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https://www.readbyqxmd.com/read/28094841/phase-2-randomized-double-blind-study-of-pracinostat-in-combination-with-azacitidine-in-patients-with-untreated-higher-risk-myelodysplastic-syndromes
#1
Guillermo Garcia-Manero, Guillermo Montalban-Bravo, Jesus G Berdeja, Yasmin Abaza, Elias Jabbour, James Essell, Roger M Lyons, Farhad Ravandi, Michael Maris, Brian Heller, Amy E DeZern, Sunil Babu, David Wright, Bertrand Anz, Ralph Boccia, Rami S Komrokji, Philip Kuriakose, James Reeves, Mikkael A Sekeres, Hagop M Kantarjian, Richard Ghalie, Gail J Roboz
BACKGROUND: The prognosis of patients with higher risk myelodysplastic syndromes (MDS) remains poor despite available therapies. Histone deacetylase inhibitors have demonstrated activity in patients with MDS and in vitro synergy with azacitidine. METHODS: A phase 2 randomized, placebo-controlled clinical trial of azacitidine and pracinostat was conducted in patients who had International Prognostic Scoring System intermediate-2-risk or high-risk MDS. The primary endpoint was the complete response (CR) rate by cycle 6 of therapy...
January 17, 2017: Cancer
https://www.readbyqxmd.com/read/28089328/usefulness-of-three-dimensional-transthoracic-echocardiograhy-in-the-localization-of-the-micra-leadless-pacemaker
#2
José Luis Martínez-Sande, Carlos Peña-Gil, Javier García-Seara, Moisés Rodríguez-Mañero, María Amparo Martínez-Monzonis, José Ramón González-Juanatey
No abstract text is available yet for this article.
January 11, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/28076892/impact-of-achievement-of-complete-cytogenetic-response-on-outcome-in-patients-with-myelodysplastic-syndromes-treated-with-hypomethylating-agents
#3
Elias Jabbour, Paolo Strati, Monica Cabrero, Susan O'Brien, Farhad Ravandi, Carlos Bueso-Ramos, Qiao Wei, Jianhua Hu, Simon Abi Aad, Nicholas J Short, Courtney Dinardo, Naval Daver, Tapan Kadia, William Wierda, Yue Wei, Simona Colla, Gautam Borthakur, Jorge Cortes, Zeev Estrov, Hagop Kantarjian, Guillermo Garcia-Manero
We reviewed 216 consecutive patients with MDS and abnormal karyotype treated with hypomethylating agents between 4/04 and 10/12. Median follow-up was 17 months. Using IWG criteria, best responses were complete response (CR) in 79 patients (37%), partial response (PR) in 4 (2%), and hematologic improvement (HI) in 10 (5%). Cytogenetic response (CyR) was achieved in 78 patients (36%): complete (CCyR) in 62 (29%) and partial in 16 (7%). CyR was achieved in 48 of 79 patients (61%) with CR, 1 of 14 (7%) with PR/HI, and in 29 of the 123 (24%) with no morphologic response...
January 11, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28052371/significance-of-recurrence-of-minimal-residual-disease-detected-by-multi-parameter-flow-cytometry-in-patients-with-acute-lymphoblastic-leukemia-in-morphological-remission
#4
Naveen Pemmaraju, Hagop Kantarjian, Jeffrey L Jorgensen, Elias Jabbour, Nitin Jain, Deborah Thomas, Susan O'Brien, Xuemei Wang, Xuelin Huang, Sa A Wang, Marina Konopleva, Sergej Konoplev, Tapan Kadia, Rebecca Garris, Sherry Pierce, Guillermo Garcia-Manero, Jorge Cortes, Farhad Ravandi
We sought to determine the significance of minimal residual disease (MRD) relapse in patients with ALL after achieving MRD negative status following induction and consolidation therapy. Between January 2003 and September 2014, 647 newly diagnosed patients were treated [HyperCVAD-based (n=531); Augmented BFM (n=116)]. 601 (93%) achieved complete remission (CR), and 546 (91%) became MRD negative. Fifty-five patients [HyperCVAD-based (n=49); Augmented BFM (n=6)] developed recurrence of MRD while still in morphological CR and are the subjects of this study...
