bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long Acting Anticoagulant Effects of Idraparinux in Patients Treated for Prophylaxis of Recurrent Venous Thromboembolism.
Authors: Harenberg Job , Joerg Ingrid , Weiss Christel , Fenyvesi Tivadar 
Published: October 2019

Abstract
Prophylaxis of recurrent venous thromboembolism (VTE) has been investigated in patients with acute VTE participating in the VanGogh DVT, PE and Extension studies for a minimum of 6 months. These patients were given a fixed dose of Idraparinux once a week subcutaneously without coagulation monitoring. The VanGogh DVT/PE studies randomized patients to Idraparinux versus INR-adjusted Warfarin. Patients were then able to follow on to the double-blind VanGogh Extension study comparing Idraparinux versus placebo. Determination of the anticoagulant effects may still be necessary for patients in acute clinical settings. After termination of the studies, the anticoagulant effects of Idraparinux were followed-up in 23 patients using Heptest coagulation method, anti-factor Xa inhibition method (aXa, chromogenic substrate S2222) and prothrombin induced clotting time (PiCT) assay. The study was accepted by the local ethics board and patients gave written informed consent. Serial blood samples were taken for up to 15 months after termination. The Heptest and PiCT methods were prolonged in all patients’ blood for 9 to 15 months after therapy termination. The chromogenic assay method showed factor-Xa inhibition for the same period of follow-up. The elimination half-life of Idraparinux was calculated at 60.5 ± 23.3 days using the Heptest method and at 55.1±15.4 days using the aXa-assay method. There were no differences noted in the half-life between patients participating in the DVT/PE and Extension study. The half-lives were independent from patients’ body weight and creatinine clearance. The complete pharmacokinetic analysis of the results will be presented. The unexpectedly long half-life may be explained by the lipophilicity of methylated Idraparinux. Overall, the data suggests a benefit from the prolonged antithrombotic effect of Idraparinux as well as an increased risk of hemorrhage after therapy termination, possibly explaining some of the van Gogh studies results.
Identification of Specific TRAV6 and TRAV23 Genes in Peripheral Blood T Cells from Patients with Diffuse Large B-Cell Lymphoma.
Authors: Li Yangqiu , Yin Qingsong , Tan Huo , Chen Shaohua , Ye Jingmei , Yang Lijian , Li Bo 
Published: October 2019

Abstract
Antigen specific T cells were identified in peripheral blood from some malignancy, for example melanoma, as well as in B-ALL. The T cells proliferation in response to tumor antigen could be identified by analysis of T cell receptor repertoire, which can display the distribution of TRAV or TRBV subfamilies and the clonaltiy of different subfamily T cells, the clonal expanded T cells are thought to be relate to antigen specific T cells in non-T-cell malignancy. In order to identify the specific T cell clone which was expected to have a specific anti-DLBL (diffuse large B-cell lymphomas) effect and to use as immunotherapeutic cells to prevent minimal residual disease in patients with DLBL, TRAV subfamily genes from clonal expanded T cells were analyzed by using RT-PCR, genescan and DNA sequencing techniques. Peripheral blood mononuclear cells from 6 cases with DLBL were used in the study. By using RT-PCR with 29 specific TRAV subfamily primers, some of TRAV subfamilies could be detected in different samples, 4 monoclonal expanded TRAV subfamily T cells were identified by genescan analysis, in which PCR products direct sequencing was performed to identify the CDR3 sequence. Specific TRAV6 and TRAV23 sequences were obtained in 3 cases respectively, however the CDR3 sequence of TRAV6 or TRAV23 form different patients were not complete identical, suggesting that they recognized and bound specifically to different DLBL-associated antigens. And the CDR3 sequences of these 4 identified genes (two TRAV6 and two TRAV23) were not be reported in Genebank. The whole sequence of both TRAV6 and TRAV23 genes were obtained by RT-PCR amplification the global rearrangement TRAV6 or TRAV23 segments. There are being registered in NCBI Genebank. The sequences will be farther used in TCR gene transfer to T cells to establish the specific anti-DLBL T cell clone and to confirm its specific cytotoxicity.
IPI and R-IPI in Korean DLBCL Patients Treated with R-CHOP.
Authors: Bae Sung-Hwa , Ryoo Hun-Mo , Kim Min Kyoung , Lee Kyung Hee , Hyun Myung Soo , Kim Hawk , Park Jea-Hoo , Lee Won-Sik , Joo Young-Don 
Published: October 2019

