bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Research on Hematological Malignancies Complicated with dic-a Single Center Report in China
Authors: Wei Qing , Niu Ting 
Published: October 2019

Abstract
Objective This study aimed to explore the most appropriate way of diagnosis and treatment among the patients with hematological malignancies complicated with disseminated intravascular coagulation (DIC) by evaluating the risk factors which would affect the prognosis and the efficiency of therapies.
Methods The data of 162 definitely-diagnosed patients in West China Hospital between 2009 and 2013 has been collected and analyzed in our retrospective study. We have summarized the information on clinical features, laboratory indicators and interventions, which has been statistically analyzed to evaluate the effect on mortality.
Results Elderly patients, AML patients accompanied with hyperleukocytosis, APL patients accompanied with differentiation syndrome combined deteriorated DIC symptoms, patients accompanied with infections, refractory/relapsed patients, patients with any of the following clinical symptoms such as gastrointestinal bleeding, intracranial hemorrhage, more than three sites of bleeding, acute renal dysfunction,acute respiratory dysfunction, acute left heart failure, MOF or shock, presented higher mortality (P<0.05).We found that there was difference in terms of mortality when we defined the cut-off value of PLT as 10×109/L (P<0.05). According to the ISTH criteria or Chinese guideline, the patients with abnormal PTAAPTTA AT-III, or ISTH score>6 had poorer prognosis. In our study, we tried to classify Fig < 1 g/L or > 4 g/L as a Fig abnormal group, the rest of the patients classified as a Fig normal group, then we found the abnormal Fig group had an increased mortality (P < 0.05). In addition, it had been found that patients who received standard chemotherapy had lower mortality (P < 0.05). With respect to non-APL patients, ones who took anti-fibrinolysis agents had similar mortality compared with the patients who didn't (P>0.05).
Conclusions Among the patients of hematological malignancies complicated with DIC, the patients with any of above clinical risk factors or abnormal laboratory indicators would have poorer prognosis. Moreover, the cut-off value of PLT should be dropped when we diagnose or evaluate this kind of patients’ prognosis. We put forward a new cut-off value of Fig as described above and it is valuable to evaluate the prognosis. The treatment of underlying diseases and substitute therapy act as basis of these patients, however, the adverse effects should be pay attention to as well as infections and acute heart failure. No benefit has been shown in the non-APL patients treated with anti-fibrinolytic agents.

Disclosures
No relevant conflicts of interest to declare.
Management of Major Bleeding Caused By Rivaroxaban and the Use of Desmopressin
Authors: Jajeh Ahmad 
Published: October 2019

Abstract
Rivaroxaban is a new anticoagulant that is substituted for Coumadin on a large scale in the treatment and prevention of Deep Vein Thrombosis DVT and Pulmonary Embolism PE. It is an oral agent that inhibits Factor Xa. The most attractive attribute of this new anticogulant is the lack of monitoring PT/INR. However, out of many cases put on Rivaroxaban a few reports of major and threatening bleed that could be fatal. Particularly, the the GI bleeding. Unfortunately, no set standard antidote or management is available when such catastrophic bleeds happen. This abstract present our experience with three major bleeding cases that presented with massive GI bleeding. Two are associated with peptic ulcer upon Upper GI endoscopy. Two males and one female age 60, 71 (males) and 71 (female). The first two patients were treated with Prothrombin complex product. The female patient presented with sever anemia of 4 grams of Hb with hematemesis and bright red blood per rectum. The Prothrombin complex product was not readly available . She was given multipe doses of Fresh Frozen Plasma FFP and multiple units of packed red blood cells. She was also given a product Profilnine which contains Factor II, IX and VII. Patient's coagulation profile of PTT, PT and Thrombin time were corrected. However, she continue to have bright blood per NG suction. Upon receiving D-DAVP Desmopressin 0.3 micrograms per Kg she stopped bleeding and EGD was done later with sclerosing treatment of gastric ulcer and ligation. Patient was given later a small dose of Prothrombine complex when was available since the last dose of Rivaroxaban was given less than 13 hours from her presentation to the hospital. All of the mentioned patients had prolongation of PT/INR/PTT at presentation. Thrombin time was monitored in all of them. All patients had survived the magor GI bleeding. D-DAVP were given to all of them.
In conclusion D-DAVP Desmopressin should be considered as an adjuvant drug in patient presentong with major GI bleeding secondary to Rivaroxaban.

