bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of Hematology-Oncology Lecture Series for Housestaff.
Authors: Steinberg Amir 
Published: October 2019

Abstract
Abstract 4554

BACKGROUND
Currently, the hospital has a floor dedicated to cancer patients. The housestaff taking care of these patients includes three interns and one hematology-oncology fellow. In addition, there is a consult service comprising another fellow, an intern, and a resident. There was a paucity of formal, didactic, teaching in place devoted to the subjects of hematology and oncology.

OBJECTIVE
the development of a monthly lecture series for housestaff rotating on a hematology-oncology rotation that would focus on three key areas:

METHODS
Topics were chosen based on pertinence. These included: leukemia, lymphoma, multiple myeloma, stem cell transplantation (these first four comprising at least 50% of patients on the unit), coagulation, breast cancer, lung cancer, colon cancer, gynecological malignancies, and pain management/supportive care. Potential speakers included full-time faculty as well as private physicians affiliated with the cancer center. Emails and/or phone calls were placed to the physicians and announcements made at division meetings and schedules developed. The plan was also for the development of a series of questions testing the housestaff at the start of their one month rotation and at the end of the rotation. Lectures were scheduled for afternoons if possible to avoid conflicts with morning rounds. Occasional morning talks were necessary to accommodate lecturers. Format of lectures was flexible (power point, dry-eraser board).

RESULTS
Overall feedback was positive for the lecture series. The two conditions affecting optimal success of the program concerned scheduling, including intern and fellow schedules as they relate to rounds and housestaff clinics and availability of when speakers could lecture and recruitment of speakers appropriate to the relevant topics. In addition, repeating the topics every month proved challenging for finding lecturing participants. The question/answer testing is still early in testing and no conclusion can be made.

CONCLUSION
A didactic lecture series is an important aspect of hematology-oncology education for housestaff. Repeating lectures every month is a challenge for several reasons. Possible interventions in the future may include:

Disclosures:
No relevant conflicts of interest to declare.
The Activation of STAT3 Contributes to the Effect of Autocrined G-CSF On the Proliferation of HL60 Cells Induced by ATRA.
Authors: Yang Weihua , Wen Peie , Liu Chuanfang 
Published: October 2019

Abstract
Abstract 4565

Background
In previous works, we detected several significant cytokines in the serum of patients with APL after treatment with ATRA, and the results revealed a close association of serum G-CSF and the number of promyelocytes or more mature granulocytes. Some of the results also indicate that ATRA in vitro has a conspicuous effect on the expression of some cytokines, such as IL-1β, IL-8, TNF, G-CSF, and so on. At least, it is showed that cytokines in serum or supernatant secreted by APL cells perhaps played an important role in the genesis of leukocytosis. However, the role of G-CSF in proliferation of APL cells has not yet been explained clearly. In the present study, we analyse the secretion and expression of cytokines in APL patients who has hyperleukocytosis, study the relationship between cytokines and leukocytosis, and detect the signal transduction pathway of cytokines.

Objective
To detect the signal pathway of IL-1β and G-CSF secreted by primary acute promyelocytic leukemia (APL) cells induced by all-trans retinoic acid (ATRA).

Methods
Primary APL cells from ATRA-treated patients were cultured in RPMI 1640, then the level of supernatant IL-1β and G-CSF were detected by ELISA assay. The expression of IL-1β or G-CSF mRNA was measured by RT-PCR, and the level of STAT1α and STAT3 evaluated by Western blot.

Results
Treated with ATRA, the peripheral blood leucocytes of patients with APL was obviously up-regulated, and peaked at 12 days averagely, of which mainly were myelocytes and metamyelocytes. The secretion of IL-1β or G-CSF in supernatant was up-regulated (P<0.05). RT-PCR assay confirmed that in the primary APL cells, with higher secretion of IL-1β and/or G-CSF, the expression of IL-1β and/or G-CSF was up-regulated, correspondingly. Cytokines and signal transduction factors analysis indicated that the expression of STAT1α protein increased in all the patients, irrelevant to the expression of IL-1β or G-CSF, but the increase of STAT3 expression was consistent with the expression and secretion of G-CSF.

Conclusion
The higher expression of G-CSF in primary APL cells induced by ATRA contributes to the activation of STAT3.

