bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Analysis of Invasive Fungal Infection after Allo-Geneic Stem Cell Transplantation
Authors: Ni Ming , Chen Baoan , Ding Jia Hua , Lin Qiang , Ma Yu 
Published: October 2019

Abstract
Object: The study was aimed to analyze the incidence, risk factors and outcome of invasive fungal infection (IFI) in allogeneic hematopoietic cell transplantation (HSCT) recipients, and to provide evidence for the prevention and treatment of IFI.
Method: 79 patients undergoing formed HSCT at this institute from Jan 2005 to Sep 2014 with intact datum, were analyzed retrospectively according to the diagnostic criteria of IFI. The data of age, sex, primary disease, the source of stem cell, HLA-identical situation, ABO matching, conditioning regimen, use of ATG, season, aGVHD, neutropenia less than 0.5×109/L, CMV infection, etiology culture, blood routine test, imaging, relapse of disease and survival were recorded. Moreover, the data of patients with IFI including usage of glucocorticoid and the neutrophil count were recorded when IFI occurred and the blood cells count after IFI.
Result: 17 patients has been diagnosed with IFI, in which 13 cases were probable and 4 cases were possible. The infection rate was 21.5%. There were 8 female and 9 male. The median age was 26 years (6-50 years).The total non relapse survival (NRS) rate was 55.6%, The NRS rate in non-infection group was 61.2% and that in infection group was 35.2%. The single-factor analysis showed matching(x2=15.061, p=0.010) and aGVHD (x2=6.983 p=0.008) were risk factors. After IFI, 8 patients died, 2 patients got complete response, 5 patients got partial response and 2 patients got stable response. The death rate was 47%, there was significant difference between two groups. The dose of glucocorticoid before IFI within 30 days was risk factor. Multiple-factor analysis further showed Ⅱ-Ⅳ degree of aGVHD (OR=4.810 p=0.012 CI:1.406-16.459 ) and matching (OR=25 p=0.007 CI:2.380-262.653) were risk factors. Moreover, before IFI, use of methylprednisolone more than 360 mg before infection (OR=0.041 P=0.017 CI:0.003-0.56) was risk factor.
Conclusion: Patients with poor matching, unrelated stem cell and Ⅱ-Ⅳ degree of aGVHD are more likely to occur IFI and those who were used more glucocorticoid are likely to die. Therefore, avoiding the risk factors might reduce the incidence rate of IFI and respect using dose of immunosupperssor before infection within 30 days may improve the patients' prognosis.

Disclosures
No relevant conflicts of interest to declare.
Towards Restoring Coagulation in Hemophilia By Antibody-Mediated Inhibition of Antithrombin
Authors: Boross Peter , Yildiz Cafer , Bakhtiari Kamran , Meijers Joost C.M. , Hack C. Erik 
Published: October 2019

Abstract
Currently hemophilia A is mainly treated with factor VIII (FVIII). However, 20-25% of the hemophiliacs develop inhibiting antibodies (inhibitors) against FVIII. Hemophiliacs with inhibitors are treated with high dose FVIII or with therapies that bypass the need for FVIII such as activated FVII (rFVIIa, NovoSeven) or activated prothrombin concentrate. These have some disadvantages including rapid clearance, price and a risk of thrombo-embolism.
In hemophilia, the balance between coagulation and anticoagulation is shifted towards the latter. This balance can be restored by administration of clotting factors but also by reducing anticoagulation mechanisms. Antithrombin (AT) constitutes a main anticoagulant mechanism as it inhibits thrombin, FXa and other activated clotting factors. In silico studies as well as observations that AT deficiency reduces bleeding in hemophilic mice and humans strongly support the concept that lowering functional AT levels bypasses the need for FVIII to generate thrombin. A Phase 1 clinical trial by Alnylam Pharmaceuticals showed that lowering AT activity by RNA-interference can boost thrombin generation in hemophilia. However, RNA-interference is an experimental therapy with unknown long term effects and is not suitable for acute treatment of bleeding as it takes weeks to become effective.
We hypothesize that monoclonal antibodies (mAbs) that block AT activity can be used as FVIII bypass therapy. Such a mAb-based therapy is suitable for on demand and for prophylactic therapy, is relatively cheap and does not require administration of activated clotting factors.
We have generated a panel of mouse anti-AT mAbs exhibiting varying binding characteristics to human AT. To assess the inhibitory activity of anti-AT mAbs, FXa activity assay was performed after FXa was incubated with normal plasma supplemented with the different anti-AT mAbs. Five anti-AT mAbs were identified that inhibit AT activity at around equimolar ratio. Inhibitory anti-AT mAbs were able to dose-dependently enhance thrombin generation in normal and hemophilic plasma. Heparin caused a marked prolongation of aPTT of normal and FVIII-deficient plasma, which was almost completely normalized by addition of the inhibitory mAb anti-AT 5G1.1, but not by anti-AT 6E7.2, indicating that these mAbs exert their inhibitory activity via different mechanisms.
These data provide initial in vitro proof-of-concept that inhibitory anti-AT mAbs can be used to improve coagulation and may be used as FVIII bypass therapy.

