tbuckley/cabot-search huggingface dataset:
Comparative outcomes of myeloablative and reduced‐intensity conditioning allogeneic hematopoietic cell transplantation for therapy‐related acute myeloid leukemia with prior solid tumor: A report from the acute leukemia working party of the European society for blood and bone marrow transplantation
Authors: Catherine J. Lee, Myriam Labopin, Dietrich Beelen, Jürgen Finke, Didier Blaise, Arnold Ganser, Maija Itälä‐Remes, Patrice Chevallier, Hélène Labussière‐Wallet, Johan Maertens, Ibrahim Yakoub‐Agha, Jean‐Henri Bourhis, Audrey Mailhol, Mohamad Mohty, Bipin N. Savani, Arnon Nagler
Journal: American Journal of Hematology (2018)

Therapy‐related acute myeloid leukemia (t‐AML) arises as a late complication following antecedent solid tumors or hematologic diseases and their associated treatments. There are limited data regarding risk factors and outcomes following allogeneic hematopoietic cell transplantation (HCT) for t‐AML following a prior solid tumor, and furthermore, the impact of myeloablative (MAC) vs reduced‐intensity conditioning (RIC) on survival is unknown. The acute leukemia working party (ALWP) of the European society for blood and bone marrow transplantation (EBMT) performed a large registry study that included 535 patients with t‐AML and prior solid tumor who underwent first MAC or RIC allogeneic HCT from 2000‐2016. The primary endpoints of the study were OS and LFS. Patients receiving RIC regimens had an increase in relapse incidence (hazard ratio [HR], 1.52; 95% confidence interval [CI] 1.02‐2.26; P = 0.04), lower LFS (HR, 1.52; 95% CI 1.12‐2.05, P = 0.007), and OS (HR, 1.51; CI 1.09‐2.09; P = 0.012 ) . There were no differences in NRM and GRFS. Importantly, LFS and OS were superior in patients receiving ablative regimens due to a decrease in relapse. As NRM continues to decline in the current era, it is conceivable that outcomes of HCT for t‐AML with prior solid tumor may be improved by careful patient selection for myeloablative regimens.
Elevated Axicabtagene Ciloleucel (CAR-19) Expansion By Immunophenotyping Is Associated with Toxicity in Diffuse Large B-Cell Lymphoma
Authors: Jay Y. Spiegel, Bita Sahaf, Nasheed Hossain, Matthew J. Frank, Gursharan Claire, Matthew Abramian, Theresa Latchford, Bertha Villa, Juancarlos Cancilla, Jean Oak, Yasodha Natkunam, Steven R. Long, Sally Arai, Laura J Johnston, Robert Lowsky, Everett H Meyer, Lori S Muffly, Robert S. Negrin, Andrew R Rezvani, Judith A Shizuru, Wen-Kai Weng, Katherine A. Kong, Crystal L. Mackall, David B. Miklos
Journal: Blood (2018)
Clinical Outcomes for Patients with Myeloid Malignancies Harboring IDH1/2mutations after Intensive Chemotherapy
Authors: Swapna Thota, Bhumika J. Patel, Hetty E. Carraway, Elizabeth A. Griffiths, Amanda Przespolewski, James E. Thompson, Teodora Kuzmanovic, Aziz Nazha, Shimoli Vipul Barot, Cassandra M. Hirsch, Bartlomiej P. Przychodzen, Sudipto Mukherjee, Meghan Scully, Aaron T. Gerds, Anjali S. Advani, Mikkael A. Sekeres, Manja Meggendorfer, Eunice S. Wang, Jaroslaw P. Maciejewski
Journal: Blood (2018)
A phase Ib/IIa study of NEO-102: A therapeutic antibody for the treatment of advanced pancreatic and colorectal cancer.
