bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iron Deficiency Anemia Is Common in Patients Receiving Chemotherapy
Authors: Jajeh Ahmad 
Published: October 2019

Abstract
Background: Iron metabolism is impaired in patients with cancer and actively receiving chemotherapy. Patients with cancer on active chemotherapy suffer with decreased appetite , poor nutrition, mucositis, gastrointestinal mucosal damage, blood loss as well as anemia of chronic disease due to cytokines release such as Tumor Necrosis Factor, Interleukins and histamins.
The purpose of this abstract is to show single institution experience with patients actively receiving chemotherapy and admitted for various reasons and found to have anemia and particularly those patients that were admitted for red blood cell transfusion. Retrospective review of three hundred and fifty patients admitted in the last two years 2014-2015 for different reasons while on chemotherapy with anemia or mainly for blood transfusion. 55% females and 45% males. 77% had solid tumors and 23% with hematological malignancies. Median age 70 years. Thirty five percent 35% of solid tumors were of GI malignancies. Seventy five percenct of all patients had low iron saturation, low serum iron with normal to high total Iron Binding Capacity TIBC. Ferritin level was low in 60% of the patients. Ferritin is a phase reactive markers was elevated in 40% of patients. All patients with elevated ferritin were having low iron saturation with low serum iron and low or normal TIBC. Sixty five 65% of patients received blood transfusion. All patients with iron deficency received intravenous elemental iron support to saturate iron stores.
In conclusion: Iron deficiency anemia is very common in patient on active chemotherapy. With Intravenous elemental iron supplemet the requirement of less future red blood transfusion and improvement of hemoglobin levels were achieved in most of patients responding to chemotherapy. Need prospective analysis on patients diagnosed with malignancies and start receiving chemotherapy to prove the value of IV iron support and less requirement of red blood cell transfusion.

Disclosures
No relevant conflicts of interest to declare.
Reduced Glutamate Channel Phosphorylation in Pain-Related Brain Areas in a Transgenic Model of Sickle Cell Disease
Authors: LeBlanc Dana Marie , Towne Brook V , Paul Jinny , Gupta Kalpna , Edwards Scott 
Published: October 2019

Abstract
Sickle cell disease (SCD) is associated with chronic, debilitating pain beginning in childhood and persisting throughout life. SCD patients also tend to exhibit elevated rates of depression and anxiety disorders, indicating a possible connection between recurring pain episodes and affective or emotional dysregulation in this population. How SCD physiologically manifests within brain circuitry to mediate this link is currently unknown. In the current study, we utilized a transgenic mouse model of SCD to measure protein kinase A (PKA)-mediated phosphorylation of the AMPA glutamate receptor channel subunit GluR1 in specific brain regions associated with central nociception and the emotional dimension of pain, including the periaqueductal gray (PAG), prefrontal cortex (PFC), and hippocampus. Transgenic sickle mice (HbSS-BERK) expressing human sickle hemoglobin display significant mechanical and thermal hyperalgesia and exhibit reductions in GluR1 phosphorylation compared to littermate controls (HbAA-BERK) in the PAG, PFC, and hippocampus. This neuroadaptation is indicative of reduced excitatory transmission potential in these pain-associated areas. In comparison, GluR1 phosphorylation is unchanged in the dorsal striatum, a brain region not traditionally associated with pain or negative emotionality. Our data are consistent with other preclinical pain models that have linked chronic, peripheral pain conditions with compromised excitatory brain signaling. These results make a strong case for greater appreciation and investigation into mechanisms of possible affective disorder in individuals suffering from SCD.

Disclosures
No relevant conflicts of interest to declare.
Phase Ib Studies of Benegrastim in Chinese Women with Breast Cancer Receiving Myelotoxic Chemotherapy
Authors: Cao Junning , Yuan Zhongyu , Huang Cheng , Ji Dongmei , Peng Rujun , Yan Xiaoqiang , Tang Tom 
Published: October 2019