Disclosures
Boross: Prothix B.V.: Employment. Hack:Prothix B.V.: Equity Ownership, Patents & Royalties.
HSCT Improve Long-Term Outcome for Patients with T-Cell Lymphoma / Leukemia (TCL)
Authors: Wang Chunyan , Zheng Runhui , Qin Pengfei , Huang Zhenqian , Tan Huo 
Published: October 2019

Abstract
Objective To evaluate the treatment outcomes of hematopoietic stem cell transplantation (HSCT) in patients with T-cell lymphom / leukemia (TCL),observe hematopoietic reconstitution and transplant-related complications.
Methods Seventeen TCL patients received HSCT from 2005 to 2013 in our hospital were retrospectively analyzed.Of the 17 patients,6 were T lymphoblastic lymphoma / leukemia (T-LBL),3 were Peripheral T-cell lymphoma / leukemia (PTL),2 were Anaplastic large cell lymphoma (ALCL),2 were Extranodal NK / T-cell lymphoma (NK / TCL),1 were Angioimmunoblastic T-cell lymphoma (ATCL) and 3 were Acute T lymphoblastic leukemia (T-ALL) with a median age of 35(19~67) years old.Ratio of male to female is 13F4. The distribution of stages was 2(14.2%),0(0%)and 12(85.7%) patients with stages II,III,and IV,respectively. The distribution according to international prognostic index (IPI) was 8(57.1%) patients in 2 score,1(7.1%) in 3 scores and 5 (35.7%) in 4 scores.
Results ‡@17 patients were successfully engrafted, the median time of absolute neutrophil count(ANC) > 0.5×109/L was 11(8~15) days, the median time of platelet > 20×109/L was 13(8~18) days. 3 cases developed I degree acute GVHD, all patients were improved after treatment. ‡AAt a median follow-up of 36 (range,12-96) months,12 patients were alive and 5 relapsed and died from TCL after ASCT. The estimated 5-year probability of DFS and OS was (72.1±15.2)% and (59.7±15.2)% for all the patients.
Conclusion The results showed that HSCT may significantly improve long-term outcome for patients with T-cell lymphoma / leukemia (TCL).

Disclosures
No relevant conflicts of interest to declare.
Long-Term Outcomes after Myeloablative Allogeneic Hematopoietic Cell Transplantation for Adult Acute Lymphoblastic Leukemia
Authors: Mustafa Ali Moaath , Abounader Donna M , Rybicki Lisa A. , Starn Jamie , Ferraro Christina , Winslow Victoria , Hamilton Betty K. , Gerds Aaron T. , Liu Hien , Dean Robert M. , Hanna Rabi , Kalaycio Matt , Bolwell Brian J. , Advani Anjali , Majhail Navneet S. , Sobecks Ronald 
Published: October 2019

