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refractory myelodysplastic syndrome

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https://www.readbyqxmd.com/read/28094068/-large-vessel-vasculitis-with-myelodysplastic-syndrome-a-rare-association
#1
J Galland, H Kawski, J-F Guichard, F Maurier
INTRODUCTION: The vasculitis can be the consequence of malignancy: most often hematologic rather than solid tumors. The association between large vessels vasculitis and myelodysplastic syndrome is rare. CASE REPORT: A 55-year-old man experienced asthenia, fever, polyarthritis and inflammatory syndrome. Haematological investigations found a type 2 refractory anemia with excess blasts (RAEB-2) with discovery of severe anemia (Hb: 7,8g/dl) and thrombopenia (platelets: 40,000/mm(3))...
January 13, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28067878/successful-haploidentical-bmt-with-post-transplant-cyclophosphamide-for-refractory-autoimmune-pancytopenia-after-cord-blood-transplant-in-pediatric-myelodysplastic-syndrome
#2
H Shima, K Isshiki, Y Yamada, F Yamazaki, T Takahashi, H Shimada
No abstract text is available yet for this article.
January 9, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28052942/refractory-primary-immune-thrombocytopenia-with-subsequent-del-5q-mds-complete-remission-of-both-after-lenalidomide
#3
Thomas Bech Mortensen, Henrik Frederiksen, Claus Werenberg Marcher, Birgitte Preiss
A patient with refractory primary immune thrombocytopenia (ITP) characterised by severe skin and mucosal bleedings was treated with several ITP-directed therapies including cyclophosphamide. He later developed therapy-related del(5q) myelodysplastic syndrome with no dysplastic morphological features in bone marrow. He remained severely thrombocytopenic, which suggests ongoing immune mediated platelet destruction. After two 3 week cycles of low-dose lenalidomide, complete cytogenetic remission and complete normalisation of platelet count were observed...
January 4, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28013105/the-effects-of-azacitidine-on-the-response-and-prognosis-of-myelodysplastic-syndrome-and-acute-myeloid-leukemia-involving-a-bone-marrow-erythroblast-frequency-of-50
#4
Tomoyuki Uchida, Masao Hagihara, Jian Hua, Morihiro Inoue
We reviewed the cases of 68 consecutive patients who were diagnosed with myelodysplastic syndrome (MDS, n=61) or acute erythroleukemia (AEL, n=7) according to the World Health Organization (WHO) 2008 criteria and had previously been treated with azacitidine, a hypomethylating agent. Fifteen MDS patients had bone marrow erythroblast frequencies of ≥50%, and 6 out of the 7 AEL patients were reclassified as MDS (refractory anemia with excess blasts [RAEB]-1: 1, RAEB-2: 5) according to the revised WHO 2016 criteria...
November 25, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27941286/adoptive-immunotherapy-utilizing-cancer-antigen-specific-t-cell-receptors
#5
Kazushi Tanimoto, Hiroshi Fujiwara
Synthetic immunology based on rapidly-advancing gene-engineering and immunobiology has made novel anticancer adoptive immunotherapies, using gene-modified T lymphocytes to express cancer antigen-specific receptors, a reality. Various technological innovations have overcome recent difficulties and achieved clear and long-lasting clinical efficacy against tumors, while seeking more powerful effector gene-modified T cells has yielded serious treatment-related adverse events. In this article, along with introducing our clinical trial for a novel anti-leukemia adoptive immunotherapy regimen using gene-modified autologous lymphocytes to express leukemia antigen Wilms Tumor 1(WT1)-specific T cell receptor (TCR) against refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), we provide an overview of the current status of this emerging treatment option and discuss its future form in the context of neoantigens encoded by mutated genes in cancer cells and immune checkpoint inhibitors...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27913534/myelodysplastic-and-myeloproliferative-disorders-of-childhood
#6
Henrik Hasle
