tbuckley/cabot-search huggingface dataset:
Re-exposure to blinatumomab after CD19-positive relapse: Experience from three trials in patients (pts) with relapsed/refractory B-precursor acute lymphoblastic leukemia (R/R ALL).
Authors: Max S. Topp, Matthias Stelljes, Gerhard Zugmaier, Phillip Barnette, Leonard T. Heffner, Tanya M. Trippett, Ralf C. Bargou, Chris Holland, Jonathan Benjamin, Mark Robert Litzow
Journal: Journal of Clinical Oncology (2015)

7051 Background: Blinatumomab is a bispecific T-cell engager antibody construct designed to link cytotoxic T cells and CD19-positive B cells, inducing tumor cell lysis. In this combined analysis, we evaluated outcomes for patients with R/R ALL enrolled in 3 open-label phase 2 studies (NCT01471782 [study 205], NCT01209286 [study 206], NCT01466179 [study 211]) who received retreatment with blinatumomab following hematologic relapse after initial blinatumomab response. Methods: Patients were < 18 (205) or ≥ 18 (206 and 211) years of age with Ph- R/R B-precursor ALL. Blinatumomab was dosed by continuous IV infusion. A cycle was 4 weeks on, 2 weeks off. The primary endpoint was hematological remission within 2 cycles. Patients with relapse following a response of ≥ 3 months duration could receive up to 3 cycles of retreatment; patients with GVHD or CNS involvement were ineligible. Results: Eleven patients received retreatment with blinatumomab (205, n = 2; 206, n = 5; 211, n = 4). Seven (64%) were male; mean (range) age was 31 (4, 77). At the time of initial treatment, 9 (81%) had ≥ 1 line of prior salvage chemotherapy; 7 (64%) had prior HSCT. Among 10 patients who achieved hematological remission during the 2 cycles of initial treatment, the median (range) duration of response prior to relapse was 9 (3-11) mo. Five (45%) patients had HSCT between first blinatumomab response and relapse. Outcomes during retreatment are shown in the table. One patient was retreated a second time and obtained a CR. Conclusions: Four (36%) patients with R/R ALL who relapsed following initial response responded to retreatment with blinatumomab. Overall, rates of adverse events occurring during retreatment were similar to those observed in the full studies. Clinical trial information: NCT01471782, NCT01209286, and NCT01466179. Retreated Patients (n = 11) Median (range) duration of retreatment, days 28 (4-85) Hematological remission (responders) 4 (36%)† Minimal residual disease (MRD) responses among responders (n=4) Complete response MRD < 10-4 - 1 (25%) 4 (100%) Patients with any AEs Grade ≥ 3 Cytokine release syndrome Neurologic AEs 10 (91%) 8 (73%) 0 (0%) 5 (45%) †≤ 5% marrow blasts and full, partial, or incomplete recovery of peripheral blood counts.
