bluuebunny/crossref_metadata_2025_split huggingface dataset:
Research of Gene Expression in Patients with Myelodysplastic Syndromes.
Authors: Chen Bao-An , Zhang Bo , Gao Chong , Xia Guo-Hua , Shao Ze-ye , Ding Jia-Hua , Chen Jian , Wang Jun , Song Hui-Hui , Bao Wen , Zhong Yue-Jiao , Pei Xiao-Ping , Wang Fei , Chen Ning-Na 
Published: October 2019

Abstract
Abstract 4433

Object
This study was aimed to investigate the expression of c-FLIPL, c-FLIPS and DLK1 mRNA in Myelodysplastic Syndromes (MDS) patients, as compared with normal people and AML patients, and to find its clinical significance.

Methods
The expression of c-FLIPL, c-FLIPS and DLK1 mRNA in bone marrow mononuclear cells (BMNNC) of 16 patients with MDS, 8 patients with AML and 3 controls were detected by RT-PCR.

Results
The expression of DLK1 mRNA was up-regulated in MDS, including RA and RAEB, as compared with controls(P<0.05). There was no significant difference in expression of DLK1 between RA and RAEB(P>0.05). The expression of DLK1 was significant higher in AML patients, compared with controls(P<0.05). There was no significant difference between MDS and AML patients(P>0.05). The expression of c-FLIPL mRNA was higher than that in controls, both in RA and RAEB(P<0.05). There was no significant difference in expression of c-FLIPL between RA and RAEB(P>0.05). In eight AML patients, c-FLIPL gene's expression was up-regulated, as compared with controls(P<0.05). Between AML and MDS patients, there was no significant difference(P>0.05); The expression of c-FLIPS mRNA had no significant difference between MDS patients and controls(P>0.05), but its expression in RAEB was significant higher as compared with RA patients and controls(P<0.05). And in AML patients, the expression of c-FLIPS was higher than that in controls(P<0.05), but there was no significant difference between AML and MDS patients(P>0.05).

Conclusion
It is concluded that the expressions of DLK1, c-FLIPL and c-FLIPS mRNA in MDS/AML patients are abnormal as compared with normal people, although there are no significant difference have been found between AML and MDS. These genes may play critical roles in escaping malignant clone of MDS from apoptosis and acquiring the ability to divide unlimitedly, they can become important indexes for evaluating of development in MDS.

Disclosures:
No relevant conflicts of interest to declare.
Impact of Therapeutics On Fatigue in Chronic Immune Thrombocytopenia (ITP).
Authors: Bussel James B. 
Published: October 2019

Abstract
Abstract 4455
Complaints of tiredness, lethargy or lack of energy are common in patients with chronic Immune ThrombocytoPenia (ITP), however they are not well understood. This study assessed whether different clinical and laboratory aspects are related to fatigue and how different therapeutic modalities might impact these symptoms.

Methods
Patients with chronic ITP older than 15 years old were enrolled from 2007-2008 at the Platelet Disorders Center at the Weill-Cornell Medical Center, NY. They completed the Short-Form 36 questionnaire (SF-36) and Fatigue severity scale (FSS) (2 standardized Health-related quality of life [HRQoL] questionnaires) and the Beck Depression Inventory (BDI). Laboratory testing included CBC, TSH, ferritin, iron + TIBC, and blood serotonin levels.

Results
83 patients with a mean age of 40.2 years (67.5% women) were enrolled. The mean platelet counts were 109,000/ul (range of 12,000-500,000/ul). Forty-one % of patients had duration of ITP of 10 years or more and 25% had had previous splenectomy. Sixty-one% were on treatment: 11% steroids, 23% Tpo-R agents and 28% “Other” (7.2 % Rigel, 13.3 % IVIG, 3.6 % anti-D, 2.4 % rituximab and 1.2% Danazol/Azathioprine). Surprisingly, analysis of the SF36 showed that the study (ITP) population is similar to the general US population and that they do not report increased fatigue or depression. These results contrast with a previous report by McMillan, AJH, 2007 (fig 1). However when the current patients were divided according to age, abnormal low scores on SF36 were observed on vitality domain (mean 50) for the age group of 45-55 years and on role physical domain (mean 48) for the age group of 55-65 years. Furthermore, differences were observed in patients stratified according to treatment (figure 2) where the mean scores for patients on the steroid group on the respective domains were lower: vitality 49 and role physical 42. The Tpo-R agonists group had better results in all SF36 domains; similar findings were seen with the FSS and BDI. The only laboratory finding is that patients with low ferritin levels had worse results on FSS.

