bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of Mortality in Neutropenic Enterocolitis Among Children and Young Adults with Acute Myeloid Leukemia in Low Middle Income Countries
Authors: Khedr Reham , Abdel Waged Mohamed , Fathy Marwa , Zekri Wael 
Published: October 2019

Abstract
Background: Neutropenic enterocolitis (NEC) is a life-threatening disease with substantial morbidity and mortality, seen primarily in patients with hematologic malignancies. The frequency of NEC has increased with the widespread use of chemotherapeutic agents such as the taxanes, which cause severe gastrointestinal mucositis. Methods: This was a retrospective study at the National Cancer Institute, Cairo University. The computerized records were screened for ultrasound or computerized tomographic scan requests for abdominal pain for all Acute myeloid pediatrics inpatients (2012-2016). Retrospective case analysis was used to collect clinical data for patients with features of NEC. D 30 Mortality was reported. Results: The incidence of NEC among our inpatients was 24% (49/203). Forty-Three children had radiologically confirmed Typhlitis, and 6 had clinical features alone. Most (93%) patients were profoundly neutropenic (ANC less than 100). All of the patients received conservative management. All of them needed ICU admission. Eighteen children had a variable period of bowel rest, including 12 patients who were supported with total parenteral nutrition. Three patients had laparotomy that revealed extensive colonic bowel necrosis (1), perforated bowel loop (1), and a perforated appendix (1). Two out of three cases of Laparotomy were diagnosed with Mucormycosis. 30-Days mortality was 44.8% (22/49). Relapsing Typhlitis in subsequent courses was observed in 6/27 (22%) patients. Fulminant gram-negative sepsis without surgical intervention was the leading cause of death in this cohort. NEC related mortality was significantly higher among patients receiving high-risk protocol with more intensive chemotherapy and in patients with other Co-Morbidities [chest infections and/ or Cardiac affection] with a P-value of 0.005 and 0.037 respectively. Also, mortality was increased among patients with more than 2 presenting clinical symptoms with a P-value of 0.01. Conclusion: Although surgical intervention should be reserved for specific complications, its delay increases the incidence of NEC related mortality. Though rare, fungal infection should be suspected especially in cases with worsening signs of typhlitis despite broad antimicrobial coverage. Early management and better supportive care of underlying Co-morbid conditions can decrease NEC related mortality.

Disclosures
No relevant conflicts of interest to declare.
A U.S. Food and Drug Administration Age Based Pooled Analysis of Cytokine Release Syndrome and Neurotoxicity in Subjects with Relapsed/Refractory Lymphoma Treated with Chimeric Antigen Receptor (CAR) T Cell Therapy
Authors: Sharma Poornima , Singh Harpreet , Bouchkouj Najat , Krauss Aviva C. , George Bindu 
Published: October 2019

Abstract
Background: With recent FDA approvals of CAR T cell therapy for the treatment of relapsed/refractory aggressive B cell non-Hodgkin lymphoma, an increasing number of older adults will be treated with this therapy. An improved understanding of the safety of CAR T cell therapy in this population is important to inform clinical decision making for the treatment of older subjects.
Methods: Data from two prospective single arm studies (n=214) of two approved CART cell products for the treatment of relapsed/refractory lymphoma were pooled and analyzed. Rates of cytokine release syndrome (CRS), as well as severity and treatment modalities (oxygen, vasopressor support, tocilizumab and steroids) were pooled and analyzed by age. Selected neuropsychiatric events were pooled and analyzed by age.
Results: Age was balanced between the two studies. The median age of subjects was 58 years (range 22-76 years). Of the 214 total subjects, 24% were 65 years of age and older.
CRS and neurotoxicity were evaluated in the subjects who received treatment with CAR T cell therapy. (Table 1).
*Two studies employed different grading methods for CRS; Lee's criteria (Lee DW et al, Blood 2014) and U Penn criteria (Porter DL et al, Blood 2014)
Conclusions: This exploratory analysis suggests overall similar rates of CRS and grade 2 and higher CRS in subjects less than 65 years as compared to 65 years of age and older. There appears to be an overall higher rate of encephalopathy and grade 3 and higher delirium/encephalopathy in adults 65 years and older compared to less than 65 years of age. The inclusion of greater numbers of patients ≥ 65 years of age in clinical trials will further inform clinicians about the safety and efficacy of CAR T cell therapy in older adults.
Table 1: Adverse Events by Age in subjects treated with CART cell therapy