Early antiretroviral therapy initiation: access and equity of viral load testing for HIV treatment monitoring
Authors: Trevor Peter, Dennis Ellenberger, Andrea A Kim, Debrah Boeras, Tsehaynesh Messele, Teri Roberts, Wendy Stevens, Ilesh Jani, Alash'le Abimiku, Nathan Ford, Zachary Katz, John N Nkengasong
Journal: The Lancet Infectious Diseases (2016)
Human leukocyte antigen (HLA) DR4 is associated with inferior progression free survival (PFS) following allogeneic hematopoietic stem cell transplantation (allo HSCT) for lymphoid malignancies
Authors: C. Aggarwal, S. Gupta, T. Hahn, S. Padmanabhan, P. L. McCarthy, M. Battiwalla
Journal: Journal of Clinical Oncology (2006)

6543 Background: HLA DR4 is associated with autoimmune disorders and response to cyclosporine immunosuppression in T-cell Large Granular Lymphoproliferative Disorder (BJH 2003;123(3)). We investigated the HLA DR4 role on graft-versus-host disease (GVHD) and graft-versus-leukemia effect in HLA-matched HSCT performed for lymphoid malignancies. Methods: We retrospectively reviewed 77 related and 22 unrelated consecutive allo HSCT patients (pts) treated between 1992 and 2003 at RPCI to investigate the influence of HLA DR4 on overall survival (OS), PFS and grade 2–4 acute and chronic GVHD (cGVHD) incidence. HLA DR B1 typing was determined by molecular (n=69) or serologic (n=30) methods. The pt proportion with one or two HLA DR4 antigens was 18% (18/99), similar to the general Caucasian population. Pt characteristics included: ALL (n=41), CLL (n=4), HD (n=7) and NHL (n=47); median age 36 y (range 6–64); Male (n=65), Female (n=34); Caucasian (&gt;95%); Total Body Irradiation (TBI) conditioning regimens (n=79); Busulfan/Cyclophosphamide (BuCy) (n=6), Thiotepa/TBI (n=23), Cy/TBI (n=9), Etoposide/Cy/TBI (n=9), Fludarabine/Melphalan (n=8), Thiotepa/Carboplatin (n=8) or other combinations (n=6). Results: There was no difference in OS between the HLA DR4 positive vs negative pts in any disease or donor subgroups (p=0.25). Nine of 18 DR4 positive pts (50%) and 20 of the 81 DR4 negative pts (25%) had disease progression (p=0.033). PFS at 33 months was 70% in the DR4 negative group and 30% in the DR4 positive group (p=0.004). In a univariate analysis, DR4 positivity, conditioning regimen and disease stage at HSCT were significant factors for PFS. However in the multivariate analysis, DR4 positivity was the only significant factor for PFS (RR=3.2, p=0.007). By preliminary analysis, 0/18 of the HLA DR4 positive pts and 13/81 HLA DR4 negative pts developed cGVHD (p=0.06). Conclusions: These results suggest that HLA DR4 positive pts have reduced cGVHD leading to increased relapse and decreased PFS with no effect on OS. Increased sensitivity of HLA DR4 lymphocytes to GVHD prophylaxis agents or reduced binding affinity for the CD4 coreceptor are possible reasons for these observations. No significant financial relationships to disclose.
Pre-instillation of tumor microparticles enhances intravesical chemotherapy of nonmuscle-invasive bladder cancer through a lysosomal pathway
Authors: Xun Jin, Jingwei Ma, Xiaoyu Liang, Ke Tang, Yuying Liu, Xiaonan Yin, Yi Zhang, Huafeng Zhang, Pingwei Xu, Degao Chen, Tianzhen Zhang, Jinzhi Lu, Zhuowei Hu, Xiaofeng Qin, Xiaoyong Zeng, Longcheng Li, Bo Huang
Journal: Biomaterials (2016)
Increased Treatment Intensity Is Not Associated with a Survival Benefit in Patients with Low and Intermediate Risk Mantle Cell Lymphoma, a Retrospective Analysis
Authors: Patrick T. Griffin, Julio C Chavez, Celeste M. Bello, Lubomir Sokol, Paul A. Chervenick, Ernesto Ayala, Jianguo Tao, Eduardo M. Sotomayor, Bijal D. Shah
Journal: Blood (2014)
PWE-378 Total pelvic floor ultrasound in pelvic floor defaecatory dysfunction: Abstract PWE-378 Table 1
Authors: AJ Hainsworth, D Solanki, M Lyons, AM Schizas, AB Williams
Journal: Gut (2015)

