bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Model of Care: A Combined Pediatric/ Adult Thrombosis and Hemostasis (PATH) Clinic – One Center's Experience.
Authors: Richardson Matthew W , Steingart Richard H 
Published: October 2019

Abstract
Abstract 4553

Background
Patients of all ages with thrombosis are frequently tested for heritable thrombophilias (HT). Similarly, patients with bleeding or bruising may be tested for heritable bleeding (HB) conditions. We developed the Pediatric/Adult Thrombosis & Hemostasis (PATH) Clinic, a once-monthly clinic where children, adults and their families in whom the diagnosis of HT or HB was established or being considered could be assessed simultaneously by a pediatric and “adult” hematologist. Reasons for the clinic's creation included 1. HT/ HB conditions are lifelong. A combined clinic aids transition from a pediatric provider to an internist at the same institution. 2. Adolescence is when many HT/ HB disorders manifest themselves. This group has medical and developmental traits that cross pediatric and internal medicine approaches and expertise. 3. Adult experience. Much treatment for pediatric thromboses is extrapolated from adult data. An adult hematologist present at the evaluation of a pediatric patient with HT provides a valuable resource for the child and pediatric hematologist. 4. The finding of HT or HB in a patient has implications for family members regardless of age. 5. Convenience. All family members can be evaluated at a single visit where several members might need screening.

Objective
To review the experience of a combined pediatric/adult clinic created to evaluate potential HT/ HB in patients of all ages.

Method
IRB-approved chart review.

Results
92 patients have been evaluated (61 for HT, 31 HB). Mean age 18 yr., median 16 yr. Female 64%. The most common reason for referral was evaluation of HT in an asymptomatic patient (42%) because of a family member having had a thrombosis or recent diagnosis of HT. Those evaluated for potential HT were less likely to be symptomatic (i.e. had not experienced a thrombosis) than those with HB (31% vs. 65%, p < 0.01). Adolescents (13–21 yr old) comprised 52% of all patients (57% of all females). Adolescents were more likely to be referred for HT than other ages (75% vs. 56%, p < 0.01).

Conclusions
The model of the PATH clinic – simultaneous evaluation of patients of all ages with or suspicion for HT/ HB by a pediatric and “adult” hematologist – may be useful to other centers. Adolescents (in transition from the pediatric to adult age group) comprised the single largest cohort, emphasizing the potential importance of a combined approach. Adolescent women were especially represented, likely due to the new potential for bleeding (menarche) leading to a diagnosis of an HB and the emergence of acquired thrombophilic risk factors (estrogen contraception and pregnancy) in this group that have implications in families with HT. Physicians in such a clinic should have particular knowledge of bleeding and thrombophilic conditions in adolescent women and of counseling for asymptomatic HT.

Disclosures:
No relevant conflicts of interest to declare.
During Terminal Differentiation, HbF-Inducing Cytokines Cause Decreased Expression and Reduced Globin Locus Occupancy of BCL11A in Human Erythroblasts.
Authors: Sripichai Orapan , Kiefer Christine M. , Lee Y. Terry , Meier Emily Riehm , Byrnes Colleen , Dean Ann , Miller Jeffery L. 
Published: October 2019