Conclusion
Although fatigue and related symptoms have been previously reported by others including an improvement with successful treatment eg in studies of the TPO-R agonists, to our surprise we did not find the same results. Whether this study population is intrinsically different or receiving different treatments, eg avoidance of steroids, might impact these results here are 2 possible hypotheses. Use of different fatigue assessments as ITP-PAQ or CDC symptom inventory and further studies addressing the role of the pro-inflammatory cytokines in these patients would be useful.

Disclosures:
No relevant conflicts of interest to declare.
TNF-α and Its Receptors in Patients with Acute Myeloid Leukemia Undergoing alloHSCT.
Authors: Kyrcz-Krzemien Slawomira , Zielinska Monika , Wieclawek Agnieszka , Czerw Tomasz , Holowiecka Aleksandra , Zielinska Patrycja , Mazurek Urszula 
Published: October 2019

Abstract
Abstract 4484

Introduction
Several studies have demonstrated, that TNF α and its receptors (sTNFR) can be used as prognostic markers for major transplant related complications (TRC) after allogeneic haematopoietic stem cell transplantation (alloHSCT). Measurement of that inflammatory cytokine and sTNFR during pretransplant conditioning and early after transplantation may also reflect the conditioning-induced tissue damage.

Patients and methods
Our study included a group of 36 adult patients with acute myeloid leukemia (AML) in complete remission, who underwent alloHSCT following standard myeloablative conditioning according to Bu/Cy protocol (17 patients) or reduced-toxicity myeloablative conditioning with treosulfan-based regimens (19 patients). 21 patients received alloHSCT from a sibling and 15 from an unrelated donor. The expression of TNF-α, TNFRI and TNFRII were analyzed using reverse transcription-polymerase chain reaction (RT-PCR) in peripheral blood mononuclear cells (PBMC) before the start of conditioning, on the day of transplantation and on day 30 after alloHSCT. We examined β-actin as well, which constitutes an endogenous amplification control and is a housekeeping gene. sTNFRI and sTNFRII serum levels were measured using an enzyme-linked immunosorbent assay (ELISA) at the same defined time points before and after alloHSCT. The Mann-Whitney U test was used to evaluate the significance of differences between the analyzed groups and the Shapiro-Wilk and Lilliefords tests to estimate data distribution.

Results
TNFRII mRNA was not detected in PBMC, but TNF-α and TNFRI mRNA as well as β-actin were discovered. The real time PCR showed significant decrease (p<0.004) in TNFRI expression on day 30 after transplantation in comparison to day 0. On day 30 expression of TNFRI was higher in patients treated with Treosulfan-based regimens than in patients treated with Bu/Cy (p=0.027). Plasma levels of sTNFRI and sTNFRII observed on day 0 and 30 were significantly elevated (p<0.05) compared with the levels prior to conditioning.

Conclusion
Our data indicate that sTNFRI and sTNFRII can be investigated as the markers reflecting the toxicity of the conditioning regimens in AML patients undergoing alloHSCT. The associations between TNF-α, TNFRI expression, serum levels of sTNFR and the clinical outcome after alloHSCT should be evaluated.

Disclosures:
No relevant conflicts of interest to declare.
Targeted Therapy by Using Tissue Specific Promoter and Granules as Storage Compartments for Therapeutic Proteins in Hematopoietic Cells.
Authors: Afsharian Parvaneh , Johansson Åsa , Persson Ann-Maj , Olsson Inge , Hansson Markus 
Published: October 2019