Abstract

Neutropenia is common in patients receiving myelotoxic chemotherapy. BenegrastimTM(F-627), a recombinant human G-CSF dimer, is an once-per-cycle therapy for prophylactic neutropenia in cancer patients after chemotherapy. Two phase I dose finding studies of benegrastim were conducted in Chinese women with stage I-IV breast cancer receiving myelotoxic chemotherapy. The aims of the studies were to evaluate the safety profile and pharmacokinetics (PK) and pharmacodynamics (PD) properties of benegrastim.
In the first study, a total of 18 patients were enrolled to receive 3 sequential dose levels of benegrastim at 80, 240 and 360 µg/kg (n=6). The patients received epirubicin/cyclophosphamide (EC) chemotherapy on day one. Benegrastim was administered to patients on day 3 by SC injection once per chemotherapy cycle for up to 4 cycles. In the second study, 15 patients were sequentially assigned to 240 µg/kg (n=7) and 320 µg/kg (n=8) of benegrastim. These patients received doxorubicin, docetaxel and cyclophosphamide (TAC) on day one, benegrastim was administered on day 2 by SC injection for up to 6 cycles. The PK/PD properties of benegrastim were evaluated in cycle one and cycle three.
Benegrastim was well tolerated in both clinical studies. The treatment emergent adverse events related to benegrastim were back pain, arthralgia, musculoskeletal pain, and rash, commonly seen in rhG-CSF therapy. The PK/PD result in patients receiving TAC in the first chemotherapy cycle is shown in Fig 1. Dose-dependent benegrastim exposure and ANC increase were demonstrated in these two clinical trials. In breast cancer patients receiving EC or TAC, benegrastim showed a non-linear pharmacokinetics. Benegrastim shortened the duration of neutropenia post chemotherapy in a dose dependent manner. In conclusion, benegrastim may provide an alternative approach to manage neutropenia, especially, severe neutropenia in patients after chemotherapy.
Figure 1. PK/PD of F-627 (benegrastim) in Chinese breast cancer patients receiving TAC in the first chemotherapy cycle. Figure 1. PK/PD of F-627 (benegrastim) in Chinese breast cancer patients receiving TAC in the first chemotherapy cycle.

Disclosures
Cao: Generon (Shanghai) Corporation Ltd.: Research Funding. Yuan:Generon (Shanghai) Corporation Ltd.: Research Funding. Huang:Generon (Shanghai) Corporation Ltd.: Employment. Ji:Generon (Shanghai) Corporation Ltd.: Research Funding. Peng:Generon (Shanghai) Corporation Ltd.: Research Funding. Yan:Generon (Shanghai) Corporation Ltd.: Employment. Tang:Generon (Shanghai) Corporation Ltd.: Employment.
DIC and Its Association with Acute Leukemia in Pre-Treatment and Post Remission Induction Phase
Authors: Naz Arshi , Farzana Tasneem , Taj Mehwish , Shamsi Tahir 
Published: October 2019

Abstract
Background:
Hematological malignancy like acute leukemia (AL) is associated with thromboembolic complications.DIC is a worst complication amongst subtypes of AL especially in APML which can be life threatening.
Study design:
Descriptive & cross-sectional study.
Place and duration of study:
National Institute of Blood Disease and Bone Marrow Transplantation; May 2011 to March 2012.
Patients and methods:
110 (75 males, 45 females)diagnosed cases of acute leukemia [43 cases of AML (27 newly diagnosed, 16 in remission induction), 67 cases of ALL (38 newly diagnosed; 29 in remission induction)]were included & 40 ascontrols.Mean age of patients was 25.3±13.8.Platelet count,PT, APTT, Fibrinogen levels, D-Dimer &FDP was done for scoring of DIC on day 0 and 28. SPSS version 17 was used for data analysis.
Results:
Platelet counts significantly improved on day 28 in AML and ALL. PT and APTT levels were significantly deranged. Plasma levels of fibrinogen were higher in both types of acute leukemia in pre-treatment phase, further increased at day 28 (<0.01). FDP significantly raised at day 0 reduced at day 28(AML & ALL). Markedly elevated levels of D-dimer in AML and ALL at day 0,but showed significant reduction at day 28(<0.01). DIC score of <5 was found in 15 (55.56%) patients of AML and 16 (100%) of ALL on day 0 and >5 score was recorded in 12(44.44%) patients of AML on day 28.
Conclusion:
Strong association of DIC was found in AML and ALL at day 0. Non overt DIC did not show any significant association with specific type of acute leukemia and it was equally expressed in both type of acute leukemia at day 0 and 28.

