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refractory myelodysplastic syndrome

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https://www.readbyqxmd.com/read/29660836/final-results-of-a-phase-2-open-label-study-of-indisulam-idarubicin-and-cytarabine-in-patients-with-relapsed-or-refractory-acute-myeloid-leukemia-and-high-risk-myelodysplastic-syndrome
#1
Rita Assi, Hagop M Kantarjian, Tapan M Kadia, Naveen Pemmaraju, Elias Jabbour, Nitin Jain, Naval Daver, Zeev Estrov, Taisuke Uehara, Takashi Owa, Jorge E Cortes, Gautam Borthakur
BACKGROUND: Indisulam possesses anticancer properties through down-regulation of various cell-cycle checkpoint molecules, thereby blocking the phosphorylation of retinoblastoma protein and inducing p53 and p21. Indisulam exhibits synergy with nucleoside analogs and topoisomerase inhibitors. METHODS: The authors designed a phase 2 study of indisulam in combination with idarubicin and cytarabine in patients who had relapsed/refractory acute myeloid leukemia AML and high-risk myelodysplastic syndrome...
April 16, 2018: Cancer
https://www.readbyqxmd.com/read/29618691/-monomac-syndrome-patient-developing-myelodysplastic-syndrome-following-persistent-ebv-infection
#2
Hideyuki Yamamoto, Hikaru Hattori, Erina Takagi, Takanobu Morishita, Yuichi Ishikawa, Seitaro Terakura, Tetsuya Nishida, Yoshinori Ito, Makoto Murata, Hitoshi Kiyoi
An 18-year-old man was diagnosed with Epstein-Barr virus (EBV) -associated hemophagocytic syndrome (HPS) and treated with prednisolone (PSL) at a previous hospital. During PSL tapering, the HPS symptoms reappeared, and the patient was referred to our hospital. Increased PSL improved the symptoms, but the EBV infection remained unresolved. At age 20, he was admitted to our hospital for newly developed pneumonia and diagnosed with myelodysplastic syndrome (refractory cytopenia with multilineage dysplasia) (MDS-RCMD; normal karyotype, IPSS: Int-1) by bone marrow examination...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29614393/lenalidomide-treatment-in-lower-risk-myelodysplastic-syndromes-the-experience-of-a-czech-hematology-center-positive-effect-of-erythropoietin-%C3%A2-prednisone-addition-to-lenalidomide-in-refractory-or-relapsed-patients
#3
Anna Jonasova, Radana Neuwirtova, Helena Polackova, Magda Siskova, Tomas Stopka, Eduard Cmunt, Monika Belickova, Alena Moudra, Lubomir Minarik, Ota Fuchs, Kyra Michalova, Zuzana Zemanova
Lenalidomide therapy represents meaningful progress in the treatment of anemic patients with myelodysplastic syndromes with del(5q). We present our initial lenalidomide experience and the positive effect of combining erythropoietin and steroids with lenalidomide in refractory and relapsed patients. We treated by lenalidomide 55 (42 female; 13 male; median age 69) chronically transfused lower risk MDS patients with del(5q) (45) and non-del(5q) (10). Response, meaning transfusion independence (TI) lasting ≥ eight weeks, was achieved in 38 (90%) of analyzed patients with del(5q), of whom three achieved TI only by adding erythropoietin ± prednisone...
March 27, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29569278/lenalidomide-treatment-of-myelodysplastic-syndromes-with-chromosome-5q-deletion-results-from-the-national-registry-of-the-italian-drug-agency
#4
Francesco Arcioni, Andrea Roncadori, Valeria Di Battista, Sante Tura, Anna Covezzoli, Sante Cundari, Cristina Mecucci
OBJECTIVE: The most typical cytogenetic aberration in myelodysplastic syndromes is del(5q), which, when isolated, is associated with refractory anemia and good prognosis. Based on high rates of erythroid response and transfusion independence, Lenalidomide (LEN) became the standard treatment. This multi-centre study was designed to supplement Italian Registry data on LEN by addressing prescription, administration appropriateness, hematological and cytogenetic responses and disease evolution...
