea , Park Pil Hwan , Kim Kyung-Hee , Lee Jae Hoon 
Published: October 2019

Abstract
Abstract 4472

Background
Because there is no single clinical or laboratory finding for the diagnosis of essential thrombocythemia (ET), a differential diagnosis of other myeloproliferative neoplasms or reactive thrombocytosis (RT) is always necessary. Developments in automated blood cell analysers can now measure various platelet indices and were used in this study to differentiate between ET and RT in patients with a platelet count of 600×103/μL or more.

Method
The subjects studied were 31 patients with ET and 224 patients with RT. The platelet counts, mean platelet volume (MPV), plateletcrit (PCT), platelet distribution width (PDW), mean platelet mass (MPM), mean platelet component concentration (MPC) and large platelets (LPLT) were measured by ADVIA 120 (Bayer Diagnostics, USA) and the sensitivity and specificity of the two groups were determined.

Results
In essential thrombocythemia, all parameters except MPC were higher than those of reactive thrombocytosis and were statistically significant. The sensitivity and specificity were 74.2% and 84.4% when the platelet count was more than 820×103/μL. The sensitivity and specificity were 80.6% and 80.0% when the plateletcrit was more than 0.63%. The sensitivity and specificity were 64.5% and 99.1%, respectively, when LPLT was more than 23×103/μL.

Conclusion
The platelet counts and platelet indices are important for the differential diagnosis of thrombocytosis. The comparison of the plateletcrit and LPLT is particularly useful when the platelet count is markedly increased.

Disclosures:
No relevant conflicts of interest to declare.
Study On Mechanism of Bone Marrow Mesenchymal Stem Cell in Treating Patients with Rheumatoid Arthritis.
Authors: Qiao Zhenhua , Ma Lihui 
Published: October 2019

Abstract
Abstract 4486

Objective
To explore mechanism of Mesenchymal stem cells in treating Rheumatoid arthritis.

Methods
(1) MSCs were isolated from Bone marrow samples of Rheumatoid arthritis(RA)patients and purified by density gradient centrifagation and cultured in vitro. Morphology, immunophenotype, and proliferative property of bMSC and colony forming unit-fibroblast (CFU-F) were measured and analyzed. (2) In an in vitro co-culture system, MSCs were observed to modulate proliferation,activation, and maturation of T and B lymphocytes of Rheumatoid arthritis(RA)patients. The expression of IL-1?ATNF-a?ATGF-β were obviously changed.(3) Bone marrow- derived BMSCs of wistar rats were isolated and cultured in vitro routinely and the fourth passage as taken for identification of specific surface antigens by flowcytometry, then were labled with 5- BrdU in vitro. The model of collagen-induced arthritis (CIA) rats were established. 5- BrdU labled BMSCs were implanted through tail vein to model rats. At 4 weeks after BMSCs transplantation, immunohistochemical examinations were used to investigate BMSCs aggregate around the knee joints.and identify the contribution of bone marrow– derived cells to joints damage repair.

Results
(1) The culture expanded cells from RA patients presented a typical fibroblast-like morphology. Cells were positive for SH2(CD105),CD71,and CD44, but negative for CD45.Their proliferative capacity and CFU-F number were similar to those of bMSCs from healthy donors. (2) MSCs significantly inhibited T,B cell proliferation. MSCs also could down-regulating the levels of IL-1, TNF and up-regulating TGF-β. (3) Flow cytometry showed that BMSCs expressed CD44, CD71and CD105, but no CD45,CD34. At 4 weeks after the cells transplantation, the implanted cells were detected in the damaged joints of the model rats, which is not founded in normal knee joints of the rats'.and at same time there are more OPG(osteoprotegerin) positive.

Conclusion
(1) In the aspect of morphology, immuno -phenotypen, proliferative property and colony forming unit-fibroblast (CFU-F),MSCs from bone marrow of RA patients are not different from those of MSCs isolated from bone marrow of normal donors,MSCs from the bone marrow of RA patients have the potentiality in clinical application.(2) Human bone marrow MSCs inhibited Tcell and Bcell activation and proliferation in patients with RA in vitro. And these immuno –modulatory effects were not MHC-restricted. (3) bone marrow mesenchymal stem cells prevents tissue damage in arthritis. Allogeneic MSCs can engraft at sites of tissue damage,and prepair damage. That provided positive results for developing effective therapy for Rheumatoid arthritis.