Authors: Sandip Pravin Patel, Michael Morse, Muhammad Shaalan Beg, Nilofer Saba Azad, Melony A. Beatson, Sharon Mavroukakis, Philip M. Arlen
Journal: Journal of Clinical Oncology (2014)

3072 Background: We have developed a chimeric monoclonal antibody (mAb) that targets a variant of MUC5AC that is expressed specifically by human pancreatic (P) and colorectal (C) tumors with minimal reactivity to normal GI mucosa. In the phase (ph) I trial of the initial formulation NEO-101, 5/19 patients (pts) had stable disease (SD) after completing their 1st course of treatment (tx) (4 doses) and overall survival (OS) of >12 months (mos) observed in 3 C and 2 P pts despite disease progression on standard (std) of care tx regimens. The current study utilizes NEO-102, a glycoengineered form of NEO-101 with improved stability and decreased RBC agglutination. Methods: A Ph Ib/IIa open label, multi-center dose-escalation clinical trial with NEO-102 is enrolling pts with advanced P and C cancer refractory to std therapy. NEO-102 is administered every 2 weeks with initial restaging at 8 weeks (after 4 doses) and every 8 weeks after if no progression. Primary objectives: measure efficacy by analysis of CT scans using RECIST criteria, OS, laboratory tests, and physical examination. Secondary objectives: determine safety and tolerability of escalating doses of NEO-102; assess pharmacokinetics (PK) and select immune responses to the mAb. Analyses of pt PBMCs for ADCC and immune cytokine profiling are underway to assess for immunologic outcome and for correlation with clinical benefit. Results: 12 pts are evaluable for toxicity (10 C, 2 P) and no DLT has been encountered. Grade 3 adverse events possibly related to NEO-102 are diarrhea and anemia. 8 pts are evaluable for efficacy at day 57, with 5 patients with SD (4/6 C, 1/2 P) and 3 with PD. The maximum number of doses administered is 9+ and the median duration of treatment has been 56+ days (Range 29-131+). Conclusions: Preliminary results with NEO-102 mAb have demonstrated signs of clinical activity based on stabilization of disease in heavily pretreated pts with P and C cancer. Safety has been established at the 3 mg/kg dose level and patients are currently being accrued to the 4 mg/kg dose level. If no DLT is observed at the current dose level, we will proceed with 4mg/kg as the dose utilized for expansion cohorts in P (30 pts) and C (40 pts). Clinical trial information: NCT01040000.
Differences in circulating angiogenic biomarkers as prognosticator for outcome in bevacizumab-treated nonsquamous non-small cell lung cancer (NSCLC) patients.
Authors: Marta Batus, Ravi Pithadia, John Kubasiak, Cristina Fhied, Zahraa Ibrahem, Shruthi Melinamani, Ibdihaj Fughhi, Wen-Rong Lie, Sanjib Basu, Mary J. Fidler, Philip D. Bonomi, Jeffrey Allen Borgia
Journal: Journal of Clinical Oncology (2014)

11037 Background: Trials evaluating role of bevacizumab in patients with advanced NSCLC have shown only modest impact in outcomes. The objective of this study was to evaluate predictive value of panel of circulating biomarkers important in cancer-induced angiogenesis in frontline treatment. Methods: Chemonaïve non-squamous patients were assigned to regimens of standard platinum-doublet chemotherapy either alone (CTx; n=20) or in combination with bevacizumab (CTx+bev; n=21). Paired pretreatment and post first cycle sera from each patient were evaluated using Human Angiogenesis Growth Factor Panel (EMD Millipore) which contains angiopoietin-2, BMP-9, EGF, endoglin, endothelin-1, FGF-1, FGF-2, follistatin, G-CSF, HB-EGF, HGF, IL-8, leptin, PLGF, VEGF-A, VEGF-C, and VEGF-D on a FlexMAP 3D system (Luminex Corp.). Serum pretreatment and differential (pre- vs. post-treatment) levels of each analyte were associated with progression-free survival (PFS) and overall survival (OS) and compared between regimens. Multivariate Cox PH analyses were used to identify interaction of markers with CTx/CTx+bev on PFS and OS. Results: Increasing levels of VEGF-A in first cycle of treatment were differentially associated (HR=4.98; p<0.001) with a worse PFS in the CTx+bev cohort versus CTX. Alternately, increasing levels of IL-8 were differentially associated with poor PFS and OS in CTx patients (p=0.003, 0.02, respectively). Increasing leptin levels were associated with a favorable OS in CTx+bev cohort, versus CTX (HR=0.36, p=0.02). Large increases in angiopoietin-2, HGF, follistatin, VEGF-C, and VEGF-D were associated with a poor OS (p<0.05), whereas large increases in FGF-1, and endothelin-1 were associated with more favorable OS (p<0.01). Conclusions: Significant relationship betweenchanging levels of angiogenic biomarkers and PFS/OS observed in our relatively small groups of patients suggests that further evaluation of angiogenic biomarkers in longitudinal studies is warranted to substantiate value of molecules for prognosticating and identifying patients more likely to benefit from frontline bevacizimab therapy.
