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refractory myelodysplastic syndrome

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https://www.readbyqxmd.com/read/29902706/constitutional-mutations-of-the-chek2-gene-are-a-risk-factor-for-mds-but-not-for-de-novo-aml
#1
Hanna Janiszewska, Aneta Bąk, Katarzyna Skonieczka, Anna Jaśkowiec, Marek Kiełbiński, Anna Jachalska, Maria Czyżewska, Bożena Jaźwiec, Małgorzata Kuliszkiewicz-Janus, Jarosław Czyż, Kazimierz Kuliczkowski, Olga Haus
CHEK2 plays a key role in cellular response to DNA damage, and also in regulation of mitosis and maintenance of chromosomal stability. In patients newly diagnosed with myelodysplastic syndrome (MDS, n = 107) or acute myeloid leukemia (AML, n = 117) congenital CHEK2 mutations (c.444 + 1G > A, c.1100delC, del5395, p.I157 T) were tested by PCR and sequencing analysis. The karyotype of bone marrow cells of each patient was assessed at disease diagnosis using classical cytogenetic methods and fluorescence in situ hybridization...
June 3, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29899740/gmp-grade-manufacturing-of-t-cells-engineered-to-express-a-defined-%C3%AE-%C3%AE-tcr
#2
Trudy Straetemans, Guido J J Kierkels, Ruud Doorn, Koen Jansen, Sabine Heijhuurs, Joao M Dos Santos, Anna D D van Muyden, Henri Vie, Béatrice Clemenceau, Reinier Raymakers, Moniek de Witte, Zsolt Sebestyén, Jürgen Kuball
γ9δ2T cells play a critical role in daily cancer immune surveillance by sensing cancer-mediated metabolic changes. However, a major limitation of the therapeutic application of γ9δ2T cells is their diversity and regulation through innate co-receptors. In order to overcome natural obstacles of γ9δ2T cells, we have developed the concept of T cells engineered to express a defined γδT cell receptor (TEGs). This next generation of chimeric antigen receptor engineered T (CAR-T) cells not only allows for targeting of hematological but also of solid tumors and, therefore, overcomes major limitations of many CAR-T and γδT cell strategies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29869384/editorial-comment-to-therapy-related-acute-myeloid-leukemia-and-myelodysplastic-syndrome-among-refractory-germ-cell-tumor-patients
#3
Takeshi Kishida
No abstract text is available yet for this article.
June 4, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/29859851/quizartinib-an-flt3-inhibitor-as-monotherapy-in-patients-with-relapsed-or-refractory-acute-myeloid-leukaemia-an-open-label-multicentre-single-arm-phase-2-trial
#4
Jorge Cortes, Alexander E Perl, Hartmut Döhner, Hagop Kantarjian, Giovanni Martinelli, Tibor Kovacsovics, Philippe Rousselot, Björn Steffen, Hervé Dombret, Elihu Estey, Stephen Strickland, Jessica K Altman, Claudia D Baldus, Alan Burnett, Alwin Krämer, Nigel Russell, Neil P Shah, Catherine C Smith, Eunice S Wang, Norbert Ifrah, Guy Gammon, Denise Trone, Deborah Lazzaretto, Mark Levis
BACKGROUND: Old age and FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutations in patients with acute myeloid leukaemia are associated with early relapse and poor survival. Quizartinib is an oral, highly potent, and selective next-generation FLT3 inhibitor with clinical antileukaemic activity in relapsed or refractory acute myeloid leukaemia. We aimed to assess the efficacy and safety of single-agent quizartinib in patients with relapsed or refractory acute myeloid leukaemia...
May 30, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29752743/therapy-related-acute-myeloid-leukemia-and-myelodysplastic-syndrome-among-refractory-germ-cell-tumor-patients
#5
Yuta Inoue, Terukazu Nakamura, Hiroyuki Nakanishi, Masakatsu Oishi, Fumiya Hongo, Koji Okihara, Shinsuke Mizutani, Junya Kuroda, Osamu Ukimura
OBJECTIVES: To analyze cases of therapy-related acute myeloid leukemia and myelodysplastic syndrome diagnosed after chemotherapy for refractory testicular and extragonadal germ cell tumor in our experience. METHODS: A total of 171 consecutive patients who were diagnosed and treated as refractory germ cell tumor and had records of detailed chemotherapy doses between April 1998 and December 2015 were retrospectively reviewed. RESULTS: Four testicular tumor patients (4/171, 2...