Abstract
Background: The addition of rituximab to CHOP chemotherapy (R-CHOP) has resulted in a marked improvement in outcome for patients with diffuse large B cell lymphoma (DLBCL). The previously estimated risk factors needed to be re-evaluated in immunochemotherapy era. Shen et al. (Blood109:1857–61, 2007) reported that a revised (R) international prognostic index (IPI) provided a more clinically relevant prediction of outcome than IPI. To assess the applicability of IPI and R-IPI in unselected Korean DLBCL patients, we conducted this study.
Methods: We performed a retrospective analysis of patients with newly diagnosed DLBCL treated with R-CHOP to assess the value of the IPI and R-IPI.
Results: From January 2004 to July 2006, 113 newly diagnosed DLBCL patients from four Korean institutes were included. Patients characteristics were: median age 54 y (range: 14–83), male 62.8%, extranodal disease 54.9%, age greater than 60y 40.7%, ECOG PS greater than 2 10.6%, elevated LDH 46.9%, more than 1 extranodal sites 17.7%, stage III/IV 40.7%. The 3 year EFS rate was 60.2% and the 3 year OS rate was 66.7%. Estimated 3 year EFS and OS according to IPI were described in the table.
Conclusions: The IPI score as well as R-IPI was an important prognostic parameter in unselected Korean DLBCL patients treated with R-CHOP.
No of Pt 3 year EFS (%) p-value 3 year OS (%) p-value No of IPI <0.001 0.001 0 22 78.6 83.3 1 40 71.8 81.9 2 28 59.3 61.8 3 16 36.5 42.4 4 6 16.7 22.8 5 1 0 0 IPI <0.001 <0.001 Low 62 74.7 82.8 Low intermediate 28 79.3 61.8 High intermediate 16 36.5 42.4 High 7 14.3 16.7 R-IPI <0.001 0.008 Very good 22 78.6 83.3 Good 68 65.8 71.6 Poor 23 28.1 34.9
The PPARß Activation Mechanism Which Suppresses the Constitutive NF-kB Activity in Human Myeloma Cell Lines.
Authors: Otsuyama Ken-ichiro , Amin Jakia , Abroun Saeid , Islam Abul , Shamsasenjan Karim , Iqbal Shamim Mohd , Kawano Michio M. 
Published: October 2019

Abstract
[Purpose] It is considered that human myeloma cells have the constitutively high NF-kB activity involved in survival and proliferation. PPAR (Peroxisome proliferator-activated receptor) ß is ubiquitously expressed in all cells and considered to be involved in the lipid metabolism and regulating the inflammatory response and cell proliferation. We already have found that adrenal cortex hormones (DHEA and DHEA-S etc), dexamethasone (Dex) and baicalein augmented the expression of reporter gene. However, it remain to be clarified the role of PPARß in human myeloma cells. We focus on the mechanism of PPARß suppressed NF-kB activity.
[Method]
To know NF-kB activity of human myeloma cells, we performed EMSA with NF-kB consensus oligo. To investigate NF-kB and PPARß after stimulation of PPAR agonist, we did EMSA with NF-kB and PPAR consensus oligo. To confirm whether it is repression according the NF-kB activity suppression accompanying PPARß activation to the interaction of PPARß and NF-kB, we conducted immunoprecipitation - western blot analysis. To check whether the expression of NF-kB target genes (cIAP1, Bcl-xL, etc) were suppressed after stimulation of PPAR agonist, we performed RT-PCR analysis.
[Result and discussion] It was suggested that human myeloma cell lines have constitutive NF-kB activity, and its activity mainly regulated p50. NF-kB activity and its target genes were repressed by stimulation of PPAR agonist. From the above, it was suggested that the activated PPARß interacted NF-kB and then its activity was suppressed.
Comprehensive Mapping of Transposon Insertions in Human Hematopoietic Neoplasias.
Authors: Burns Kathleen H. 
Published: October 2019