March 22, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29550383/liposomal-grb2-antisense-oligodeoxynucleotide-bp1001-in-patients-with-refractory-or-relapsed-haematological-malignancies-a-single-centre-open-label-dose-escalation-phase-1-1b-trial
#5
Maro Ohanian, Ana Tari Ashizawa, Guillermo Garcia-Manero, Naveen Pemmaraju, Tapan Kadia, Elias Jabbour, Farhad Ravandi, Gautam Borthakur, Michael Andreeff, Marina Konopleva, Miranda Lim, Sherry Pierce, Susan O'Brien, Yesid Alvarado, Srdan Verstovsek, William Wierda, Hagop Kantarjian, Jorge Cortes
BACKGROUND: Activating mutations of tyrosine kinases are common in leukaemias. Oncogenic tyrosine kinases use the growth factor receptor-bound protein 2 (Grb2) for signal transduction, leading to activation of mitogen-activated protein kinase (MAPK) 1 and MAPK3 (ERK2 and ERK1). We hypothesised that inhibition of Grb2 would suppress ERK1 and ERK2 activation and inhibit leukaemia progression. To inhibit Grb2, a liposome-incorporated antisense oligodeoxynucleotide that blocks Grb2 protein expression, BP1001, was developed...
April 2018: Lancet Haematology
https://www.readbyqxmd.com/read/29544767/diagnosis-and-management-of-aspergillus-diseases-executive-summary-of-the-2017-escmid-ecmm-ers-guideline
#6
A J Ullmann, J M Aguado, S Arikan-Akdagli, D W Denning, A H Groll, K Lagrou, C Lass-Flörl, R E Lewis, P Munoz, P E Verweij, A Warris, F Ader, M Akova, M C Arendrup, R A Barnes, C Beigelman-Aubry, S Blot, E Bouza, R J M Brüggemann, D Buchheidt, J Cadranel, E Castagnola, A Chakrabarti, M Cuenca-Estrella, G Dimopoulos, J Fortun, J-P Gangneux, J Garbino, W J Heinz, R Herbrecht, C P Heussel, C C Kibbler, N Klimko, B J Kullberg, C Lange, T Lehrnbecher, J Löffler, O Lortholary, J Maertens, O Marchetti, J F Meis, L Pagano, P Ribaud, M Richardson, E Roilides, M Ruhnke, M Sanguinetti, D C Sheppard, J Sinkó, A Skiada, M J G T Vehreschild, C Viscoli, O A Cornely
The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended...
March 12, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29535124/efficacy-and-safety-of-biologics-in-relapsing-polychondritis-a-french-national-multicentre-study
#7
Guillaume Moulis, Grégory Pugnet, Nathalie Costedoat-Chalumeau, Alexis Mathian, Gaëlle Leroux, Jonathan Boutémy, Olivier Espitia, Laurence Bouillet, Sabine Berthier, Jean-Baptiste Gaultier, Pierre-Yves Jeandel, Amadou Konaté, Arsène Mékinan, Elisabeth Solau-Gervais, Benjamin Terrier, Daniel Wendling, Fanny Andry, Camille Garnier, Pascal Cathébras, Laurent Arnaud, Aurore Palmaro, Patrice Cacoub, Zahir Amoura, Jean-Charles Piette, Philippe Arlet, Maryse Lapeyre-Mestre, Laurent Sailler
OBJECTIVES: To assess the efficacy and the safety of biologics in a cohort of patients with relapsing polychondritis (RP). METHODS: We conducted a French multicentre retrospective cohort study including patients treated with biologics for RP. Efficacy outcomes were clinical response (partial or complete) and complete response during the first 6 months of exposure, plus daily corticosteroid dose at 6 months. Other outcomes were adverse drug reactions (ADRs), persistence of biologics and factors associated with a response...
March 13, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29516766/impact-on-acute-myeloid-leukemia-relapse-in-granulocyte-colony-stimulating-factor-application-a-meta-analysis
#8
Xiaoqin Feng, He Lan, Yongsheng Ruan, Chunfu Li
OBJECTIVES: This meta-analysis evaluated the impact of granulocyte colony-stimulating factor (G-CSF) added to chemotherapy on treatment outcomes including survival and disease recurrence in patients with acute myeloid leukemia (AML). METHODS: Medline, Cochrane, EMBASE, and Google Scholar databases were searched until 19 September 2016 using search terms. Studies that investigated patients with AML who underwent stem-cell transplantation were included. RESULTS: The overall analysis revealed a significant improvement in overall survival (OS) (P = ...