Venetoclax As Monotherapy or in Combination: Patterns of Use and Predictors of Outcomes in an International Multicenter Study of CLL Patients
Authors: Anthony R. Mato, Lindsey E. Roeker, Toby A. Eyre, Chadi Nabhan, Nicole Lamanna, Brian T. Hill, Danielle M. Brander, Paul Barr, Frederick Lansigan, Bruce Cheson, Arun K Singavi, Maryam Yazdy, Nirav N Shah, John N. Allan, Erica B Bhavsar, Joanna Rhodes, Kaitlin Kennard, Stephen J. Schuster, Annalynn M Williams, Alan P Skarbnik, Andre Goy, Catherine C. Coombs, Hande H. Tuncer, Chaitra S. Ujjani, Ryan Jacobs, Allison M. Winter, John M. Pagel, Neil Bailey, Anna Schuh, Mazyar Shadman, Andrea Sitlinger, Hanna Weissbrot, Sivraj Muralikrishnan, Amy A Kirkwood, Christopher P. Fox
Journal: Blood (2018)
Surgery or conservative management for Achilles tendon rupture?
Authors: Nicola Maffulli, Giuseppe M Peretti
Journal: BMJ (2019)

Acute ruptures of the Achilles tendon are common and can lead to major functional limitations, with noticeable loss of strength and endurance. 1Many such patients fail to resume sporting activities in the short term, and the injury produces ongoing problems even after 10 years. 2 Modern management aims to promptly maximise function and minimise complications.Much of recent research has tried to determine the optimal methods of either surgical or non-surgical treatment using a randomised controlled trial study design, with the primary outcome in most of such studies being the prevention of re-ruptures.In a linked systematic review and meta-analysis, Ochen and colleagues (
Outcomes in Adult Acute Promyelocytic Leukemia (APL): A Real World Scenario
Authors: Rajani Priya Yedla, Venkateswar Rao Pydi, Nageswara Reddy Palukuri, Ravichandran Ambalathandi, Stalin Chowdary Bala, Meher Lakshmi Konatam, Sadashivudu Gundeti
Journal: Blood (2018)
Triple Negative Myelofibrosis and Myelodysplastic Syndrome with Fibrosis: Clinico-Biological Characterization and Correlation with Gene Mutations
Authors: Juan Gonzalo Correa, Alberto Alvarez-Larrán, Monica Lopez-Guerra, Juan Carlos Hernandez Boluda, Mar Tormo, María Rozman, Daniel Martínez, Dolors Colomer, Jordi Esteve, Francisco Cervantes
Journal: Blood (2018)
Response by Chao et al to Letter Regarding Article, “Oral Anticoagulation in Very Elderly Patients With Atrial Fibrillation: A Nationwide Cohort Study”
Authors: Tze-Fan Chao, Gregory Y.H. Lip, Shih-Ann Chen
Journal: Circulation (2018)

In Response:We thank Aldaas et al for their comments regarding our recently published article on stroke prevention in very elderly patients (≥90 years of age) with atrial fibrillation (AF). 1 We agree that the patient number treated with non-vitamin K antagonist oral anticoagulants (NOACs) in our study was small (n = 978), especially for those treated with apixaban (n = 60).In Taiwan, dabigatran was introduced in June 2012, rivaroxaban in February 2013, and apixaban in June 2014, and therefore patient numbers treated with apixaban were limited during our study period (years 2012-2015).We appreciate the enthusiasm of Aldaas et al for apixaban, and their comment that our results may not be generalized to the worldwide practice because they consider that apixaban is "widely prescribed."However, apixaban is not necessarily the most commonly prescribed anticoagulant in every country, and warfarin is still widely used globally. 2Also, we did not aim to focus on the comparisons of any specific NOACs to warfarin.Compared with warfarin, apixaban was associated with less major bleeding, less total bleeding, and less intracranial hemorrhage among patients aged ≥75 years. 