Disclosures
No relevant conflicts of interest to declare.
Quality Initiative in Clinical Practice: A Single Institution Appraisal of Quality Metrics in the Management of Newly Diagnosed Diffuse Large B-Cell Lymphoma Based on the American Society of Hematology Practice Improvement Module
Authors: Bischin Alina , Aboulafia David M. , Vishnu Prakash , Knopf Kevin , Chen Ruqin 
Published: October 2019

Abstract

ABSTRACT
Background: In 2014, the American Society of Hematology (ASH) established a practice improvement module (PIM) incorporating quality metrics for management of diffuse large B cell lymphoma (DLBCL). Such PIMs have allowed physicians to monitor the quality of care in their practice. We implemented a DLBCL quality improvement initiative (QII) at our institution in January, 2015. In an appraisal of this initiative, we reviewed the ASH PIM metrics and included several others to assess adherence to guidelines for treatment of DLBCL and to examine the need for institutional improvement.
Methods: Patients who were newly diagnosed with DLBCL and received treatment at our institution from January 2006 through December 2017 were identified. Electronic medical records were reviewed for documentation of ASH PIM quality measures (e.g., key pathologic features of DLBCL, lymphoma staging, screening for hepatitis B virus (HBV) infection in patients receiving rituximab-based chemotherapy, etc). We also reviewed the proportion of patients who had assessment of prognosis by revised International Prognostic Index (r-IPI) score, testing for hepatitis C (HCV), HIV viral infections, chemotherapy education, and the addition of rituximab in the treatment regimen of CD20+ DLBCL.
Results: Following implementation of the QII, our institution saw improvement in most quality metrics. Particularly significant were improvements in reporting of key molecular features (45.45% to 91.6%, P < 0.0001), screening for HBV (41.82% to 91.67%, P < 0.001) and HIV infections (33.94% to 87.5%, P < 0.0001). All patients post-QII had a PET-CT scan for staging of DLBCL and there was a significantly lower use of bone marrow biopsy (61.2% to 33.33%, P = 0.011).
Conclusion: Implementation of a quality initiative and employing standardized metrics can aid in improving institutional quality of care for patients with newly diagnosed DLBCL, and allows opportunity to build and ensure better adherence to evolving national and professional patient care guidelines.
Figure. Figure.

Disclosures
No relevant conflicts of interest to declare.
Human Treg Can Suppress Th17 Inflammatory Cytokine Secretion Independent of IL-2 Deprivation
Authors: Adair Patrick , Parvathaneni Kalpana , Kim Yong Chan , Scott David W. 
Published: October 2019

Abstract
Human Th17 cells are an inflammatory subset of CD4+ (CD4) T helper cells implicated in host of debilitating diseases and disorders such as multiple Sclerosis, rheumatoid arthritis, and psoriasis, as well as inhibitor formation in Hemophilia A. Although it is well established that regulatory CD4T cells (Tregs) can suppress other T helper (Th) effector cells (e.g. Th1, Th2, etc), their ability to suppress human Th17 cells is unresolved. This is attributed to several factors including plasticity between Treg and Th17 cells, the observation that Th17 cells express less IL-2 (and by extension are less dependent on IL-2) than other Th effector cells and consequently are less susceptible to Treg suppression via IL-2 deprivation. Using autologous naïve Tregs and effector memory CCR6+ CD4 T cells differentiated to Th17 cells from healthy human donor peripheral blood mononuclear cells, we performed a kinetic analysis of the IL-2 sensitivity via phosphorylated STAT5 expression. We show that Treg and Th17 cells have similar rates of pSTAT5 expression in vitro. We also show that both cell types have similar expression levels of the high affinity IL-2a receptor, CD25, following activation. Despite this, naïve Tregs successfully abrogated the secretion of IL17A by Th17 cells following 12hr co-culture. Furthermore, this abrogation is dependent on the strength of Treg activation and does not involve cytotoxic mechanisms, as viability of the Th17 cells remain high. These results suggest that human Tregs can suppress inflammatory IL-17A secretion from effector memory Th17 cells via mechanisms independent of IL-2 deprivation but dependent on strength of activation through Treg T-cell receptor. (Supported by NIH grant R01 HL126727)

Disclosures
No relevant conflicts of interest to declare.
The Comparison of Melphalan Administration on Day 3 with Administration on Day 1 on Neutrophil and Platelet Engraftment in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation
Authors: Unal Ali , Kaynar Leylagül , Yıldızhan Esra , Keni Nermin , Güven Zeynep , Eser Bulent , Cetin Mustafa 
Published: October 2019

