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low-risk myelodysplastic syndromes

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https://read.qxmd.com/read/30852241/lenalidomide-and-prednisone-in-low-and-intermediate-1-ipss-risk-non-del-5q-patients-with-myelodysplastic-syndromes-phase-2-clinical-trial
#1
Rami S Komrokji, Najla H Al Ali, Eric Padron, Christopher Cogle, Sara Tinsley, David Sallman, Jeffrey E Lancet, Alan F Lis
PURPOSE: To test the hypothesis that combination treatment with lenalidomide and prednisone will yield a higher erythroid response rate in patients with non-del(5q) lower-risk myelodysplastic syndromes compared to the historical clinical trial data with lenalidomide monotherapy, which reported a 26% transfusion independence rate. PATIENTS AND METHODS: The study enrolled 25 patients with lower-risk myelodysplastic syndromes by the International Prognostic Scoring System who were transfusion dependent or who had symptomatic anemia and prior erythroid stimulating agent failure or low chance of response...
January 2, 2019: Clinical Lymphoma, Myeloma & Leukemia
https://read.qxmd.com/read/30745302/anti-cd117-antibody-depletes-normal-and-myelodysplastic-syndrome-human-hematopoietic-stem-cells-in-xenografted-mice
#2
Wendy W Pang, Agnieszka Czechowicz, Aaron C Logan, Rashmi Bhardwaj, Jessica Poyser, Christopher Y Park, Irving L Weissman, Judith A Shizuru
The myelodysplastic syndromes (MDS) represent a group of clonal disorders that result in ineffective hematopoiesis and are associated with an increased risk of transformation into acute leukemia. MDS arises from hematopoietic stem cells (HSCs); therefore, successful elimination of MDS HSCs is an important part of any curative therapy. However, current treatment options, including allogeneic hematopoietic cell transplantation (HCT), often fail to ablate disease-initiating MDS HSCs, and thus have low curative potential and high relapse rates...
February 11, 2019: Blood
https://read.qxmd.com/read/30738461/-application-of-two-parameter-scoring-system-based-on-cd105-and-cd117-in-mds-diagnosis
#3
Chen Zheng, Ya-Zhe Wang, Xiao-Ying Yuan, Yan Chang, Hong-Xia Shi, Yue-Yun Lai, Xiao-Jun Huang, Yan-Rong Liu
OBJECTIVE: To study the value of flow cytometric scoring system in the diagnosis of myelodysplastic syndromes (MDS). METHODS: The phenotypes of erythroid and immature cells were analyzed retrospectively in 130 MDS patients, 19 healthy controls and 89 pathological controls, all of them were well clinically immunophenotyped. The 4-parameter scoring system reported in the literature was studied, including myeloblast-related cluster size, B-progenitor-related cluster size, lymphocyte to myeloblast CD45 ratio, and granulocyte to lymphocyte side scatter ratio...
February 2019: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://read.qxmd.com/read/30738460/-expression-and-function-of-mir-99a-5p-in-bone-marrow-of-patients-with-mds
#4
Ying LE, Xu-Pai Zhang, Yan-Qiu Xiong, Hong-Ying Li, Wei-Hua Zhao, Yuan Long, Jun Luo, Peng Cheng, Zhen-Fang Liu
OBJECTIVE: To detect the expression of miR-99a-5p in myelodysplastic syndrome (MDS), to predict the target genes and to analyze its function by using bioinformatics. METHODS: The expression levels of bone marrow miR-99a-5p in MDS patients were detected by qRT-PCR, and the correlation of miR-99a-5p expression with clinical pathological characteristics, percentage of marrow blasts , chromosome karyotype and peripheral blood hemogram were analyzed. The target genes of miR-99a-5p were predicted by Targetscan, Miranda and Microcosm, and the intersection of the predicted results of 3 softwares was used as a potential target gene for miR-99a-5p...
