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https://www.readbyqxmd.com/read/29134664/a-phase-ii-trial-of-ruxolitinib-in-combination-with-azacytidine-in-myelodysplastic-syndrome-myeloproliferative-neoplasms
#1
Rita Assi, Hagop M Kantarjian, Guillermo Garcia-Manero, Jorge E Cortes, Naveen Pemmaraju, Xuemei Wang, Graciela Nogueras-Gonzalez, Elias Jabbour, Prithviraj Bose, Tapan Kadia, Courtney D Dinardo, Keyur Patel, Carlos Bueso-Ramos, Lingsha Zhou, Sherry Pierce, Romany Gergis, Carla Tuttle, Gautam Borthakur, Zeev Estrov, Rajyalakshmi Luthra, Juliana Hidalgo-Lopez, Srdan Verstovsek, Naval Daver
Ruxolitinib and azacytidine target distinct disease manifestations of myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPNs). Patients with MDS/MPNs initially received ruxolitinib BID (doses based on platelets count), continuously in 28-day cycles for the first 3 cycles. Azacytidine 25 mg/m(2) (Day 1-5) intravenously or subcutaneously was recommended to be added to each cycle starting cycle 4 and could be increased to 75 mg/m(2) (Days 1-5) for disease control. Azacytidine could be started earlier than cycle 4 and/or at higher dose in patients with rapidly proliferative disease or with elevated blasts...
November 14, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29119847/myeloid-lymphoid-neoplasms-with-fgfr1-rearrangement
#2
Paolo Strati, Guilin Tang, Dzifa Y Duose, Saradhi Mallampati, Rajyalakshmi Luthra, Keyur P Patel, Mohammad Hussaini, Abu-Sayeef Mirza, Rami S Komrokji, Stephen Oh, John Mascarenhas, Vesna Najfeld, Vivek Subbiah, Hagop Kantarjian, Guillermo Garcia-Manero, Srdan Verstovsek, Naval Daver
Myeloid/lymphoid neoplasms with FGFR1 rearrangement are a rare entity. We present a multicenter experience of 17 patients with FISH-confirmed FGFR1 rearrangement. The clinical presentation at diagnosis included myeloproliferative neoplasm (MPN) in 4 (24%) patients, acute leukemia (AL) in 7 (41%), and concomitant MPN with AL in 6 (35%). The two most frequently observed cytogenetic abnormalities were t(8;13)(p11.2;q12)(partner gene ZMYM2) and t(8;22)(p11.2; q11.2)(BCR). Seventy-eight percent of tested patients had a RUNX1 mutation, of whom all had AL...
November 9, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29108809/response-to-symptoms-and-prehospital-delay-in-stroke-patients-is-it-time-to-reconsider-stroke-awareness-campaigns
#3
Rafael García Ruiz, Julia Silva Fernández, Rosa María García Ruiz, Marta Recio Bermejo, Ángel Arias Arias, Pablo Del Saz Saucedo, Rafael Huertas Arroyo, Ana González Manero, Ana Santos Pinto, Santiago Navarro Muñoz, Enrique Botia Paniagua, José Abellán Alemán
BACKGROUND: Despite recent advances in acute stroke care, reperfusion therapies are given to only 1%-8% of patients. Previous studies have focused on prehospital or decision delay. We aim to give a more comprehensive view by addressing different time delays and decisions. METHODS: A total of 382 patients with either acute stroke or transient ischemic attack were prospectively included. Sociodemographic and clinical parameters and data on decision delay, prehospital delay, and first medical contact were recorded...