Disclosures
No relevant conflicts of interest to declare.
Clinical, Instrumental, Serological and Histological Findings Suggest That Hemophilia B May be Less Severe Than Hemophilia A
Authors: Castaman Giancarlo , Melchiorre Daniela , Linari Silvia 
Published: October 2019

Abstract
Background: Recent evidences suggest that patients with severe hemophilia B (HB) may have a less severe disease compared to severe hemophilia A (HA).
Objectives: to investigate clinical, radiological, laboratory and histological differences in the arthropathy of severe HA and HB.
Patients/Methods: 70 HA and 35 HB patients with at least one joint bleeding were consecutively enrolled. In all patients were assessed: joint bleedings (<10, 10-50, >50), regimen of treatment (prophylaxis/on demand), WFH, Pettersson and ultrasound (US) scores, serum sRANKL and OPG. Expression of RANK, RANKL and OPG was also evaluated in synovial tissue from 18 HA and 4 HB patients. Chi-square test, T-test, Mann-Whitney and Spearman's rank correlation coefficient were performed.
Results: The percentage of patients with either 10-50 or >50 hemarthrosis was greater in HA than in HB (p< 0.001 and p = 0.03, respectively); that with <10 hemarthrosis was higher in HB (p < 0.0001). The mean value of WFH (36.6 vs 20.2;p <0.0001) and US scores (10.9 vs 4.3;p <0.0001) were significantly higher in HA patients. Serum OPG and s RANKL were decreased in HA versus HB (p<0.0001 and p=0.006, respectively) and also in HA patients with>50 hemarthrosis. The expression of OPG was markedly reduced in synovial tissue from HA patients.
Conclusions: The reduced number of hemarthrosis, the lower WFH and US scores and higher OPG levels in serum and expression in synovial tissue in HB suggest that HB is a less severe disease than HA. OPG reduction seems to play a pivotal role in the progression of arthropathy in HA.

Disclosures
No relevant conflicts of interest to declare.
Autosomal Recessive Inherited Bleeding Disorders in Pakistan, a Cross Sectional Study from Selected Regions
Authors: Naz Arshi , Jamal Mohammad younus , Amanat Samina Tufail , Patel Humayun , Agha Akbar , Razik fazal-E- , Ahmed Nisar , Imran Ayisha , Shamsi Tahir 
Published: October 2019

Abstract
INTRODUCTION: Incidence of autosomal recessive disorders is rare, includes deficiencies of clotting factors I, II, V, VII, X, XI, XIII, vitamin K dependent clotting factors, combined factor V & VIII, Von Willebrand disease type 3, Glanzmann Thrombasthenia and Bernard Soulier syndrome.
OBJECTIVE: Spectrum of autosomal recessive bleeding disorders (ARBDs] among Pakistani patients.
PATIENTS AND METHODS: This cross-sectional study was carried out at Karachi, Lahore, Islamabad and Peshawar. PT,aPTT, BT, and fibrinogen levels done. Patients with prolonged APTT were tested for factors VIII and IX. If FVIII was low, von Willebrand factor: antigen (vWF: Ag) and von Willebrand factor: ristocetin cofactor (vWF: RCo) were performed. When PT and aPTT both were prolonged, FII, FV, and FX were tested. Peripheral film and platelet aggregation studies were done for platelet disorders. Urea clot solubility test was done at the end.
RESULTS: Out of429 patients, 148 were diagnosed with Hemophilia A, remaining 281 patients had ARBDs. 95 (33.8%) had VWD type 3. Fibrinogen deficiency was found in 34 (12%), Glanzmann Thrombasthenia in 27 (9.6%), factor XIII in 13 (4.6%), factor VII in 12 (4.3%), factor V in 9 (3.2%), 8 (2.8%) in vitamin K dependent clotting factors, , Bernard Soulier in 7 patient (2.5%),factor X in 2 (0.7%), factor II in 2 (0.7%), factor XI and combined factor V and VIII in 1 (0.4%)patients each. 70 patients (16.3%) remained undiagnosed.
CONCLUSION: VWD type 3 is the most common deficiency followed by fibrinogen deficiency. Glanzmann thrombasthenia was the third most common ARBD.

Disclosures
No relevant conflicts of interest to declare.
Treatment and Outcome of the Patients with Donor-Type Aplasia after Bone Marrow Transplantation in Children with Aplastic Anemia
Authors: Jeong Kumhee , Cho Joo Hyun , Cheon Kyeong Ryeol , Jang Hae In , Baek Hee Jo , Kook Hoon 
Published: October 2019

