bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-Effectiveness of Rituximab As Maintenance Treatment for Relapsed Follicular Lymphoma: Results of a Population Based Study
Authors: Blommestein Hedwig M , Issa Djamila E , Pompen Marjolein , Révil Cédric , Hoogendoorn Mels , Joosten Peter , Zweegman Sonja , Huijgens Peter C. , Uyl-de Groot Carin A. 
Published: October 2019

Abstract
Abstract 4277

OBJECTIVES:
Effectiveness of rituximab maintenance treatment among patients with relapsed follicular lymphoma (FL) has been established in a randomised setting (EORTC20981 trial). Although the golden standard, results might not be generalisable to unselected real-world patient populations. Outcomes research was conducted to calculate real-world cost-effectiveness of second line rituximab maintenance compared to observation in FL patients in the Netherlands.

METHODS:
Two Dutch population-based registries, PHAROS and HemoBase respectively, collected information on patient characteristics, treatment, and resource utilisation on patients diagnosed with FL in the past 20 years. Patients responding to second line chemotherapy were included in the observation or maintenance group. A Markov model was applied to calculate real-world cost-effectiveness.

RESULTS:
Although 735 FL patients entered the registries, only 57 and 49 patients were eligible and included in the observation and maintenance group, respectively. Median age was 61 years and similar in both groups. Differences between the groups were found for second line treatment with rituximab (77% and 92% in the observation and maintenance group p<0.05) and years since diagnosis (p<0.01). Besides, the proportion of people with a partial response was higher in the observation group (60%) compared to the maintenance group (33%). The maintenance group showed higher 3-year overall survival (75% versus 63%) and longer time till next treatment (p<0.01). Compared to the trial, our real-world population was older and fewer patients were diagnosed with stage IV FL. Real-world prescription of rituximab was comparable to the trial although cycles were prescribed more frequent. Daily practice data combined with trial efficacy data resulted in cost-effectiveness ratios between € 3,614 and € 5,246 per life year gained and €3,555 and € 5,156 per quality-adjusted life year.

CONCLUSIONS:
Real-world FL patients were not identical to trial patients emphasising the importance of studying real-world data. Nevertheless, these data also suggest that rituximab is an effective treatment in daily life. However, analysing non-randomised groups is challenging. Careful interpretation is required since observed dissimilarities between the groups suggested the representation of different types of patients. Nevertheless, real-world cost-effectiveness for second line rituximab maintenance was favourable compared to other haematological treatments.

Disclosures:
Pompen: Roche Netherlands: Employment. Révil:Roche Netherlands: Employment.
Expression and Effect of CTCF in Pediatric Acute Lymphoblastic Leukemia
Authors: Zhu Lin , Zhang Han , Liu Xiao , Du Chaohao , Zhu Shanshan , Zhang Wei , Zhao Xiaoxi , Li Zhigang , Bao Shilai , Zheng Huyong 
Published: October 2019

Abstract
Abstract 4298
Acute lymphoblastic leukemia (ALL) is the most frequent-occurring malignant neoplasm in children, but the pathogenesis of the disease remains unclear. In a microarray assay using samples from 100 Chinese children with ALL, CTCF was found to be up-regulated. DNA-binding nuclear protein CTCF (encoded by CTCF gene) is a highly conserved zinc finger protein involved in multiple cellular processes including transcriptional activation/repression, insulation, imprinting and × chromosome inactivation. It has been shown to be associated with cell apoptosis and differentiation in tumors; however, the biological function of CTCF in pediatric ALL is presently unknown.
To investigate the expression features of CTCF in pediatric ALL cells, matched newly diagnosis (ND), complete remission (CR) and relapse (RE) bone marrow samples from 24 patients were collected. Ten ND-CR paired samples (n=20) were selected to detect the mRNA levels of CTCF by Q-PCR. Besides, the protein levels of CTCF at different stages of disease progression were measured by western blot in all patients (20 ND-CR paired samples, n=40; 4 ND-CR-RE matched samples, n=12). To further explore the role of CTCF in the pathogenesis of leukemia, the potential effect of CTCF on the cell apoptosis in lymphoblastic cells was investigated by flow cytometry.
We identified significant up-regulation of CTCF in the ND samples. Importantly, the expression of CTCF returned to normal level after CR, but rebounded in the RE samples. Knock-down of CTCF resulted in nearly 3–fold and 15–fold increases in early and late apoptosis of leukemic cells respectively, which indicated that CTCF is an anti-apoptotic factor and plays an anti-apoptotic role in lymphoblastic cells.
Our results indicate that CTCF may represent a promising indicator of disease progression as well as reflecting the ongoing therapeutic effects of treatment. Furthermore, CTCF serves as an anti-apoptotic factor and potentially contributes to leukemogenesis in pediatric ALL patients.