November 3, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29047158/hyper-cvad-plus-nelarabine-in-newly-diagnosed-adult-t-cell-acute-lymphoblastic-leukemia-and-t-lymphoblastic-lymphoma
#4
Yasmin Abaza, Hagop M Kantarjian, Stefan Faderl, Elias Jabbour, Nitin Jain, Deborah Thomas, Tapan Kadia, Gautam Borthakur, Joseph D Khoury, Jan Burger, William Wierda, Susan O'Brien, Marina Konopleva, Alessandra Ferrajoli, Partow Kebriaei, Bouthaina Dabaja, Steven Kornblau, Yesid Alvarado, Naval Daver, Naveen Pemmaraju, Prithviraj Bose, Philip Thompson, Hind Al Azzawi, Mary Kelly, Rebecca Garris, Preetesh Jain, Guillermo Garcia-Manero, Jorge Cortes, Farhad Ravandi
Nelarabine, a water soluble prodrug of 9-β-D-arabinofuranosylguanine (ara-G), is a T-cell specific purine nucleoside analogue. Given its activity in relapsed and refractory T acute lymphoblastic leukemia (T-ALL) and T lymphoblastic lymphoma (T-LBL), we sought to define its role in the frontline treatment of adult patients. Therefore, we conducted a single arm phase 2 study to determine the safety and efficacy of nelarabine in combination with hyper-CVAD in newly diagnosed patients. For induction/consolidation, patients received eight cycles of hyper-CVAD alternating with high-dose methotrexate and cytarabine plus two cycles of nelarabine given at a dose of 650 mg/m(2) intravenously daily for 5 days...
October 19, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29027261/prognostic-significance-of-additional-chromosomal-abnormalities-at-the-time-of-diagnosis-in-patients-with-chronic-myeloid-leukemia-treated-with-frontline-tyrosine-kinase-inhibitors
#5
Ahmad Alhuraiji, Hagop Kantarjian, Prajwal Boddu, Farhad Ravandi, Gautam Borthakur, Courtney DiNardo, Naval Daver, Tapan Kadia, Naveen Pemmaraju, Sherry Pierce, Guillermo Garcia-Manero, William Wierda, Srdan Verstovsek, Elias Jabbour, Jorge Cortes
Additional cytogenetic abnormalities (ACA) are considered a high risk feature in chronic myeloid leukemia (CML). However, its prognostic significance at the time of diagnosis in the setting of new tyrosine kinase inhibitors (TKIs) is less well understood. Patients with CML in CP with or without ACA at diagnosis treated with frontline TKIs in prospective clinical trials were analyzed for outcomes. Among 603 patients treated, 29 (5%) had ACA. Patients with ACA included 2 of 72 (2.8%) treated with imatinib 400 mg, 9 of 207 (4...
October 13, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28972430/life-after-ponatinib-failure-outcomes-of-chronic-and-accelerated-phase-cml-patients-who-discontinued-ponatinib-in-the-salvage-setting
#6
Prajwal Boddu, Abdul Rashid Shah, Gautam Borthakur, Srdan Verstovsek, Guillermo Garcia-Manero, Naval Daver, Tapan Kadia, Farhad Ravandi, Nitin Jain, Ahmad Alhuraiji, Jan Burger, Steven Kornblau, Sherry Pierce, Sara Dellasala, Elias Jabbour, Hagop Kantarjian, Jorge Cortes
Ponatinib is a pan-tyrosine kinase inhibitor (TKI) with efficacy in multirefractory CML patients who have failed other TKIs. Despite excellent response rates, resistance or intolerance may develop. We conducted a retrospective review of the outcome of patients with chronic (CP) and accelerated (AP) phase CML refractory to prior TKI who discontinued ponatinib for resistance or intolerance. Nineteen CP patients, discontinued due to resistance (n = 13), toxicity (n = 5) and to pursue stem cell transplantation (n = 1)...
October 3, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28927784/safety-and-efficacy-of-blinatumomab-in-combination-with-a-tyrosine-kinase-inhibitor-for-the-treatment-of-relapsed-philadelphia-chromosome-positive-leukemia
#7
Rita Assi, Hagop Kantarjian, Nicholas J Short, Naval Daver, Koichi Takahashi, Guillermo Garcia-Manero, Courtney DiNardo, Jan Burger, Jorge Cortes, Nitin Jain, William Wierda, Salim Chamoun, Marina Konopleva, Elias Jabbour
OBJECTIVE: The treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia has been revolutionized with the introduction of tyrosine kinase inhibitors (TKIs) and the combination of these agents with chemotherapy. Blinatumomab is a bispecific anti-CD3/CD19 monoclonal antibody with clinical activity as single-agent in the relapsed setting and independent of BCR-ABL1 mutational status, including T315I. The combination of blinatumomab with a TKI may further improve outcomes for this high-risk population, including higher eradication of minimal residual disease and minimize the use of chemotherapy...
