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Mikkael Sekeres

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https://www.readbyqxmd.com/read/28255022/molecular-features-of-early-onset-adult-myelodysplastic-syndrome
#1
Cassandra M Hirsch, Bartlomiej P Przychodzen, Tomas Radivoyevitch, Bhumika Patel, Swapna Thota, Michael J Clemente, Yasunobu Nagata, Thomas LaFramboise, Hetty Carraway, Aziz Nazha, Mikkael A Sekeres, Hideki Makishima, Jaroslaw P Maciejewski
Myelodysplastic syndromes are typically diseases of older adults. Early onset patients may have distinct molecular and clinical features or reflect a demographic continuum. The identification of differences between early onset patients and those diagnosed at a traditional age has the potential to advance understanding of the pathogenesis of myelodysplasia and may lead to formation of distinct morphologic subcategories. We studied a cohort of 634 patients with various subcategories of myelodysplastic syndrome and secondary acute myeloid leukemia, stratifying based on age at presentation and clinical parameters...
March 2, 2017: Haematologica
https://www.readbyqxmd.com/read/28223278/impact-of-genetic-alterations-in-stem-cell-transplantation-for-myelodysplasia-and-secondary-acute-myeloid-leukemia
#2
Tetsuichi Yoshizato, Yasuhito Nannya, Yoshiko Atsuta, Yusuke Shiozawa, Yuka Iijima-Yamashita, Kenichi Yoshida, Yuichi Shiraishi, Hiromichi Suzuki, Yasunobu Nagata, Yusuke Sato, Nobuyuki Kakiuchi, Keitaro Matsuo, Makoto Onizuka, Keisuke Kataoka, Kenichi Chiba, Hiroko Tanaka, Hiroo Ueno, Masahiro M Nakagawa, Bartlomiej Przychodzen, Claudia Haferlach, Wolfgang Kern, Kosuke Aoki, Hidehiro Itonaga, Yoshinobu Kanda, Mikkael A Sekeres, Jaroslaw P Maciejewski, Torsten Haferlach, Yasushi Miyazaki, Keizo Horibe, Masashi Sanada, Satoru Miyano, Hideki Makishima, Seishi Ogawa
Genetic alterations, including mutations and copy number alterations, are central to the pathogenesis of myelodysplastic syndromes and related diseases (myelodysplasia), but their roles in allogeneic stem-cell transplantation have not fully been studied in a large cohort of patients. We enrolled 797 patients who had been diagnosed with myelodysplasia at initial presentation and received transplantation via the Japan Marrow Donor Program. Targeted-capture sequencing was performed to identify mutations in 69 genes, together with copy number alterations, whose effects on transplantation outcomes were investigated...
February 21, 2017: Blood
https://www.readbyqxmd.com/read/28184031/outcome-of-patients-treated-for-myelodysplastic-syndromes-without-deletion-5q-after-failure-of-lenalidomide-therapy
#3
Thomas Prebet, Andrea Toma, Thomas Cluzeau, Mikkael A Sekeres, Norbert Vey, Sophie Park, Najla Al Ali, Marie M Sugrue, Rami Komrokji, Pierre Fenaux, Steven D Gore
Anemia is a key survival prognostic factor in lower-risk myelodysplastic syndromes (MDS). Lenalidomide (LEN) can correct anemia in 25% of MDS patients without deletion 5q (del5q). As this therapy will inevitably fail, understanding the outcome of these patients will facilitate development of subsequent treatment strategies. To answer this question, an international retrospective study focused on LEN-treated lower-risk, non-del5q, MDS patients was performed. We analyzed the overall survival after LEN failure, its prognostic factors and the impact of post LEN treatment options...