Abstract
Hematopoietic stem cell transplantation (HSCT) from an HLA-matched donor is the treatment of choice for children with aplastic anemia (AA). However, graft failure (GF), either primary or secondary, remains an important and life-threatening complication. Recently, donor-type aplasia, defined as bone marrow aplasia with full donor chimerism among secondary GF, has been identified after HSCT. Clinical characteristics of donor-type aplasia after HSCT and its treatment and outcome in children with AA were retrospectively reviewed. Forty-two children with AA underwent allogeneic HSCT with 10-year overall survival rate of 85.7%. While primary GF developed in 1 (2.4%), secondary GF was seen in 12 at a median of 8 months (range: 2.0-28.5 months). Among them, 11 developed a donor-type aplasia with the cumulative incidence of 26.2%. Low infused cell number (P=0.002), immunosuppressive therapy (IST) prior to HSCT (P=0.003) and preceding transfusion >40 times (P=0.008) were associated with the development of donor-type aplasia. The survival of patients with donor-type aplasia was 81.8%. Six patients were treated with stem cell rescue as follows: peripheral blood stem cell (PBSC) boost, 3; PBSC boost followed by secondary HSCT, 2; and secondary HSCT, 1. All but 1 who had a longest interval from 1st HSCT to stem cell rescue (54.4 months) showed restoration of graft function. The remaining 5 patients were managed with conservative measures including transfusions. No one showed spontaneous improvement with the median follow-up of 30.1 months (range, 4.2 to 43.0 months). Two patients died of graft failure and infection. Altogether, 4 patients still remain transfusion-dependent. Donor-type aplasia after HSCT for AA is not uncommon. Stem cell rescue, either with PBSC boost or secondary HSCT after conditioning should be attempted to obtain sustained graft function. For those who do not have availability for stem cell rescue, a novel treatment, such as thrombopoietin receptor agonist, should be considered for the future.

Disclosures
No relevant conflicts of interest to declare.
A Novel DLL1-Anti-CD19 Chimeric Protein Effectively Targets Notch Activation to B-Cell Acute Lymphoblastic Leukemia and Induces Cell Death
Authors: Wiersma Rebecca E , Kannan Sankaranarayanan , Somanchi Srinivas S. , Zeng Lizhi , Zweidler-McKay Patrick A. 
Published: October 2019

Abstract
Background: Acute lymphoblastic leukemia (ALL) is the most prevalent form of cancer in children, and those who relapse continue to have poor survival. Therefore, the development of improved and specifically targeted treatment options is vital. The Notch pathway has been shown to act as a tumor suppressor in B-ALL via cell type specific induction of growth-inhibiting and pro-apoptotic pathways. In this study, we aim to therapeutically activate Notch signaling in B-ALL via targeting the Notch ligand DLL1 to B cells using an anti-CD19 scFv chimeric protein.
Methods: A soluble chimeric protein composed of the extracellular domain of the Notch ligand DLL1 linked to a validated anti-CD19 scFv was isolated from HEK-293 producer cells. Human B-ALL (SB, Nalm6) and T-ALL (Jurkat) lines were treated with DLL1-anti-CD19scFv chimeric protein, and expression of the Notch target gene HES1 and effects on cell growth and survival were measured.
Results: Both B- and T-ALL lines express Notch1 and Notch2 receptors on the cell surface. Exposure of B-ALL cells to DLL1-anti-CD19scFv chimeric protein led to an increase of Notch signaling, measured via 3-14 fold increase in HES1 mRNA expression. As expected, surface expression of the Notch receptors decreased upon chimera exposure, as Notch receptors are cleaved and destroyed upon activation. Importantly, exposure of the B-ALL lines to the chimeric protein led to a maximum 60% decrease in cell counts over 3-4 days, in contrast to T-ALL, where exposure did not effect growth significantly.
Conclusions: This study demonstrates that Notch signaling can be feasibly activated in human B-ALL cells through a soluble DLL1-anti-CD19 scFv chimeric protein. Activation of Notch signaling via this method leads to growth inhibition and cell death in B-ALL, but not T-ALL cells. Based on our findings, we suggest that this soluble DLL1-anti-CD19 chimera may be a potential therapeutic approach for B-ALL, and further in vivo testing is warranted.