Abstract
Abstract 457
Genetic association studies and gene regulation studies demonstrate that the transcription factor BCL11A is a regulator of fetal hemoglobin (HbF) expression in humans. Cytokine signal transduction also regulates fetal hemoglobin expression in cultured adult human erythroblasts. To further explore the potential for BCL11A in the cytokine-mediated induction of HbF during adult erythropoiesis, transcript and protein expression levels of BCL11A were measured during erythroblast differentiation. BCL11A expression was detected at all stages of erythroid differentiation with the highest level expression in proerythroblasts during the first week in culture under both low-HbF (%HbF ≤3) and high-HbF (%HbF ≥30) culture conditions. Despite a reduction in BCL11A mRNA expression, Western analyses failed to demonstrate reduced levels of BCL11A nuclear protein expression at the proerythroblast stage of differentiation. However, BCL11A protein expression in the high-HbF producing cells was reduced relative to the low-HbF cells during the later period of culture as the cells underwent terminal differentiation. During this later culture period, hemoglobinization occurred, and cells grown in the high-HbF condition revealed a pancellular distribution of HbF compared with a heterocellular distribution in the low-HbF culture condition. Chromatin immunoprecipitation further demonstrated that the addition of HbF-inducing cytokines caused a nearly complete loss of BCL11A chromatin occupancy within the beta-globin locus under the high-HbF culture condition. Specifically, the loss of chromatin occupancy was detected in a region approximately 3 kb downstream of the (A)gamma-globin gene. Further examination of this genomic region demonstrated several BCL11A binding domains located on a cluster of non-coding, intronless RNAs previously named “BGL3” that possess an expression pattern in vivo that is largely restricted to the fetal-liver. In addition to increased and pancellular expression of fetal hemoglobin in the high-HbF erythroblasts, the loss of BCL11A chromatin occupancy in that region of the beta-globin locus was associated with increased expression of BGL3 mRNA (GenBank: AY034471) measured by RT-PCR. These findings demonstrate that defined combinations of cytokines regulate the expression level and chromatin occupancy of BCL11A in adult human erythroblasts as they undergo terminal differentiation. In addition to inheritance and ontogeny, the data also support a role for BCL11A in the regulation of HbF by cytokine signal transduction.

Disclosures:
No relevant conflicts of interest to declare.
Biological Characteristics of Bone Marrow-Derived Mesenchymal Stem Cells From a Patient with β-Thalassemia.
Authors: Yoon Jinsun , Song Sung Heon , Kim Seoju , Kim Eun Shil , Kong Gu , Kim Byung-Kook , Lee Young 
Published: October 2019

Abstract
Abstract 4579
Thalassemia syndromes are considered as a heterogeneous group of inherited anemias leading to decrease or loss of synthesis of one or more globin chain subunits of the adult hemoglobin tetramer (Hb A). Beta-thalassemia results from a decrease in β-chain production of hemoglobin relative to alpha-chain production. Hematopoietic stem cell transplantation from HLA-identical siblings is curative for thalassemia syndrome. Bone marrow (BM)-derived mesenchymal stem cells (MSCs) are primitive, undifferentiated cells which are capable of self-renewal, and differentiating morphologically and functionally into different cell lineages including adipocytes, chondrocytes, myocytes, astrocytes, tenocytes, and hepatocytes. There have been contrasting data on whether BM derived MSCs are altered in various hematological disorders including leukemia, multiple myeloma, and myelodysplastic syndrome as well as autoimmune disease. To date, functional characterization of MSCs has never been performed in thalassemia syndrome. In the present study, we isolated BM-derivied MSCs from a patient with β-thalassemia in order to compare phenotypic and functional characteristics to those from normal healthy donor. No differences were observed between MSCs from β-thalassemia and those from normal healthy donor in terms of morphology, phenotype, karyotype, multi-differentiation capacity. In mitogen-stimulated T cell proliferation assay and mixed lymphocyte reaction, MSCs from β-thalassemia strongly inhibited the proliferation of allogeneic T cells in association with reduced proportion of CD3+, CD4+ and CD8+ cells. Furthermore, the fraction of CD4+CD25+Foxp3+ cells (Treg cells) was increased under the culture with MSCs from β-thalassemia, suggesting that MSCs from β-thalassemia exerts normal immunomodulatory function. In addition, β-thalassemia-derived MSCs expressed hematopoietic cytokines and supported hematopoiesis which were comparable to those from normal BM-dereived MSCs. In summary, β-thalassemia-derived MSCs exhibited normal phenotype, karyotype as well as normal immunomodulatory function, and autologous MSCs from patients with β-thalassemia may be an attractive source of stem cell in terms of hematopoietic support as well as immunomodulatory activity.