February 8, 2017: Oncotarget
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
#4
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/28031539/recurrent-genetic-defects-on-chromosome-5q-in-myeloid-neoplasms
#5
Naoko Hosono, Hideki Makishima, Reda Mahfouz, Bartlomiej Przychodzen, Kenichi Yoshida, Andres Jerez, Thomas LaFramboise, Chantana Polprasert, Michael J Clemente, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Masashi Sanada, Edward Cui, Amit K Verma, Michael A McDevitt, Alan F List, Yogen Saunthararajah, Mikkael A Sekeres, Jacqueline Boultwood, Seishi Ogawa, Jaroslaw P Maciejewski
BACKGROUND: Deletion of chromosome 5q (del(5q)) is the most common karyotypic abnormality in myeloid neoplasms. MATERIALS AND METHODS: To define the pathogenic molecular features associated with del(5q), next-generation sequencing was applied to 133 patients with myeloid neoplasms (MDS; N = 69, MDS/MPN; N = 5, sAML; N = 29, pAML; N = 30) with del(5q) as a sole abnormally or a part of complex karyotype and results were compared to molecular features of patients diploid for chr5...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/27992414/dynamics-of-clonal-evolution-in-myelodysplastic-syndromes
#6
Hideki Makishima, Tetsuichi Yoshizato, Kenichi Yoshida, Mikkael A Sekeres, Tomas Radivoyevitch, Hiromichi Suzuki, Bartlomiej Przychodzen, Yasunobu Nagata, Manja Meggendorfer, Masashi Sanada, Yusuke Okuno, Cassandra Hirsch, Teodora Kuzmanovic, Yusuke Sato, Aiko Sato-Otsubo, Thomas LaFramboise, Naoko Hosono, Yuichi Shiraishi, Kenichi Chiba, Claudia Haferlach, Wolfgang Kern, Hiroko Tanaka, Yusuke Shiozawa, Inés Gómez-Seguí, Holleh D Husseinzadeh, Swapna Thota, Kathryn M Guinta, Brittney Dienes, Tsuyoshi Nakamaki, Shuichi Miyawaki, Yogen Saunthararajah, Shigeru Chiba, Satoru Miyano, Lee-Yung Shih, Torsten Haferlach, Seishi Ogawa, Jaroslaw P Maciejewski
To elucidate differential roles of mutations in myelodysplastic syndromes (MDS), we investigated clonal dynamics using whole-exome and/or targeted sequencing of 699 patients, of whom 122 were analyzed longitudinally. Including the results from previous reports, we assessed a total of 2,250 patients for mutational enrichment patterns. During progression, the number of mutations, their diversity and clone sizes increased, with alterations frequently present in dominant clones with or without their sweeping previous clones...
February 2017: Nature Genetics
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
#7
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...
February 2017: Transfusion
https://www.readbyqxmd.com/read/27855285/computational-drug-treatment-simulations-on-projections-of-dysregulated-protein-networks-derived-from-the-myelodysplastic-mutanome-match-clinical-response-in-patients
#8
Leylah Drusbosky, Cindy Medina, Regina Martuscello, Kimberly E Hawkins, Myron Chang, Jatinder K Lamba, Shireen Vali, Ansu Kumar, Neeraj Kumar Singh, Taher Abbasi, Mikkael A Sekeres, Mar Mallo, Francesc Sole, Rafael Bejar, Christopher R Cogle
Although the majority of MDS patients fail to achieve clinical improvement to approved therapies, some patients benefit from treatment. Predicting patient response prior to therapy would improve treatment effectiveness, avoid treatment-related adverse events and reduce healthcare costs. Three separate cohorts of MDS patients were used to simulate drug response to lenalidomide alone, hypomethylating agent (HMA) alone, or HMA plus lenalidomide. Utilizing a computational biology program, genomic abnormalities in each patient were used to create an intracellular pathway map that was then used to screen for drug response...
January 2017: Leukemia Research
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
#9
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/27621331/myelodysplastic-syndromes-going-gently-into-that-good-night
#10
Mikkael A Sekeres
No abstract text is available yet for this article.
September 2016: Journal of Oncology Practice
https://www.readbyqxmd.com/read/27618752/precision-medicine-in-myelodysplastic-syndromes-and-leukemias-lessons-from-sequential-mutations
#11
Aziz Nazha, Mikkael A Sekeres
Precision medicine can be simply defined as the identification of personalized treatment that matches patient-specific clinical and genomic characteristics. Since the completion of the Human Genome Project in 2003, significant advances have been made in our understanding of the genetic makeup of diseases, especially cancers. The identification of somatic mutations that can drive cancer has led to the development of therapies that specifically target the abnormal proteins derived from these mutations. This has led to a paradigm shift in our treatment methodology...