Disclosures:
No relevant conflicts of interest to declare.
Investigation of the Mechanistic Events Governing Platelet Release.
Authors: Thon Jonathan Noah , Anderson-Daniels Jordan M. , Braithwaite Matthew , Larson Mark K. , Hoffmeister Karin M. , Hartwig John H. , Italiano Joseph 
Published: October 2019

Abstract
Abstract 4590
Megakaryocytes generate platelets by remodeling their cytoplasm into long proplatelet extensions from which platelets release. While the mechanics of proplatelet elongation have been studied, the terminal steps of platelet production remain poorly understood. To understand the mechanics of platelet release, we developed a novel gradient sedimentation protocol to isolate released proplatelets. This has enabled us to define and quantify different stages in platelet maturation and identify a new intermediate stage in platelet production—the preplatelet. Preplatelets are anucleate discoid particles considerably larger (2-10μm) than platelets that have the capacity to reversibly convert into barbell-shaped proplatelets. Video-microscopy of GFP-tubulin expressing cells reveals that preplatelets elongate and twist into barbell forms by a process mediated by microtubule-based forces. α-Granules and dense granules present in the preplatelet translocate between platelet-sized swellings during barbell proplatelet formation, and ultimately concentrate at the terminal loops. Fission releases two mature platelets from the barbell ends, and isolated proplatelets will mature into bona fide platelets in culture over a 5-day period. Correspondingly, mature platelets are generated within 2 hours post-transfusion of fluorescently-tagged proplatelets into recipient mice. Released proplatelets were plated on extracellular matrix proteins (fibrinogen, laminin, fibronectin, collagen, matrigel) or a BSA control, and cultured for 24 hours to recapitulate the bone marrow vascular niche and determine whether these cell-substrate interactions mediate platelet release. Fibrinogen and laminin binding increased platelet release roughly 4-fold, suggesting cell-substrate interactions in the bone marrow vascular niche and surrounding vasculature are critical for the final stages or platelet production. These findings confirm that proplatelets mature into multiple individual platelets both in vivo/vitro, and begin to define the mechanistic events leading to platelet production.

Disclosures:
No relevant conflicts of interest to declare.
Non-Invasive Urinary Markers of Renal Dysfunction in Sickle Cell Disease.
Authors: Mohtat Davoud , Moulton Thomas , Driscoll M. Catherine , Woroniecki Robert P 
Published: October 2019

Abstract
Abstract 4621
Renal failure is one of the major complications of sickle cell disease (SCD), affecting 5-18% of the patients. Microalbuminuria (MA), which has a prevalence of 26.5% in all children with SCD, is used as a marker of preclinical glomerular damage and renal disease progression. However, measuring MA alone may miss renal damage involving tubular proteins. We hypothesize that sickle cell nephropathy subjects will have increased urinary excretion of Transforming Growth Factor Beta-1 (TGF β1) and Neutrophil Gelatinase–Associated Lipocalin (NGAL) as compared to age-matched controls (CTR). We also hypothesize that urinary excretion of these proteins will be associated with severity of anemia in SCD. Enzyme-Linked Immunosorbent Assay (ELISA) kits were used to detect urinary excretion of TGF β1/NGAL, and corrected to urine creatinine. Mean age, gender, and race were not statistically different among the groups. Urinary excretion of TGF β1 was significantly higher in SCD subjects (26.4 pg/mg Cr +/-1.5) vs. CTR (14.9 pg/mg Cr +/-2.4), (p<0.00001). There was no difference in urinary NGAL between the SCD subjects vs. CTR. SCD patients with hemoglobin less than 9gm/dl had higher urinary TGF β1 than SCD patients with milder anemia (p=0.002). Urinary TGF β1 was lower in SCD patients on hydroxyurea (23.61+/-2.6), vs. those who were (27.69+/-1.8), p=0.08. Surprisingly, there were no correlation between urinary TGF β1 and urinary microalbumin or estimated glomerular function, indicating that microalbuminuria and serum creatinine are poor measures of renal injury in SCD patients.
Our data suggests that urinary TGF β1 may serve as a urinary biomarker to monitor the progression of renal disease in SCD. This assumption needs to be tested prospectively.

Disclosures:
No relevant conflicts of interest to declare.
Cognitive Dysfunction in Children and Adolescents with Sickle Cell Disease without Evidence of Stroke: Preliminary Results.
Authors: Silva Janete , Leite Ana , Maia Heber , Thomé Ursula , Moura Patricia , Lobo Clarisse Lopes 
Published: October 2019

Abstract
Abstract 4623

INTRODUCTION
Sickle cell disease (SCD) is the most frequent cause of stroke in children. It is possible that cognitive dysfunction occurs in the absence of identifiable stroke due to silent cerebrovascular disorders.

