bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Incidence and Investigation of In-Hospital Pulmonary Embolism In Patients Receiving Dalteparin Prophylaxis Following Elective Knee Replacement at Two Hospitals
Authors: Linkins Lori Ann , Warne Connor , Crowther Mark A. 
Published: October 2019

Abstract
Abstract 4388

Background:
The incidence of in-hospital pulmonary embolism (PE)in patients who received dalteparin prophylaxis following elective total knee replacement (TKR) at a tertiary care centre was reported to be surprisingly high at 4.6% (Kerr et al, Thromb Haemost 2010, 103:123-128).

Objective:
To compare the incidence and investigation of in-hospital PE between two centres that used dalteparin prophylaxis following elective TKR.

Method:
Charts of consecutive patients who underwent elective TKR and received dalteparin prophylaxis between January and June 2008 were retrospectively reviewed. A standardized case report form was used to abstract data on patient age, gender, type of surgery, risk factors for venous thromboembolism (VTE)(i.e. active cancer, prior history of VTE, hormonal therapy), results of imaging studies performed for suspected VTE, and in-hospital death. Electronic records were reviewed for 90 days after the date of surgery to capture subsequent studies for VTE performed at the same institution. Because the original study identified postoperative day 3 (POD#3) as the day that the majority of investigations were ordered for PE, a subgroup of 100 patients were randomly selected at each site, and data were abstracted on vital statistics which may have raised suspicion of PE: requirement for at least 2 litres of oxygen to keep oxygen saturation ≥ 92% or heart rate > 100 beats per minute or systolic blood pressure < 100 mmHg (These values were selected based on data from the original study).

Results:
The protocol at both hospitals dictated that the first dose of dalteparin (5,000 units subcut) was to be given on POD#1. At Hospital A only, 54 patients (12%) received dalteparin 2,500 units subcut 6 hours after surgery (personal practice of one surgeon).
None of the in-hospital PEs were fatal. The incidence of VTE (non-fatal and fatal) after discharge is less reliable because patients may have presented for medical attention at centres other than the hospital where they underwent surgery or died at home.
In the POD#3 substudy, the proportion of patients investigated for in-hospital PE was 11% and 3%, at Hospital A and Hospital B, respectively and the proportion of patients investigated for PE who were diagnosed with PE was 54% (6/11) and 0, respectively. The proportion of patients with at least one vital statistic which may have raised suspicion of PE on POD#3(hypoxia, tachycardia, hypotension) was similar at the two sites (45% vs 43%).

Conclusion:
The higher incidence of in-hospital PE in one of two hospitals using the same method of thromboprophylaxis following elective TKR was likely the result of a more aggressive approach to investigation. The clinical importance of detecting these emboli is uncertain.

Disclosures:
Crowther: Pfizer: Consultancy; Leo Pharma: Research Funding; Boehringer Ingelheim: Research Funding.
Effect of Very Dose Warfarin therapy Upon the Markers of Activcation of Clotting Following Major Joint Replacement Surgery
Authors: Bern Murray M. , Adcock Dorothy , Wheaton Diane , McCree Paula , Deeran Elisabeth 
Published: October 2019

Abstract

Abstract 4395
Prophylaxis against post-operative deep vein thrombosis using low dose warfarin is appealing as it is inexpensive and with low risk of hemorrhage. Investigators have examined this issue with variable outcomes. Critical to our thinking is that the drug must be started prior to the elective surgical intervention in order to be an effective antithrombotic agent, while not causing potential hemorrhagic anticoagulation. This abstract describes the effect of such a regimen on the generation of markers of coagulation activation, comparing fixed very low dose warfarin (1 mg daily) to variable dose warfarin among patients having elective replacement of hip or knee surgery. The fixed low dose warfarin is begun 7 days prior to surgery and continued 28 days post operatively. Variable dose warfarin is begun at 5 mg the night prior to surgery and is continued for 28 days post operatively with the target INR 2.0–2.5, adjusted twice per week. For this study the markers of coagulation activation are prothrombin fragment F1+2 and thrombin-anti-thrombin complex (T-AT). They are measured prior to start of warfarin therapy (baseline), on the morning of surgery (OR Day), and on postoperative days 3 and 28. PIVKA II is measured at the same time points as a measure of warfarin activity other than the INR. For this study 10 patients for each group are taken from a larger group of patients participating in a randomized prospective study of this regimen now in progress. Both studies are IRB approved. Table 1 demonstrates the results.
As expected the PIVKA II is increased over normal for both groups by OR Day and on post-operative days 3 and 28. Greater increases in PIVKA II, as expected, occur among patients receiving variable dose warfarin, as this group received higher doses. The T-AT is elevated by post-operative day 3 and is returned to normal on post-operative day 28 in both groups. At each time point the T-AT values are equal for the two study groups. The F1+2 values are modestly increased for both groups on post-operative day 3, with better suppression of F1+2 generation by the variable dose regimen on day 28. In conclusion, the fixed low dose warfarin regimen is as effective as the variable dose warfarin as measured by the generation of T-AT, and is possibly somewhat less effective as determined by the generation of F1+2. The clinical significance of this difference is unknown, especially given the suppression of the T-AT. None of these patients suffered postoperative thromboembolic disease.