Disclosures:
Zhang: Beijing Health System High-level Technical Personel Plan: Research Funding. Zheng:Beijing Health System High-level Technical Personel Plan: Research Funding.
Association of Polymorphisms of Cytosine Arabinoside- Metabolizing Enzyme Gene with Therapy Efficacy for Acute Myeloid Leukemia
Authors: Xu Peipei , Chen Baoan , Liu Ran , Feng Jifeng , Cheng Lu , Xia Guohua , Li Yufeng , Qian Jun , Ding Jiahua , Zhu Han , Lu Zuhong 
Published: October 2019

Abstract
Abstract 4328

Background
The cytosine arabinoside (Ara-C)-based chemotherapy is the major remedial measure for acute myeloid leukemia (AML). Deoxycytidine kinase (DCK) and cytidine deaminase (CDA) are the key enzymes in the metabolism of Ara-C. Many single nucleotide polymorphisms (SNPs) and haplotypes of DCK and CDA, which contribute to susceptibility to Ara-C, have been identified in Africans and Europeans. However, there has been no report about the relation among three SNPs in DCK (rs115543896, rs72552079, and rs111454937) and two SNPs in CDA (rs2072671 and rs60369023), and their clinical response to Ara-C for a Chinese population. In this study, we aimed to investigate whether these five SNPs are associated with the therapeutic outcomes of Ara-C-based chemotherapy regimens in patients with AML.

Methods
A total of 151 patients with AML in a Chinese population were enrolled in our study. SNPs genotyping were performed using the MassARRAY system (Sequenom) by means of the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) method.

Results
The results illustrated that DCKrs111454937 AA genotype was more frequent in patients with higher platelet count, and A allele frequency was significantly higher in the group £40 years, lower white blood count (WBC) patients group and the group with platelet counts >60′109/L. Meanwhile, both DCKrs72552079 TC (OR=1.225, 95% CI=1.225–9.851, P=0.0192) and CDArs60369023 GA (OR=9.851, 95% CI=1.31–77.93, P=0.0263) significantly improved Ara-C-based chemotherapy response. While DCKrs11554389 AA (OR=0.147, 95% CI=0.027–0.801, P=0.0267) was associated with the decrease of Ara-C-based chemotherapy response.

Conclusion
It is evident that the DCK and CDA polymorphisms might be the important markers for the AML patients' therapy outcomes in a Chinese population.

Disclosures:
No relevant conflicts of interest to declare.
The Results of Chemotherapy for the Elderly Acute Myelogenous Leukemia Patients
Authors: Kim Daesik , Park Yong , Lee Suk-young , Lee Se Ryeon , Sung Hwa Jung , Kim Seok Jin , Kim Byung Soo , Choi Chulwon 
Published: October 2019

Abstract
Abstract 4346

Background
Despite of advances in the treatment for acute myelogenous leukemia (AML), the response of chemotherapy for the elderly is still poor and there is no definite guideline for the elderly AML patients.

Methods
The retrospective analysis with medical chart review was taken to the 82 patients over 65 years old and treated with AML from January 2003 to April 2012 at the Korea University Medical Center. The efficacy of chemotherapy for the elderly patients was evaluated and subgroup analysis was taken to determine which conditions are more effective to the chemotherapy.

Results
Median overall survival period of 82 patients were 3.9 months. 52 patients were treated with chemotherapy (33 patients were standard dose idarubicin plus cytarabine, 19 patients were low dose cytarabine) and 30 patients received best supportive care only. Among the standard chemotherapy group, there were 16 cases of remission (48.5%) after induction chemotherapy. The treatment related mortality was 24.2% and the most common cause was pneumonia sepsis. Median overall survival period of standard chemotherapy group was 7.9 months. In a multivariate analysis, significant factors for longer overall survival were performance status, no underlying heart disease, no fever at diagnosis, high platelet count, low blast count and standard induction chemotherapy. In the subgroup analysis, the efficacy of chemotherapy was observed in the relatively younger patients group (HR 0.437, P =.022), De novo AML group (HR 0.421, P =.025), no underlying heart disease group (HR 0.421, P =.031), high WBC count group (HR 0.306, P =.026), Low platelet count group (HR 0.12, P <.001), high blast counts group (HR 0.233, P =.005), high LDH group (HR 0.21, P=.001).