Myelodysplastic syndrome (MDS) and myeloproliferative disorders are rare in children; they are divided into low-grade MDS (refractory cytopenia of childhood [RCC]), advanced MDS (refractory anemia with excess blasts in transformation), and juvenile myelomonocytic leukemia (JMML), each with different characteristics and management strategies. Underlying genetic predisposition is recognized in an increasing number of patients. Germ line GATA2 mutation is found in 70% of adolescents with MDS and monosomy 7. It is challenging to distinguish RCC from aplastic anemia, inherited bone marrow failure, and reactive conditions...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913457/treatment-of-blastic-plasmacytoid-dendritic-cell-neoplasm
#7
Jill M Sullivan, David A Rizzieri
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare myeloid malignancy with no defined standard of care. BPDCN presents most commonly with skin lesions with or without extramedullary organ involvement before leukemic dissemination. As a result of its clinical ambiguity, differentiating BPDCN from benign skin lesions or those of acute myeloid leukemia with leukemia cutis is challenging. BPDCN is most easily defined by the phenotype CD4(+)CD56(+)CD123(+)lineage(-)MPO(-), although many patients will present with variable expression of CD4, CD56, or alternate plasmacytoid markers, which compounds the difficulty in differentiating BPDCN from other myeloid or lymphoid malignancies...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27911138/phase-1-dose-escalation-study-of-oral-abexinostat-for-the-treatment-of-patients-with-relapsed-refractory-higher-risk-myelodysplastic-syndromes-acute-myeloid-leukemia-or-acute-lymphoblastic-leukemia
#8
Norbert Vey, Thomas Prebet, Claire Thalamas, Aude Charbonnier, Jerome Rey, Ioana Kloos, Emily Liu, Ying Luan, Remus Vezan, Thorsten Graef, Christian Recher
Histone deacetylase (HDAC) inhibitor abexinostat is under investigation for the treatment of various cancers. Epigenetic changes including aberrant HDAC activity are associated with cancers, including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL). In this phase 1 dose-escalation study, 17 patients with relapsed/refractory higher-risk MDS, AML, or ALL received oral abexinostat (60, 80 [starting dose], 100, or 120 mg) twice daily (bid) on Days 1-14 of 21-day cycles...
December 2, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27883945/recent-advances-in-the-treatment-of-lower-risk-non-del-5q-myelodysplastic-syndromes-mds
#9
REVIEW
Antonio Almeida, Pierre Fenaux, Alan F List, Azra Raza, Uwe Platzbecker, Valeria Santini
Patients with lower-risk myelodysplastic syndromes (MDS) are affected primarily by symptoms of chronic anemia and fatigue rather than progression to acute myeloid leukemia. Severe thrombocytopenia, although less common in lower-risk MDS, is associated with increased risk of bleeding. For anemic patients, the principal aim of treatment is to improve anemia and decrease red blood cell transfusions. For transfusion-dependent patients with lower-risk MDS without chromosome 5q deletion [non-del(5q) MDS], there are limited effective treatments...
January 2017: Leukemia Research
https://www.readbyqxmd.com/read/27860411/secondary-primary-malignancies-during-the-lenalidomide-dexamethasone-regimen-in-relapsed-refractory-multiple-myeloma-patients
#10
Rouslan Kotchetkov, Esther Masih-Khan, Chia-Min Chu, Eshetu G Atenafu, Christine Chen, Vishal Kukreti, Suzanne Trudel, Rodger Tiedemann, Donna E Reece
Lenalidomide in combination with dexamethasone (Len-dex) represents a highly effective treatment in relapsed/refractory multiple myeloma (RRMM) patients. However, an increased risk of secondary primary malignancies (SPMs), including myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) has been described in patients receiving lenalidomide. In order to assess the incidence and features of this complication, we reviewed 195 patients with RRMM treated with Len-dex at our institution. The median follow-up time from diagnosis of MM was 73 months (10-234 months) and from initiation of Len-dex was 19 months (1-104 months)...