OBJECTIVE
To evaluate SCD compromises cognitive functions of patients with no radiological nor clinical evidence of stroke.

METHODS
Thirty eutrophic children with SCD, with normal neurological examination and imaging (brain CT) and without past cerebrovascular disease were submitted to neuropsychological assessment between 2002 and 2008. The neuropsychological battery included the following tests: WISC-III, BTN (battery of neuropsychological tests, assessing laterality), Rey complex figure (visual perception and memory), and behavioral screening for ADHD, learning disorders and antisocial behavior.

RESULTS
66.7% of patients were male. The average age of patients was 9.6 years (6 - 15 years). The mean total IQ was 78.8 (50 - 105) and the executive IQ was 77.9 (47 - 108), both at the borderline limit. The verbal IQ mean was 84.9 (55 - 113), on lower average. Verbal comprehension verbal was on average 87.4 (58 - 115). The results of visual memory was at the lower limit of normal (mean percentile 16 to 18). There was no correlation between the rates of behavior disorders (inattention, hyperactivity, learning difficulties and conduct disturbance) and IQ results. There was no statistically significant difference between the results of males and females or between age groups. 40% of the sample had not developed manual preference.

CONCLUSION
The subjects of this sample showed significant cognitive impairment in the absence of clinical or radiological evidence of cerebrovascular disease. The study has limitations as the sample size, the imaging technique used and neuropsychological battery comprehensiveness, but the results are quite suggestive of a relationship between SCD and cognitive impairment. The research group is developing a study with a larger sample (100 patients) to clarify the correlations between these findings. This will be important to outline earlier neuroprotective measures, which will provide improvements in neurodevelopment, learning, quality of life and social inclusion.

Disclosures:
No relevant conflicts of interest to declare.
The Eveluation of Pulmonary Functions in Children with Sickle Cell Anemia.
Authors: Kurt Cem , Sasmaz Ilgen , Antmen Bulent , Kilinc Yurdanur , Kurdak Sadi , Kuleci Sedat 
Published: October 2019

Abstract
Abstract 4628

Aim
In this study we evaluated to pulmonary functions and determined relations of these findings with clinical parameters in children with sickle cell anemia (SCA) who were at follow up in our pediatric heamatology clinic.

Materials and Methods
24 children with sickle cell anemia and 9 healthy children as control group include to the study. Complete blood count, hemoglobin electrophoresis and biochemical values were eveluated for both groups. At pulmonology department, the carbonmonoxide diffusion test performing for both groups. At the same day spirometric respiratory function evaluation and exercise test performed both groups at department of sports physiology. The data recieved are compared statistics.

Results
HbS, HbF, SGPT, ferritin, total bilirubine, direkt bilirubine and Fe++ values were high at patient group (p<0.05). Hemoglobin and hematocrit values were low at patient group according to control group as expected (p<0.05). The number of SCA patient who had one-three venoocclusive crises (VOC) were 14 (58.3%), patient who had three or more VOC were 7 (29.2%) and patient who had no VOC were 3 (12.5%). The number of patient who had acute chest syndrome (ACS) were 5 (20.9%) and 19 patients had no ACS (79.1%). Ýmpaired isole carbonmonoxide diffusion test was established at the 62.5% of the patient's. At patient group, spirometric FEV1 and MEF25 measurement were found lower than the control group (p<0.05). At exercise test VO2/HR rate were lower for patient group (p<0.05). VE/VO2 rate (p=0.023) and R (p=0.016) measurement were found higher.

Conclusion
Pulmonary gas transfer was found difficult in patients with SCA. Respiratory airways established obstructed in spirometric evaluation. Obstructive defficiensies have to be follow up. Oxygen pulse and respiratory exchange rates were determined low and more oxygen usage was observed for aerobic metabolic activity. With these results, ýt can be say that chronic inflamation process at lung due to oxygen radicals and hipoksemia in sickle cell patients, the aerobic respiratory load was increased.

Disclosures:
No relevant conflicts of interest to declare.
Modified Vaccinia Ankara Virus (MVA) Induces a Th1-Polarized Immune Response in Antigen-Presenting Cells (APCs).
Authors: Flechsig Christin , Suezer Yasemin , Kapp Markus , Sutter Gerd , Einsele Hermann , Grigoleit Götz Ulrich 
Published: October 2019

Abstract
Abstract 4650

Introduction
MVA is one of the most promising vaccine candidates for infectious diseases as well as for malignancies. Astonishingly, little information exists about the mechanism by which immune responses to MVA are generated. It was shown that among leukocytes - which are essential for the generation of cellular and humoral immune responses - APCs like dendritic cells, monocytes and B cells are preferentially infected. But little is known about the effects on APCs. Therefore we wanted to analyze in more detail the general effects of MVA infections on different immune cells.