Abstract
Allogeneic hematopoietic cell transplantation (alloHCT) is a curative therapy for high-risk acute lymphoblastic leukemia (ALL). However, long-term outcomes after alloHCT for adult ALL have not been well described. We conducted a retrospective cohort study of 72 consecutive adult ALL patients who underwent a first myeloablative alloHCT at our institution from January 2000-December 2013. Median age at HCT was 38 yrs (range, 18-62), 40 (56%) were male, 18 (38%) had high HCT CI score, 14 (19%) had prior CNS leukemia and 35 (49%) had BCR-ABL+ disease. Donor source was HLA-matched related donor for 50% patients and 90% received PBSC as graft source. All patients were transplanted in CR (72% were in 1st or 2nd CR) and 92% received T-cell replete grafts. Median time from diagnosis to alloHCT was 5 months (range, 2-90). The incidences of grade II-IV and III-IV acute GvHD, chronic GvHD and extensive chronic GvHD were 43%, 13%, 51% and 36%, respectively. The median follow-up for our cohort is 76 months. At 6 years after HCT, probability of overall survival (OS) was 33% (95% CI, 21-44%) and relapse-free survival (RFS) was 30% (95% CI, 19-42%), and the cumulative incidence of relapse was 36% (95% CI, 25-48%) and non-relapse mortality (NRM) was 37% (95% CI, 26-49%). The most common causes of death were relapse (43%) and infection (21%); majority of relapses occurred within the first 2-years post-transplantation. There were no second cancer related deaths. In multivariable analyses, factors significantly associated with OS were HCT CI score (HR 2.69 for high vs. low/int., P=0.002) and CMV status (HR 2.62 for donor+ vs. others, P=0.05). HCT CI score was the only predictive factor for RFS (HR 2.26 for high, P=0.007). We also compared outcomes by BCR-ABL status. BCR-ABL+ patients were older (median age 42 vs. 36 yrs, p=0.02), had low HCT CI score (34% vs 22%, p=0.01), were more likely to be in CR1 (74% vs. 32%, p=0.002), and as a result, proceeded to HCT sooner after diagnosis (median 4 vs 7 months, p=<0.001). For BCR-ABL+ and BCR-ABL- patients, 6 year OS was 41% and 25%, RFS was 40% and 21%, relapse was 27% and 45% and NRM was 38% and 36% (P=NS for all comparisons). Myeloablative alloHCT can provide long-term survival for selected high-risk adult ALL patients. Relapses are relatively uncommon after 2 years post-transplant. Long-term NRM is high in this population and we did not observe a plateau in its incidence until 7.5 years post-transplant, suggesting the need for long-term follow up to prevent and manage late complications of alloHCT.
Figure 1. Figure 1.

Disclosures
Majhail: Gamida Cell Ltd.: Consultancy; Anthem Inc.: Consultancy.
Transfection CXCR3 Gene into Lymphocytic Leukemia Cell Lines By Lentiviral Vector
Authors: Ding Wenjiao , Feng Xiaoqin , Li Chunfu 
Published: October 2019

Abstract
Objective: Chemokine receptors and their ligands play important roles in the leukemia-initiating cell activity ,BCP-ALL progression and CNS infiltrating. To study the role of chemokine receptor CXCR3 in the mechanism of leukemia cell infiltration of the CNS, CXCR3 overexpression cell lines should be established. Lentivirus generally does not interfere with proto-oncogene and can express long-term and stable, so it is a good vector for genetic research on hematopoietic cells and T cells.
Methods: Mouse CXCR3 gene fragment was extracted by PCR from T vector which was kept in our lab. After the extraction, CXCR3 fragment and linearized LV5 lentivirus overexpressing vector(with GFP+-puro) were digested with NotI and BamHI.After this,we used T4 DNA ligase to connect them, making the target gene (CXCR3) cloned into LV5 vector, to obtain recombinant shuttle plasmid. Next,we mixed the shuttle plasmid with packaging plasmids (pGag/Pol, pRev, pVSV-G), packaged lentivirus, collected, tested viral titer and sequenced target gene by DNA sequencing. Then the constructed CXCR3 overexpression lentivirus transfected Jurkat and L1210 cell lines, at the same time MOI achieved to 100, twice infection and adding polybrene 5ug/ml to increase lentivirus transfection efficiency. After GFP expression was observed under fluorescent microscope, we used puromycin to select transfected cells and tested the expression of CXCR3 on cell surface by flow cytometry analysis of Anti-Mouse CD183 (CXCR3).
Results: After we sequenced the target mouse CXCR3 gene, viral titer reached to 1×10^9 TU/ml and GFP expression was observed after transfection 96h (<10%) on lymphocytic leukemia cell lines. Through puromycin selection, GFP+ cells surpassed 90% and CXCR3 overexpression group had upregulated 30%-90% compared with control group.
Conclusion: Chemokine receptor CXCR3 had been successful transfected into lymphocytic leukemia cell lines and had stably high expression. The effect of CXCR3 in leukemic invasion and leukemia progression can be further studied using constructed CXCR3 overexpression lymphocytic cell lines.