Disclosures
No relevant conflicts of interest to declare.
The Prospective Use of Prothrombin Complex Concentrates in an Administrative Region of the Province of Quebec.
Authors: Bogaty Chloë , Breton Carolle , Laliberte Johanne , Marceau Daniele , Marceau Daniele 
Published: October 2019

Abstract
Introduction:
Prothrombin complex concentrates (PCCs) are used in the rapid reversal of warfarin and all other vitamin K deficiencies in patients with a major bleed or who require an urgent procedure. The Local Advisory Committee on Transfusion Medicine standardised a protocol for the use of PCCs, outlining the indications and contra-indications for their use.
Methods:
The charts of all patients having received PCCs between a two year period at the 4 hospital centers of region 12 were reviewed to evaluate the respect of guidelines, adherence to the protocol, and the clinical outcomes of patients.
Results:
From Nov. 2009 to Nov. 2011, 129 patients were treated with PCCs: 97 (75%) in the emergency department, 14 (11%) in the intensive care unit, 16 (12%) on medical or surgical floors, and 2 (1.5%) in the operating room. 116 prescriptions (90%) respected the guidelines; among the extra, 4 (3%) were for elective surgeries and 3 (2.3%) for an elevated INR without evidence of bleeding. One patient did not have an INR prior to administration, 10 (8%) did not have a repeat INR 30-minutes post-administration, and Vitamin K was omitted in 10 cases (8%). The prescription is based on weight: 120 (93%) received the correct dose, 3 (2.3%) received too high a dose, and 5 (3.8%) received too low a dose. The clinical outcome was favourable in 94 cases (73%), with rapid reversal of the INR and eventual discharge from hospital. 22 (17%) died during hospitalization and 10 (8%) were lost to follow-up due to transfer to a neurosurgical facility. The INR was less than 1.4 in 86% of cases 30-minutes post-administration. 6 (4.6%) thromboembolic complications occurred: two pulmonary embolisms, two deep vein thrombosis, one stroke, one disseminated intravascular coagulation. Five had resumed warfarin, but none had a therapeutic INR.
Conclusion:
Our review demonstrates that the majority of physicians correctly apply the recommended practice guidelines for the use of PCCs, that these are effective at rapidly reversing the INR, and are associated with favourable clinical outcomes in the majority of cases. However, thromboembolic events are frequent, emphasizing that anticoagulation therapy should be resumed quickly once clinically appropriate

Disclosures
No relevant conflicts of interest to declare.
Over-Expression of Heme Oxygenase-1 in Peripheral Blood Predicts the Progression and Relapse Risk of Chronic Myeloid leukemia
Authors: Wang Jishi , Wei Sixi , Wang Yating , Chai Qixiang , Fang Qin , Zhang Yaming , Lu Yinghao 
Published: October 2019