January 4, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28040720/myelodysplastic-syndromes-version-2-2017-nccn-clinical-practice-guidelines-in-oncology
#5
Peter L Greenberg, Richard M Stone, Aref Al-Kali, Stefan K Barta, Rafael Bejar, John M Bennett, Hetty Carraway, Carlos M De Castro, H Joachim Deeg, Amy E DeZern, Amir T Fathi, Olga Frankfurt, Karin Gaensler, Guillermo Garcia-Manero, Elizabeth A Griffiths, David Head, Ruth Horsfall, Robert A Johnson, Mark Juckett, Virginia M Klimek, Rami Komrokji, Lisa A Kujawski, Lori J Maness, Margaret R O'Donnell, Daniel A Pollyea, Paul J Shami, Brady L Stein, Alison R Walker, Peter Westervelt, Amer Zeidan, Dorothy A Shead, Courtney Smith
The myelodysplastic syndromes (MDS) comprise a heterogenous group of myeloid disorders with a highly variable disease course. Diagnostic criteria to better stratify patients with MDS continue to evolve, based on morphology, cytogenetics, and the presence of cytopenias. More accurate classification of patients will allow for better treatment guidance. Treatment encompasses supportive care, treatment of anemia, low-intensity therapy, and high-intensity therapy. This portion of the guidelines focuses on diagnostic classification, molecular abnormalities, therapeutic options, and recommended treatment approaches...
January 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28040461/the-micra-leadless-transcatheter-pacemaker-implantation-and-mid-term-follow-up-results-in-a-single-center
#6
José Luis Martínez-Sande, Javier García-Seara, Moisés Rodríguez-Mañero, Xesús Alberte Fernández-López, Laila González-Melchor, Alfredo Redondo-Diéguez, Rocío González-Ferreiro, José Ramón González-Juanatey
INTRODUCTION AND OBJECTIVES: Currently, studies on the leadless pacemaker (Micra) have mostly been limited to clinical trials with less than 6 months' follow-up and they often fail to reflect real population outcomes. We sought to evaluate electrical parameters at implantation and chronologically during follow-up, as well as the safety of this new technique. METHODS: This prospective, observational study included 30 consecutive patients, all ≥ 65 years, with an indication for single-chamber pacemaker implantation...
December 28, 2016: Revista Española de Cardiología
https://www.readbyqxmd.com/read/28038805/nutritional-status-is-related-to-heart-failure-severity-and-hospital-readmissions-in-acute-heart-failure
#7
Rosa María Agra Bermejo, Rocío González Ferreiro, Alfonso Varela Román, Inés Gómez Otero, Omar Kreidieh, Patricia Conde Sabarís, Moisés Rodríguez-Mañero, María Moure González, Ana Seoane Blanco, Alejandro Virgós Lamela, Alberto García Castelo, Jose Ramón González Juanatey
BACKGROUND: Malnutrition is common in hospitalized heart failure (HF) patients and predicts adverse outcomes. The relationship between nutritional status and outcomes in HF has been partially studied. Our aim was to determine the relationship between the nutritional status and the long-term prognosis in patients hospitalized for acute HF. METHODS: We analyzed 145 patients admitted consecutively to a cardiology department for acute HF. Nutritional status was measured with the CONUT method, a validated scale based on laboratory testing (albumin; cholesterol; lymphocytes) during hospitalization...
December 19, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28029524/-external-lumbar-drainage-with-volumetric-continuing-infusion-pump-in-patients-with-cerebrospinal-fluid-leak-a-case-series
#8
Ana Belén Manso Melgosa, Helena García Gutiérrez, Mónica Fernández Porras, Ana Berta Castrillo Manero, Belén Pérez Marijuán
OBJECTIVE: To describe the incidence and complications arising in a number of cases of patients with cerebrospinal fluid leak treated by external lumbar drainage with infusion pump (IP) volumetric continuous from 2001 to 2014. Quantify cerebrospinal fluid leak closed by lumbar drainage with IP. METHODS: Retrospective descriptive case series study. POPULATION: patients undergoing transsphenoidal pituitary surgery, Chiari surgery and laminectomy, that developed postoperative cerebrospinal fluid leak treated with continuous external lumbar drainage by IP...