3herefore, if more patients in the NOAC group of our study were treated with apixaban, an even lower risk of major bleeding or intracranial hemorrhage could have been observed, which could further strengthen our conclusion that NOACs perform better than warfarin even among the very elderly AF population.Most importantly, in our study, only 3.9% of patients ≥90 years of age received warfarin in the era without NOACs, and the proportion was 16.1% (7.1% with warfarin and 9.0% with NOACs) in the era with NOACs.The increment in the prescriptions of oral anticoagulants, especially for NOACs, demonstrates how the introduction of NOACs, as a more convenient and safer choice, could substantially change the stroke prevention landscape among very elderly AF patients.Ultimately, stroke prevention is the cornerstone of AF management, and should be offered to patients with ≥1 stroke risk factors, 2 as part of the holistic approach to improve outcomes in AF patients. 4,
Management of Cytokine Release Syndrome in AML Patients Treated with Flotetuzumab, a CD123 x CD3 Bispecific Dart® Molecule for T-Cell Redirected Therapy
Authors: Kenneth Jacobs, Cedric Viero, John Godwin, Jan Baughman, Jichao Sun, Kang Ying, John Muth, Shengyan Hong, Norbert Vey, Kendra L. Sweet, Geoffrey L. Uy, Farhad Ravandi, Matthew C Foster, David A. Rizzieri, Martha L. Arellano, Michael P. Rettig, Max S. Topp, Gerwin Huls, Helene Lelièvre, Stefania Paolini, Fabio Ciceri, Matteo Giovanni Carrabba, Bob Lowenberg, John F. DiPersio, Jon Wigginton, Jan K Davidson-Moncada
Journal: Blood (2018)
Abstract 11740: Role of Physical Fitness in Statin Induced Type II Diabetes Mellitus
Authors: Puneet Narayan, Charles Faselis, Anubhav Kumar, Eric Nylen, Apostolos Tsimploulis, Mark Blackman, Andreas Pittaras, Michael Doumas, Peter Kokkinos
Journal: Circulation (2016)

Introduction: Several studies have now shown statin use predisposes to the development of type II diabetes mellitus (DM). We evaluated high risk Veterans to identify factors influencing the incidence of statin induced DM, Methods: Non-diabetic patients (n= 5143; age: 58.9±10.9 yrs), completed a routine exercise tolerance testing at Washington DC and Palo Alto Veterans Affairs Medical Centers at baseline. All had a normal exercise response. We established five fitness categories based on age-stratified quintiles of peak metabolic equivalents (MET) achieved: Least-fit (4.5±1.1 METs; n= 1007); Low-Fit (6.2±1.1 METs; n=1159); Moderately-Fit (7.3±1.2 METs; n=1061); Fit (8.4±1.1 METs; n=1073) and Highly-Fit (11.0±2.3 METs; n=843). Multivariable Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals [CI] for incidence of DM across fitness categories. The model was adjusted for age, BMI, gender, race, resting blood pressure, hypertension, smoking status and medications. The Least-fit category was the referent. Results: During a follow-up of 10.01 years after initiation of statin therapy, 1110 patients developed DM (21.5 events per 1000 person years of follow-up). The association between fitness status and incidence of DM was inverse and graded. The risk was 8% lower for each 1-MET increase in exercise capacity (HR=0.92, CI: 0.89-0.94). When considering fitness categories, DM risk was similar for individuals in the three lowest fitness categories. However, the risk was 22% lower (HR=0.78; CI: 0.64-0.94) for fit individuals (peak exercise capacity: 8.4±1.1 METs) and 42% lower for those in the highest fitness category (peak exercise capacity: 11.0±2.3 METs; HR= 0.58; CI: 0.46-0.73). Conclusions: High levels of physical fitness were protective against development of statin induced type II DM in this high risk Veteran population.