<h3>Introduction</h3> Defaecation proctography is gold standard for pelvic floor defaecatory dysfunction assessment but entails radiation. Total pelvic floor ultrasound (USS) allows a safe, dynamic assessment in clinic. The aim was to determine accuracy of USS, compared to proctography, for anatomical findings in women with pelvic floor defaecatory dysfunction. Secondary aims were identification of USS predictors of a trapping rectocoele, significant enterocoele and surgical treatment. <h3>Method</h3> All consecutive women undergoing investigation for defaecatory dysfunction between May 2011 and November 2014 were retrospectively reviewed by an interpreter blinded to symptoms and results. The following data were collated; The presence/absence of a rectocoele, intussusception and enterocoele, and grade of intussusception for both modalities. The presence of a trapping rectocoele and/or significant enterocoele for proctography. Subsequent treatment (biofeedback/surgery) was recorded. <h3>Results</h3> 393 underwent USS and proctography. 69 were excluded (images unavailable (24), incomplete (38) or poor quality (5) or tests performed over 2 months apart (2)). Of the 324 included mean length of follow up was 22 months. On proctography 283 had a rectocoele (111 trapping), 142 intussusception and 80 an enterocoele (40 significant). On ultrasound 284 had a rectocoele, 105 intussusception and 55 an enterocoele. 46 underwent surgery. Using proctography as gold standard USS had the following results. Rectocoeles detected on both transperineal and transvaginal USS were more likely to produce barium trapping on proctography (p &lt; 0.05) and require surgery (p &lt; 0.05). An enterocoele detected on USS was more likely a significant enterocoele on proctography (p &lt; 0.05). Agreement between the grading of intussusception by USS and proctography was moderate (intra-class correlation coefficient 0.52). <h3>Conclusion</h3> Transperineal USS is highly sensitive for detecting rectocoele. A rectocoele visible on both transperineal and transvaginal USS is significantly more likely to produce trapping on proctography and require surgery. Also, an enterocoele detected on USS is significantly more likely to descend onto the lower rectum during proctography. USS may be used as a screening tool to identify those patients who may benefit from defaecation proctography for further treatment planning, including surgery. This may avoid performing defaecation proctography on all patients. <h3>Disclosure of interest</h3> None Declared.
Nudge This: It is a Rational Fact That Donors Can Save the 22 People Who Die Daily Awaiting Organ Transplantation
Authors: Michael C. Freed
Journal: The American Journal of Bioethics (2016)

Increased organ donation is a public health need. In the United States, 22 people die daily awaiting organ transplantation (Organ Procurement and Transplantation Network [OPTN] 2016). Arguably, thi...
Should adult medulloblastoma patients at low risk receive adjuvant chemotherapy? Long-term results of a prospective study
Authors: E. Franceschi, A. Tosoni, M. Ermani, V. Blatt, P. Amistà, G. Sotti, S. Bartolini, D. Grosso, L. M. Pasetto, A. A. Brandes
Journal: Journal of Clinical Oncology (2007)

2018 Background: Due to the rarity of medulloblastoma (MB) in adults, the few studies available on this condition are retrospective, and the follow-up tends to be short. Furthermore, the different therapeutic strategies used in these patients makes it difficult to assess survival rates and prognostic factors. Methods: Between January 1989 and February 2001, a prospective phase II trial was performed to evaluate the efficacy of treatment for adults with medulloblastoma. Patients were completely staged with a neuroradiological examination of the brain and neuraxis and by CSF cytology, according to Chang’s staging system. Low risk patients received radiotherapy alone, while high risk patients were given 2 cycles of upfront chemotherapy followed by radiotherapy and adjuvant chemotherapy. The results of the preliminary analysis of this study at a median follow-up of 3.7 years are reported elsewhere. The present papers reports on the long- term results of the same trial. Results: After a median follow up of 7.6 years, among a total of 36 enrolled adults with medulloblastoma, overall progression free survival (PFS) and overall survival (OS) at 5 years were 72% (range 59% to 84%) and 75% (62% to 91%), respectively. No difference was found between low and high risk patients in terms of PFS and OS at 5 years: in low-risk patients the 5-year PFS was 80% (range, 59–100%) and the 5-year OS, 80% (range, 58 - 100%); in high-risk patients the 5-year PFS was 69% (range, 54 -89%) and the 5-year OS, 73% (range, 58 - 92%). Conclusions: A long-term follow-up is essential to evaluate the real impact of treatments in adult patients with MB. Since there is no significant difference between low-risk and high-risk patients for PFS and OS, the use of chemotherapy is also questionable in low-risk patients. No significant financial relationships to disclose.