Abstract 1103
Poster Board I-125
Our genomes are replete with mobile DNAs, many of which are retrotransposons that have accumulated over time by “copy-and-paste” mechanisms involving reverse transcription of RNA intermediates. Subsets of human transposable elements have been recently active or remain active today, resulting in many insertional polymorphisms in modern populations. In vitro studies in human tumor cell lines have unequivocally shown that expressed retrotransposons can generate new insertions and potentiate large scale genomic rearrangements. Though normally transposon sequences are highly methylated and thus stably suppressed in somatic cells, loss of methylation has been described in some malignant states, including chronic lymphocytic leukemia (CLL), multiple myeloma (MM), and ‘blast crisis’ phase chronic myeloid leukemia (CML). This has led to speculation that derepressed transposons contribute to clonal evolution of these pathologies, though experimental evidence for this has been lacking due to an inability to detect new genomic insertions. In collaboration with Jef Boeke's laboratory, I have developed an array-based transposon insertion profiling method (TIP-chip) for mapping mobile retrotransposons in the human genome. Early application of this technology in leukemia patients and leukemia cell lines shows numerous novel insertions of L1 LINEs, AluYb SINEs, and HERV-K transposons, including several insertions in genes known to be involved in leukemogenesis. We expect the technology will add a new dimension to our understanding of the human genome, including genetic predispositions to cancer development, and will enable tests of the hypothesis that insertional mutagenesis by endogenous transposons is a driving force in hematopoietic malignancies.

Disclosures
No relevant conflicts of interest to declare.
Correlations Between Host Cellular Immune Responses and Adenovirus (AdV) Associated Complications in Pediatric Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Guérin Valérie , Dalle Jean-Hugues , Pedron Béatrice , Yakouben Karima , Cordeiro Debora Jorge , Peltier Lucas , Ouachée-Chardin Marie , Baruchel Andre , Sterkers Ghislaine 
Published: October 2019

Abstract
Abstract 1145
Poster Board I-167

Rational
Correlations between host AdV-specific immunity and the risk of AdV-associated complications remain to be clarified for improving patients care in allogeneic hematopoietic-stem cell transplantation (HSCT) setting, particularly for pediatric patients. In immunocompromised individuals, high number of AdV-specific IFNg secreting T-cells appears to be associated with AdV control. Infusion of IFNg-secreting AdV-specific T-cells has been shown to cure patients with severe AdV infection. We realized an in vitro study to correlate host cellular immune response and AdV associated complications.

Material and Methods
In this study, CD4+ T-cell AdV-specific immune-recovery was relied to AdV-infection in 40 pediatric patients (median age: 7.60 years) who underwent allogeneic HSCT after either Bu-based or TBI-based fully myelo-ablative conditioning regimen. HSCT were performed for haematological malignancies. Patients received CSA +/- short course MTX as GvHD prophylaxis. Monitoring for AdV infection in transplanted patients consisted of weekly PCR during at least the first 3 months following HSCT. Antiviral chemotherapy was initiated if AdV-DNA levels were over 2000 copies/ml. Blood samples from 34 healthy children (median age: 5.4 years) and 31 healthy adults were analyzed as reference. Proliferative-responses were assessed by 3HT incorporation and cytokine-responses by intracytoplasmic flow-cytometry assay.

Results
In conclusion,

Disclosures
No relevant conflicts of interest to declare.
Clinical Significance of EBV-Associated LPD After Cord Blood Transplantation.
Authors: Satou Maho , Kimoto Tomiko , Yamada Kayo , Kondou Osamu , Tokimasa Sadao , Yasui Masahiro , Ohta Hideaki , Inoue Masami , Kawa Keisei 
Published: October 2019

Abstract
Abstract 1161
Poster Board I-183

Introduction
The number of cord blood transplantation (CBT) is rapidly increasing. In this setting, development of Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD) appears to be at high risk. To clarify this issue, we retrospectively analyzed EBV serology and clinical course of 57 patients who received CBT during the past 12 years.

Patients and methods
We underwent 79 CBT until 2008. Fifty-seven patients were available for assessing EBV serology. The mean age of patients was 63 months (range, 6m-28y5m). The underlying disease was hematologic malignancy (n=27), hematologic non-malignancy (n=10), autoimmune disease (n=2), solid tumor (n=7), and EBV-associated T/NK-LPD (n=11).