Abstract
Objective: High dose chemotherapy followed by ASCT is the most important step of MM treatment. Melphalan, an alkylating agent, is the most preferable drug for conditioning regimens and dosage and timing is important with regards to side effects or engraftment timing. Engraftment time is determinative on infections and hospitalization duration.
Methods: We compared the neutrophil and thrombocyte engraftments retrospectively in patients with multiple myeloma who received melphalan 200 mg/m2 single dose on day -3 and day -1 as conditioning regimen. There were 29 patient receiving melphalan on day -1 and 42 patient on day -3.
Results: The mean neutrophil engraftment times for day -1 group and day -3 group were 12,8 ±2.4 days and 10,4±1.3 days, respectively (p < 0,001). The mean thrombocyte engraftment times for day -1 group and day -3 group were 13,48 ±3,7 days and 12,7±3,3 days, respectively (p :0,36). In day -3 group, there was no failure neither in neutrophil nor in thrombocyte engraftment but 1 patient could just get thrombocyte engraftment on day 33. In day -1 group, 2 patients could not get engraftment failure.
Conclusion: Administration of melphalan on day -3 is better than on day -1 in terms of neutrophil engraftment and hence in terms of hospitalisation duration.

Disclosures
No relevant conflicts of interest to declare.
Demographics and Survival in Primary Effusion Lymphoma: SEER Database Analysis
Authors: Khoury John , Willner Christopher Allen , Gbadamosi Bolanle , Gaikazian Susanna , Jaiyesimi Ishmael 
Published: October 2019

Abstract
Background: Primary effusion lymphoma (PEL) is one of the least common of the AIDS-related lymphomas, accounting for less than 4% of cases. The optimal treatment for primary effusion lymphoma (PEL) remains unclear and there is a paucity of data regarding this neoplasm, which carries a uniformly poor prognosis. Antiretroviral therapy in addition to chemotherapy has shown to improve survival in a few small retrospective studies.
Methods: Between 2002 and 2014, all cases of PEL were extracted from the population-based cancer registries of the Surveillance Epidemiology and End Results program (SEER). Instances of PEL were identified with the ICD-O-3 (9678) histological code. Frequency, demographics, and survival data were assessed using SPSS statistical software.
Results: A total of 117 cases of PEL were identified. PEL was significantly more prevalent in men (89.7%) and in Caucasians (77.8%) with median age at diagnosis of 49 years. Median overall survival in the entire cohort was 6 months; CI, 3.7 to 8.2 months. Of all PEL cases, 62.4% received chemotherapy and 37.6% did not. Those who received chemotherapy had a median overall survival of 10 months vs less than one month when compared to subjects who did not receive chemotherapy (p = 0.002). PEL was the cause of death in 40.2% of the cases. PEL-specific median overall survival was markedly higher (29.000 months) than that of the entire cohort. Multivariable analysis demonstrated that age and race were not associated with mortality. Chemotherapy was associated with decreased mortality risk (HR, 0.45; CI, 0.28 -0.74; p = 0.002)
Conclusions: In confirmation of previously published data, the highest incidence of PEL was found in Caucasian males. Subjects who received chemotherapy were found to have improved overall survival outcome. Other factors not related to PEL were associated with early mortality in this population.

Disclosures
No relevant conflicts of interest to declare.
Academic Centers Are Associated with Improved Survival Outcomes in High Risk Diffuse Large B-Cell Lymphoma Patients
Authors: Ermann Daniel A. , Noble Victoria Vardell , Kallam Avyakta , Armitage James O. 
Published: October 2019