Methods
Primary human peripheral blood mononuclear cells (PBMCs) and isolated leukocyte populations in particular monocyte derived DCs, monocytes and B cells were infected with (wildtype) wtMVA or MVA-gfp (green fluorescent protein) to verify the infection. Subsequently changes in surface markers and cytokine expression were assessed.

Results
Among PBMCs and specific isolated leukocyte populations, monocytes, DCs and B cells were most susceptible to MVA infection. NK cells showed a lower and T cells a very low infection rate. Surprisingly, selected monocytes were less susceptible to MVA as compared to unselected ones. This phenomenon is due to phagocytosis of other infected PBMCs by monocytes. Furthermore we could show that MVA causes a downregulation of CD14 on iDCs and monocytes as well as of CD25, CD80, and CD86 on B cells. Furthermore, there was a slight downregulation of CD1a on iDCs and mDCs and of CD80 on iDCs. On the other hand MVA caused an upregulation of HLA-DR on monocytes and additionally a slight upregulation of CD40 on iDCs. Moreover, MVA evoked a slight upregulation of CD83 on iDCs but a slight downregulation on mDCs. Above all, we could demonstrate that MVA induces an upregulation of CXCL10 in iDCs, mDCs, monocytes, and B cells, and an upregulation of TNFα, IL-6, and IL-12p70 in iDCs, mDCs, and monocytes. In addition, we revealed a downregulation of CXCL8 in monocytes as well as of IL-β in B cells.

Conclusions
These results suggest that MVA induces a Th1-polarized immune response in APCs. Thus, MVA seems to be an appropriate vaccine vector for antiviral immunotherapy of stem cell transplant recipients.

Disclosures:
No relevant conflicts of interest to declare.
Analysis of Risk Factors for Overall Survival at 5 Years in 96 Patients after Allogeneic Hematopoietic Cell Transplantation.
Authors: Ding Jiahua , Ding Jiahua 
Published: October 2019

Abstract
Abstract 4669
The aim was to analyze the risk factors for overall surrival at 5 years in 96 patients undergoing allogeneic hematopoietic stem cell transplantation by retrospec- tive analysis. 11 clinical parameters were selected for univariate analysis by using a Cox regression: age, sex, morbid rate, HLA locus, donor type, donor-recipient blood type, conditioning regimen, aGVHD, HC, VOD and IP. Factors significant at the 0.1 level on univariate analysis were evaluated by multivariate analysis by a Cox regres- sion. The cumulative incidence of aGVHD and patients survival rate were calculated by the method of Kaplan and Meier. 95 patients achieved sustained donor engraftment except one patients not. The median time of leukocyte engraftment was 13 days. The incidence rates of grades I∼IV acute GVHD was 43.75%.one of grades I aGVHD was 11.46%,gradesIIaGVHD was 19.79%,grades III∼‡WaGVHD was 12.50%. Ten patients relapsed and 38 dead,the overall survival at 5 years was 60.42%. The COX method analysis showed that aGVHD and disease states at transplant significantly im- proved OS. In conclusions, The key to improve the outcome of allo-HSCT is to red- uce the incidence and severity of aGVHD, meanwhile selecting the suitable disease state of CR1 at transplantation to treat the patients in advanced refractory and recure- nt situation.

Disclosures:
No relevant conflicts of interest to declare.
Mesenchimal Stroma Cells From Patients with Myelodysplastic Syndrome and Acute Myeloid Leukemia Show Distinct Cytogenetic and DNA-Mutation Data as Compared with Bone Marrow Leukemic Blasts.
Authors: Blau Olga , Hofmann Wolf-Karsten , Baldus Claudia D , Thiel Gundula , Nolte Florian , Schuemann Elke , Benlasfer Ouidad , Sindram Annette , Thiel Eckhard , Blau Igor W. 
Published: October 2019