May 11, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/29743397/-transplantation-associated-thrombotic-microangiopathy-confirmed-by-renal-biopsy
#6
Satoshi Miyamoto, Shunsuke Kimura, Yosuke Hosoya, Daisuke Hasegawa, Hisashi Ishida, Atsuro Daida, Toshihiro Matsui, Yuri Yoshimoto, Shinsuke Hirabayashi, Takuya Fujimaru, Tadashi Kumamoto, Shin-Ichiro Mori, Koyu Suzuki, Atsushi Manabe
An eight-year-old girl with myelodysplastic syndrome (refractory cytopenia) received a bone marrow transplant (BMT) from an unrelated donor because of immunosuppressive therapy failure. Following administration of foscarnet for cytomegalovirus reactivation at day40 post-BMT, serum creatinine increased, and proteinuria, hematuria, and hypertension gradually exacerbated and became prolonged. However, neither schistocytosis nor other organ damage was evident. At six months post-BMT, renal biopsy revealed diffuse glomerular damage with glomerular lobulation, a double contour of the glomerular basement membrane, erythrocyte congestion and thrombi in the glomerular endocapillaries, and mesangiolysis, confirming the diagnosis of transplantation-associated thrombotic microangiopathy (TA-TMA)...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29741506/recent-advances-in-the-cellular-and-molecular-understanding-of-myelodysplastic-syndromes-implications-for-new-therapeutic-approaches
#7
Andrew M Brunner, David P Steensma
It has been more than 10 years since any new disease-modifying therapies have received regulatory approval for indications related to myelodysplastic syndromes (MDS). Advances in our collective biological understanding of MDS in the last decade, however, have made it possible to hope that effective therapeutics can be designed to improve MDS-associated cytopenias and patients' quality of life, and perhaps even delay clonal progression and extend survival. Classes of MDS-associated mutations and disordered biological pathways targeted by developmental therapeutics include the following: aberrant messenger RNA splicing, neomorphic enzymes in the citric acid cycle with oncogenic activity, overactivated tyrosine and serine-threonine kinases, epigenetic and chromatin remodeling alterations, abnormal telomere dynamics, and failed protection of DNA integrity...
January 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29675620/management-of-anemia-in-low-risk-myelodysplastic-syndromes-treated-with-erythropoiesis-stimulating-agents-newer-and-older-agents
#8
REVIEW
Roberto Castelli, Riccardo Schiavon, Valentina Rossi, Giorgio Lambertenghi Deliliers
The myelodysplastic syndromes (MDSs) are clonal hematopoietic stem cell disorders. The International Prognostic Score System (IPSS) groups MDS in lower-risk (IPSS low and intermediate-1) and higher-risk disease (IPSS intermediate-2 and high). AML transformation is the main concern in higher-risk MDS, while anemia and transfusion dependency represent the major issues for low-risk MDS patients. Improving erythropoiesis, and eliminating fatigue and symptoms, is the main therapeutic goal for low-risk MDS patients...
April 19, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29669775/a-case-of-autoimmune-haemolytic-anaemia-after-39-cycles-of-nivolumab
#9
Hira Shaikh, Nour Daboul, Mary Albrethsen, Salman Fazal
With growing use of nivolumab, rare but serious side effects have surfaced in some patients. We present a case of autoimmune haemolytic anaemia that developed after 39 cycles of nivolumab. A 78-year-old man with metastatic lung adenocarcinoma, refractory to multiple lines of chemotherapy was switched to nivolumab. After around 2 years of stable course on nivolumab, he developed transfusion-dependent anaemia with haemoglobin of 8.6 g/dL. Nivolumab was held immediately. Bone marrow biopsy findings were inconclusive of myelodysplastic syndrome...
April 18, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29668607/successful-treatment-of-high-risk-myelodysplastic-syndrome-with-decitabine-based-chemotherapy-followed-by-haploidentical-lymphocyte-infusion-a-case-report-and-literature-review
#10
Yuanyuan Ma, Jianliang Shen, Li-Xin Wang
RATIONALE: The current therapy for elderly patients with high-risk myelodysplastic syndromes (MDSs) remains unsatisfactory. Decitabine, which has been approved to treat MDS, cannot eliminate malignant clones of MDS. PATIENT CONCERNS: A 68-year-old woman presented with multiple divergent bleeding points in the subcutaneous tissue of the limb. Two years earlier, she had been diagnosed with invasive ductal carcinoma of the left breast and had undergone left modified radical mastectomy and local radiation therapy...
April 2018: Medicine (Baltimore)
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
#11
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
#12
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
#13
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
#14
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 anaemia 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, haematological 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
#15
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
#16
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...
May 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29535124/efficacy-and-safety-of-biologics-in-relapsing-polychondritis-a-french-national-multicentre-study
#17
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 Mékinian, 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
#18
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
#19
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
#20
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
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