Results
Forty-six (80.7%) of the 57 recipients were EBV seropositive before CBT (sero+/). Nineteen (41.3%) of 46 EBV seropositive recipients before CBT became EBV seronegative after CBT (sero+/sero-). Five patients (8.8%) developed EBV-associated post-transplantation LPD. Three of the 5 LPD patients arose from 27 patients of sero+/sero+ group, and the time of onset of LPD was 2-6 months after CBT. Two of them died of LPD. The remaining 2 patients arose from 19 patients of sero+/sero- group, and the time of onset of LPD was 6-9 months. These 2 patients were successfully treated. None of the 11 patients (6 in sero-/sero- group and 5 in sero-/sero+ group) developed LPD.

Discussion
Among EBV seropositive patients, about 60% of them remained seropositive (endogenous infection group), and 40% of them became seronegative after CBT. The latter group is likely to experience exogenous infection (secondary primary infection). In both instances, incidence of LPD seems to be quite high. Therefore regular monitoring of EBV serology and EBV-DNA load after CBT should be essentially required for all CBT patients.

Disclosures
No relevant conflicts of interest to declare.
Clinical Characteristics and GVL Effect of Chronic Graft-Versus-Host disease Following Reduced-Intensity Umbilical Cord Blood Transplantation (RICBT).
Authors: Wake Atsushi , Uchida Naoyuki , Ishiwata Kazuya , Araoka Hideki , Tsuji Masanori , Nakano Nobuaki , Yamamoto Hisashi , Takagi Shinsuke , Kato Daisuke , Matsuno Naofumi , Seo Sachiko , Asano-Mori Yuki , Masuoka Kazuhiro , Makino Shigeyoshi , Yoneyama Akiko , Taniguchi Shuichi 
Published: October 2019

Abstract
Abstract 1162
Poster Board I-184

Backgrounds
Umbilical cord blood can be an alternative stem cell source for the patients of hematological diseases. However, little is known about chronic GVHD (cGVHD) and graft versus leukemia/lymphoma (GVL) effect in reduced-intensity cord blood transplantation (RICBT). We had been demonstrated that cGVHD in CBT is tolerable compared with that in BMT and that the occurrence of cGVHD could result in good prognosis. Here, we analyzed the clinical picture of chronic GVHD following RICBT and the GVL effect.

Methods
We reviewed medical records of 192 patients with hematological diseases who had received CBT between Jan. 2004 and Dec. 2008 who had been free from disease progression for more than 100 days after RICBT at Toranomon Hospital, Tokyo, Japan. Median age was 54 years (17-82). Most of them had diseases in advanced status (n=168). Most of the pre-transplant conditioning were reduced intensity consisted of fludarabine, melphalan and TBI 4Gy (n=157). GVHD prophylaxis were tacrolimus (Tac) alone (n=99) and Tac plus mycophenolate mofetil (MMF) (n=93). HLA disparities were as follows; 6/6 (n=9), 5/6 (n=38), 4/6 (n=142), and 3/6 (n=3). Underlying diseases were AML (n=58), myelodysplastic syndrome (n=36), ALL (n=23), lymphoma (n=64) and others (n=11).

Results
The Median observation period after the transplantation was 924 days (range, 109–1944). Chronic GVHD was admitted in 114 patients (59.4%) consisted of limited type 88 (45.8%) and extensive type 26 (13.5%) in classical criteria, and mild type 96 (50.0%), moderate type 15 (7.8%), and severe type 3 (1.6%) in NIH consensus criteria of cGVHD. The target organs of cGVHD were skin 87.5%, liver 40.6%, and mouth mucous membranes 32.8 %, eye 23.4%, and the lungs only 7.8% (COP3 and BOS2). Except 21 cases ( 10.9%) required systemic steroid or MMF therapy. The median of Karnofsky score of cGVHD was 90%(40-100). During observation period, no patients except one patient caused by heart failure were died of cGVHD. In multivariate analysis, high-risk disease (p=0.019) and preceding acute GVHD (p=0.026) are related to the occurrence of cGVHD, and cGVHD increased overall survival (p<0.01) and suppressed recurrence of the disease (p<0.01).

Conclusion
Although the frequency of cGVHD was not low, the severity was mild, and the death related to cGVHD is rare in RICBT. NIH consensus criteria is useful for the evaluation of cGVHD severity. Some effect of GVL may play a role on better survival and lower relapse rate in RICBT.