Surgical site infection after primary debulking surgery for epithelial ovarian cancer: Predictors and impact on survival.
Authors: Christine Wei-Yin Tran, Michaela McGree, Amy Weaver, Jan Martin, Maureen Lemens, William Cliby, Sean Christopher Dowdy, Jamie Nadine Bakkum-Gamez
Journal: Journal of Clinical Oncology (2014)

5554 Background: Surgical site infection (SSI) following epithelial ovarian cancer (EOC) primary debulking surgery (PDS) occurs in 10-15% of patients. Perioperative factors associated with SSI as well as the impact of SSI on EOC survival were determined. Methods: All EOC cases that underwent PDS between 1/1/03 and 12/31/11 were retrospectively reviewed. SSIs were defined according to the American College of Surgeons National Surgical Quality Improvement Program and limited to the first 30 postoperative days. Bowel leaks were considered organ/space SSIs. Logistic regression models were fit to identify factors associated with SSI. Cox proportional hazards models were utilized to evaluate the association of patient and perioperative characteristics (including SSI as a time-dependent covariate) with overall survival (OS) and disease-free survival (DFS). Results: Among 888 cases, 96 (10.8%) developed an SSI: 32 superficial SSI, 2 deep SSI, and 62 organ/space SSI. Factors independently associated with superficial SSI were increasing BMI (OR 1.41 [95% CI, 1.12, 1.76] per 5 kg/m2), increasing operative time (1.24 [1.02, 1.50] per hour), and advanced stage (III/IV) (10.22 [1.37, 76.20]). Factors independently associated with organ/space SSI were history of GERD (2.13 [1.23, 3.71]), surgical complexity (intermediate 3.11 [1.02, 9.49]; high 8.07 [2.60, 25.09]), and residual disease (RD) (measureable ≤1cm 1.77 [0.96, 3.27]; >1cm (3.36 [1.48, 7.61]). Occurrence of superficial (HR 1.69 [1.12, 2.57]) or organ/space (HR 1.46 [1.07, 2.00]) SSI was independently associated with worse OS in a multivariable model adjusted for the following factors (p<0.05): age, ECOG performance status, ASA level, FIGO stage, ascites, RD, and histology. SSI occurrence did not independently influence DFS. History of stroke, ascites, and increasing RD and stage were associated with worse DFS. Conclusions: Development of SSI after PDS worsens OS. Most risk factors for SSI are not modifiable. Alternative measures to lower rates of superficial and organ/space SSI are needed as reduction of SSI may improve OS. Preoperative identification of SSI risk factors may also assist in risk assessment and operative decision making.
Use of FDG PET scanning to evaluate 5-FU myocardial toxicity as a global metabolic effect rather than vascular spasm.