Abstract
Abstract 4697
Bone marrow mesenchymal stroma cells (BMSC) are key components of the hematopoietic microenvironment. BMSC from patients with acute myeloid leukemia (AML) and myelodisplasic syndrome (MDS) display functional and quantitative alterations. To gain insight into these questions, we carried out cytogenetic analyses, FISH, FLT3 and NPM1 mutation examinations of both hematopoietic (HC) and BMSC derived from 53 AML and 54 MDS patients and 35 healthy donors after in vitro culture expansion. Clonal chromosomal aberrations were detectable in BMSC of 12% of patients. Using FISH we have assume that cytogenetic markers in BMSC were always distinct as the aberrations in HC from the same individual. 17% and 12% of AML patients showed FLT3 and NPM1 mutations in HC, respectively. In BMSC, we could not detect mutations of NPM1 and FLT3, independent from the mutation status of HC. For control analysis, BMSC cultures from 35 healthy donors were prepared under the same conditions. BMSC from healthy donors did show normal diploid karyotypes and absence of specific DNA-mutations of NPM1 and FLT3.
Our data indicate that BMSC from MDS and AML patients are not a part of malignant clone and characterized by genetic aberrations. Lack of aberrations as detected in HC and appearance of novel clonal rearrangements in BMSC may suggest enhanced genetic susceptibility and potential involvement of BMSC in the pathogenesis of MDS and AML.

Disclosures:
No relevant conflicts of interest to declare.
High Progenitor Cell Frequency at Diagnosis Predicts High Minimal residual Disease Level in Childhood ALL.
Authors: Ebinger Martin , Witte Kai , Lang Peter J. , Handgretinger Rupert 
Published: October 2019

Abstract
Abstract 4705
Acute lymphoblastic leukemia (ALL) as the most frequent childhood malignancy exhibits a favorable prognosis, yet a significant proportion of patients suffer a relapse. Comparable to acute myeloblastic leukemia, immature leukemic cells may be resistant to therapy and initiate a new population of leukemic cells. 42 patients with childhood ALL treated according to the ALL-BFM 2000 protocol were included in the present study. We determined an aberrant immunophenotype of the leukemic population at diagnosis and investigated the expression of CD34, CD38 and CD45 in leukemic blasts. The fraction of immature leukemic cells defined by CD34+/CD38-/CD45low at time of diagnosis as well as level of minimal residual disease (MRD) at day 33 and day 80 was determined. This is the first study to show a significant correlation of the initial fraction of immature leukemic cells with minimal residual disease levels at day 33 and day 80 in childhood ALL. Thus the initial level of this CD34+/CD38-/CD45low population may serve as marker for adverse prognosis in pediatric ALL.

Disclosures:
No relevant conflicts of interest to declare.
The Serum Fas and Fas Ligand levels in Childhood Acute Leukemias.
Authors: Kiziltas Alev , Antmen Bulent , Sasmaz Ilgen , Kilinc Yurdanur , Yilmaz Mustafa , Yigin Akin 
Published: October 2019

Abstract
Abstract 4724

Aim
Abnormalities and alterations in apoptosis mechanism may lead to cancer development. Cystean proteases enzymes, called caspases, appear to be involved in both the initial signaling events. There are many proteins that trigger intrinsic and extrinsic pathway and induce apoptosis signals. Fas and its specific ligand that known as Fas Ligand are the best defined dead receptors and have functions in apoptosis regulation with many tumor types. Fas binds the ligand on the cytotoxic T cells and start apoptosis. Objectives of this study were to determine serum levels of Fas and Fas Ligand at the time of diagnosis in childhood acute leukemias that may be play important role in apoptosis mechanism.

Patients and Methods
In this study, we investigated serum Fas and Fas Ligand levels by using ELISA method in childhood acute leukemias. Twenty-nine cases with acute lymphoblastic leukemia and twenty-three cases with acute myeloblastic leukemia at the ages of 1-18 years are included this study. The age distrubition of the control group varied 1-15 years consisted of twenty-seven children. We investigated serum Fas and Fas Ligand levels at the time of diagnosis from peripheral blood samples.

Results
The comparison of the mean values of Fas and Fas Ligand levels in acute leukemia patients groups and control group have shown important difference as statistically (p<0,05). The mean values of Fas and Fas Ligand levels were higher in ALL and AML patients. The comparison of the mean values of Fas and Fas ligand levels in ALL and AML patients have shown no difference (p>0,05). The comparison of the Fas levels in ALL patients according to immunophenotypes; CALLA(+) B-ALL have higher mean level than T-ALL and shown important difference as statistically (p<0,05). The comparison of the mean values of Fas level at the diagnosis in ALL patients who had relapsed and patients who had remission have shown important difference (p<0,05). The mean values of Fas level were found higher in relapsed ALL patients. In these results showed that Fas and Fas ligand may play important role in apoptosis mechanism.

Disclosures:
No relevant conflicts of interest to declare.