Disclosures:
No relevant conflicts of interest to declare.
Lentiviral Short Hairpin RNA Silencing of DNM3Decreases Megakaryoycte Progenitor Proliferation and Inhibits the Formation of the Demarcation Membrane System.
Authors: Reems Jo Anna , Wang Wenjing , Sijie Sun , Wu Xiaoping , Gilligan Diana M. 
Published: October 2019

Abstract
Abstract 4594
Dynamin 3 (DNM3) is a mechanochemical enzyme, which participates in membrane dynamics by hydrolyzing nucleotides to link cell membranes to the actin cytoskeleton. Recently, we identified DNM3 to be differentially up-regulated during megakaryocyte (MK) development and reported that DNM3 participates in the proliferation of MK progenitors. We report here that dynamin 3 not only participates in MK progenitor amplification, but is also involved in the formation of the demarcation membrane system (DMS). To explore the role of dynamin 3 during MK development, we used three different lentiviral DNM3 shRNA constructs to infect human umbilical cord blood (UCB) CD34+ cells that were then cultured to differentiate along the MK lineage. Relative to controls, CD34+ cells transfected with DNM3 shRNAs significantly decreased the total number of cells produced in culture as well as the number of colony forming unit-megakaryocytes (CFU-MKs). As a result, the total number of CD41+ and CD61+ progeny cells was also reduced. To investigate the role dynamin 3 plays during the maturation of MKs, a Src family kinase inhibitor, SU6656, was used to induce high polyploidization and the development of a complex DMS in the UT-7/mpl cell line. The styryl membrane dye di-8-ANEPPS was used to monitor the formation of the DMS. In the absence of SU6656 treatment, UT-7/mpl cells showed a peripheral staining pattern that was indicative of cells that did not have extensive plasma membrane invaginations. In contrast, the staining pattern of UT-7/mpl cells treated with SU6656 clearly showed a well-developed plasma membrane system with invaginations. When DNM3 was silenced in SU6656 treated UT-7/mpl cells the results showed a significant reduction in di-8-ANEPPS staining relative to empty vector and non-specific negative controls. These findings are consistent with the conclusion that dynamin 3 participates in the morphogenesis of the DMS.

Disclosures:
No relevant conflicts of interest to declare.
Demographic and Socio-Economic Features of a Cohort of Adult Sickle Cell Disease Patients.
Authors: Haider Syed N , Tang Jun , Osarogiagbon Raymond U. 
Published: October 2019

Abstract
Abstract 4616

Introduction
Despite improvements in diagnosis, preventive care and treatment, care of sickle cell disease (SCD) patients remains difficult. The majority are from lower socio-economic strata, poorly educated and from single parent households. The racial divide between patients (who tend to be almost all black) and their health care providers (who tend to be predominantly non black) can adversely affect the quality of care when stereotypes are assumed. We examined the demographic and socio-economic features of patients in our adult sickle cell disease program.

Patients and Methods
We retrospectively reviewed data on 118 patients that entered our program between February 2005 and October 2008. Our catchment area included parts of rural Mississippi, Tennessee and Arkansas as well as a major urban community. We reviewed the following demographic characteristics: age, gender, patient's marital status, parent's marital status, employment status, highest level of education, health insurance status and referral source. We then contrasted the characteristics of those with SC (which tends to be milder) with SS/Sβ0 sickle cell disease (which is phenotypically more severe). Continuous variables were evaluated using t-test. Chi-square test was used to assess categorical variables.

Results
The results are depicted in the table.

Conclusions
We describe the demographic and socio-economic features of a cohort of 118 patients seen in an academic center with a diverse catchment area. In spite of adverse family circumstances, relatively high proportion of the cohort was college educated (32%) or graduated from high school/GED (55%). 61% of the patients are either currently employed or current students. These results are quite contrasting to the general perception about the adult sickle cell disease population.

Disclosures:
No relevant conflicts of interest to declare.
Non Transferrin Bound Labile Plasma Iron and Iron Overload in Sickle Cell Disease: a Comparative Study Between Sickle Cell Disease and β Thalassemic Patients.
Authors: Koren Ariel , Fink Daniel , Admoni Osnat , Tennenbaum-Rakover Yardena , Levin Carina 
Published: October 2019

Abstract
Abstract 4625

BACKGROUND
Blood transfusions are the standard of care in β thalassemia and transfusions are also indicated in Sickle Cell Disease (SCD) patients with hypersplenism, recurrent vaso-occlusive crises and for stroke prevention. Iron overload caused by blood transfusions in thalassemia and in SCD may affect morbidity and mortality. Recent studies of iron overload in SCD suggest that the biologic features of SCD and the chronic inflammatory state may protect SCD patients from iron damage.

DESIGNS AND METHODS
In view of the controversy regarding the effect of iron overload in patients with SCD we studied the iron status, including non transferrin bound iron (NTBI) and labile plasma iron (LPI) levels in a cohort of thirty six SCD patients and compare the results with 43 thalassemia patients.