Disclosures:
Adcock: Esoterix Laboratory Services, Inc: Employment.
Evidence of Common Mechanisms Underlying the Survival Advantage of the PIG-A mutant and 13q- Hematopoietic Stem Cell Clones In Patients with Immune-Mediated Bone Marrow Failure
Authors: Hosokawa Kohei , Katagiri Takamasa , Sugimori Naomi , Qi Zhirong , Espinoza Luis J. , Sanada Masashi , Ogawa Seishi , Nakao Shinji 
Published: October 2019

Abstract
Abstract 4429

Background:
Numerical karyotypic abnormalities of undetermined significance are occasionally detected in patients with bone marrow failure (BMF), including aplastic anemia (AA) and low-risk myelodysplastic syndrome (MDS). BMF patients with 13q deletions (13q-) are likely to respond to immunosuppressive therapy (IST) without a propensity to develop into leukemia (Ishiyama K et al, Br J Haematol; 117: 747. 2002), and they possess small populations of glycosylphosphatidyl-inositol anchored protein (GPI-AP)- deficient granulocytes and erythrocytes more frequently than patients with normal karyotypes%, 15 with AA and 8 with MDS) of 1705 patients. The proportion of 13q- clones in all metaphase cells ranged from 5% to 100% with a median of 27.5%. Fourteen of the 23 (61%) patients showed 13q- alone and 9 (39%) showed other karyotypic abnormalities in addition to 13q-. GPI-AP- cells that accounted for 0.009% to 6.7% (median 0.148%) of granulocytes were detected in all (100%) of the 14 patients with 13q- alone, while the prevalence of increased GPI-AP- cells in patients with 13q- plus other abnormalities and those with a normal karyotype was 44% and 43%, respectively. A FISH analysis of PB granulocytes in individual patients revealed apparently lower percentages of GPI-AP- granulocytes than those of 13q- granulocytes, indicating that the GPI-AP- granulocytes were derived from non 13q- HSCs. Ten patients with 13q- alone were treated with IST (ATG+cyclosporine in 4 and cyclosporine alone in 6) and all of them achieved either a partial remission or a complete remission. The SNP array analysis of 5 patients revealed common deletion of a 15 Mb (13.3 to 14.3) region containing the RB gene. Wild-type and PIG-A mutant K562 cells were incubated in the presence of TGF-beta, which can inhibit leukemic cell proliferation by down-regulating phosphorylated RB protein (pRB), to determine whether the RB gene loss in 13q- HSCs has any connection with a proliferative advantage of PIG-A mutant HSCs. PIG-A mutant K562 cells were less sensitive to TGF-beta inhibition of proliferation and down-regulation of pRB levels than wild-type K562 cells.

Conclusion:
The markedly high prevalence of increased GPI-AP- cells and good response to IST indicate that the presence of 13q- clones is highly associated with the immune pathophysiology of BMF. Decreased sensitivity to inhibitory signals by TGF-beta due to RB gene loss in 13q- HSCs and the loss of GPI-AP-type TGF-beta receptors in PIG-A mutant HSCs may therefore be a common mechanism that confers a survival advantage to these mutant HSCs over normal HSCs in patients with immune-mediated BMF.

Disclosures:
No relevant conflicts of interest to declare.
Detection and Analysis of Autoantigens on the Membrane of Bone Marrow Cells In the Patients with BMMNC- Coomb's Test(+) Hemocytopenia
Authors: Fu Rong , Liu Hui , Shao Zonghong , Wang Jun , Li Lijuan 
Published: October 2019

Abstract
Abstract 4434

Objective
To investigate the autoantigens on the membrane of bone marrow cells in the patients with bone marrow mononuclear cell Coomb's(BMMNC-Coomb's) test(+) Immuno-related pancytopenia(IRP),for further purification and cloning.