Abstract
Background:
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, and is characterized as a heterogenous disease associated with varying outcomes. The International Prognostic Index (IPI) has been the standard for baseline prognostic assessment in these patients. In this study we aimed to determine the impact of treatment facility (academic versus non-academic centers) on overall survival outcomes in DLBCL patients stratified by IPI score risk groups, with a focus on high risk disease as this is associated with poorer outcomes.
Methods:
The 2018 National Cancer Database (NCDB) was utilized for patients diagnosed with DLBCL between 2004-2015. Patients were then stratified based on IPI risk score from low to high risk. Four risk groups were formed: low (0-1), low-intermediate (2), high-intermediate (3), and high (4-5). Overall survival was calculated using Kaplan-Meyer analysis with bivariate cox proportional hazard ratios to compare survival by facility type (academic or community centers) within these risk groups.
Results:
A total of 160,137 patients were identified. Of these cases 31.8% were classified as low risk, 21.9% were low-intermediate risk, 22.2% were high-intermediate risk, and 24% were high risk. 59.3% of patients were treated at a community center and 40.7% were treated at academic centers. Treatment at academic centers was associated with a significantly improved overall survival (OS) for each risk category. Median survival (in months) for high risk IPI score DLBCL was 47.9 months in community and 61.1 months in academic centers (p<.0001). Median survival for high-intermediate risk score was 48.3 months in community and 87.3 months in academic centers (p<.0001). Median survival for low-intermediate score was 90.3 months in community and 122.8 months in academic centers (p<.0001). Median survival for low risk score was 132 months in community and 148 months in academic centers (p<.0001). Hazard ratios for academic center versus community center for high risk, high-intermediate, low-intermediate and low risk are 0.768, 0.71, 0.848 and 0.818 respectively (p<.0001).
Conclusions:
Facility type is significantly associated with improved survival outcomes across all IPI based risk groups for DLBCL. This benefit is especially significant in higher risk disease where positive outcomes are less common, suggesting treatment at academic centers may be particularly beneficial in these patients. Some of the possible reasons for this difference may include provider experience, increased access to resources, and opportunity for clinical trials. Further investigations into the factors contributing to such disparities should be done to help standardize care and improve outcomes.

Disclosures
No relevant conflicts of interest to declare.
Efficacy and Safety of Hydroxyurea in the Treatment of Sickle Cell Anemia Children in Jos, North Central Nigeria
Authors: Ofakunrin Akinyemi Olugbenga David , Adekola Kehinde U. , Oguche Stephen , Okpe Edache Sylvanus , Sagay Atiene Solomon 
Published: October 2019

Abstract
Introduction: Sickle Cell Anaemia (SCA) is a genetic disorder with significant morbidity and mortality, and Nigeria accounts for the highest burden of the disease worldwide. Hydroxyurea has been shown to positively modify the disease pathogenesis, but its use is low among Nigerian SCA patients because of efficacy and safety concerns. Hence, this study evaluated the efficacy, tolerability and safety of hydroxyurea in Nigerian children with SCA.
Methods: A Quasi-experimental study with a before and after design using hydroxyurea as the intervention in 54 SCA children aged 4-17years, who have had at least two or more painful vaso-occlusive events requiring parenteral analgesia in the previous 12 months.
The number of Vaso-Occlusive Crisis (VOC), Acute Chest Syndrome (ACS), blood transfusions and hospitalisations in the previous 12 months obtained from the subjects' hospital records; and percentage fetal haemoglobin, Packed Cell Volume (PCV), White Blood Cell Counts (WBC) and Platelet Counts at baseline and after 12 months of hydroxyurea therapy were compared.The research participants were observed clinically for tolerability and adverse events of hydroxyurea while haematologic toxicity of hydroxyurea was monitored using complete blood count at specified intervals.
Wilcoxon Signed-Rank Test was used to compare the differences in the median values of the clinical and haematologic parameters at baseline and after 12 months of hydroxyurea therapy and a p-value of < 0.05 was considered statistically significant.
Results: The number of VOCs and hospitalisations reduced from the median baseline values of 3(2-3) and 2(2-3) respectively to 0(0), (p <0.0001). Blood transfusions as well as ACS declined from 48.1% and 11.2% at baseline to 5.6% and 0.0% respectively (p <0.05). The median PCV increased from 26.0(22.0-27.0) % to 28.0(25.8-30.2) % (p <0.0001) while the median WBC reduced from 11.1(7.3-14.6) x 109/L to 6.2(4.8-10.4) x 109/L (p < 0.0001) and the median platelet counts reduced from 411(264-496) x 109/L to 347(251-402) x 109/L (p= 0.009). A dose-dependent and reversible leucopenia was observed among six children (11.1%), otherwise, hydroxyurea was safe and well tolerated in the study population.
Conclusion: These findings suggest that hydroxyurea is efficacious, tolerable and safe in SCA children in Jos, Nigeria. The findings could serve as part of an educational template that could help improve the level of utilisation of hydroxyurea among sickle cell anaemia children in Jos, Nigeria.