Disclosures:
No relevant conflicts of interest to declare.
No Impact of Dectin-1 Polymorphism Y238X On the Outcome of Hematopoietic Stem Cell Transplantation, but a Role for Candida in Acute Graft-Versus-Host Disease.
Authors: van der Velden Walter J.F.M. , Plantinga Theo , Feuth Ton , Donnelly Peter , Netea Mihai , Blijlevens Nicole N.A. 
Published: October 2019

Abstract
Abstract 4498
Dectin-1 is a C-type lectin receptor that recognizes b-1,3-glucan, and plays an important role in antifungal immunity. The recently discovered dectin-1 Y238X polymorphism, which results in “loss-of-function” has been shown associated with increased Candida colonization of stem cell transplantation (SCT) recipients. Besides its role in antifungal immunity Dectin-1 exhibits a broader function in immunity. Stimulation of Dectin-1 with β-glucan affects antigen presentation, modulates T-lymphocytic (CD4+, both Th1 and Th17, and CD8+) and B-lymphocytic responses, and induces cytokine production including interleukin (IL) 10, IL-12 and IL-23. These specific T-cell responses and cytokines are of particular interest in SCT because they are involved in graft-versus-leukemia (GvL) effects as well as in the pathogenesis of graft-versus-host disease (GvHD). Therefore we now performed a retrospective study in 140 patients on the impact of the Y238X polymorphism on the outcome of myeloablative T cell-depleted matched related SCT. The allele frequency of the Y238X polymorphism was 6.6%, with 10.7% of patients and 15.7% of donors bearing the polymorphism. All were heterozygous and at least one polymorphism was present in 28 of 140 (20%) patient-donor pairs. We found no impact of the polymorphism on the occurrence of acute and chronic GvHD, non-relapse and relapse related mortality, nor disease-free and overall survival. Interestingly, patients from patient-donor pairs bearing the wild-type allele who were colonized with Candida had an increased incidence of acute GvHD compared to non-colonized patients (41.9% vs. 20.4%, OR=2.6 95%CI:1.02-6.58, P=0.04). However, this seemed to be the other way round for patients from pairs with the Y238X polymorphism (23.5% colonized vs. 30% not colonized, OR=0.7, ns). Therefore we hypothesize that the loss-of-function of dectin-1 increases colonization through deficient mucosal immunity, but prevents inflammatory complications resulting from colonization (Figure 1). This might explain the lack of an effect of the Dectin-1 Y238X polymorphism on outcome measures of SCT.
Figure 1: Simplified hypothesis on the role of dectin-1, polymorphism Y238X, and Candida colonization on acute GvHD and possibly GvL. Figure 1:. Simplified hypothesis on the role of dectin-1, polymorphism Y238X, and Candida colonization on acute GvHD and possibly GvL.
In case of Candida colonization (left) activation of the dectin-1 receptor influences immune responses and allo-reactivity increasing the incidence of acute GvHD. In the presence of the loss-of-function polymorphism Y238X (right), although Candida colonization is increased, due to the loss-of-function of dectin-1, no changes in the allo-reactive T-cell responses occur.

Disclosures:
No relevant conflicts of interest to declare.
Dengue Virus Associated Hemophagocytic Syndrome with Neurogical Manifestations in Children: A Case Report.
Authors: Soler-Rosario Yadira , Barrios Nilka J. , Garcia Ricardo , Fernandez-Sein Alicia , Rivera Enid 
Published: October 2019

Abstract
Abstract 4516
Dengue fever, caused by dengue virus, can cause increased vascular permeability, which leads to a bleeding diathesis or disseminated intravascular coagulation known as Dengue Hemorrhagic Fever (DHF). Hemophagocytocytic Syndrome (HPS) with neurological manifestations is an uncommon presentation of DHF. There are no reports of virus associated with HPS and neurological manifestations in the pediatric literature. Hemophagocytic Syndrome (HPS) is a clinico-pathologic entity characterized by proliferation of T lymphocytes and macrophages leading to cytokine overproduction. HPS may be diagnosed in association with malignant, genetic, or autoimmune diseases. Dengue virus is considered non-neurotropic, however neuroinvansion has been reported. We present the case of a 10 month old female patient who developed DHF, manifested with upper GI bleeding, hypotension and pancytopenia. The infant subsequently developed dengue shock syndrome, with thrombocytopenia, intravascular hemolysis, coagulopathy, elevated transaminase, hyperbilirubinemia, and creatine kinase (CK) of 2,876U/L. She required artificial hemodynamic and blood components support. During her course of illness, she developed ecchymosed, purpuric bullae lesions of the skin in the distal upper extremities. Her IgM ELISA for Dengue virus was positive. Bone marrow aspiration and biopsy was diagnostic for HPS. The patient was initiated on IV steroids and antibiotics therapy. An improvement was noticed on day 8 of illness and was weaned off completely of all artificial support by the day 9. A complete recovery of her hematological, transaminase, billirubin, and coagulation parameters was noticed on day 12. A repeated bone marrow aspirate and biopsy examination was normal. Patient's recovery was significant by muscle weakness (MCG grade ≤3), hypotonia, reduced tendon reflex and increased CK suggestive of possible myositis. The cerebrospinal fluid and magnetic resonance imaging studies of the brain were normal. She was given IV immunoglobulin (500mg/kg) for 2 consecutive days with remarkable neurological improvement including a normal CK (56U/L).She was weaned of steroids completely on day 20.Dengue virus infection was confirmed by a positive serology result at the convalescent stage. On day 23 she had a complete clinical recovery. To our knowledge, this is the first case reported of dengue virus-associated HPS and neurological manifestations in a pediatric patient with DHF. Clinicians should consider that the occurrence of HPS and neurological manifestations in children could de due to dengue virus infection.

Disclosures:
No relevant conflicts of interest to declare.