Methods
20 newly diagnosed IRP patients, 10 AA patients, 10 MDS patients and 10 healthy donors as controls were enrolled in this study.The level of autoantibody-IgG in bone marrow was measured by Western blot; The autoantigens targeted by autoantibody IgG in IRP were identified from membrane protein extracts by SDS-PAGE and Western blot.

Results
The level of autoantibody IgG in bone marrow of untreated IRP patients was 75% (15/20), which was significantly higher than that of AA or MDS patients (0%) and normal controls(10%)(P<0.01). Autoantibody IgG in IRP could react with several autoantigens with approximate MWs of 25–30kDa, 60–65 kDa, 73 kDa and 83 kDa. Positive rates of individual autoantigens were 35%,50%,20% and 10%,respectively.

Conclusion
Autoantibody IgG reacted with membrane antigens could be found in bone marrow in IRP patients. The molecular weights of the autoantigens were mainly 25–30kDa, 60–65 kDa, 73 kDa and 83 kDa. The result showed that autoantibody IgG played an important role in IRP.

Disclosures:
No relevant conflicts of interest to declare.
Successful Mobilization of Peripheral Blood Stem Cells After Intensive Bendamustine Pre-Treatment In Patients with Multiple Myeloma
Authors: Pönisch Wolfram , Wiesler Julia , Leiblein Sabine , Edel Elvira , Al-Ali Haifa K. , Basara Nadezda , Hegenbart Ute , Heiß Christiane , Niederwieser Dietger W , Goldschmidt Hartmut 
Published: October 2019

Abstract
Abstract 4439

Introduction
The alkylating agent bendamustine has structural similarities to both alkylating agents and purine analogs, and is effective in the treatment of patients with multiple myeloma. So far, no data are available on stem cell toxicity or on stem cell mobilization. Since autologous stem cell transplantation is an established treatment for multiple myeloma after primary treatment, we were interested in analysing the experience of stem cell mobilization after bendamustine treatment.

Material and Methods
A retrospective analysis over a period of fifteen years was carried out in 56 (34 male and 22 female) patients with multiple myeloma after bendamustine pretreatment at the university hospitals Leipzig and Heidelberg. Patients had a median age of 58 (range 31–72) years. The median number of cycles was 3 (range 1–10) and the cumulative bendamustine dose ranged from 120 to 2400 mg/qm. The mobilization regimen in 37 cases was either cyclophosphamide 4 g/qm (n=33) or 7 g/qm (n=4) followed by G-CSF (2×5 ug/kg s.c.). Alternative regimens such as CAD, CED, TCED and others were used for mobilization in the remaining 19 patients. Apheresis was started as soon as peripheral blood CD34+ counts exceeded 10×106/l with a harvest target of 4×106 CD34+/kg using 4 times the blood volume. The minimal accepted target was 2×106 CD34+/kg.

Results
Stem cell harvest was successful in 54 of the 56 patients. In one patient the peripheral blood CD34+ cell count failed to reach 10 × 106/l and no apheresis was performed. In one further patient a rapid decrease in peripheral blood CD34+ counts resulted in insufficient recovery of stem cells in the apheresis product. In 18 out of 54 patients (33%) the target was reached with a single apharesis. The median number of aphareses in the 54 patients was 2 (range 1–7) and the median CD34+ cell-count obtained was 5.5 (range 1.7–20.4) × 106/kg. Engraftment was successful in 52/53 patients receiving a stem cell transplant. One patient was successfully harvested and did not receive the transplant yet.

Conclusion
From this retrospective analysis we conclude that mobilization of PBSC is possible after intensive bendamustine pretreatment.

Disclosures:
Niederwieser: Bristol-Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau. Goldschmidt:Celgene: Membership on an entity's Board of Directors or advisory committees; Ortho Biotech: Membership on an entity's Board of Directors or advisory committees; Ortho Biotech: Research Funding; Celgene: Research Funding; Chugai Pharma: Research Funding; Amgen: Research Funding.
Dasatinib Promotes BIM Dependent Apoptosis Via MEK/ERK without Need for Permanent BCR-ABL Inhibition
Authors: Simara Pavel , Stejskal Stanislav , Martina Peterkova , Koutna Irena , Racil Zdenek , Mayer Jiri 
Published: October 2019