Disclosures
No relevant conflicts of interest to declare.
Disparities in Foundation and Federal Support and Development of New Therapeutics for Sickle Cell Disease and Cystic Fibrosis
Authors: Farooq Faheem , Strouse John J 
Published: October 2019

Abstract
BACKGROUND: Sickle cell disease (SCD) and cystic fibrosis (CF) are rare inherited disorders of similar severity. Disparities in funding between these two diseases have been long recognized and likely contribute to limited access to care and treatments for sickle cell disease. Private investment in therapeutics for these and other orphan diseases has greatly increased in the past ten years. We hypothesized that these increased private expenditures may help correct disparities in research publications, clinical trials, and FDA approval of new therapies.
METHODS: We compared funding and research output for SCD and CF between 2008-2012 versus 2013-2017. We estimated disease-specific funding using NIH Research Portfolio Online Reporting Tools and the Form 990 financial reports for foundation expenditures of multiple organizations dedicated to each disease from 2008-2016. We developed a comprehensive search strategy to identify relevant publications in PubMed and new postings of US based interventional clinical trials by disease. In addition, we reviewed FDA drug approvals and new indications for each disease from 2008-2017.
RESULTS: Average annual NIH funding per affected individual was 3.4-fold greater for CF than SCD from 2008 to 2016. Between 2008-2012, private foundation funding was 161-fold greater for CF than SCD. Between 2013-2016, private funding was 971-fold greater for CF than SCD. There were 1.8 times as many PubMed publications for CF compared to SSD. There was no significant difference in PubMed publications between the two time periods. There was a significant increase in interventional clinical trials for SCD between 2013-2017, with the largest increase coming from university/philanthropic funded trials. However, CF has significantly increased FDA drug approvals of both novel compounds and novel indications.
CONCLUSIONS: Although the US prevalence of SCD is three times greater than CF, the amount of federal and private foundation research funding is magnitudes greater for CF. Foundation funding for CF benefited significantly from revenue based on the successful development of targeted therapies. However, despite the significant funding difference, the number of clinical trials for SSD are comparable to CF and have increased over the past few years. Research productivity as measured by articles indexed in PubMed, and new drug approvals remain substantially higher for cystic fibrosis despite greatly increased industry investment in orphan diseases.

Disclosures
Strouse: Global Blood Therapeutics: Consultancy.
Recombinant Activated Coagulation Factor VII (rFVIIa) for Treatment of the Tracheobronchial Bleeding in Mechanically Ventilated (MV) Thrombocytopenic Patients (pts)
Authors: Galstian Gennadii M. , Polevodova Olesya A. , Zorenko Vladimir Yu. , Savchenko Valeriy G. 
Published: October 2019

Abstract
Introduction and Objectives: MV in thrombocytopenic pts could be complicated by life threatening tracheobronchial bleeding. The systemic treatment with tranexamic acid or rFVIIa increases the risk of thromboembolic events. Presented in airspace tissue factor (TF) reacts as a cofactor in augmenting the activity of FVIIa 1000-fold. Topical treatment of the inhalation with rFVIIa has not been studied yet. The aim of the study was to evaluate hemostatic effect of rFVIIa inhalation for treatment of the tracheobronchial bleeding in MV thrombocytopenic pts.
Materials and Methods: The results of rFVIIa inhalation were investigated in 5 acute leukemia pts (2 males, 3 female). All pts were mechanically ventilated through tracheostomy tube and had life threatening tracheobronchial bleeding. Before intervention all pts had low platelet count 50-120х109/l (median 65 х109/l), lowered Quick prothrombin (55-64%, median 58%), prolonged APTT (55-57s).
Results. All pts received rFVIIa as an inhalation over five to ten minutes. For inhalation rFVIIa (Koagil VII, Generium, Russia, Vial of 2.4 mg) was diluted in 10 ml of isotonic saline. If, after 20 min, there is no response to rFVIIa second dose of rFVIIa (2.4 mg) as an inhalation was administrated. Bleeding was stopped in 3/5 pts, in 2 pts the intensity of bleeding decreased. There were no changes in APTT and Quick prothrombin registered. Median plasma FVII activity before inhalation was 82%, after inhalation - 73%. There were no changes on the TEG (figure 1). Thus, despite local hemostatic effect we did not registered systemic effects of rFIIa after inhalation
Conclusion. Topical treatment of the tracheobronchial bleeding with rFVIIa inhalation provided hemostatic effect. There were not be systemic adverse effects in as much as the alveolocapillary membrane does not allow the transmembranous passage of rFVIIa.

Disclosures
No relevant conflicts of interest to declare.