Conclusion
The result of chemotherapy in the elderly AML patients is poor. However the results of the chemotherapy will be better if the patients are selected appropriately through subgroup analysis.

Disclosures:
Choi: the korean society of hematology: Membership on an entity's Board of Directors or advisory committees.
Practical Experience of Thromboprophylaxis After Lower Limb Replacement – Rivaroxaban Versus Enoxaparin
Authors: Kim Kyoung Ha , Ham Nam Seok , Kim Yang Ki , Choi Hyung Suk , Suh You Sung , Jeon Young Woo , Kim Han Jo , Kim Se Hyung , Bae Sang Byung , Park Sung Kyu , Won Jong-Ho , Hong Dae Sik , Park Hee Sook 
Published: October 2019

Abstract
Abstract 4369

BACKGROUND
Since October 2010, rivaroxaban has been approved by Korean government to be covered by national health insurance reimbursement system as thromboprophylaxis after total hip arthroplasty and total knee arthroplasty. However, there is no available data on outcomes of rivaroxaban as thromboprophylaxis in Korea. We performed a retrospective study to compare the efficacy and safety of venous thromboembolism prophylaxis with enoxaparin or rivaroxaban in 195 consecutive patients undergoing major orthopaedic surgery at our center.

METHODS
This study retrospectively reviewed the medical records of the 195 patients who underwent a total hip replacement arthroplasty or total knee replacement arthroplasty and received thromboprophoylaxis with enoxaparin or rivaroxaban at Soonchunhyang University Hospital between March 2009 and May 2012.
Each patient's medical records included information on age, sex, comorbidities (active malignant disease, renal insufficiency), treatment details (type of surgery, type of anesthesia, duration of surgery,), duration of prophylaxis, efficacy (death, pulmonary embolism, deep vein thrombosis), safety (major bleeding, cerebrovascular accident), cause of drug interruption.

RESULTS
Of 195 patients, 129 patients received thromboprophylaxis with enoxaparin (group 1; our hospital standard since March 2009), 66 received rivaroxaban (group 2; our hospital standard since February 2011). Symptomatic venous thromboembolism was found in 0.7 % of patients in the group 1 (1/129 patients) compared to 1.5 % of group 2 (1/66 patients; p=0.627). No significant differences in the rates of symptomatic VTE were found. However, patients with received rivaroxaban had significantly more rates of major bleeding (0 in group 1 vs 3% (2/66 patients) in group 2; p=0.047). Although group 1 patients were planed receiving thromboprophylaxis with rivaroxaban from day one post operatively, mean time from the end of surgery to first rivaroxaban intatake was 4.2 days.

CONCLUSIONS
Despite lower compliance in rivaroxaban group, venous thromboembolism prophylaxis with rivaroxaban is not inferior to prophylaxis with enoxaparin with regard to the prevention of symptomatic venous thromboembolisms. But, more bleeding complications and wound problems revealed in rivaroxaban group. Further studies and experiences are needed to assess the efficacy and safety of rivaroxaban in clinical practice.

Disclosures:
No relevant conflicts of interest to declare.
The Expressions of CD114, CD117 and STAT5 in CD34+CD59− and CD34+CD59+ Bone Marrow Cells of the Patients with Paroxysmal Nocturnal Hemoglobinuria
Authors: Fu Rong , Ding Shaoxue , Shao Zonghong , Li Lijuan , Liu Hui , Wang Honglei , Zhang Tian 
Published: October 2019

Abstract
Abstract 4404

Objective:
To measure the expressions of granulocyte colony-stimulating factor receptor (G-CSFR, CD114) and stem cell factor receptor (C-KIT, CD117) on the membrane of CD34+CD59− and CD34+CD59+ bone marrow cells of the patients with paroxysmal nocturnal hemoglobinuria(PNH), and the signaling pathway protein STAT5 within the cytoplasm of those cells.

Methods:
The expressions of CD114 and CD117 on the cell membrane and STAT5 protein within the cytoplasm of bone marrow CD34+CD59+ and CD34+CD59− cells from 26 PNH patients and 14 normal controls were examined by flow cytometry (FCM).