Abstract
Abstract 4472
Chronic myeloid leukaemia (CML) is a clonal disorder of haematopoietic stem cells, characterized by constitutively active BCR-ABL kinase. It was previously shown, that transient inhibition of BCR-ABL by tyrosin kinase inhibitor (TKI) dasatinib induces apoptosis in CML cells (Shah 2008). Dasatinib mediated apoptosis is accompanied by increasing expression level of proapoptotic protein BIM and inhibition of its degradation in proteasome.
Our aim is to find alterations in BCR-ABL downstream pathways and changes in BIM expression after pulse (wash-out after 20min) or continuous treatment with TKI dasatinib alone or in combination with proteasome inhibitor bortezomib in K562 cells.
Higher mRNA levels of BIM were confirmed in both transiently and continuously treated (100nM dasatinib) K562 cells compared to low dose continuous (1nM dasatinib) treatment. Western blot analysis of BCR-ABL induced signalling pathways activity revealed, among others, sustained inhibition of MEK/ERK pathway even in the case of re-activation of BCR-ABL after drug wash-out. MEK/ERK inhibition leads to activation of proapoptotic BIM expression and inhibition of its degradation. We used bortezomib, a reversible inhibitor of proteasome, in order to test the block of BIM degradation in dasatinib treated cells. However, we have not found any difference in cell viability caused by adding of 30nM bortezomib to dasatinib treated cells neither in continuous or transient exposure. These findings suggest that equal increase of BIM in the case of pulse and continuous dasatinib treatment is caused by MEK/ERK inhibition in cells with restored BCR-ABL activity.
This project is supported by grants from the Ministry of Education of Czech Republic NPVII (2B06052) and MSM-0021622430. The substance (dasatinib) for this project was supplied by BMS company.

Disclosures:
Mayer: BMS: Consultancy, Research Funding.
High Adherence to Tyrosine Kinase Inhibitors Seems to Be Related to Best Cytogenetic Responso In the Hasford Lower Risk Graup In Chronic Myeloid Leukemia.
Authors: Almeida Maria Helena , Pagnano Katia B. , Souza Helia , Miranda Eliana C M , Souza Carmino De 
Published: October 2019

Abstract
Abstract 4477
Tyrosine kinases Inhibitors (TKI) of first and second generation are presently the choice of treatment for chronic myeloid leukemia (CML) and adherence to the treatment is an important factor to obtain good therapeutic results. We used the World Health Organization adherence definition that enrolls a global person's behavior including how the medication is used, diet, and/or lifestyle change.

Objective:
To evaluate the adherence to TKI in patients with CML and to identify factors that can affect adherence to TKI treatment.

Methods:
A prospective and observational analysis was performed with 122 patients taking TKI, in a public institution. The median of observation time was 169 days (131-240). We used the Hasford scale to risk assessment of diagnosis. The adherence was calculated using the mean medication possession ratio (MPR), calculated as total days’ dose of TKI divided by the number of the days in the observation time. Statistical analysis began with descriptive analysis and after that we applied Pearson or Spearman's correlation and t-Test, what it is adequate, considering significant p-value £ 0.05.

Results:
A total of 122 patients were evaluated: 92 (75.5%) were taking Imatinib, 16 (13%) Nilotinib, 09 (7.5%) Dasatinib and 5 (4%) Bosutinib. The mean age was 48 (20-82) years. The majority of patients were male (61%) and the median of TKI treatment time was 45 months (7-114). There were 103 (84.5%) patients in first line treatment, 17 (14%) in second line and 2 (1.5%) in third line. Considering all patients, median and mean of adherence was 96% and 90% whereas 23% of patients had 100% of MPR. There was a significant difference between adherence distribution and cytogenetic results, best adherent patients had most complete and major cytogenetic response (p= 0.01) in CML Hasford lower risk group. In all patients, the MPR decreased with longer use of TKI treatment (p= 0.02) and with longer time of diagnosis (P= 0.002). The adherence was superior in patients participating in clinical trials (p= 0.01) and using second generation TKI (p= 0.001).

Conclusion:
The best adherence was correlated to a better cytogenetic response in Hasford lower risk group. Longer time of treatment was related to a poorer adherence, suggesting a continuous approach by health team can make a difference.

Disclosures:
No relevant conflicts of interest to declare.
Comorbidities and Conmedication Use In Patients with Chronic Myelogenous Leukemia.
Authors: Oliveria Susan A , Yood Marianne Ulcickas , Hirji Ishan , Cziraky Mark , Davis Catherine 
Published: October 2019

Abstract
Abstract 4492

Introduction:
Few studies have evaluated the presence of comorbidities and the complexity of conmedication among CML patients in the real-world setting. No studies have used automated claims and medical record review to obtain comprehensive CML diagnosis, treatment, comorbidity, and conmedication information.