January 14, 2017: Annual Review of Medicine
https://www.readbyqxmd.com/read/27538433/connect-mds-aml-design-of-the-myelodysplastic-syndromes-and-acute-myeloid-leukemia-disease-registry-a-prospective-observational-cohort-study
#12
David P Steensma, Medrdad Abedi, Rafael Bejar, Christopher R Cogle, Kathryn Foucar, Guillermo Garcia-Manero, Tracy I George, David Grinblatt, Rami Komrokji, Xiaomei Ma, Jaroslaw Maciejewski, Daniel A Pollyea, Michael R Savona, Bart Scott, Mikkael A Sekeres, Michael A Thompson, Arlene S Swern, Melissa Nifenecker, Mary M Sugrue, Harry Erba
BACKGROUND: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are myeloid neoplasms in which outgrowth of neoplastic clones disrupts normal hematopoiesis. Some patients with unexplained persistent cytopenias may not meet minimal diagnostic criteria for MDS but an alternate diagnosis is not apparent; the term idiopathic cytopenia of undetermined significance (ICUS) has been used to describe this state. MDS and AML occur primarily in older patients who are often treated outside the clinical trial setting...
August 19, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27535995/cytopenia-levels-for-aiding-establishment-of-the-diagnosis-of-myelodysplastic-syndromes
#13
LETTER
Peter L Greenberg, Heinz Tuechler, Julie Schanz, Guillermo Sanz, Guillermo Garcia-Manero, Francesc Solé, John M Bennett, David Bowen, Pierre Fenaux, Francois Dreyfus, Hagop Kantarjian, Andrea Kuendgen, Alessandro Levis, Luca Malcovati, Mario Cazzola, Jaroslav Cermak, Christa Fonatsch, Michelle M Le Beau, Marilyn L Slovak, Otto Krieger, Michael Luebbert, Jaroslaw Maciejewski, Silvia M M Magalhaes, Yasushi Miyazaki, Michael Pfeilstöcker, Mikkael Sekeres, Wolfgang R Sperr, Reinhard Stauder, Sudhir Tauro, Peter Valent, Teresa Vallespi, Arjan A van de Loosdrecht, Ulrich Germing, Detlef Haase
No abstract text is available yet for this article.
October 20, 2016: Blood
https://www.readbyqxmd.com/read/27502092/improving-prognostic-modeling-in-myelodysplastic-syndromes
#14
REVIEW
Aziz Nazha, Mikkael A Sekeres
Myelodysplastic syndromes (MDSs) are a heterogeneous group of disorders characterized by the accumulation of complex genetic alterations that drive disease pathogenesis and outcome. Several prognostic models have been developed over the last two decades to risk stratify patients with MDS. These models mainly used clinical variables including blast percentage, cytopenias, cytogenetics, transfusion dependency, and age. Recently, somatic mutations in specific genes have been shown to impact overall survival in MDS and can be incorporated into established prognostic models to improve their predictive abilities...
December 2016: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/27489629/a-case-of-mistaken-identity-when-lupus-masquerades-as-primary-myelofibrosis
#15
Edy Hasrouni, Heesun J Rogers, Ali Tabarroki, Valeria Visconte, Fabiola Traina, Manuel Afable, Mikkael A Sekeres, Jaroslaw P Maciejewski, Ramon V Tiu
INTRODUCTION: Autoimmune myelofibrosis is an uncommon hematologic disease characterized by anemia, bone marrow myelofibrosis, and an autoimmune feature. Myelofibrosis is often associated with other conditions, including infections, nutritional/endocrine dysfunction, toxin/drug exposure, and connective tissue diseases, including scleroderma and systemic lupus erythematosus. Absence of clonal markers (JAK2) and heterogeneity of the symptoms often complicate the diagnosis. CASE PRESENTATION: Here, we present two cases of systemic lupus erythematosus-induced autoimmune myelofibrosis...
2013: SAGE open medical case reports
https://www.readbyqxmd.com/read/27354479/long-day-s-journey-into-night-for-lower-risk-myelodysplastic-syndromes
#16
EDITORIAL
Mikkael A Sekeres
No abstract text is available yet for this article.