Disclosures
No relevant conflicts of interest to declare.
Rapamycin Induced Acute Myelogenous Leukemia U937 Cell Autophagy and Apoptosis
Authors: Xu Wenfeng , Li Chunfu , Feng Xiaoqin , He Yuelin 
Published: October 2019

Abstract
Objective: To investigate the autophagy and apoptosis on acute myelogenous leukemia U937 cell induced by rapamycin.
Methods: U937 cells was subcultured, and was set up blank control group (normal) and rapamycin treated groups (3 groups, 12h, 24h, 48h). The rapamycin treated groups were separately treated by 2¦ÌM concentration of rapamycin after 12h, 24h and 48h. The cell morphology of U937 cells treated by rapamycin was observed after 12h 24h and 48h. The survival rate of cells was detected by CCK-8 method. Cell apoptosis was detected by flow cytometry using Annexin V-FITC/PI double labeled. Use real-time PCR to detect the level of mRNA expression in autophagy specific protein maker LC3-¢òin different treated times by rapamycin. Rapamycin LC3 protein expression levels after treatment was detected by western blot method.
Results: Visible under inverted microscope, the rapamycin treatment groups¡¯ cell number reduced gradually after cultured 12h, 24h and 48h, smaller volume, cell rupture, increase the nucleus pycnosis and cellular debris(Figure 1). With the extension of time, U937 cells survival rate is falling, compared with control group, with statistical significance(P=0.031; P<0.05). Rapamycin treatment U937 cells after 12 h, 24 h and 48 h, U937 cell apoptosis rate increased, compared with control group, with statistical significance (P=0.027; P< 0.05, Figure2). Rapamycin treatment U937 cells after 12 h, 24 h and 48 h, LC3-¢ò mRNA expression and protein expression were cut, compared with control group, with statistical significance(P=0.029; P<0.05, Figure 3).
Conclusion: Rapamycin can induce autophagy and apoptosis of U937 cells. Autophagy protein LC3-¢ò in gene and protein expression level lowered, LC3-¢ò may play an important role in regulating the leukemia cell autophagy.

Disclosures
No relevant conflicts of interest to declare.
CLAG-Based Induction Therapy in Previously Untreated High Risk AML Patients
Authors: Seiter Karen , Germani Stephanie , Martin Julie , Raffa Rosemarie , Reilly Michele , Ahmed Nasir , Baskind Paul , Liu Delong 
Published: October 2019

Abstract
The CLAG regimen (G-CSF 300 mcg sc, cladribine 5 mg/m2 over 2 hours, and cytarabine 2 gm/m2 over 4 hours beginning 2 hours after cladribine, all daily times 5 days) was originally devised by Robak et al (Leuk Lymphoma 2000; 36:121-9) as induction therapy for patients with relapsed or refractory acute myeloid leukemia. Fifty percent of patients achieved a CR with a median duration of 22.5 weeks. This group subsequently added mitoxantrone to the regimen (Wrzesien-Kus A, et al. Ann Hematol 2005; 84:557-64). We treated 20 patients with previously untreated acute myeloid leukemia who were considered unsuitable for our intensive high-dose cytarabine, high-dose mitoxantrone frontline induction regimen either due to age or cardiac dysfunction with CLAG-based therapy. Patients with a cardiac ejection fraction above 50% additionally received either mitoxantrone (mito) or idarubicin (ida), 12 mg/m2 times 3 days, concurrently with CLAG. Of 20 patients treated, 5 received CLAG, 12 received CLAG-ida and 3 received CLAG-mito. The median age was 64 years (range 42-79 years). There were 13 men and 7 women. Six patients had received prior chemo and/or RT for a previous malignancy. In addition 3 patients had a prior MPD and 1 had prior MDS (total of 10 patients with secondary AML). Patients had a median of 3 comorbidities (range 0-7). Cytogenetic risk was good: 2 patients (however one was FLT3 ITD+), intermediate: 10 patients, poor: 8 patients. Only one patient was FLT3 ITD+. Responding patients (CR or PR) received 1 (5 pts), 2 (2 pts), 3 (8 pts) or 4 (2 pts) cycles of CLAG+/- ida or mito followed by allogeneic stem cell transplant (4 pts), hidac (2 pts) or decitabine maintenance (4 pts). Most patients responded to therapy. There were 13 formal CRs (65%), 1 CRp (5%), 3 PR (15%, defined as 6-10% blasts on marrow with complete hematologic recovery in the peripheral blood), 2 failures (10%) and one early death (5%). Other than the early death, treatment was well tolerated with few toxicities other than neutropenic fever and cytopenias. Estimated overall survival by Kaplan Meier analysis is 29.6 months (95% CI 20.1-39.2 months). Duration of response is 32.3 months (95% CI 21.6-43.1 months).
CLAG-based therapy is a well-tolerated, efficacious induction strategy in previously-untreated patients with high risk AML. CLAG-based regimens should be studied in a broader group of newly diagnosed AML patients.
Figure 1. Figure 1. Figure 2. Figure 2.

Disclosures
Off Label Use: Use of cladribine in AML.