Abstract
Abstract 4508
Systemic administration of immunotherapeutics often give rise to severe side effects. A local deposition, using secretory lysosomes of hematopoietic cells as vehicles for delivery, may overcome this problem. Our research regarding sorting mechanisms of granule proteins have led to a new therapeutic idea – targeted therapy with hematopoietic cells as carriers. Exogenous proteins are expressed, and the gene product is directed for secretory lysosome or granule storage. These organelles are unique storage compartments in neutrophils for biological active proteins, designated for inflammatory foci. The exogenous proteins, would accordingly, be locally released at the site of inflammation. Our model construct, soluble TNF receptor 1 (sTNFR), can be directed for storage by adding a transmembranous region and a sorting signal. We have earlier shown that this construct, retrovirally expressed in murine hematopoietic progenitor cells, are destined for granule targeting. Furthermore, we have transplanted transduced murine progenitor cells with modified granule content, and found stable expression and inducible release of sTNFR1 in vivo. Our goal is cell linage specific expression in order to selectively express sTNFR1 with a transmembranous region and a signal peptide for granule targeting. To achieve this, lactoferrin, perforin and MPO promoters, including regulatory elements, have been inserted into vectors (we use a retroviral vector with self-inactivating LTRs). The vectors is retrovirally transduced into murine hematopoietic progenitor cells, and the cells are cultured during cytokine driven differentiation and analyzed by FACS and Western blotting. Our results suggest that a concept of using secretory organelles of hematopoietic cells as vehicles for therapeutic agents in vivo may become feasible. It will be possible to test this principle by experiments in animal models of inflammatory and malignant diseases. Likewise, development of this concept may give new information on secretory lysosome function and secretion at inflamed/malignant sites.

Disclosures:
No relevant conflicts of interest to declare.
Five Pro-Inflammatory Molecules Polymorphisms Analysis in Ischemic Cerebrovascular Disease (ICD).
Authors: Moreno Vanessa P. , García-Raso Aránzazu , García-Bueno María José , García Araceli , Sánchez Carmen , Subirá Dolores , LLamas Pilar 
Published: October 2019

Abstract
Abstract 4514

Introduction
Ischemic cerebrovascular disease (ICD) is a multifactorial entity whose anatomopathological substrate is the pro-inflammatory state links to atherosclerosis. The inflammatory cells migrate to vascular endothelium unleashing atheroma plaque formation and pro-inflammatory cytoquine release.

Objective
The purpose of this case-control study is to analyze the ICD risk associated to polymorphisms MCP-1 -2518 G/A, IL6 -174 G/C, IL 1B -511 C/T, IL1B +3954 C/T, IL1A -889 C/T.

Methods and patients
A total of 282 ICD diagnosed patients (134 female and 148 male; mean age 68,2±14,9 years) and 287 controls without thrombotic history (143 Female and 144 male; mean age 65,8±14 years) were analysed. AH, DM, dyslipidemia and smoking habit data were collected for each group. Polymorphisms were analysed by PCR-RFLP. Seric IL6 was measured by ELISA. Statistic Analysis was made with Stata v.10 software.

Results
Stroke subtype distribution was: atherothrombotic (32,8%), inhabitual and indeterminate (28,9%), cardioembolic (24,5%), and lacunar (13,7%). Risk factors were more frequent in patients with AH and DM showed a higher prevalence: (OR: 1.684 IC 95%:1.161- 2.443, p:0.006) and (OR: 2.393, IC95%:1.447- 3.956, p:0.01) respectively. Logistic regression was used to determinate polymorphisms distribution. Results are shown in table 1. Analysis of IL-1 polymorphisms showed a synergic relation in IL1A -889 C/T (p:0.05; OR: 0.625; IC95%:0.388-1.008). The G allele IL6 –174 G/C carriers group presented higher seric IL6 levels than C allele carriers, 5.85 pg/ml (2.9- 34.5) vs 4.94pg/ml (2.5- 11.4) respectively. IL-6 genotype frequency G/G + G/C vs C/C was analyzed. Atherothrombotic stroke IL-6 genotype frequency was G/G + G/C (24.3%) vs C/C (12.0%) (p: 0.082).

Conclusion
There is no association between MCP-1 -2518 G/A, IL6 -174 G/C, IL 1B -511 C/T, IL1B +3954 C/T, IL1A -889 C/T polymorphisms and ischemic stroke. We found a synergic effect between IL1 mutations. The G allele IL6 –174 G/C carriers group presented higher seric IL6 levels than C allele carriers. The analysis performed by ICD subtypes showed an association between IL6 G allele and atherothrombotic subtype.
* SETH and MMA GRANT

Disclosures:
No relevant conflicts of interest to declare.
Experience with Hemophagocytic Lymphohistiocytosis at a Single Institution.
Authors: Park Meerim , Koh Kyung Nam , Bae Keun Wook , Lee Mee Jeong , Im Ho Joon , Seo Jong Jin , Moon Hyung Nam 
Published: October 2019

Abstract
Abstract 4517

Background
Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), whether primary or secondary, is a serious and potentially life- threatening histiocytic disorder and generally fatal without immune modulating chemotherapy. This study aimed to define the clinical spectrum and treatment outcome in Korean children.