August 18, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28926144/characterization-of-tp53-mutations-in-low-grade-myelodysplastic-syndromes-and-myelodysplastic-syndromes-with-a-non-complex-karyotype
#8
Wei Wang, Mark J Routbort, Zhenya Tang, Chi Young Ok, Keyur P Patel, Naval Daver, Guillermo Garcia-Manero, L Jeffrey Medeiros, Sa A Wang
OBJECTIVES: Although commonly associated with high-grade myelodysplastic syndrome (MDS) and MDS with a complex karyotype, TP53 mutations also occur in low-grade MDS and MDS with a non-complex karyotype. In latter cases, their clinicopathological features and the characteristics of TP53 mutations remain poorly characterized. METHODS: 176 MDS cases with TP53 mutations were stratified and characterized based on their karyotype and histologic subtype. RESULTS: Among 176 cases, 17% had a non-complex karyotype and 24% were low-grade MDS...
September 19, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28919634/achievement-of-a-negative-minimal-residual-disease-state-after-hypomethylating-agent-therapy-in-older-patients-with-aml-reduces-the-risk-of-relapse
#9
P Boddu, J Jorgensen, H Kantarjian, G Borthakur, T Kadia, N Daver, Y Alvarado, N Pemmaraju, P Bose, K Naqvi, M Yilmaz, S Pierce, M Brandt, C D DiNardo, E J Jabbour, M Konopleva, G Garcia-Manero, J Cortes, F Ravandi
No abstract text is available yet for this article.
September 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28885734/chronic-myelomonocytic-leukemia-masquerading-as-cutaneous-indeterminate-dendritic-cell-tumor-expanding-the-spectrum-of-skin-lesions-in-chronic-myelomonocytic-leukemia
#10
Sanam Loghavi, Jonathan L Curry, Guillermo Garcia-Manero, Keyur P Patel, Jie Xu, Joseph D Khoury, Carlos A Torres-Cabala, Priyadharsini Nagarajan, Phyu P Aung, Bernard R Gibson, Brandon P Goodwin, Brent C Kelly, Brinda R Korivi, L Jeffrey Medeiros, Victor G Prieto, Hagop M Kantarjian, Carlos E Bueso-Ramos, Michael T Tetzlaff
Chronic myelomonocytic leukemia (CMML) is a hematopoietic stem cell neoplasm exhibiting both myelodysplastic and myeloproliferative features. Cutaneous involvement by CMML is critical to recognize as it typically is a harbinger of disease progression and an increased incidence of transformation to acute myeloid leukemia. Cutaneous lesions of CMML exhibit heterogeneous histopathologic features that can be challenging to recognize as CMML. We describe a 67-year-old man with a 3-year history of CMML who had been managed on single-agent azacitidine with stable disease before developing splenomegaly and acute onset skin lesions...
September 8, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28867245/proposal-of-a-novel-clinical-score-to-predict-heart-failure-incidence-in-long-term-survivors-of-acute-coronary-syndromes
#11
Moisés Rodríguez-Mañero, Alberto Cordero, Omar Kreidieh, Jose Mª García-Acuña, Jose Seijas, Rosa María Agra-Bermejo, Charigan Abou-Jokh, Leyre Álvarez-Rodríguez, Diego Álvarez-Iglesias, Ramón López-Palop, Belen Cid, Pilar Carrillo, Jose R González-Juanatey
INTRODUCTION: HF remains a frequent complication following MI and adversely affects prognosis. The objective of this study was to identify predictors of HF following MI and to design a risk score for its prediction. METHODS: Retrospective study of all consecutive patients admitted for MI. Primary end point was time to incident HF. Patients with previous history of HF were excluded. Death was modelled as competing risk. RESULTS: 5737 patients were included...
December 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28859185/salvage-chemoimmunotherapy-with-inotuzumab-ozogamicin-combined-with-mini-hyper-cvd-for-patients-with-relapsed-or-refractory-philadelphia-chromosome-negative-acute-lymphoblastic-leukemia-a-phase-2-clinical-trial
#12
Elias Jabbour, Farhad Ravandi, Partow Kebriaei, Xuelin Huang, Nicholas J Short, Deborah Thomas, Koji Sasaki, Michael Rytting, Nitin Jain, Marina Konopleva, Guillermo Garcia-Manero, Richard Champlin, David Marin, Tapan Kadia, Jorge Cortes, Zeev Estrov, Koichi Takahashi, Yogin Patel, Maria R Khouri, Jovitta Jacob, Rebecca Garris, Susan O'Brien, Hagop Kantarjian
Importance: The outcome of patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) is poor. Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to calicheamicin, has single-agent activity in R/R ALL. Objective: To evaluate the efficacy and safety of inotuzumab ozogamicin plus low-intensity chemotherapy in patients with R/R ALL. Design, Setting, and Participants: A single-arm, phase 2 study of adults with R/R B-cell ALL conducted at The University of Texas MD Anderson Cancer Center, Houston...