Results:
The percentage of CD114 positive cells in CD34+CD59− cells of PNH patients was (43.23±19.77)%,which was significantly lower than that in CD34+CD59+ cells of PNH patients (73.72±17.42) (P<0.01) or normal controls (65.91±13.70)% (P<0.01). There was no statistic difference between the two latter (P>0.05). The percentage of CD117 positive cells in CD34+CD59− cells of PNH patients was (49.20±26.80)%,which was significantly lower than that in CD34+CD59+ cells of PNH patients (67.62±17.41) (P<0.01) or normal controls (70.21±12.68)% (P<0.01). There was no statistic difference between the two latter (P>0.05). The STAT5 MFI in CD34+CD59− and CD34+CD59+ cells of PNH patients and CD34+CD59+ cells of normal controls was (270.01±181.26), (205.05±146.16), (227.39±156.65) respectively. There was no statistic difference among the three groups (P>0.05).

Conclusions:
In PNH, CD114 and CD117 expressed lower on bone marrow PNH clone cells than normal clone cells, but the expressions of signaling pathway protein STAT5 within the cytoplasm was normal.

Disclosures:
No relevant conflicts of interest to declare.
Homoharringtonine Contributes to Imatinib Sensitivity by Blocking EphB4/RhoA Pathway in Ph+ Myeloid Leukemia
Authors: Xiaoli Liu , Huang Bintao , Du Qingfeng , Zhang Jinfang , Xu Na , Xu Lulu , Xiao Xiaozhen , Zhou Xuan 
Published: October 2019

Abstract
Abstract 4420

Objective:
The purpose was to investigate the role of the EphB4 in imatinib (IM) resistance and the mechanism why the homoharringtonine (HHT)+IM regimen gained more treatment profits than simple HHT or IM treating myeloid leukemia.

Method:
The stable under-expressing EphB4 cells (K562-R-EphB4-sh) were obtained. The cell viability and IC50 under the incubation of IM or HHT+IM was tested by MTT. PE Annexin V apoptosis detected the apoptosis rate of K562-R cells. Subcutaneous K562 xenograft models were established. The activated signal proteins in cells and tissues such as RhoA, MEK and ERK were tested by Western blot.

Result:
K562-R-EphB4-sh cell and xenograft were sensitivity to IM. Activated RhoA was not involved in K562-R-EphB4-sh cell and xenograft tissue. But phosphorylation of MEK/ERK was overexpression in K562-R-EphB4-sh cell and tissue. The apoptosis rate reached 58.71 ± 2.39% with K562-R cell incubated with HHT+IM, which was higher to K562-R cell incubated with IM (P=0.002). IC50 of K562-R cell incubated by IM was 5.45 mg/L. But under the stimulation of HHT+IM, IC50 of K562-R decreased from 5.45 to 1.17 mg/L (P<0.001). K562-R xenograft volumes significantly decreased with IM+HHT treatment comparing with before treatment (1692.82 ± 317.14 mm3 versus 975.56 ± 132.42 mm3, P<0.001). HHT blocked the expressions of EphB4/RhoA in K562-R cell and xenograft, but HHT cannot down-regulate the expression of P- MEK/ERK.

Conclusions:
A new marker of IM resistance mediated by the activation of EphB4/RhoA pathway. HHT+IM regimen gained more treatment profits than simple HHT or IM treating myeloid leukemia by blocking EphB4/RhoA pathway in Ph+ myeloid leukemia.

Disclosures:
No relevant conflicts of interest to declare.
Chronic Myelogenous Leukemia in the Era of Tyrosine Kinase Inhibitors: Is Sokal Score Still a Valid Predictor of Prognosis?
Authors: Jain Shivi , Agrawal Kireet , Singh Abhijai , Pattali Shinoj , Haidau Augustin , Kovarik Paula , Catchatourian Rose 
Published: October 2019

Abstract
Abstract 4422

Background:
In the era when the Sokal score was developed (1984), Tyrosine kinase inhibitors (TKI's) were not available for treatment of Chronic Myelogenous Leukemia (CML). With the treatments available then, the 2-year survival in the low risk group was 90% and in the intermediate and high-risk groups was 65%. Since TKI's were approved for treatment of CML in 2001, overall estimated survival at 5 years has improved to 89%.

Aim:
To evaluate risk stratification by Sokal score as an indicator of prognosis in patients with CML in the present era of tyrosine kinase inhibitors.

Methods:
Sokal Score is a prognostic score used to risk stratify patients as low-risk, intermediate-risk and high-risk based on diagnosis based on the spleen size, platelet count, age and blast count. Seventy-eight (78) subjects diagnosed with CML and treated at John H. Stroger Hospital of Cook County between 2000 and 2011 were retrospectively analyzed after institutional review board approval. Ten (10) subjects with blast crisis at diagnosis were excluded from this study. Effect of race, sex, age, white cell count, amount of reticulin fibrosis in bone marrow biopsy, total peripheral blood eosinophil and basophil counts, Lactate Dehydrogenase level, spleen and liver size at diagnosis and, risk stratification by Sokal score on overall survival was evaluated using standard statistical analysis.