March 8, 2018: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29500545/effect-of-qinghuang-powder-combined-with-bupi-yishen-decoction-in-treating-patients-with-refractory-cytopenia-with-multilineage-dysplasia-through-regulating-dna-methylation
#9
Qing-Bing Zhou, Xiao-Hong Yang, Hong-Zhi Wang, De-Xiu Wang, Yong-Gang Xu, Xiao-Mei Hu, Feng-Qin Xu, Rou Ma
OBJECTIVE: To explore the effect of Qinghuang Powder (QHP, ) combined with Bupi Yishen Decoction (BPYS, ) on myelodysplastic syndromes (MDS) patients with refractory cytopenia with multilineage dysplasia (RCMD) and determine the change of DNA methylation in MDS-RCMD patients after the treatment of Chinese medicine formula. METHODS: All 308 MDS-RCMD patients were treated with QHP combined with BPYS for 2 months at least, absolute neutrophil count (ANC), hemoglobin (Hb), platelets (PLT), primitive bone marrow cells and chromosome karyotype were chosen as the main evaluation indexes to analyze the treatment effect according to criteria from the MDS International Working Group...
March 2, 2018: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/29449681/secondary-philadelphia-chromosome-acquired-during-therapy-of-acute-leukemia-and-myelodysplastic-syndrome
#10
Habibe Kurt, Lan Zheng, Hagop M Kantarjian, Guilin Tang, Farhad Ravandi-Kashani, Guillermo Garcia-Manero, Zimu Gong, Hesham M Amin, Sergej N Konoplev, Mark J Routbort, Xin Han, Wei Wang, L Jeffery Medeiros, Shimin Hu
The Philadelphia chromosome resulting from t(9;22)(q34;q11.2) or its variants is a defining event in chronic myeloid leukemia. It is also observed in several types of de novo acute leukemia, commonly in B lymphoblastic leukemia, and rarely in acute myeloid leukemia, acute leukemia of ambiguous lineage, and T lymphoblastic leukemia. Acquisition of the Philadelphia chromosome during therapy of acute leukemia and myelodysplastic syndrome is rare. We reported 19 patients, including 11 men and 8 women with a median age of 53 years at initial diagnosis...
February 14, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29444931/complete-remission-with-reduction-of-high-risk-clones-following-haploidentical-nk-cell-therapy-against-mds-and-aml
#11
Andreas T Björklund, Mattias Carlsten, Ebba Sohlberg, Lisa L Liu, Trevor Clancy, Mohsen Karimi, Sarah Cooley, Jeffrey S Miller, Monika Klimkowska, Marie Schaffer, Emma Watz, Kristina I Wikstrom, Pontus Blomberg, Bjorn E Wahlin, Marzia Palma, Lotta Hansson, Per Ljungman, Eva Hellström-Lindberg, Hans-Gustaf Ljunggren, Karl-Johan Malmberg
PURPOSE: To evaluate the safety, efficacy and immunobiological correlates of allogeneic NK cell-based therapy in primary chemotherapy-refractory or relapsed high-risk myelodysplastic syndrome (MDS), secondary AML (MDS/AML), and de novo AML patients. EXPERIMENTAL DESIGN: Sixteen patients received fludarabine/cyclophosphamide conditioning combined with total lymphoid irradiation followed by adoptive immunotherapy with IL-2-activated haploidentical NK cells. RESULTS: NK cell infusions were well tolerated with only transient adverse events observed in the 16 patients...
February 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29433555/sf3b1-deficiency-impairs-human-erythropoiesis-via-activation-of-p53-pathway-implications-for-understanding-of-ineffective-erythropoiesis-in-mds
#12
Yumin Huang, John Hale, Yaomei Wang, Wei Li, Shijie Zhang, Jieying Zhang, Huizhi Zhao, Xinhua Guo, Jing Liu, Hongxia Yan, Karina Yazdanbakhsh, Gang Huang, Christopher D Hillyer, Narla Mohandas, Lixiang Chen, Ling Sun, Xiuli An
BACKGROUND: SF3B1 is a core component of splicing machinery. Mutations in SF3B1 are frequently found in myelodysplastic syndromes (MDS), particularly in patients with refractory anemia with ringed sideroblasts (RARS), characterized by isolated anemia. SF3B1 mutations have been implicated in the pathophysiology of RARS; however, the physiological function of SF3B1 in erythropoiesis remains unknown. METHODS: shRNA-mediated approach was used to knockdown SF3B1 in human CD34+ cells...