Authors: Andrew Peter Dean, Dom Higgs, Peter Robins, Paul Stobie, Philip Craven, Ciara Daly, Samantha Carija
Journal: Journal of Clinical Oncology (2018)

792 Background: This is the first ever case series which presents a series of PET images that conclusively demonstrate reversible abnormal myocardial glucose utilisation in 7 patients with normal coronary arteries occurring during 5-FU infusions. Fluoropyrimidine induced myocardial toxicity is estimated to occur in 9% of cases, with some instances proving fatal. Traditionally some hypothesised coronary artery spasm as the mechanism of action behind such events and an animal study suggesting dysfunction of the Krebs cycle, with depletion of high-energy phosphate compounds, was largely ignored. Having observed abnormal myocardial FDG uptake in a patient with chest pain undergoing FDG PET scanning, we prospectively evaluated a further 6 patients presenting with cardiac symptoms whilst receiving infusional 5-FU. Methods: Over an eighteen-month period, 7 patients experienced cardiac like chest pain during 5FU infusion. All were investigated for cardiac ischaemia as per institutional protocol (serial troponin, ECGs and coronary artery imaging), as well as FDG PET scanning to assess FDG uptake in the myocardium. Results: All 7 cases showed reduced FDG uptake throughout the myocardium, with the ventricular blood pool demonstrating a higher affinity for FDG than the myocardium itself. All 7 cases showed normal physiological uptake of FDG in the myocardium on previous and subsequent PET imaging. Imaging of the myocardium and coronary arteries in all cases showed no structural vascular disease. Conclusions: All cases demonstrated a global pattern of reduced FDG myocardial uptake that could not be isolated to a single coronary territory. Angiography or myocardial perfusion scanning demonstrated no significant coronary artery disease, and there were no features consistent with coronary artery spasm found on ECG. This supports the hypothesis that 5FU inhibits physiological myocardial glucose utilisation, thus acting as a direct myocardial toxin. We believe our findings warrant further investigation into the metabolic effects of 5FU on myocardial tissue.
The HALO study: A phase I-II of the oral HSP90 inhibitor Debio0932 in combination with SOC in first- and second-line therapy of advanced NSCLC.
Authors: Jesus Corral Jaime, Luis Paz-Ares, Mariano Provencio, Jaafar Bennouna, Santiago Ponce-Aix, Ruth Plummer, Jean-Pierre Delord, Nicolas Isambert, Jose Manuel Trigo, Riccardo Belli, Silvano Brienza, Claudio Zanna, Daniela Purcea, Virginia Calvo, Miriam Alonso, Hélène Senellart, Sandrine Hiret, Alex Martinez Marti, Enriqueta Felip
Journal: Journal of Clinical Oncology (2014)

TPS2632^ Background: Debio0932 is an oral second-generation Heat Shock Protein 90 (HSP90) inhibitor, structurally unrelated to geldanamycin. In multiple pre-clinical models Debio0932 has demonstrated anti-tumor activity both as monotherapy and in combination with conventional anticancer agents. Debio0932 monotherapy was well tolerated in cancer patients up to 1000 mg daily (QD) and showed signs of activity in patients with Non-Small Cell Lung Cancer (NSCLC). Methods: The HALO (HSP90 inhibition And Lung cancer Outcomes) study is recruiting patients with Stage IIIb or IV NSCLC (EGFR wild type or unknown mutation) and consists of three parts. Part A is an open-label dose escalation of Debio0932 administered QD in 21-day treatment cycles in combination with standard of care (SOC) for first and second line treatment of advanced NSCLC. Cisplatin + gemcitabine (SCC) or cisplatin + pemetrexed (Non SCC NSCLC) are used as first-line SOC whereas docetaxel is used for later lines of therapy. The starting dose is 100 mg and will be escalated up to 1000 mg. Part B is a double-blind, placebo-controlled study in which 138 untreated advanced NSCLC patients will be randomized to receive placebo or Debio0932 at the dose recommended in part A in combination with first-line SOC. The primary endpoint of Part B is 6-month progression free survival (PFS); secondary endpoints include best overall response rate (ORR), duration of objective response, change in tumor size from baseline until 6 months and overall survival (OS). Patients who subsequently develop progressive disease are newly randomized to double-blind treatment with docetaxel +/- Debio0932 (Part C). Approximately 100 patients are expected to enter part C. The primary endpoint of part C is the change from baseline tumour size at month 6; secondary endpoints include best ORR, duration of objective response, 6-month PFS, and OS. Extensive PK, PD and pharmacogenomic assessments are included. As of January 2014 58 patients have been enrolled in the study Part A at all dose levels (Debio0932 100 mg to 1000 mg QD). MTD was not reached yet. One DLT occurred in the cisplatin + gemcitabine arm at Debio0932 250 mg dose and one in the docetaxel arm at Debio0932 1000 mg dose. Clinical trial information: NCT01714037.