Clinical Efficacy of Sorafenib in Patients with Acute Myeloid Leukemia (AML) and Activating FLT3-Mutations.
Authors: Thomas Schroeder, Christian Saure, Ingmar Bruns, Fabian Zohren, Akos G. Czibere, Nelly Nancy Safaian, Roland Fenk, Rainer Haas, Guido Kobbe
Journal: Blood (2009)
S49 A Self-Management Programme of Activity Coping and Education (SPACE) For COPD: Results from a Randomised Controlled Trial: Abstract S49 Table 1
Authors: K Mitchell-Wagg, V Warrington, L Apps, L Sewell, J Bankart, M Steiner, M Morgan, S Singh, S Singh
Journal: Thorax (2012)

<h3>Introduction</h3> The NHS Outcomes Strategy for COPD has identified self-management as an approach targeted at reducing the impact of COPD.<sup>1</sup> Previous self-management programmes have either been unsupported, such as brief education or action plans, or have been of high intensity, equivalent with pulmonary rehabilitation. Furthermore, no studies have specifically tested self-management in patients managed in primary care. SPACE is a supported self-management programme that adopts a light touch approach. This study aimed to test the effectiveness of SPACE in patients with COPD in primary care. <h3>Methods</h3> 184 patients [101 male; mean (SD) age 69 (9) yrs; FEV11.44 (0.56) l; BMI 27.56 (5.26) kg/m2] with COPD were recruited and randomised to either SPACE or usual care. Patients who received SPACE were introduced to a manual by a healthcare professional and received two telephone calls at 2 and 4 weeks. Measures were taken at baseline, 6 weeks and 6 months. The primary outcome was the Chronic Respiratory Questionnaire (CRQ) dyspnoea. Secondary outcomes were CRQ fatigue, emotion and mastery, Incremental Shuttle Walk Test (ISWT), Endurance Shuttle Walk Test (ESWT) and Hospital Anxiety and Depression Scale (HADS). HADS was analysed on a sub-group of those scoring ≥8 at baseline. Repeated measures ANOVA was conducted to test the effect of time and intervention. Results <h3>Results</h3> are displayed in table 1. <h3>Conclusions</h3> SPACE can bring about gains in HRQoL, endurance capacity and reduced depression for those at risk, that are maintained over 6 months. These are important patient outcomes which suggest self-management skills of emotional and medical management have been gained. <h3>Reference</h3> Department of Health. ‘An Outcomes Strategy for COPD and Asthma: NHS Companion Document.’ May 2012.
Co-Existent Hyperdiploidy Does Not Abrogate The Poor Prognosis Associated With Adverse Cytogenetics In Myeloma
Authors: Charlotte Pawlyn, Lorenzo Melchor, Eileen M Boyle, Annamaria Brioli, Martin F Kaiser, Walter Gregory, Mark T Drayson, Graham Jackson, Fiona M Ross, J. Anthony Child, Gareth J Morgan, Faith E Davies
Journal: Blood (2013)
Plasma Lipidomic Profiles Improve on Traditional Risk Factors for the Prediction of Cardiovascular Events in Type 2 Diabetes Mellitus
Authors: Zahir H. Alshehry, Piyushkumar A. Mundra, Christopher K. Barlow, Natalie A. Mellett, Gerard Wong, Malcolm J. McConville, John Simes, Andrew M. Tonkin, David R. Sullivan, Elizabeth H. Barnes, Paul J. Nestel, Bronwyn A. Kingwell, Michel Marre, Bruce Neal, Neil R. Poulter, Anthony Rodgers, Bryan Williams, Sophia Zoungas, Graham S. Hillis, John Chalmers, Mark Woodward, Peter J. Meikle
Journal: Circulation (2016)

Background: Clinical lipid measurements do not show the full complexity of the altered lipid metabolism associated with diabetes mellitus or cardiovascular disease. Lipidomics enables the assessment of hundreds of lipid species as potential markers for disease risk. Methods: Plasma lipid species (310) were measured by a targeted lipidomic analysis with liquid chromatography electrospray ionization–tandem mass spectrometry on a case-cohort (n=3779) subset from the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation). The case-cohort was 61% male with a mean age of 67 years. All participants had type 2 diabetes mellitus with ≥1 additional cardiovascular risk factors, and 35% had a history of macrovascular disease. Weighted Cox regression was used to identify lipid species associated with future cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) and