RESULTS
Our results indicate that none of the SCD patients had clinical symptoms of iron overload. Only two SCD patients had NTBI values in the grey zone (0.4 units) and none had positive values. By contrast, 14 patients with Thalassemia Major and 3 with Thalassemia Intermedia had NTBI values above 0.6, level that are in the positive pathological range. Similarly, four thalassemia patients, but only one SCD patient had positive LPI levels.

CONCLUSIONS
The parameters of iron status in SCD patients, even after frequent transfusions are different when compared to patients with thalassemia. The low NTBI and LPI levels found in patients with SCD are in keeping with the absence of clinical signs of iron overload in this disease.

Disclosures:
Koren: Novartis Oncology: Research Funding. Levin:Novartis Oncology: Research Funding.
Lack of Sustained Benefit of Red Cell Exchange in Patients with Sickling Hemoglobinopathies and Coexisting Warm Autoantibody Hemolysis.
Authors: Baron Beverly , Baron Joseph M. 
Published: October 2019

Abstract
Abstract 4626

Introduction
Red cell exchange (RCE) can be beneficial in the management of patients (pts) with sickling hemoglobinopathies by rapidly reducing hemoglobin (Hb) S levels and raising Hb A levels, thereby decreasing hemolysis and improving organ perfusion. We present 2 pts with sickle beta+ thalassemia (SBT) whose clinical courses were complicated by coexisting warm autoantibody hemolysis and prolonged refractory pain. They had less benefit from RCE than expected due to rapid rebound of Hb S levels and decline in Hb A levels within 48 to 72 hrs after RCE. Each subsequently improved with immunosuppressive therapy.

Case Reports
We report 2 African American female pts with SBT who presented with severe anemia, high absolute reticulocyte counts (arc), evident hemolysis, and lack of sustained response of their Hb levels to red cell transfusions. Each had multiple alloantibodies and warm autoantibodies. Patient 1 (see Fig. A), age 34 years, presented with anemia (initial Hb 7.5 g/dL), arc 267 K/μL, and total serum bilirubin (bili) 4.3 mg/dL. Between hospital days 5 and 8, she received 8 units of compatible red cells, but her Hb the next day was only 5.7 g/dL. She then underwent a 5 unit RCE (starting Hb S was 79.3%, Hb A was 14%). Hb S fell to 60.6% the next day; Hb A rose to 33%. Three days post RCE, arc was 854 K/μL, Hb S rose to 68.5%, and Hb A fell to 24.8%. Subsequently intravenous immune globulin (IVIG) was given (48 g per day for 3 days). Her Hb stabilized, began to rise, and she experienced clinical improvement. Patient 2 (see Fig. B), age 36 years, also presented with anemia (Hb 6.8 g/dL), arc 694 K/μL, and bili 2.7 mg/dL. Over the first 10 hospital days she received 3 units of red cells. She was on prednisone (5 mg daily) maintenance for warm autoantibody (IgG) hemolysis. On day 13 a 4 unit RCE was performed. Pre-RCE Hb S was 61.9%, Hb A was 26.9%. Post RCE Hb S was 40.5%, Hb A 50.9%, but 48 hrs post RCE, Hb S level had risen to 52.8% and Hb A fell to 38.8%. Arc was 843 K/μl; Hb was 6.3 g/dL. Prednisone dose was increased to 100 mg per day, and IVIG (2 gm total per kg body weight) was given. Her Hb stabilized and she improved clinically.

Conclusions
Lack of sustained benefit from RCE in these pts likely resulted from 2 factors: (1) high reticulocyte counts, leading to rapid replacement of Hb S cells; and (2) shortened survival of Hb A cells, secondary to their destruction by the warm autoantibodies. Immunosuppressive therapy targeted to the autoimmune component of the anemia provided substantial clinical benefit.