February 12, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29433052/association-of-red-cell-distribution-width-with-clinical-outcomes-in-myelodysplastic-syndrome
#13
Yuta Baba, Bungo Saito, Shotaro Shimada, Yohei Sasaki, So Murai, Maasa Abe, Shun Fujiwara, Nana Arai, Yukiko Kawaguchi, Nobuyuki Kabasawa, Hiroyuki Tsukamoto, Yui Uto, Hirotsugu Ariizumi, Kouji Yanagisawa, Norimichi Hattori, Hiroshi Harada, Tsuyoshi Nakamaki
Studies showed red cell distribution width (RDW) can improve the detection of morphological changes in red blood cells and the understanding of their contribution to dyserythropoiesis in myelodysplastic syndrome (MDS). The purpose of the study was to evaluate dyserythropoiesis in MDS by RDW analysis and to explore the utility of RDW in clinical practice. We retrospectively analyzed laboratory and clinical data of 101 patients (59 patients was refractory anemia (RA) according to the French-American-British (FAB) classification)...
April 2018: Leukemia Research
https://www.readbyqxmd.com/read/29429612/the-effect-of-lenalidomide-on-health-related-quality-of-life-in-patients-with-lower-risk-non-del-5q-myelodysplastic-syndromes-results-from-the-mds-005-study
#14
Valeria Santini, Antonio Almeida, Aristoteles Giagounidis, Uwe Platzbecker, Rena Buckstein, C L Beach, Shien Guo, Arman Altincatal, Chengqing Wu, Pierre Fenaux
BACKGROUND: The phase III MDS-005 study compared lenalidomide versus placebo in red blood cell transfusion-dependent (RBC-TD) patients with lower-risk non-del(5q) myelodysplastic syndromes (MDS), ineligible/refractory to erythropoiesis-stimulating agents. Lenalidomide-treated patients were more likely to achieve transfusion independence (TI) ≥ 8 weeks (26.9% vs. 2.5%; P < .001) and hemoglobin increase ≥ 1.5 g/dL (19.4% vs. 2.5%) versus placebo. PATIENTS AND METHODS: Patients were randomized 2:1 to oral lenalidomide 10 mg once daily or placebo once daily (both on 28-day cycles)...
February 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29415943/-relationship-between-clinical-features-and-somatic-gene-mutations-in-myelodysplastic-syndrome
#15
Nobuhiro Hirasawa, Mamiko Sakata-Yanagimoto, Yasuhito Nannya, Keiichiro Hattori, Yasuhito Suehara, Takayasu Kato, Yasuhisa Yokoyama, Naoki Kurita, Naoshi Obara, Seishi Ogawa, Yuichi Hasegawa, Shigeru Chiba
Recent progress in sequencing studies has suggested that somatic mutations can be used in clinical sequencing for predicting prognosis and selecting treatment options in myelodysplastic syndrome (MDS). A 48-year-old man was diagnosed with refractory cytopenia with multilineage dysplasia that is classified as a subtype of high-risk MDS based on both revised International Prognostic Scoring System and refined WHO classification based Prognostic Scoring System. He received a bone marrow transplant from an HLA-matched sibling donor at X+87 months because of disease progression...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29365392/-gene-mutations-from-511-myelodysplastic-syndromes-patients-performed-by-targeted-gene-sequencing
#16
B Li, J Y Wang, J Q Liu, Z X Shi, S L Peng, H J Huang, T J Qin, Z F Xu, Y Zhang, L W Fang, H L Zhang, N B Hu, L J Pan, S Q Qu, Z J Xiao
Objective: To study the characteristics of gene mutations in Chinese myelodysplastic syndromes (MDS) patients. Methods: A total of 511 Chinese patients with MDS performed 112-gene targeted sequencing were retrospectively analyzed. Results: Eighty-three distinct mutant genes were found in 511 patients with MDS. Amongst these, the most frequent mutations was associated with epigenetics (50%) , followed by spliceosome (37%) , signal transduction (34%) , transcription factors (24%) and cell cycle/apoptosis (17%) ...