cardiovascular death during a 5-year follow-up period. Multivariable models combining traditional risk factors with lipid species were optimized with the Akaike information criteria. C statistics and NRIs were calculated within a 5-fold cross-validation framework. Results: Sphingolipids, phospholipids (including lyso- and ether- species), cholesteryl esters, and glycerolipids were associated with future cardiovascular events and cardiovascular death. The addition of 7 lipid species to a base model (14 traditional risk factors and medications) to predict cardiovascular events increased the C statistic from 0.680 (95% confidence interval [CI], 0.678–0.682) to 0.700 (95% CI, 0.698–0.702; P &lt;0.0001) with a corresponding continuous NRI of 0.227 (95% CI, 0.219–0.235). The prediction of cardiovascular death was improved with the incorporation of 4 lipid species into the base model, showing an increase in the C statistic from 0.740 (95% CI, 0.738–0.742) to 0.760 (95% CI, 0.757–0.762; P &lt;0.0001) and a continuous net reclassification index of 0.328 (95% CI, 0.317–0.339). The results were validated in a subcohort with type 2 diabetes mellitus (n=511) from the LIPID trial (Long-Term Intervention With Pravastatin in Ischemic Disease). Conclusions: The improvement in the prediction of cardiovascular events, above traditional risk factors, demonstrates the potential of plasma lipid species as biomarkers for cardiovascular risk stratification in diabetes mellitus. Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT00145925.
Correlation of KIT expression with higher FLT3 mutations and impact on clinical outcome in patients newly diagnosed with acute myeloid leukemia (AML).
Authors: Hassan Alkhateeb, Mark Robert Litzow, Firas Baidoun, Shahrukh Hashmi, William J. Hogan, Mrinal M. Patnaik, Michelle A. Elliott, Dong Chen, Aref Al-Kali
Journal: Journal of Clinical Oncology (2014)

7067 Background: KIT (CD 117) is a transmembrane tyrosine kinase protein receptor encoded by the c-kit protooncogene. KIT mutations were described in AML and impart a prognostic impact on patients (pt) with core binding factor. However, its expression effect on clinical phenotype and outcome is unknown. Methods: A retrospective, single institution study of cases with AML at Mayo Clinic between 2003 - 2011 was performed. Pts with blasts KIT expression studied by flow cytometry at diagnosis were included. Appropriate IRB approval was obtained in accordance with the Helsinki declaration. Comparison between groups’ medians was done using Wilcoxon test, while survival estimates were calculated using Kaplan-Meier curves. Results: Out of 154 pts who had KIT analysis, KIT+ (>20% of blasts) was in 134 (87%). Median age is 62 year, with median white blood cell (WBC) 9 x109, Hemoglobin (Hgb) 9.3 g/dl, platelet (PLT) 56 x109, peripheral blood (PB) blast 10%, bone marrow (BM) blasts 56%. Cytogenetics (CG) was diploid in 55% pt. NCCN grouping for CG was favorable, intermediate and poor in 8%, 71%, 21%. FLT3 was mutated in 25%, NPM1 in 38% pts. CR was found in 105 (68%) pts; 77 relapsed. Median OS is 577 days. Group 1 (KIT-) had median age 62 year, Hgb 9.3 g/dl, PLT 82 x109, WBC 18 x109, PB blasts 34%, BM blasts 71%. CG was favorable, intermediate and poor in 8%, 58%, 33%. NPM1 and FLT3 were mutated in 50%, 0, respectively. CR was obtained in 75% with 55% suffering a relapse. Group 2 (KIT+) had median age 62 year, Hgb 9.4 g/dl, PLT 56 x109, WBC 9 x109, PB blasts 19%, BM blasts 55%. CG was favorable, intermediate and poor in 8%, 74%, 18%. NPM1 and FLT3 were mutated in 37% and 29%. CR was found in 67% with 51% relapsing. Upon comparison, mutated FLT3 was more frequent in group 2 vs 1 (p=0.002). Median OS was not statistically different between group 1 vs 2 (447 vs 592 days, p= 0.25). On multivariate analysis, only NCCN grouping (p=0.006) affected mOS but not age, WBC, PB/BM blasts, or KIT. Conclusions: KIT expression was prevalent in AML pts. We found for the first time that KIT- AML pts did not have mutated FLT3 (0%) but KIT expression did not impact clinical outcome. Additional prospective studies are needed to confirm our results.