Patients and Method
Patients who were diagnosed with HLH/MAS at Asan Medical Center between October 1997 and April 2009 were identified and charts were reviewed.

Results
Twenty-six patients (16 male, 10 female) were evaluated during 13 - year period. Median age at diagnosis was 29.5 months (range: 0 - 180 months). Twelve patients had HLH secondary to underlying disorders, including viral infection, autoimmune disease. Epstein-Barr virus (EBV) - associated HLH was present in 9 patients, 1 of whom died, while 4 of 17 non-EBV associated patients died. Initial treatment with intravenous immunoglobulin (IVIG) was given to 9 patients and they had no response to IVIG. Eventually, all the patients except two underwent full protocol therapy (HLH 1994/2004) and the 2 patients died of rapid disease progression with delayed diagnosis. Seven patients revealed disease reactivation, median 3 months from HLH protocol therapy, and further treatment using the same regimen induced second remission of short duration. Seven patients (26.9%) had evidence of central nervous system disease at the time of diagnosis and neurological symptoms consisted of seizure, irritability, vomiting. Five of them are long-term survivors including one who received allogeneic stem cell transplantation (SCT) and all 5 patients show normal neurological function after treatment. The familial form of HLH was identified in 3 patients and all received allogeneic SCT from unrelated donor in second remission. They are still alive without relapse. At a median follow-up of 17.5 months, the estimated one-year overall survival rate was 82.8 ± 7.9 %.

Conclusion
Treatment outcomes using HLH 1994/2004 protocols in Korean children have become comparable to those reported in an international collaborative study. And allogeneic SCT represents a curative treatment for familial form of HLH. Further studies are required to more precisely define clinical spectrum and treatment outcome.

Disclosures:
No relevant conflicts of interest to declare.
Hodgkin's Lymphoma in the Elderly Patient: Impact of Age and Co-Morbidities On Outcomes.
Authors: Nakkar Samer , Pacioles Toni , Ballester Gabriela , Tirona Maria , Ballester Oscar F 
Published: October 2019

Abstract
Abstract 4529

Introduction
Age older than 45 years is a recognized independent prognostic factor for patients with Hodgkin's Lymphoma (HL), and it is part of the International Prognostic Score (IPS) system. This score system was based on data derived from selected patients included in clinical trials. It is unclear from these studies if age affects primarily disease biology or the ability of older patients to tolerate therapy.

Patients and Methods
We retrospectively reviewed all consecutive patients with newly diagnosed HL at our institution. Data collected included their IPS and a co-morbidity score (CoM) which includes assessment of co-existing cardiac, hepatic, pulmonary, renal and other morbidities.

Results
Forty five patients were identified. Twenty nine patients (64%) were younger than 45 years and 16 (35%) were 45 years or older. Patients were treated wit ABVD (adriamycin, bleomycin, vinblastine and DTIC) chemotherapy, with or without radiotherapy, except for 4 patients who were accrued to clinical trials. An IPS of 2 or more was documented in 17% of younger patients as compared to 71% of those older. There was a significant association between age and IPS score (p= 0.001). Similarly, there was a significant association between age and CoM score (p= 0.01). A CoM score of 4 or higher was seen in only 7.6% of the younger population but in 46.6% of the older patients. With a median follow up of 62 months, overall survival is 86 % for the entire population. Overall survival for the younger patients is 93% and for the older 71% (p= 0.01). Five of the six documented deaths occurred in patients 45 years or older, and 4 of these 5 were seen in patients over 60 years of age. Crude death rates for patients <45 (n= 29), 45 to 59 (n= 9) and 60 or older (n= 7) are: 3.4%, 11% and 57% respectively.

Conclusions
Older patients are more likely to present with high IPS and CoM scores which explain at least in part their poor outcomes. A high mortality rate in patients >60 years underscores the need to explore new therapeutic approaches in the older population.

Disclosures:
No relevant conflicts of interest to declare.
Chemotherapy Induced Neutropenic Fever Seen at Emergency Room: A Review of 102 Cases.
Authors: Lim Joo Han , Yi Hyeon Gyu , Lee Moon Hee , Kim Hoon , Kim Chul Soo 
Published: October 2019

Abstract
Abstract 4530

Introduction
Febrile neutropenia (FN) is a major toxicity of chemotherapy in cancer patients requiring prompt medical measures. Although the FN is a situation of oncologic emergency, the diagnosis and treatment may vary among institutions, and how fast the patients are being treated often depends on competence of House Officers at Emergency Room (ER). There has been limited data regarding the clinical outcome of patients with FN who were brought to ER.