Disclosures
No relevant conflicts of interest to declare.
Cell Line-Dependent Synergy Between the PARP Inhibitor Veliparib and the Proteasome Inhibitor Bortezomib in the Killing of Myeloma Cells
Authors: Xu Alex , Mazumder Amitabha , Borowiec James A. 
Published: October 2019

Abstract
One hallmark of multiple myeloma is its genetic instability, leading to extensive molecular heterogeneity. This has led to the hypothesis that a high level of DNA repair is needed to counterbalance the continual genotoxic stress seen in these cells. One important DNA repair pathway involves PARP (poly-ADP ribose polymerase 1 and 2). With the goal of developing improved therapies against myeloma, we examined for potential synergy between the PARP inhibitor veliparib and agents currently used to treat myeloma.
In these pre-clinical studies, various myeloma cell lines including OPM2.2 and RPMI 8226 are being tested. Cells in triplicate are exposed to myeloma therapeutics (e.g., bortezomib, doxorubicin, cyclophosphamide) in the presence and absence of a sub-lethal dose of veliparib. Cells are incubated for 48 h and viability then assayed by luminescence using CellTiter-Glo (Promega).
Dependent on the cell line, we found that veliparib can be synthetically lethal with other agents. For example, testing OPM2.2 cells, we found that 50 µM veliparib caused a ~7-fold decrease in the bortezomib LC50 from 7.1 nM (bortezomib alone) to 1.0 nM (bortezomib and veliparib; see Figure). We note that the concentration of veliparib employed was significantly below the LC50 of veliparib (410 µM) for these same OPM2.2 cells. In contrast, RPMI 8226 cells did not show a significant synergy between bortezomib and veliparib, even though the LC50 of each agent alone was similar to that found for OPM2.2 cells.
We are currently examining the synergy between veliparib and other chemotherapeutic agents and additional myeloma cell lines. These studies will determine the generality of a potential synthetic lethality between these agents, and reveal whether use of a PARP inhibitor has the potential to provide improved treatment options against myeloma.

Disclosures
No relevant conflicts of interest to declare.
Variable Support Towards ASCO Recommendations for Venous Thromboembolism (VTE) Prophylaxis and Treatment in Patients with Cancer
Authors: Matzdorff Axel , Schwindel Uwe , Mueller Michael , Hutt Hans Joachim 
Published: October 2019

Abstract
Objectives: To determine the support of physicians for the recently published ASCO evidence-based clinical practice guidelines for venous thromboembolism (VTE) prophylaxis and treatment in patients with cancer (J Clin Oncol. 2015;33:654-6).
Methods: ASCO key recommendations were presented as part of three CME seminars to physicians not specialized in hem/onc or hemostasis. In addition two specialists in the field discussed a list of arguments for and against each of the recommendations considering (1) quality of scientific evidence underlying each recommendation, (2) feasibility in daily practice including sensitivity to patients preferences, and (3) medicolegal implications and reimbursement aspects. After each presentation attendees were asked to fill out a questionnaire on how much they supported the ASCO recommendations and each of the pro&con arguments.
Results: A total of 89 physicians attended the three meetings. 56 questionnaires were returned. The ASCO recommendations with the highest degree of support were:
‒ Patients undergoing major cancer surgery should receive prophylaxis for 7-10 days and even 4 weeks after major abdominal or pelvic surgery with high-risk features (84% pro)
‒ LMWH should be given for the initial treatment as well as for long-term secondary prophylaxis (80% pro).
The recommendations with the lowest degree of support were:
‒ Patients with cancer should be educated about signs and symptoms of VTE. They should be periodically assessed for VTE (59% pro).
‒ Anticoagulation should not be used to extend survival of patients with cancer in the absence of other indications (56% pro).
Conclusion: After presenting ASCO recommendations as part of CME training the degree of physicians' support was still at best moderate and sometimes even close to neutrality. In daily medical practice scientific evidence has no priority to clinical practicability, patients preferences, medicolegal aspects and cost-restrictions. Guideline authors should complement their recommendations with advice from their own practice on how to implement guidelines in daily care and how they manage financial and medicolegal restrictions. In addition there is an unmet need for more education on VTE prophylaxis and treatment among physicians not specialized in hem/onc or hemostasis who are caring for cancer patients.

Disclosures
Matzdorff: AMGEN - e. Honoraria: Honoraria; Aspen Germany: Honoraria; Bayer: Equity Ownership; Boehringer Ingelheim: Honoraria; Behring: Honoraria; Bristol Myers Squibb: Honoraria; GlaxoSmithKline: Honoraria; LEO Pharma: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Equity Ownership, Honoraria. Schwindel:LEO Pharma GmbH: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria; Amgen: Honoraria; Nordic Pharma: Honoraria. Hutt:LEO Pharma GmbH: Employment.
Increased Outpatient Care Can Reduce Hospital Stays for Sickle Cell Patients
Authors: Landau Danny A. , Steininger Kaitlyn , Landis Erica 
Published: October 2019