October 28, 2016: Enfermería Clínica
https://www.readbyqxmd.com/read/28024152/ubiquitination-of-hnrnpa1-by-traf6-links-chronic-innate-immune-signaling-with-myelodysplasia
#9
Jing Fang, Lyndsey C Bolanos, Kwangmin Choi, Xiaona Liu, Susanne Christie, Shailaja Akunuru, Rupali Kumar, Dehua Wang, Xiaoting Chen, Kenneth D Greis, Peter Stoilov, Marie-Dominique Filippi, Jaroslaw P Maciejewski, Guillermo Garcia-Manero, Matthew T Weirauch, Nathan Salomonis, Hartmut Geiger, Yi Zheng, Daniel T Starczynowski
Toll-like receptor (TLR) activation contributes to premalignant hematologic conditions, such as myelodysplastic syndromes (MDS). TRAF6, a TLR effector with ubiquitin (Ub) ligase activity, is overexpressed in MDS hematopoietic stem/progenitor cells (HSPCs). We found that TRAF6 overexpression in mouse HSPC results in impaired hematopoiesis and bone marrow failure. Using a global Ub screen, we identified hnRNPA1, an RNA-binding protein and auxiliary splicing factor, as a substrate of TRAF6. TRAF6 ubiquitination of hnRNPA1 regulated alternative splicing of Arhgap1, which resulted in activation of the GTP-binding Rho family protein Cdc42 and accounted for hematopoietic defects in TRAF6-expressing HSPCs...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/28006851/poor-outcomes-associated-with-der-22-t-9-22-and-9-9p-in-patients-with-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-receiving-chemotherapy-plus-a-tyrosine-kinase-inhibitor
#10
Nicholas J Short, Hagop M Kantarjian, Koji Sasaki, Farhad Ravandi, Heidi Ko, C Cameron Yin, Guillermo Garcia-Manero, Jorge E Cortes, Rebecca Garris, Susan M O'Brien, Keyur Patel, Maria Khouri, Deborah Thomas, Nitin Jain, Tapan M Kadia, Naval Daver, Christopher B Benton, Ghayas C Issa, Marina Konopleva, Elias Jabbour
In patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with chemotherapy plus a tyrosine kinase inhibitor (TKI), the prognostic impact of additional chromosomal abnormalities (ACAs) is not well-established. We evaluated the prognostic impact of individual ACAs in 152 patients with Ph+ ALL receiving first-line intensive chemotherapy plus either imatinib (n=36), dasatinib (n=74) or ponatinib (n=42). ACAs were identified in 118 patients (78%). Compared to outcomes of patients without ACAs, ACAs were not associated with differences in either relapse-free survival (RFS; P=0...
December 22, 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/28003274/long-term-outcome-of-acute-promyelocytic-leukemia-treated-with-all-trans-retinoic-acid-arsenic-trioxide-and-gemtuzumab
#11
Yasmin Abaza, Hagop M Kantarjian, Guillermo Garcia-Manero, Elihu Estey, Gautam Borthakur, Elias Jabbour, Stefan Faderl, Susan O'Brien, William Wierda, Sherry Pierce, Mark Brandt, Deborah McCue, Rajyalakshmi Luthra, Keyur Patel, Steven Kornblau, Tapan Kadia, Naval Daver, Courtney DiNardo, Nitin Jain, Srdan Verstovsek, Alessandra Ferrajoli, Michael Andreeff, Marina Konopleva, Zeev Estrov, Maria Foudray, David McCue, Jorge Cortes, Farhad Ravandi
The combination of all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of standard risk newly diagnosed patients with acute promyelocytic leukemia (APL). A recent study demonstrated the efficacy of this regimen with added gemtuzumab ozogamycin (GO) in high-risk patients. We examined the long-term outcome of newly diagnosed APL patients treated at our institution on three consecutive prospective clinical trials using the combination of ATRA, ATO, with or without GO...
December 21, 2016: Blood
https://www.readbyqxmd.com/read/27923552/preleukaemic-clonal-haemopoiesis-and-risk-of-therapy-related-myeloid-neoplasms-a-case-control-study
#12
Koichi Takahashi, Feng Wang, Hagop Kantarjian, Denaha Doss, Kanhav Khanna, Erika Thompson, Li Zhao, Keyur Patel, Sattva Neelapu, Curtis Gumbs, Carlos Bueso-Ramos, Courtney D DiNardo, Simona Colla, Farhad Ravandi, Jianhua Zhang, Xuelin Huang, Xifeng Wu, Felipe Samaniego, Guillermo Garcia-Manero, P Andrew Futreal
BACKGROUND: Therapy-related myeloid neoplasms are secondary malignancies that are often fatal, but their risk factors are not well understood. Evidence suggests that individuals with clonal haemopoiesis have increased risk of developing haematological malignancies. We aimed to identify whether patients with cancer who have clonal haemopoiesis are at an increased risk of developing therapy-related myeloid neoplasms. METHODS: We did this retrospective case-control study to compare the prevalence of clonal haemopoiesis between patients treated for cancer who later developed therapy-related myeloid neoplasms (cases) and patients who did not develop these neoplasms (controls)...