Patients and Methods
We evaluated the clinical manifestations, therapeutic outcomes, and risk factors of FN in a retrospective analysis of 102 adult patients who visited ER from January 1, 2006 to March 31, 2009. FN was defined as a body temperature >38°C and a neutrophil count >0.5 × 109/L on the day of fever or the day after.

Results
The ECOG performance status (PS) was 0 in 15 patients, 1 in 67, and 2 in 20. The patients had a mean age of 57 years (range, 25–84). Fifty four patients were male, 52 female. Underlying diagnosis was lymphoma in 30, and soid tumors other than lymphoma in 72. The mean ANC was 436.8/mm3 (range, 0–1000); 4 patients had an ANC of <10/mm3. Twenty-three patients (22.5%) died of complications related to FN. There was no statistical difference in therapeutic outcome between tumor types, i.e. lymphoma versus non-lymphoma (p=.521), PS (p=.438), sex (p=.099), depth of neutropenia (p=.162), or time intervals from visiting ER to starting antibiotic therapy (p=.414). Age was important prognostic factor in therapeutic outcome. The median age in fatal cases was 62 years where as that of non-fatal cases was 54 (p=.016). Bacteremia was documented in 19 patients among whom 10 (53%) died. Mortality was significantly higher in patients with blood culture proven bacteria than patients whose blood culture yielded no organism (p=.013).

Conclusion
Cases of FN seen at ER showed substantial mortality especially in elderly patients. Given the rising age in cancer diagnosis as well as therapeutic intervention, higher mortality rate associated with chemotherapy induced FN in elderly patients needs further study seeking the way to reduce the risk of death

Disclosures:
No relevant conflicts of interest to declare.
Jamshidi needle Biopsy of the Sternal Bone Marrow.
Authors: Davila Enrique 
Published: October 2019

Abstract
Abstract 4548
The aspiration and biopsy of the bone marrow is one of the most valuable and important tests in hematology, oncology and medicine. It is a high yield, safe, fast and informative test performed frequently in medical practice with minimal complications. For reasons of ease and safety, bone marrow aspiration and biopsy are usually obtained from the posterior iliac crest. I reviewed my experience in obtaining 37 consecutive bone marrow biopsies from the sternum using a Jamshidi needle (gauge 11; external diameter 3.048 mm) in 36 consecutive patients (twice in one patient) over a 9 year period, in whom a posterior iliac crest study could not be done.

Technique
After performing the sternal bone marrow aspiration in the usual manner, a small skin incision is made over the sternum with a scalpel. The Jamshidi needle is introduced at approximately a 90 degree angle in the middle of the sternum at the level of the 3rd intercostal space. After a ”give” is felt, indicating that the needle has reached the bone marrow cavity, the tip of the needle is angled downwards at 45 degrees or less and with a clockwise - counterclockwise movement, the needle is advanced for 3 to 10 mm. After a slight change of angle aiming at “breaking” the distal attachment of the bone marrow piece, the needle is slowly withdrawn with the same rotatory movements. In no case did I feel that I had reached the inner table of the sternum. All patients were observed and examined 20 minutes and 24 hours after the procedure.

Results
There were 22 inpatient and 15 outpatient procedures. The reasons that precluded the performance of the preferred posterior iliac crest bone marrow biopsy were: immobility in 17 patients, obesity in 13, prior radiation in 3 and other in 4. The final diagnosis was a malignant disorder in 17 patients (leukemia, lymphoma, myelodysplasia, plasma cell dyscrasia or metastatic cancer). All but one were new diagnoses. In 20 cases the final diagnosis was a benign hematological disorder or a non diagnostic bone marrow examination. In 9 occasions (mostly obese patients and patients with prior radiation therapy) a previous attempt at performing a posterior iliac crest biopsy had failed. The only complications were the development of a tumor nodule in the needle tract in one patient with an aggressive, Burkitt's type lymphoma and a small superficial hematoma in a patient with a highly vascular metastatic breast cancer.
The bone marrow core biopsy of the sternum, performed as described, in the hands of an experienced practitioner is a safe and helpful test in the evaluation of the bone marrow cytology, architecture and anatomy in selected patients in whom the performance of the preferred posterior iliac crest biopsy cannot be done.

Disclosures:
No relevant conflicts of interest to declare.