Results:
In our population, 27/68 (39.7%) were more than 45 years old, 30/68 (44.11%) were African American, 20/68 (29.4%) were Hispanic, male to female ratio was 2.4:1. WBC>100,000 was observed in 25/68 (51.4%), 57/68 (83.8%) had LDH>200IU/L, 50/68 (73.5%) had palpable splenomegaly >5cm at the time of diagnosis and 67/68 (99%) of subjects had reticulin fibrosis in bone marrow. Of these, 35/67 (52.2%) had mild, 12/67 (17.9%) had moderate and 20/67 (29.8%) had severe fibrosis. According to Sokal score risk stratification, 22/68 (32.3%) were low risk, 40/68 (58.8%) were intermediate risk and 6/68 (8.8%) were high risk at diagnosis. Five year overall survival (OS) in our population was 90%. On univariate analysis, risk stratification by Sokal score at diagnosis was statistically significant for Overall Survival. Subjects with low risk score had better OS as compared to intermediate and high-risk subjects (P=0.007, HR 11.596, 95%CI 1.946–69.103). Similarly, subjects with intermediate score had better OS compared to high-risk group (P=0.007, HR 0.140, 95%CI 0.020–0.539).

Conclusion:
Sokal Score is still a valid predictor of prognosis in this new age of tyrosine kinase inhibitors and can still be used for risk stratification at diagnosis for chronic phase CML patients.

Disclosures:
No relevant conflicts of interest to declare.
Low-Dose Uroacitides(CDA-II) Downregulates Telomerase Activity and Inhibits Proliferation in the Telomerase-Expressing Maliganant Cell Lines Through Inactivation of Akt Signaling Pathway
Authors: Huang Jian , Jin Jie 
Published: October 2019

Abstract
Abstract 4920
Uroacitides, another name CDA-II (cell differentiation agent II), is a mixture product and isolated from healthy human urine in China. It is characterized as a novel molecular targeting agent for cancer therapy. Multiple active components, such as peptides (MW 400–2800), organic acids, pigments and phenylacetylglutamine, with different mechanisms of action act concurrently to contribute to the anticancer effect of CDA-II. We have reported that high-dose CDA-II could induce acute myeloid leukemia (AML) cell apoptosis. Here, in the light of the important role of telomerase in malignant transformation. We evaluated the effect of low-dose CDA-II on telomerase activity (TA) and regulation in various malignant cell lines. CDA-II caused a dose-dependent inhibition of TA (up to 80% at a concentration of 0. 5 mg/mL) in Hela (cervix uteri cancer), MCF-7(breast cancer), SW480(colon cancer), RPMI8226(myeloma), HL-60 (AML), Raji (Burkitt lymphoma), L428 (Hodgkin's disease). Low-dose CDA-II did not affect the activity of other DNA polymerases. Inhibition of TA was associated with 60% inhibition of proliferation. The inhibition of proliferation was associated with a decrease in the S phase of the cell cycle and an accumulate of cells in G1 phase. No apoptosis was observed. Inhibition of TA was caused by dephosphorylation of Akt and by early downregulation of hTERT transcription. Other steps of telomerase regulation were not affected by low-dose CDA-II. This study demonstrated an additional cellular target of low-dose CDA-II that causes inhibition of TA and cell proliferation.

Disclosures:
No relevant conflicts of interest to declare.
Mechanism of Gambogic Acid-Induced Apoptosis in DB Cells
Authors: Xu Jingyan , Ouyang Jian , Zhou Min , Zhang QiGuo , Zhou Rong-Fu 
Published: October 2019

Abstract
Abstract 4923
This study was purposed to explore the apoptotic effect of gambogic acid on DB cells and its mechanism. The DB cells were treated with GA at different concentrations(2, 1, 0. 5, 0 ug/ml) in 24 hr. Annexin V-fluorescein-isothiocyanate/propidium iodide was used to detect apop tosis of DB cells. Western blot was used to determine the expressions of P53, Bcl-2 and Bax. The results showed that the Gambogic acid dose-dependently induced the apoptosis of DB cells in 24 hr, downregulated the expression of Bcl-2, upregulated the expressions of Bax, and the expression of P53 did not change. It is concluded that gambogic acid induces the apoptosis of DB cells through Bax upregulation, Bcl-2 downregulation without influence on P53.

Disclosures:
No relevant conflicts of interest to declare.