Methods:
Medical and pharmacy claims from HealthCore Integrated Research Database™ (8.5 million covered US lives during study time period) were used to identify patients with CML (2001 – 2005). Information on comorbidities and conmedications was obtained using claims data supplemented with medical record review. For the current analysis, conmedication use and the presence of comorbidities were assessed for one year following imatinib initiation.

Results:
Two hundred and sixteen CML patients treated with imatinib were included in this analysis. Mean age at imatinib initiation was 51 years and 42.6% were female. The mean number of unique medications for treated patients was 19 (median = 9) in the one-year follow-up. Of all medications prescribed within 1-year of CML treatment initiation, approximately 40% had dosing restrictions (i.e. administration required with/without meals) and dosing of more than once per day. The proportion of patients experiencing 1, 2, 3, and 4+ comorbidities was 22%, 16%, 17%, and 29%, respectively. Analyses were also conducted to explore the complexity (based on dosing guidelines and intake restrictions) of each medication and specific comorbidities. Thirty-four percent % of the conmedications had no intake restrictions while 11% had specific intake restrictions (e.g. take on empty stomach) and 15% had dosing guidelines of more than once per day. Forty-one percent of conmedications had both dosing restrictions and dosing of more than once per day.

Conclusion:
In addition to their CML diagnosis, patients experience a number of other comorbidities, some of which require complex management regimens. This is the first study to use medical record review to validate exposure and CML diagnosis and use claims and medical record review to obtain comprehensive information on comorbidities and conmedications. Additional data are being collected (and will be presented) on this cohort to extend follow-up through 2010, expand the number of CML patients included, and obtain complete information on all CML treatments and comorbidities.

Disclosures:
Hirji: Bristol-Myers Squibb: Employment. Davis:Bristol-Myers Squibb: Employment.
Imatinib Therapy for Chronic Myeloid Leukemia: An Experience From Eastern India.
Authors: Dasgupta Swati , Ray Ujjal , Mukhopadhyay Soma , Bose Chinmoy Kumar , Sarkar Sanjoy , Gharami Firoj , Dey Subhasish , Basak Jayasri , Mukhopadhyay Ashis 
Published: October 2019

Abstract
Abstract 4498

Background:
Chronic Myeloid Leukemia(CML) is an myloproliferative disorder characterized by the expansion of clone of hematopoietic cells that carries the Philadelphia chromosome(Ph).The Ph chromosome results from a reciprocal translocation between the long arms of chromosome 9 and 22,t(9;22) (q34;q11).The molecular consequence of this translocation is a fusion gene. Imatinib inhibits constitutively active BCR-ABL tyrosine kinase of Chronic Myeloid Leukemia (CML).This is a novel molecule, which inhibits the protein product of this fusion gene and hence has been used in the treatment of CML. We are now report 51 months of median follow-up data and focus on 645 number of patients who received Imatinib as a primary treatment from 2002 to 2010.

Materials and Methods:
We included total 645 patients of CML during the period of January 2002 to June 2010.The age range was 02–87 years with median age being 36±11.6 years. Among 645 patient 366 was male and 280 female. A total 645 patients 608was in chronic phase, 31 in accelerated phase and 5 patients had blast crisis at the time of presentation. At present the molecular status of the disease has been detected by RT PCR, Flowcytometry (By Fluorescence Activated Cell sorter, FACS), Karyotyping and FISH.As a runtime protocol we have used Imatinib as 400 mg/day as standard dose at chronic phase, 600 mg/day in accelerated phase and 800 mg/day in blast crisis.We have studied a comparative analysis of Hematological parameter values.

Result:
The best observed average rate of complete hematological response was 97%, complete cytogenetic response was 50%, complete molecular response 35% with partial response in 45% and poor response in 15%.After 1 year levels of BCR-ABL transcripts had fallen in 52% patients and after 4 years levels had fallen in 79%.

Conclusion:
At 51 months of median follow-up in our study, comparative analysis of haematological parameters like haemoglobin, Total Count, Platelet Count between patient and normal population revels that pre-treatment value against normal value is very significant. The post treatment value of the haematological parameters is very close to the normal values and hence it can be proved that Imatinib therapy is effective. We observed that Imatinib drug is tolarence in case of 90% patients and resistance in about 10 % patient. So, we can conclude that Imatinib is an effective and safe drug for CML patient.

Disclosures:
No relevant conflicts of interest to declare.