Abstract
Introduction: Sickle cell disease is associated with frequent hospitalizations and emergency room visits when patients enter vasooclusive crisis. This is associated with lengthy hospitalization that can be time life interrupting for patients, increase hospital cost, and limit bed availability for other patients. Some patients with sickle cell have higher inpatient requirements than others due to the frequency of crisis. Recognizing the issues associated with this, we began scheduling patients for frequent outpatient IV fluids and pain medication to try and prevent ER visits and lengthy hospital stays. We are reporting the experience of three of our patients who have had the most frequent hospitalizations and emergency room visits.
Methods: Patients who had the highest rate of hospitalizations and emergency room visits were offered regular outpatient intravenous and pain medication during the week (up to four times per week) on an as needed basis. Chairs were reserved for these purposes so on demand therapy could be offered without significant delays. The number of ER visits and hospital stays were counted from 12 months before and 12 months after we started offering this. For one of the three patients, data on length of hospital stay could not be accurately determined due to a lengthy hospitalization for infection rather than sickle cell pain crisis, but his emergency room visits were still counted. Basic hospitalization cost for daily hospital charge was also considered, but additional costs such as drug administration, diet, imaging, etc. were not.
Results: In the 12 months prior to starting regular outpatient IV fluids, there were 48 aggregate emergency room visits compared to 26 in the 12 months after, a reduction of 38%. Inpatient hospital days before were 91 before and 46 post (49%). Cost for hospital days were reduced from $224497 to $113480 (49%).
Conclusion: While offering more outpatient support to our sickle cell patients with the highest hospital demand, we can cut hospital days in half, and limit ER visits and also reduce the cost for inpatient care. Increasing outpatient support, when feasible, should be considered for sickle cell patients who require regular hospitalizations.
Figure 1. Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Impact of a Cancer Associated Thrombosis Clinic on Reducing Hospitalization for Venous Thromboembolism: The Cleveland Clinic Experience
Authors: Afzal Amber , Khorana Alok A. , Ornstein Moshe , McCrae Keith 
Published: October 2019

Abstract
INTRODUCTION:
Cancer patients with venous thromboembolism (VTE) have threefold increase in all cause hospitalization and days of hospitalization than cancer patients without VTE. Hospitalization with VTE is also associated with higher overall all cause inpatient cost (PMID 23430767). We hypothesized that a centralized cancer-associated thrombosis clinic instituted at the Cleveland Clinic in August 2014 would reduce hospital admissions for this indication and impact the cost of healthcare.
METHODS:
The study population comprised two cohorts: cancer patients admitted with a new diagnosis of VTE to the Cleveland Clinic Main Campus between August 1 and December 31 in 2013 before initiation of the cancer-associated thrombosis (CAT) clinic and between August 1 and December 31 in 2014 after initiation of CAT clinic. Patients who were accepted as transfers from outside hospitals were excluded from the study.
RESULTS:
In the pre CAT clinic study period, there were 101 admissions. Of these, 51 (50%) were admitted primarily for a thromboembolic event whereas the rest had VTE as a secondary diagnosis. In the post CAT clinic study period, there were 94 admissions. Of these, 42 (44.7%) were admitted primarily for a thromboembolic event. The baseline characteristics of the two study groups are detailed in table 1.
There was a reduction in hospital admissions for VTE by 9 admissions in the post CAT clinic period (RR 0.89, RRR 11%, p 0.252). The median length of hospital stay per patient was 3 days, reducing the total days of hospitalization by 27 days in post CAT clinic period. Figure 1
CONCLUSION:
We demonstrated that a centralized CAT clinic can reduce but not eliminate admissions for VTE. Larger health care systems should consider the development of such a service for the management of VTE in cancer patients as it can lead to significant cost savings and reduce unnecessary exposure of this vulnerable patient population to hospital environment
Table 1. Characteristic Pre CAT clinic period (N) Post CAT clinic period (N) Patients admitted with VTE as primary diagnosis 51 42 Median age (years) 62.41±12.85 61.6±13.4 Female patients 22 (44%) 26 (39%) Solid tumor diagnosis 42 (82.4%) 36 (70.6%) Hematological malignancy 9 (17.6%) 6 (11.8%) DVT 16 (31.4%) 12 (28.6%) PE 35 (68.6%) 30 (71.4%) PE patients with high PESI score (Class III/IV) 33 (94%) 28 (93%) Median length of hospital stay (days) 3 (1-27) 2.5(1-16)
Figure 1. Figure 1.

Disclosures
Khorana: Pfizer: Consultancy, Honoraria; sanofi: Consultancy, Honoraria; Leo Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria. McCrae:Janssen Scientific Affairs: Membership on an entity's Board of Directors or advisory committees.