Abstract
Background There are limited eligible clinical markers at present to monitor the progress of chronic myeloid leukemia (CML). Heme oxygenase-1 (HO-1), as one of the most important oxidation-regulating enzymes in vivo, suggests the onset and progression of cancer when highly expressed. Furthermore, HO-1 level is related with the occurrence and development of hematological diseases. But the relationship between HO-1 expression and progression/relapse of CML has seldom been studied hitherto. This study aimed to investigate the relationship between them to find out a new molecular marker for prediction.
Methods A total of 60 peripheral blood and bone marrow (BM) samples from 25 CML patients in different phases were collected respectively to detect the expressions of HO-1 and bcr/abl using real-time PCR. Routine blood test was performed to detect the changes of leukocyte and platelet counts. The proportion of primitive cells in BM was detected by flow cytometry. The relationship between high HO-1 expression and CML progression and relapse was explored by the analysis of variance by Wilcoxon test and linear regression analysis. The diagnostic accuracy and cutoff values were determined by receiver operating characteristic curve.
Results Relative expression of HO-1 mRNA in CML patients peripheral blood was significantly higher than that of donors (P <0.0001), which were 0.57±3.78 and (1.417±1.125)×10–6, respectively. HO-1 expression level in CML patients was 0.061 5±0.062 4, which decreased to 0.009 4±0.006 7 upon CMoR, and remained remarkably higher 0.016 3±0.017 5 than that of normal donors (1.417±1.125)×10–6, P <0.001. When relapse occurred, HO-1 expression significantly increased from 0.020 6±0.021 0 to 3.852±10.285 in CMoR stage and undergoing relapse. According to progression of CML, HO-1 expression level in CML patients increased from CP (0.009 5±0.017 6) to AP (0.028 0±0.055 7) and then to BP (0.276 7± 0.447 0) . And there was a linear correlation between HO-1 expression and proportion of primitive CML cells. The diagnostic accuracies and cutoff values of HO-1 expression for CML-CP, CML-AP, and CML-BP were 1.0, 0.748, and 0.965, respectively, as well as 0.000 070, 0.001 917, and 0.020 696, respectively.
Conclusion HO-1 may be a potential molecular indicator for the progression and relapse of CML.

Disclosures
No relevant conflicts of interest to declare.
Synergistic Lethal Effects Between Gemcitabine and Arsenic Trioxide on Non-Hodgkin Lymphoma Cell Lines Is Associated with Modulation of PI3K/Akt Signaling Pathway
Authors: Zhang Mingwan , Xu Xiaojun , Ye Yongbin , Guo Ziwen , Bai Xiaochun , Wang Jing , Zhou Ruiqing , Qiu Dafa , He Huiqing , He Xin , Yi Wenfang , Weng Guangyang , Kunyuan Guo 
Published: October 2019

Abstract
OBJECTIVE: To explore the synersistic lethal effects of gemcitabine(GEM) with arsenic trioxide(ATO) on proliferation and apoptosis in the non-Hodgkin lymphoma cells ,and the major molecular signaling pathway involved in these effects.
METHODS: Human non-Hodgkin lymphoma cell lines Jurkat and Raji were used to determine the effects of GEM and ATO (alone or in combination) in vitro, as well as the PBMCs.Cell proliferation was measured by CCK-8 analysis. Cell cycle distribution and apoptosis were monitored by flow cytometry. The self-renewal and proliferating ability of cells were examined by methylcellblose conlony-forming units(CFU)assay.The activation of casepase-3, Bcl-2, and Akt was assessed by Western blot analysis.
RESULTS: ATO and GEM inhibited cell viability in a dose- and time-dependent manner, and induced cell cycle arrest and apoptosis.
The combination of ATO and GEM displays a synergistic or at least additive antitumor activity in vitro against cells than each single treatment. An obvious inhibition of NHL cells proliferation and an increased population of cells in apoptosis were observed in the combination treatment group, but not on PBMCs. ATO combined GEM at IC20 concentration did caused 50% inhibition of NHL cells proliferation. Afterwards, the rest of NHL cells were strongerly arrested in G0/G1 stage by ATO and GEM than each single treatment. Additionally, combination treatment also significantly reduced the ability of colony formation in NHL cells than treatment with either agent alone. Moreover, ATO blocked the Akt signaling pathway, subsequently inhibited Bcl-2 expression, reactivated cleaved caspase-3, while GEM did not. The combination group augmented these effects than each single agent.
CONCLUSIONS: ATO and GEM might be a potential candidate of the combination therapy for treatinghumanrefractory and relapsed malignant lymphoma, which also might be a salvage approach for patients who will be autologous transplantation in clinical trials; these effects were apparently associated with the modulation of PI3K/Akt signaling pathway.