November 18, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27807503/clinical-management-of-myelodysplastic-syndrome-myeloproliferative-neoplasm-overlap-syndromes
#11
Joseph A Clara, David A Sallman, Eric Padron
The myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are a unique group of hematologic malignancies characterized by concomitant myelodysplastic and myeloproliferative features. According to the 2008 WHO classification, the category includes atypical chronic myeloid leukemia (aCML), chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), MDS/MPN-unclassifiable (MDS/MPN-U), and the provisional entity refractory anemia with ring sideroblasts and thrombocytosis (RARS-T). Although diagnosis currently remains based on clinicopathologic features, the incorporation of next-generation platforms has allowed for the recent molecular characterization of these diseases which has revealed unique and complex mutational profiles that support their distinct biology and is anticipated to soon play an integral role in diagnosis, prognostication, and treatment...
September 2016: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/27801326/-study-of-abnormal-iron-metabolism-parameters-and-iron-overload-in-patients-with-myelodysplastic-syndromes
#12
L L Song, Q Q Zheng, C Xiao, J Guo, D Wu, J Y Su, L Y Zhou, C K Chang
Objective: To investigate the abnormalities of iron metabolism parameters, the prevalence and risk factors of iron overload and clinical characteristics of patients with myelodysplastic syndromes(MDS). Methods: Retrospective investigation was used to observe abnormal iron metabolism parameters and clinical characteristics of newly diagnosed 94 MDS patients in our center from June 2015 to March 2016. Results: Of 94 patients, 71(75.53%)had a hemoglobin level of less than 100 g/L at diagnosis. Iron overload was observed in 52(55...
October 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/27801319/-analysis-of-the-impact-of-decitabine-treatment-cycles-on-efficacy-and-safety-in-patients-of-myelodysplastic-syndrome-refractory-anemia-with-excess-blasts
#13
X P Luo, Z F Xu, T J Qin, Y Zhang, H L Zhang, L W Fang, L J Pan, N B Hu, S Q Qu, B Li, Z J Xiao
Objective: To explore the impact of decitabine treatment cycles on efficacy and adverse events(AEs)in patients of myelodysplastic syndrome-refractory anemia with excess blasts(MDSRAEB). Methods: A total of fifty-six patients with MDS-RAEB who received decitabine 20 mg·m(-2)·d(-1)by IV infusion daily for 5 consecutive days every 4 weeks at a single institute in China were enrolled from December 2008 to March 2016. Their clinical features, efficacy, predictors of efficacy and AEs were analyzed retrospectively...
October 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/27790720/a-phase-2-trial-of-high-dose-lenalidomide-in-patients-with-relapsed-refractory-higher-risk-myelodysplastic-syndromes-and-acute-myeloid-leukaemia-with-trilineage-dysplasia
#14
Amer M Zeidan, B Douglas Smith, Hetty E Carraway, Ivana Gojo, Amy DeZern, Steven D Gore
Limited therapies exist for patients with refractory and relapsed (RR) higher-risk myelodysplastic syndromes (HR-MDS) and acute myeloid leukaemia with trilineage dysplasia (AML-TD). High dose (HD) lenalidomide (50 mg) has activity as frontline therapy in elderly AML but there is limited data in the RR setting. This phase II trial included patients with RR HR-MDS or AML-TD at 2 doses of lenalidomide (15 or 50 mg) on days 1-28 of 42-day cycles. The primary endpoint was response rate using the 2006 International Working Group criteria...
October 28, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27776290/good-riddance-to-the-term-refractory-anemia-in-myelodysplastic-syndromes
#15
David P Steensma
The term "refractory anemia" was used in 1937 by Cornelius Parker Rhoads to describe patients whose anemia did not improve after treatment with liver extract or iron salts, and this term has been used to denote patients with certain subtypes of myelodysplastic syndromes (MDS) since the 1976 and 1982 French-American-British (FAB) classifications of acute leukemias and MDS. In 2016, the World Health Organization (WHO) proposed elimination of "refractory anemia" in a more general proposal for reclassification of myeloid neoplasia...