Disclosures
No relevant conflicts of interest to declare.
Impact of Missing KIR Ligands in HLA-Matched Unrelated Donor HSCT.
Authors: Sun Aining , Li Weiyang , Depei Wu , He Jun , Bao Xiaojing , Zhou Lina 
Published: October 2019

Abstract
Abstract 1185
Poster Board I-207

Objective:
To analyze the prognostic impact of missing ligands for inhibitory killer-immunoglobulin receptor(KIR) in HLA-matched hematopoietic stem cell transplantation(HSCT) using unrelated donor.

Methods:
HLA genotype of 51 patients (ALL 22 cases, AML 13 cases, CML 14 cases, MDS 1 cases and HAL 1 cases) and their matched unrelated donors was determined by polymerase chain reaction sequence oligonucleotide probes(PCR-SSOP) and sequence specific primers (PCR-SSP). The KIR genotype was determined by PCR-SSP.

Results:
Patients were divided into those with(n=37) and those without(n=14) missing 1 or more HLA class I ligands for donor inhibitory KIR. The period of platelet reconstruction was shorter in patients [ 13 d(10d∼27d)] with missing KIR ligands than those[14d(12d∼21d)] without missing KIR ligands(P=0.046). There was no significant difference in neutrophil recovery, ≥II° acute GVHD(13.5% vs 35.7%, P>0.05) and extensive chronic GVHD (16.2% vs 28.6%, P>0.05) between the two groups. The 3-year continuous complete remission(CCR) rate for patients with and without missing KIR ligands was 73.6% and 37.4%, respectively(P=0.183). The 3-year overall survival(OS) rate for the two groups was 77.5% and 52.4%, respectively(P=0.533).

Conclusions:
In HLA-matched unrelated donor HSCT, missing KIR ligands may be associated with enhanced engraftment, decreased severe GVHD, improved CCR and OS.

Disclosures:
No relevant conflicts of interest to declare.
Clinical Relevance of Circulating Poly-Ubiquitin as a Prognostic Indicator in Chronic Lymphocytic Leukemia.
Authors: Ma Wanlong , Kantarjian Hagop M. , Wang Xiuqiang , O'Brien Susan , Yeh Chen-Hsiung , Zhang XI , Estrov Zeev , Sferruzza Anthony , Weirda William , Keating Michael , Albitar Maher 
Published: October 2019

Abstract
Abstract 1240
Poster Board I-262
The ubiquitin-proteasome pathway is implicated in the pathogenesis of many hematological malignancies. We have reported that proteasome activities in plasma samples can be detected in patients with chronic lymphocytic leukaemia (CLL). Here we examined the correlation of plasma ubiquitin protein levels with clinical behavior in CLL patients. Using the Meso Scale Discovery (MSD) platform, we quantified poly-ubiquitin levels in plasma samples from 138 patients with CLL and 101 healthy control subjects, and examined the associations of ubiquitin levels with various clinical and laboratory variables and overall survival. Patients with CLL had significantly higher levels of poly-ubiquitin proteins (median=158.2; range=35.0-281.2) than did normal control subjects (median=57.3; range=22.0-160.2) (P<0.001). Poly-ubiquitin levels showed no correlation with Rai stage, performance status, beta-2 microglobulin (B2M), or the mutation status of IgVH. However, when considered as a continuous variable, poly-ubiquitin levels correlated negatively with survival. Higher levels of poly-ubiquitin were associated with longer survival (P=0.04). In a multivariate model incorporating poly-ubiquitin, B2M, and IgVH mutation status only B2M (P=0.00004) and poly-ubiquitin P=0.04) levels, but not IgVH mutation status (P=0.12), were independent predictors of survival. When a cut- point corresponding to the upper quartile was used, patients with poly-ubiquitin levels >193 ng/mL had significantly better survival than did those with lower levels. Using B2M and poly-ubiquitin in combination allowed us to stratify patients into 3 different groups : survival was greatest in patients with high poly-ubiquitin and low B2M levels, lowest in those with low poly-ubiquitin and high B2M levels, and intermediate in those with high levels of B2M and ubiquitin or low levels of both (P<0.00001). In conclusion, these findings confirm the importance of the proteasome-ubiquitin system in the pathophysiology of CLL. Moreover, our data also suggest that plasma levels of poly-ubiquitin, along with B2M, should be explored as a prognostic factor in CLL.

Disclosures
No relevant conflicts of interest to declare.