August 31, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28844816/guadecitabine-sgi-110-in-treatment-naive-patients-with-acute-myeloid-leukaemia-phase-2-results-from-a-multicentre-randomised-phase-1-2-trial
#13
RANDOMIZED CONTROLLED TRIAL
Hagop M Kantarjian, Gail J Roboz, Patricia L Kropf, Karen W L Yee, Casey L O'Connell, Raoul Tibes, Katherine J Walsh, Nikolai A Podoltsev, Elizabeth A Griffiths, Elias Jabbour, Guillermo Garcia-Manero, David Rizzieri, Wendy Stock, Michael R Savona, Todd L Rosenblat, Jesus G Berdeja, Farhad Ravandi, Edwin P Rock, Yong Hao, Mohammad Azab, Jean-Pierre J Issa
BACKGROUND: The hypomethylating drugs azacitidine and decitabine have shown efficacy in myelodysplastic syndromes and acute myeloid leukaemia, but complete tumour responses are infrequent and of short duration, possibly because of the short half-lives and suboptimal bone marrow exposure of the drugs. Guadecitabine, a next-generation hypomethylating drug, has a longer half-life and exposure than its active metabolite decitabine. A phase 1 study established 60 mg/m(2) guadecitabine for 5 days as an effective treatment schedule...
October 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28841236/phase-1-dose-escalation-multicenter-trial-of-pracinostat-alone-and-in-combination-with-azacitidine-in-patients-with-advanced-hematologic-malignancies
#14
Yasmin M Abaza, Tapan M Kadia, Elias J Jabbour, Marina Y Konopleva, Gautam Borthakur, Alessandra Ferrajoli, Zeev Estrov, William G Wierda, Ana Alfonso, Toh Han Chong, Charles Chuah, Liang-Piu Koh, Boon-Cher Goh, Julie E Chang, Daniel E Durkes, Maria Cielo Foudray, Hagop M Kantarjian, Xiao Qin Dong, Guillermo Garcia-Manero
BACKGROUND: Pracinostat is a potent histone deacetylase inhibitor with antitumor activity in both solid tumor and acute myeloid leukemia (AML) cell lines. Pracinostat is reported to have modest clinical activity in patients with advanced solid tumors. Given the higher preclinical sensitivity of hematologic malignancies to pracinostat, the authors conducted a phase 1 study to assess the safety, maximum tolerated dose, recommended phase 2 dose, efficacy, pharmacokinetics, and pharmacodynamics of pracinostat in patients with advanced hematological malignancies...
August 25, 2017: Cancer
https://www.readbyqxmd.com/read/28838278/time-to-response-and-survival-in-hypomethylating-agent-treated-acute-myeloid-leukemia
#15
Prajwal Boddu, Hagop Kantarjian, Guillermo Garcia-Manero, Farhad Ravandi, Elias Jabbour, Gautam Borthakur, Naval Daver, Naveen Pemmaraju, Sherry Pierce, Jorge Cortes, Tapan M Kadia
No abstract text is available yet for this article.
August 25, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28835440/clonal-chromosomal-abnormalities-appearing-in-philadelphia-negative-metaphases-during-cml-treatment
#16
Ghayas C Issa, Hagop Kantarjian, Graciela Nogueras Gonzalez, Gautam Borthakur, Guilin Tang, William Wierda, Koji Sasaki, Nicholas J Short, Farhad Ravandi, Tapan Kadia, Keyur Patel, Raja Luthra, Alessandra Ferrajoli, Guillermo Garcia-Manero, Mary Beth Rios, Sara Dellasala, Elias Jabbour, Jorge E Cortes
Clonal chromosomal abnormalities in Philadelphia chromosome-negative metaphases (CCA/Ph-) emerge as patients with chronic phase chronic myeloid leukemia (CP-CML) are treated with tyrosine kinase inhibitors (TKI). We assessed the characteristics and prognostic impact of 598 patients with CP-CML treated on clinical trials with various TKIs. CCA/Ph- occurred in 58 patients (10%) and the most common were - Y in 25 (43%) and trisomy 8 in 7 patients (12%). Response to TKI therapy was similar for patients with CCA/Ph- and those without additional chromosomal abnormalities (ACAs)...