January 2017: Lancet Oncology
https://www.readbyqxmd.com/read/27919910/ph-like-acute-lymphoblastic-leukemia-a-high-risk-subtype-in-adults
#13
Nitin Jain, Kathryn G Roberts, Elias Jabbour, Keyur Patel, Agda Karina Eterovic, Ken Chen, Patrick Zweidler-McKay, Xinyan Lu, Gloria Fawcett, Sa A Wang, Sergej Konoplev, Richard C Harvey, I-Ming Chen, Debbie Payne-Turner, Marcus Valentine, Deborah Thomas, Guillermo Garcia-Manero, Farhad Ravandi, Jorge Cortes, Steven Kornblau, Susan O'Brien, Sherry Pierce, Jeffrey Jorgensen, Kenna R Mills Shaw, Cheryl L Willman, Charles G Mullighan, Hagop Kantarjian, Marina Konopleva
Ph-like acute lymphoblastic leukemia (ALL) is a high-risk subtype of ALL in children. There are limited and conflicted data on the incidence and prognosis of Ph-like ALL in adults. Patients with newly-diagnosed B-ALL who received frontline chemotherapy at MD Anderson Cancer Center underwent gene expression profiling of leukemic cells to identify Ph-like ALL. Patients received hyper-CVAD (80%) or augmented-BFM (20%) regimen. Of 148 patients, 33.1% had Ph-like, 31.1% had Ph+, and 35.8% had other B-ALL subtypes (B-other)...
December 5, 2016: Blood
https://www.readbyqxmd.com/read/27878822/wide-variations-in-blood-product-transfusion-practices-among-providers-who-care-for-patients-with-acute-leukemia-in-the-united-states
#14
Alexander B Pine, Eun-Ju Lee, Mikkael Sekeres, David P Steensma, Daniel Zelterman, Thomas Prebet, Amy DeZern, Rami Komrokji, Mark Litzow, Selina Luger, Richard Stone, Harry P Erba, Guillermo Garcia-Manero, Alfred I Lee, Nikolai A Podoltsev, Lisa Barbarotta, Stephanie Kasberg, Jeanne E Hendrickson, Steven D Gore, Amer M Zeidan
BACKGROUND: Transfusion of blood products is a key component of the supportive management in patients with acute leukemia (AL). However high-quality trial evidence and clinical outcome data to support specific transfusion goals for blood products for patients with AL remain limited leading to diverse transfusion practices. The primary objective of this study was to determine the spectrum of transfusion patterns in a variety of care settings among providers who treat AL patients. STUDY DESIGN AND METHODS: A 31-question survey queried providers caring for AL patients about the existence of institutional guidelines for transfusion of blood products, transfusion triggers for hemoglobin (Hb), platelets (PLTs), and fibrinogen in various settings including inpatient and outpatient and before procedures...
November 22, 2016: Transfusion
https://www.readbyqxmd.com/read/27849645/current-management-of-patients-with-chronic-myelomonocytic-leukemia
#15
Ana Alfonso, Guillermo Montalban-Bravo, Guillermo Garcia-Manero
PURPOSE OF REVIEW: The present review will focus on the current management of patients with chronic myelomonocytic leukemia (CMML) as well as in future therapeutic perspectives. RECENT FINDINGS: CMML is a clonal hematopoietic stem cell disorder characterized by peripheral blood monocytosis and myelodysplastic and myeloproliferative alterations in the bone marrow. Clinical behavior of the disease can be heterogeneous, with some patients having an indolent form of the disease, whereas others experience an aggressive course with decreased survival and eventual transformation to leukemia...
January 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/27795561/a-clinical-trial-for-patients-with-acute-myeloid-leukemia-or-myelodysplastic-syndromes-not-eligible-for-standard-clinical-trials
#16
G Montalban-Bravo, X Huang, E Jabbour, G Borthakur, C D DiNardo, N Pemmaraju, J Cortes, S Verstovsek, T Kadia, N Daver, W Wierda, Y Alvarado, M Konopleva, F Ravandi, Z Estrov, N Jain, A Alfonso, M Brandt, T Sneed, H-C Chen, H Yang, C Bueso-Ramos, S Pierce, E Estey, Z Bohannan, H M Kantarjian, G Garcia-Manero
Most clinical trials exclude patients with poor performance or comorbidities. To study whether patients with these characteristics can be treated within a clinical trial, we conducted a study for patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) with poor performance, organ dysfunction or comorbidities. Primary endpoint was 60-day survival. Study included stopping rules for survival and response. Treatment consisted on a combination of azacitidine and vorinostat. Thirty patients (16 with MDS, 14 with AML) were enrolled...