December 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29337223/sequential-conditioning-with-thiotepa-in-t-cell-replete-hematopoietic-stem-cell-transplantation-for-the-treatment-of-refractory-hematologic-malignancies-comparison-with-matched-related-haplo-mismatched-and-unrelated-donors
#17
Rémy Duléry, Anne-Lise Ménard, Sylvain Chantepie, Jean El-Cheikh, Sylvie François, Jérémy Delage, Federica Giannotti, Annalisa Ruggeri, Eolia Brissot, Giorgia Battipaglia, Florent Malard, Ramdane Belhocine, Simona Sestili, Anne Vekhoff, François Delhommeau, Oumédaly Reman, Ollivier Legrand, Myriam Labopin, Marie-Thérèse Rubio, Mohamad Mohty
The results of conventional allogeneic stem cell transplantation (SCT) in refractory hematologic malignancies are poor. Sequential strategies have shown promising results in refractory acute myelogenous leukemia (AML), but have not been validated in a haploidentical (Haplo) transplant setting. We have developed a new sequential approach combining chemotherapy with broad antitumor activity (thiotepa 10 mg/kg, etoposide 400 mg/m2 , and cyclophosphamide 1600 mg/m2 from day -15 to day -10), followed after 3 days of rest by a reduced-intensity conditioning regimen (fludarabine 150 mg/m2 , i...
January 11, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29331635/sotatercept-with-long-term-extension-for-the-treatment-of-anaemia-in-patients-with-lower-risk-myelodysplastic-syndromes-a-phase-2-dose-ranging-trial
#18
Rami Komrokji, Guillermo Garcia-Manero, Lionel Ades, Thomas Prebet, David P Steensma, Joseph G Jurcic, Mikkael A Sekeres, Jesus Berdeja, Michael R Savona, Odile Beyne-Rauzy, Aspasia Stamatoullas, Amy E DeZern, Jacques Delaunay, Gautam Borthakur, Robert Rifkin, Thomas E Boyd, Abderrhamane Laadem, Bond Vo, Jennie Zhang, Marie Puccio-Pick, Kenneth M Attie, Pierre Fenaux, Alan F List
BACKGROUND: Myelodysplastic syndromes are characterised by ineffective erythropoiesis leading to anaemia. Sotatercept (ACE-011) is a novel activin receptor type IIA fusion protein that acts as a ligand trap to neutralise negative regulators of late-stage erythropoiesis. The aim of the study was to establish a safe and effective dose of sotatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes. METHODS: This open-label, multicentre, dose-ranging, phase 2 trial took place at 11 treatment centres in the USA and France...
February 2018: Lancet Haematology
https://www.readbyqxmd.com/read/29322849/safety-profile-of-lenalidomide-in-patients-with-lower-risk-myelodysplastic-syndromes-without-del-5q-results-of-a-phase-3-trial
#19
Antonio Almeida, Pierre Fenaux, Guillermo Garcia-Manero, Stuart L Goldberg, Stefanie Gröpper, Anna Jonasova, Norbert Vey, Carmen Castaneda, Jianhua Zhong, C L Beach, Valeria Santini
The safety profile of lenalidomide use in lower-risk myelodysplastic syndromes (MDS) patients with del(5q) is well-established, but less is known in non-del(5q) patients. We provide safety data from a randomized, phase 3 trial evaluating lenalidomide in 239 patients with lower-risk non-del(5q) MDS ineligible/refractory to erythropoiesis-stimulating agents (ESAs). Compared with placebo, lenalidomide was associated with a higher incidence of grade 3-4 treatment-emergent adverse events (TEAEs; 86% vs. 44%), but not risk of infection (p = ...
January 11, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29296959/somatic-mutations-in-children-with-gata2-associated-myelodysplastic-syndrome-who-lack-other-features-of-gata2-deficiency
#20
Kevin E Fisher, Amy P Hsu, Christopher L Williams, Hadi Sayeed, Brian Y Merritt, M Tarek Elghetany, Steven M Holland, Alison A Bertuch, Maria Monica Gramatges
Approximately 10% of children with primary myelodysplastic syndrome (MDS) have germ line GATA2 mutations, leading to the proposal that all children with primary MDS and certain cytogenetic findings, including monosomy 7, be tested for germ line GATA2 mutations regardless of family history or other clinical features associated with GATA2 deficiency. In adults with familial GATA2 -MDS, those with somatic mutations in ASXL1 experience rapid disease progression to acute myeloid leukemia (AML) and poor prognosis after stem cell transplantation; however, the prevalence of somatic mutations in primary pediatric GATA2 -MDS is unclear...
February 28, 2017: Blood Advances
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