Disclosures
No relevant conflicts of interest to declare.
Influence of MDR1 C3435T Genotype, Sokal Score and Hasford Score on the Overall Survival of Chronic Myelid Leukemia Patients Treated with Imatinib
Authors: Francis Jose , Biswajit Dubashi , Sundaram Rajan , Pradhan Suresh Chandra , Chandrasekaran Adithan 
Published: October 2019

Abstract
Aim: Imatinib is considered as the first-line drug of choice for the treatment of CML who is positive for Philadelphia chromosome. To correlate various prognostic scores (Sokal, Hasford and Eutos) and pharmacogenetic markers like ABCG2 421 C>A, SLC22A1 1386C>A, SLC22A1 1022C>T, SLC22A1 1222A>G, ABCB1 3435T>C, ABCB1 2677 G>T/A with the overall and progression-free survival in CML patients.
Methods: The patients who were started on imatinib from December 2009 to January 2014 at Regional Cancer Centre (RCC), JIPMER, Puducherry, India were recruited into the study. DNA was extracted from peripheral blood using phenol-chloroform method. The genotype status was identified using RT-PCR technique (AB7300, Applied Biosystems) using validated SNP genotyping kits. The influence of various factor on OS and PFS was determined using log-rank test (SPSS Ver 20.0).
Results: A total of 119 patients was identified as BCR/ABL positive and started on Imatinib treatment. Out of this 113 patients were in Chronic phase and six were in Accelerated phase. The median age of the patient group wad 39 years (18-74). The median overall survival and progression-free survival was found to be 25 months and 19 months respectively. The three yr overall survival was 94.5%. None of the prognostic scores or genotypes correlated with progression-free survival of the patients in this study cohort. The low-risk category of Sokal and Hasford groups had a statistically better overall survival compared to intermediate and high-risk groups (p value 0.030 and 0.014 using log-rank test analysis). The Mutant alleles for MDR1 C3435T had a better overall survival compared to other genotypes (p value <0.001 using log-rank test).
Conclusion: The Sokal score and Hasford score, not the Eutos score were better predictors of overall survival in our study. Out of the pharmacogenetic markers analyzed, MDR1 C3435T polymorphism had an influence on the overall survival.
Acknowledgments: The study was supported by the Science and Engineering Research Board (SERB) research grant (SB/FT/LS-147/2012).

Disclosures
No relevant conflicts of interest to declare.
Molecular Aberrations of Chronic Neutrophilic Leukemia: The CSF3R and SETBP1 Mutations
Authors: Cui Yajuan , Li Bing , Gale Robert Peter , Jiang Qian , Xu Zefeng , Qin Tiejun , Zhang Peihong , Zhang Yue , Xiao Zhijian 
Published: October 2019

Abstract
Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN) characterized by sustained elevated neutrophil levels with <10% immature cells according to WHO criteria. Recently, oncogenic mutations affecting the granulocyte-colony stimulating factor receptor (CSF3R) were reported to be highly prevalent in CNL. SET binding protein 1(SETBP1) mutations were also reported in some CNL cases. We reviewed clinical suspected 12 “CNL” patients and performed CSF3R and SETBP1 sequencing. All the 6 who met WHO criteria for CNL carried CSF3R T618I mutation. Four of the 6 also had SETBP1 mutations and a 5th had a CALR mutation (c.1154-1155insTTGTC). Two other who met these criteria but also had monoclonal gammopathy with uncertain significance (MGUS) had no CSF3R, SETBP1 or CALR mutation. The rest 4 carried infection or tumor and thus were excluded. We conclude including CSF3R and SETBP1 mutations into WHO criteria for CNL may improve diagnostic accuracy and may have therapeutic implications.