October 31, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27774847/differential-response-to-hypomethylating-agents-based-on-sex-a-report-on-behalf-of-the-mds-clinical-research-consortium-mds-crc
#17
Amy E DeZern, Amer M Zeidan, John Barnard, Wesley Hand, Najla Al Ali, Francis Brown, Cassie Zimmerman, Gail J Roboz, Guillermo Garcia-Manero, David P Steensma, Rami S Komrokji, Mikkael A Sekeres
First-line therapy for higher-risk myelodysplastic syndromes (MDS) includes decitabine (DAC) or azacitidine (AZA). Variables have not identified differential response rates between these. We assessed the influence of patient sex on outcomes including overall survival (OS) in 642 patients with higher-risk MDS treated with AZA or DAC. DAC-treated patients (35% of females, 31% of males) had marginally better OS than AZA-treated patients (p = .043), (median OS of 18.7 months versus 16.4 months), but the difference varied strongly by sex...
October 24, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27763690/chronic-myeloid-leukemia-among-patients-with-a-history-of-prior-malignancies-a-tale-of-dual-survivorship
#18
Paul B Koller, Hagop M Kantarjian, Graciela M Nogueras-Gonzalez, Elias Jabbour, Srdan Verstovsek, Gautam Borthakur, Zeev Estrov, William G Wierda, Guillermo Garcia-Manero, Alessandra Ferrajoli, Farhad Ravandi, Susan M O'Brien, Jorge E Cortes
BACKGROUND: Some patients with chronic myeloid leukemia (CML) have a history of previous malignancies. To the authors' knowledge, outcomes for CML diagnosed in these patients have not been well described. The current study was conducted to determine the outcome of patients with CML and a history of prior malignancies. METHODS: The current study included patients who were enrolled in clinical trials of tyrosine kinase inhibitors as initial therapy for CML in chronic phase from July 2000 to January 2014...
October 20, 2016: Cancer
https://www.readbyqxmd.com/read/27760759/kir-gene-haplotype-an-independent-predictor-of-clinical-outcome-in-mds-patients
#19
Kate Stringaris, David Marin, A John Barrett, Robert Hills, Catherine Sobieski, Kai Cao, Jerome G Saltarrelli, May Daher, Hila Shaim, Nathaniel Smith, David Linch, Rosemary Gale, Christopher Allen, Takuya Sekine, Rohtesh Mehta, Richard Champlin, Elizabeth J Shpall, Hagop Kantarjian, Guillermo Garcia-Manero, Katayoun Rezvani
Myelodysplastic syndromes (MDSs) are a group of hematopoietic disorders affecting the myeloid lineage, characterized by cytopenias and clonal evolution to acute myeloid leukemia (AML). We hypothesized that natural killer (NK) cells and their activating killer immunoglobulin-like receptors (aKIRs) influence the immune surveillance and clinical outcome of patients with MDSs. Here, we first examined the distribution of aKIR genes and haplotype in 2 independent cohorts of MDS and AML patients. The median number of aKIR genes was lower in MDS patients than healthy controls (2 vs 3 genes; P = ...
December 15, 2016: Blood
https://www.readbyqxmd.com/read/27741352/phase-2-study-of-low-dose-clofarabine-plus-cytarabine-for-patients-with-higher-risk-myelodysplastic-syndrome-who-have-relapsed-or-are-refractory-to-hypomethylating-agents
#20
Elias Jabbour, Stefan Faderl, Koji Sasaki, Tapan Kadia, Naval Daver, Naveen Pemmaraju, Keyur Patel, Joseph D Khoury, Carlos Bueso-Ramos, Zachary Bohannan, Farhad Ravandi, Gautam Borthakur, Srdan Verstovsek, Darla Miller, Rita Maduike, Chitra Hosing, Hagop M Kantarjian, Guillermo Garcia-Manero
BACKGROUND: The outcome of patients with higher risk myelodysplastic syndromes (MDS) after hypomethylating agent (HMA) failure is poor. This study evaluated the safety and activity of a combination of low-dose clofarabine and cytarabine for these patients. METHODS: Seventy patients with higher risk MDS who had no response, progressed, or relapsed after at least 4 cycles of HMA therapy were treated. RESULTS: The median age was 72 years. Thirty-nine percent of the patients had high-risk disease according to the International Prognostic Scoring System, and 50% of the patients had poor-risk cytogenetics...
October 14, 2016: Cancer
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