August 23, 2017: Blood
https://www.readbyqxmd.com/read/28789846/additive-value-of-the-crusade-score-to-the-grace-score-for-mortality-risk-prediction-in-patients-with-acute-coronary-syndromes
#17
Alberto Cordero, Moisés Rodriguez-Manero, Jose M García-Acuña, Ramón López-Palop, Belen Cid, Pilar Carrillo, Rosa Agra-Bermejo, Violeta González-Salvado, Diego Iglesias-Alvarez, Vicente Bertomeu-Martínez, Jose R González-Juanatey
INTRODUCTION: Acute coronary syndrome (ACS) treatments increase bleeding complications that also impair prognosis. Bleeding risk scores reclassification of actual mortality risk estimated by the GRACE score might improve overall estimation. METHODS: Observational and prospective study of all ACS patients admitted in two hospitals. Mortality risk was assessed by the GRACE score and bleeding risk by the CRUSADE score. We analyzed the net reclassification improvement (NRI) of adding the CRUSADE score to the GRACE score...
October 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28774880/randomized-phase-2-study-of-low-dose-decitabine-vs-low-dose-azacitidine-in-lower-risk-mds-and-mds-mpn
#18
RANDOMIZED CONTROLLED TRIAL
Elias Jabbour, Nicholas J Short, Guillermo Montalban-Bravo, Xuelin Huang, Carlos Bueso-Ramos, Wei Qiao, Hui Yang, Chong Zhao, Tapan Kadia, Gautam Borthakur, Naveen Pemmaraju, Koji Sasaki, Zeev Estrov, Jorge Cortes, Farhad Ravandi, Yesid Alvarado, Rami Komrokji, Mikkael A Sekeres, David P Steensma, Amy DeZern, Gail Roboz, Hagop Kantarjian, Guillermo Garcia-Manero
Hypomethylating agents (HMAs) improve survival in patients with higher-risk myelodysplastic syndromes (MDS) but are less well-studied in lower-risk disease. We compared the safety and efficacy of low-dose decitabine vs low-dose azacitidine in this group of patients. Adults with low- or intermediate 1-risk MDS or MDS/myeloproliferative neoplasm (MPN), including chronic myelomonocytic leukemia, according to the International Prognostic Scoring System, were randomly assigned using a Bayesian adaptive design to receive either azacitidine 75 mg/m(2) intravenously/subcutaneously daily or decitabine 20 mg/m(2) intravenously daily for 3 consecutive days on a 28-day cycle...
September 28, 2017: Blood
https://www.readbyqxmd.com/read/28760297/progress-in-myelodysplastic-syndromes-clinicopathologic-correlations-and-immune%C3%A2-checkpoints
#19
Juliana E Hidalgo-López, Rashmi Kanagal-Shamanna, Andrés E Quesada, Beenu Thakral, Zhihong Hu, Takayuki Mitsuhashi, Mariko Yabe, Guillermo Garcia-Manero, Carlos E Bueso-Ramos
BACKGROUND: Myelodysplastic syndromes (MDS) are a group of clonal neoplasms characterized by ineffective hematopoiesis. Hypomethylating agent (HMA) therapy is one of the mainstays of MDS therapy. Failure of HMA therapy is related to poor outcome; hence, new therapeutic approaches are warranted in these patients. In MDS, the immune system has a pivotal role in modulation of hematopoiesis and clonal expansion. In neoplastic conditions, immune checkpoint (PD-1 and CTLA4 molecules) hide tumor cells from immune surveillance...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28755687/response-to-ecg-july-2017
#20
Moisés Rodríguez-Mañero, Javier García-Seara, José Luis Martínez-Sande
No abstract text is available yet for this article.
August 2017: Revista Española de Cardiología
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