October 17, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27748021/characteristics-of-the-phenotypic-abnormalities-of-bone-marrow-cells-in-childhood-myelodysplastic-syndromes-and-juvenile-myelomonocytic-leukemia
#16
Anita F Oliveira, Aline Tansini, Daniel O Vidal, Luiz F Lopes, Konradin Metze, Irene Lorand-Metze
BACKGROUND: Immunophenotyping of bone marrow (BM) hemopoietic precursors is useful for diagnosis of adult myelodysplastic syndrome (MDS), but data concerning pediatric patients are limited. We analyzed immunophenotypic features of BM cells at diagnosis of children who were referred to the Brazilian Pediatric Cooperative Group of Myelodysplastic Syndromes. METHODS: Diagnosis was based on clinical information, peripheral blood counts, BM cytology and cytogenetics...
October 17, 2016: Pediatric Blood & Cancer
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
#17
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
https://www.readbyqxmd.com/read/27721426/isocitrate-dehydrogenase-mutations-in-myeloid-malignancies
#18
B C Medeiros, A T Fathi, C D DiNardo, D A Pollyea, S M Chan, R Swords
Alterations to genes involved in cellular metabolism and epigenetic regulation are implicated in the pathogenesis of myeloid malignancies. Recurring mutations in isocitrate dehydrogenase (IDH) genes are detected in approximately 20% of adult patients with acute myeloid leukemia (AML) and 5% of adults with myelodysplastic syndromes (MDS). IDH proteins are homodimeric enzymes involved in diverse cellular processes, including adaptation to hypoxia, histone demethylation, and DNA modification. The IDH2 protein is localized in the mitochondria and is a critical component of the tricarboxylic acid (TCA, also called the 'citric acid' or Krebs) cycle...
October 10, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27715070/-clinically-relevant-possibilities-and-limits-of-differential-diagnosis-of-megaloblastic-anemia-and-myelodysplastic-syndrome%C3%A2-refractory-anemia-type-in-bone-marrow-biopsies
#19
Petra Vašeková, Peter Szépe, Ján Marcinek, Tomáš Balhárek, Lukáš Plank
INTRODUCTION: Megaloblastic anemia (MA) represents a subtype of macrocytic anemia caused by impaired DNA synthesis, mostly due to folate and vitamin B12 deficiency. Its mildest forms lead to macrocytosis without concomitant anemia, but more severe forms to thrombocytopenia and/or leucopenia as well. In majority of the cases, the diagnosis of MA dose not represent a serious clinical problem, however, other causes of macrocytosis including myelodysplastic syndrome (MDS) must be excluded...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27714772/mammalian-target-of-rapamycin-inhibition-with-temsirolimus-in-myelodysplastic-syndromes-mds-patients-is-associated-with-considerable-toxicity-results-of-the-temsirolimus-pilot-trial-by-the-german-mds-study-group-d-mds
#20
Martin Wermke, Claudia Schuster, Florian Nolte, Haifa-Kathrin Al-Ali, Philipp Kiewe, Claudia Schönefeldt, Christiane Jakob, Malte von Bonin, Leopold Hentschel, Ina-Maria Klut, Gerhard Ehninger, Martin Bornhäuser, Gustavo Baretton, Ulrich Germing, Regina Herbst, Detelef Haase, Wolf K Hofmann, Uwe Platzbecker
The mammalian-target of rapamycin (also termed mechanistic target of rapamycin, mTOR) pathway integrates various pro-proliferative and anti-apoptotic stimuli and is involved in regulatory T-cell (TREG) development. As these processes contribute to the pathogenesis of myelodysplastic syndromes (MDS), we hypothesized that mTOR modulation with temsirolimus (TEM) might show activity in MDS. This prospective multicentre trial enrolled lower and higher risk MDS patients, provided that they were transfusion-dependent/neutropenic or relapsed/refractory to 5-azacitidine, respectively...
October 7, 2016: British Journal of Haematology
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