Disclosures:
No relevant conflicts of interest to declare.
Human Germinal Center-Associated Lymphoma (HGAL) Protein Expression Is Associated with Improved Failure-Free Survival in Brazilian Patients with Classical Hodgkin Lymphoma.
Authors: Azambuja Denize , Lossos Izidore , Biasoli Irene , Morais José Carlos , Britto Luciana , Scheliga Adriana , Pulcheri Wolmar , Natkunam Yaso , Spector Nelson 
Published: October 2019

Abstract
Abstract 4632

BACKGROUND
The HGAL gene has prognostic value in diffuse large B-cell lymphoma and expression of its cognate protein is germinal center–specific. A previous study had suggested that HGAL protein expression might also be related to outcome in patients with Hodgkin lymphoma.

PATIENTS AND METHODS
The aim of the current study was to confirm the prognostic impact of HGAL protein expression in an independent, well-characterized cohort of 232 classic Hodgkin lymphoma patients treated uniformly with the ABVD regimen from 1997 to 2004 in Brazil. The median follow-up was 6.2 years.

RESULTS
Tissue microarray analysis showed HGAL staining in 188 specimens (81%). The overall survival was better in patients with young age, early-stage, absence of B symptoms, low-risk international prognostic score (IPS) and good performance status. Failure-free survival was superior in patients with early-stage disease, low-risk IPS and HGAL-positive patients. The estimated 5-year failure-free survival for HGAL-positive and HGAL-negative patients was 82% and 67%, respectively (P=0.03). When stage, B symptoms and performance status were included along with HGAL in a multivariate analysis, advanced stage and absence of HGAL staining were independent predictors of a worse failure-free survival.

CONCLUSION
This study confirms and validates recent findings of a correlation between HGAL expression and outcome in classical Hodgkin lymphoma.

Disclosures:
No relevant conflicts of interest to declare.
BK-Viruria and Hemorrhagic Cystitis – a Retrospective Analysis of a Patient Cohort After Allogeneic Bone Marrow Transplantation for Hematological Malignancies.
Authors: Ostermann Helmut , Rieger Christina T , Peterson Lisa 
Published: October 2019

Abstract
Abstract 4657

Background
BK-virus-associated hemorrhagic cystitis is a major issue among patients with hematologic malignancies after allogeneic bone marrow transplantation and associated with significant morbidity and mortality. Risk factors for its development are still poorly understood and sufficient data lacking. This is a retrospective analysis of all patients with viruria after allogeneic BMT of the years 2007-2008 transplanted at the centre for BMT of the University of Munich.

Methods
All patients displaying at least one event of viruria in the period of January 2007 until December 2008 were included in this analysis. We recorded demographic factors, transplantation setting, clinical manifestation of HC, conditioning regimens, GvHD, immunosuppression and relevant co-infections.

Results
56 patients (39 ‰/ 17 š) with median age of 48,5 years were recorded. Underlying diseases were AML (31 pts. / 55,3%), ALL (8 pts./14,2%), CLL (2 pts./ 3,5%), malignant lymphoma (5 pts./ 8,9%), multiple myeloma (4 pts./ 7,1%) and other hematological malignancies (6 pts./ 10,7%). 18 patients were transplanted from a related, 38 from an unrelated donor, two of those from cord blood. 29 patients (51.8%) were registered alive at the time of data collection, 23 patients (41%) were recorded deceased, 4 patients (7,1%) could not be tracked.
The concomitant or preceeding incidence of GvHD received a special interest in our analysis. Notably, 47 pts. (84%) showed clinically apparent manifestation of GvHD, only 9 pts. (16%) displayed no sign of GvHD. Of these, 22 pts. (39%) developed an overall grade III (severe) and grade IV (life-threatening) GvHD. Furthermore, 27 pts. (48%) developed a grade III GvHD and 11 pts. (19,6%) a grade IV GvHD of a single organ, giving an overall of 67,6% of grade III or IV single organ-GvHD in this patient collective. The organ system most affected was the skin, 47pts. (84%), followed by the gut, 21 pts. (37,5%), the liver, 10 pts. (17,8%) and other organ systems 4 pts. (7,1%).

Conclusion
BK-viruria is a frequent event among patients with bone marrow transplantation for hematological malignancies. Among our patient collective, we observed a high incidence of high grade GvHD. Whether there is an independent risk factor for both or there is a causative link between these two events is not clear. However, our retrospective analysis represents one of the largest data collections regarding BK-virus-infections in allogeneic BMT patients so far and further studies are required.

Disclosures:
No relevant conflicts of interest to declare.