September 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27335276/time-dependent-changes-in-mortality-and-transformation-risk-in-mds
#17
Michael Pfeilstöcker, Heinz Tuechler, Guillermo Sanz, Julie Schanz, Guillermo Garcia-Manero, Francesc Solé, John M Bennett, David Bowen, Pierre Fenaux, Francois Dreyfus, Hagop Kantarjian, Andrea Kuendgen, Luca Malcovati, Mario Cazzola, Jaroslav Cermak, Christa Fonatsch, Michelle M Le Beau, Marilyn L Slovak, Alessandro Levis, Michael Luebbert, Jaroslaw Maciejewski, Sigrid Machherndl-Spandl, Silvia M M Magalhaes, Yasushi Miyazaki, Mikkael A Sekeres, Wolfgang R Sperr, Reinhard Stauder, Sudhir Tauro, Peter Valent, Teresa Vallespi, Arjan A van de Loosdrecht, Ulrich Germing, Detlef Haase, Peter L Greenberg
In myelodysplastic syndromes (MDSs), the evolution of risk for disease progression or death has not been systematically investigated despite being crucial for correct interpretation of prognostic risk scores. In a multicenter retrospective study, we described changes in risk over time, the consequences for basal prognostic scores, and their potential clinical implications. Major MDS prognostic risk scoring systems and their constituent individual predictors were analyzed in 7212 primary untreated MDS patients from the International Working Group for Prognosis in MDS database...
August 18, 2016: Blood
https://www.readbyqxmd.com/read/26992944/the-efficacy-of-current-prognostic-models-in-predicting-outcome-of-patients-with-myelodysplastic-syndromes-at-the-time-of-hypomethylating-agent-failure
#18
LETTER
Aziz Nazha, Rami S Komrokji, Guillermo Garcia-Manero, John Barnard, Gail J Roboz, David P Steensma, Amy E DeZern, Katrina Zell, Cassie Zimmerman, Najla Al Ali, Elias Jabbour, Molly D Greenberg, Hagop M Kantarjian, Jaroslaw P Maciejewski, Alan F List, Mikkael A Sekeres
No abstract text is available yet for this article.
June 2016: Haematologica
https://www.readbyqxmd.com/read/26968357/rigosertib-versus-best-supportive-care-for-patients-with-high-risk-myelodysplastic-syndromes-after-failure-of-hypomethylating-drugs-ontime-a-randomised-controlled-phase-3-trial
#19
Guillermo Garcia-Manero, Pierre Fenaux, Aref Al-Kali, Maria R Baer, Mikkael A Sekeres, Gail J Roboz, Gianluca Gaidano, Bart L Scott, Peter Greenberg, Uwe Platzbecker, David P Steensma, Suman Kambhampati, Karl-Anton Kreuzer, Lucy A Godley, Ehab Atallah, Robert Collins, Hagop Kantarjian, Elias Jabbour, Francois E Wilhelm, Nozar Azarnia, Lewis R Silverman
BACKGROUND: Hypomethylating drugs are the standard treatment for patients with high-risk myelodysplastic syndromes. Survival is poor after failure of these drugs; there is no approved second-line therapy. We compared the overall survival of patients receiving rigosertib and best supportive care with that of patients receiving best supportive care only in patients with myelodysplastic syndromes with excess blasts after failure of azacitidine or decitabine treatment. METHODS: We did this randomised controlled trial at 74 hospitals and university medical centres in the USA and Europe...
April 2016: Lancet Oncology
https://www.readbyqxmd.com/read/26858309/a-multi-institution-phase-i-trial-of-ruxolitinib-in-patients-with-chronic-myelomonocytic-leukemia-cmml
#20
Eric Padron, Amy Dezern, Marcio Andrade-Campos, Kris Vaddi, Peggy Scherle, Qing Zhang, Yan Ma, Maria E Balasis, Sara Tinsley, Hanadi Ramadan, Cassandra Zimmerman, David P Steensma, Gail J Roboz, Jeffrey E Lancet, Alan F List, Mikkael A Sekeres, Rami S Komrokji
PURPOSE: To conduct a phase I clinical trial exploring the safety and efficacy of ruxolitinib, a JAK1/2 inhibitor, for chronic myelomonocytic leukemia (CMML). EXPERIMENTAL DESIGN: Patients with CMML-1 were included without regard to previous therapy. Key exclusion criteria included an absolute neutrophil count (ANC) <0.25 × 10(3) cells/dL and a platelet count <35 × 10(3) cells/dL. Four cohorts were enrolled using a "rolling six" study design, with doses ranging from 5 to 20 mg twice daily of ruxolitinib in 5-mg dose escalations...
August 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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