Disclosures
No relevant conflicts of interest to declare.
The Effects of CCL3 on Osteoblast Inhibition in Myeloma-Induced Bone Disease
Authors: Fu Rong , Zhao Sijie , Shao Zonghong 
Published: October 2019

Abstract
Multiple myeloma (MM) is a hematologic malignancy characterized by the accumulation of monoclonal plasma cells in the bone marrow. A common manifestation of the disease is bone destruction that caused by increased osteoclastic bone resorption and decreased bone formation. Suppression of osteoblast activity appears to persist even in patients enjoying long-term complete remission that without any detectable MM tumor cells. CCL3, also known as MIP-1α, is a pro-inflammatory and chemoline. To investigate if CCL3, a recently described osteoclast stimulatory factor,was possibly involved in the inhibition of osteoblast in MM-induced bone disease,osteoblast from BM of MM patients and healthy donors were cultured in vitro. Our results showed the proliferation and osteogenic potential of osteoblasts from MM patients were suppressed. MM-derived OBs expressed higher levels of CCR1 compared with normal controls. It’s an indication that CCL3 is able to influence OBs in MM bone disease (MBD).We cultured MM-derived OBs in osteogenic media and then stimulated them with CCL3 in the absence or presence of neutralizing antibody against CCL3. Our data suggested that CCL3 impaired matrix mineralization and suppressed osteocalcin (OCN).Gene expression analysis of osteoblastic transcription factors in CCL3-treated OBs revealed a Runx2 and Osterix downregulation. CCL3 antibody at least partially restored OBs activity with an upregulation of OCN levels and Runx2 and Osterix expression. These results showed that CCL3 may contribute to OB/OC imbalance by inhiting OBs’ dedifferentiation and function in MBD.

Disclosures
No relevant conflicts of interest to declare.
Impact of Novel Treatments on Multiple Myeloma Survival
Authors: Robinson David , Kaura Satyin , Kiely Daniel , Hussein Mohamad A. , Nersesyan Knar , Durie Brian G. M. 
Published: October 2019

Abstract
BACKGROUND: Multiple myeloma survival has significantly improved with the introduction of new therapeutic classes in the early 2000s. The magnitude of improvement in survival with better tolerated therapy is essentially transforming the disease from an acute condition, to a potentially manageable chronic disease . The impact of further advances in multiple myeloma therapy is not yet known but can be projected based on analysis of historical data and positive outcomes that are expected for future clinical trials.
METHODOLOGY: Analysis of data from the Surveillance, Epidemiology and End Results (SEER) were performed using SEERStat software. The first part of this analysis compares the median relative survival, based on cohort analysis, and five year relative survival, based on period analysis, for different time periods that coincided with the introduction of newer, better tolerated, more effective therapies for treating multiple myeloma. The second part of this analysis attempts to estimate future changes in survival, that may potentially result from additional disease modifying therapies planned to become available over the next 5-10 years. This will be accomplished through analysis of evidence-based metrics including extrapolation from early phase clinical trial data and validation with key opinion leaders.
RESULTS: Median, cumulative and 5 year relative survival of multiple myeloma have improved over the last decade primarily as a result of the introduction of newer therapies such as thalidomide, lenalidomide and bortezomib. Based on analysis of SEER data, median relative survival from the 1980s to 2000 showed modest changes, averaging approximately 30 months through the two decades. Thereafter, median survival increased to nearly 50 months by 2007 (FIGURE 1). Five year relative survival improved from about 30% in 1990 to over 46% in 2010 (FIGURE 2).
SUMMARY: This analysis highlights the dramatic improvements in multiple myeloma survival over the last three decades in the U.S., and demonstrates the transformative impact and value of novel therapies for multiple myeloma. The most substantial improvements were observed during the period between 2001 and 2007, when multiple myeloma median survival rates increased by 45%. This improvement has predominantly been driven by the introduction of novel classes of drugs and agents, including immunomodulatory and proteasome inhibitors. Over the next 10 years we expect to see a similar trend, where further advances in the treatment of multiple myeloma will yield additional novel therapies that could result in improvements of comparable or better magnitude.
FIGURE 1 FIGURE 1.
FIGURE 2 FIGURE 2.

Disclosures
Kaura: Celgene: Employment, Equity Ownership. Kiely:Celgene: Employment, Equity Ownership. Hussein:Celgene: Employment, Equity Ownership. Durie:Celgene: Advisory Board Celgene, IRC Onyx, DMC Millennium, IRC J&J Other.