Роль вісмуту в лікуванні гастродуоденальної патології (огляд літератури та власні дослідження)
Authors: Yu.M. Stepanov, L.M. Mosiichuk
Journal: GASTROENTEROLOGY (2016)

У статті подана історія створення колоїдного субцитрату вісмуту та розглянуті основні механізми його дії на слизову оболонку шлунка, як цитопротективної, так і антихелікобактерної. Викладені сучасні дані світових досліджень щодо застосування субцитрату вісмуту як компонента антибактеріальної терапії з метою підвищення ефективності ерадикації, особливо в умовах розвитку резистентності до базових препаратів. Наведені результати власних досліджень, що присвячені вивченню динаміки змін структурної перебудови слизової шлунка у хворих на хронічний атрофічний гастрит протягом 3 років після проведення ерадикації H.рylori. Застосування терапії першої лінії з додаванням препарату Де-Нол дозволило досягти ерадикації в 94,3 % обстежених та позитивних мікроструктурних змін слизової оболонки шлунка.
Anti-PD-1 increases the clonality and activity of tumor infiltrating antigen specific T cells induced by a potent immune therapy consisting of vaccine and metronomic cyclophosphamide
Authors: Genevieve M. Weir, Olga Hrytsenko, Tara Quinton, Neil L. Berinstein, Marianne M. Stanford, Marc Mansour
Journal: Journal for ImmunoTherapy of Cancer (2016)

Future cancer immunotherapies will combine multiple treatments to generate functional immune responses to cancer antigens through synergistic, multi-modal mechanisms. In this study we explored the combination of three distinct immunotherapies: a class I restricted peptide-based cancer vaccine, metronomic cyclophosphamide (mCPA) and anti-PD-1 treatment in a murine tumor model expressing HPV16 E7 (C3).
Clinical Characteristics of Early and Late Non-Infectious Pulmonary Complications Following Cord Blood Transplantation.
Authors: Atsushi Wake, Naoyuki Uchida, Kazuya Ishiwata, Shinsuke Takagi, Masanori Tsuji, Daisuke Kato, Hisafumi Yamamoto, Sachiko Seo, Naofumi Matsuno, Kazuhiro Masuoka, Shigesaburo Miyakoshi, Shigeyoshi Makino, Akiko Yoneyama, Shuichi Taniguchi
Journal: Blood (2007)
Retrospective Matched-Pair Analysis Of The Efficacy and Safety Of Bortezomib Plus Dexamethasone Versus Bortezomib Monotherapy In Patients (Pts) With Relapsed Multiple Myeloma (MM)
Authors: Meletios A. Dimopoulos, Robert Z. Orlowski, Thierry Facon, Pieter Sonneveld, Kenneth C. Anderson, Meral Beksac, Lotfi Benboubker, Huw Roddie, Anna Potamianou, Catherine Couturier, Huaibao Feng, Ozlem Ataman, Helgi van de Velde, Paul G. Richardson
Journal: Blood (2013)