February 2019: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://read.qxmd.com/read/30737780/residential-ambient-benzene-exposure-in-the-united-states-and-subsequent-risk-of-hematologic-malignancies
#5
Lauren R Teras, W Ryan Diver, Emily L Deubler, Daniel Krewski, Christopher R Flowers, Jeffrey M Switchenko, Susan M Gapstur
Benzene is considered a carcinogen, mostly based on evidence of causality for myeloid leukemia from high levels of exposure in occupational studies. We used United States Environmental Protection Agency National Ambient Toxics Assessment (NATA) estimates of low-level ambient benzene to examine potential associations for the general public between benzene exposure and risk of hematologic cancers. Exposure was estimated by linking participants' residential address to the NATA benzene estimates for that census tract...
February 9, 2019: International Journal of Cancer. Journal International du Cancer
https://read.qxmd.com/read/30733271/a-phase-ii-study-of-guadecitabine-in-higher-risk-myelodysplastic-syndrome-and-low-blast-count-acute-myeloid-leukemia-after-azacitidine-failure
#6
Marie Sébert, Aline Renneville, Cécile Bally, Pierre Peterlin, Odile Beyne-Rauzy, Laurence Legros, Marie-Pierre Gourin, Laurence Sanhes, Eric Wattel, Emmanuel Gyan, Sophie Park, Aspasia Stamatoullas, Anne Banos, Kamel Laribi, Simone Jueliger, Luke Bevan, Fatiha Chermat, Rosa Sapena, Olivier Nibourel, Cendrine Chaffaut, Sylvie Chevret, Claude Preudhomme, Lionel Adès, Pierre Fenaux
High-risk myelodysplastic syndrome/acute myeloid leukemia patients have a very poor survival after azacitidine failure. Guadecitabine (SGI-110) is a novel subcutaneous hypomethylating agent, which results in extended decitabine exposure. This multicenter phase II study evaluated the efficacy and safety of guadecitabine in high-risk myelodysplastic syndrome and low blast count acute myeloid leukemia patients refractory or relapsing after azacitidine. We included 56 patients with a median age of 75 years (IQR 69-76)...
February 7, 2019: Haematologica
https://read.qxmd.com/read/30713125/a-phase-ii-study-to-determine-the-safety-and-efficacy-of-the-oral-inhibitor-of-indoleamine-2-3-dioxygenase-ido-enzyme-incb024360-in-patients-with-myelodysplastic-syndromes
#7
Rami S Komrokji, Sheng Wei, Adam W Mailloux, Ling Zhang, Eric Padron, David Sallman, Jeffrey E Lancet, Sara Tinsley, Lisa A Nardelli, Javier Pinilla-Ibarz, Pearlie K Epling-Burnette, Alan F List
BACKGROUND: INCB024360 is an oral inhibitor of the enzyme indoleamine 2,3-dioxygenase (IDO), which catalyzes the degradation of tryptophan to kynurenine. Preclinical data suggest that IDO1 inhibition by INCB024360 will increase T cell proliferation, and decrease T regulatory cells and myeloid derived suppressor cells suppressive activity. We conducted a phase II study to explore activity and pharmacodynamics of INCB024360 in patients with myelodysplastic syndromes. PATIENTS AND METHODS: All patients were treated with INCB024360 600 mg orally twice a day for at least 16 weeks...
December 20, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://read.qxmd.com/read/30666432/the-incidence-and-risk-factors-of-hepatic-veno-occlusive-disease-after-hematopoietic-stem-cell-transplantation-in-taiwan
#8
Chien-Chang Lee, Hsiu-Hao Chang, Meng-Yao Lu, Yung-Li Yang, Shu-Wei Chou, Dong-Tsamn Lin, Shiann-Tarng Jou, Ming Yao, Chi-Cheng Li, Su-Peng Yeh, Mei-Hui Chen, Jyh-Pyng Gau, Sin-Syue Li, Po-Nan Wang, Yi-Chang Liu, Tso-Fu Wang, Tran-Der Tan, Ming-Yang Lee, Ming-Sun Yu, Chuan-Cheng Wang, Shih-Chiang Lin, Yeu-Chin Chen, Yung-Cheng Su, Ko-Ying Su, Kai-Hsin Lin
Hepatic veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT). We conducted this study to investigate the incidence and risk factors of hepatic VOD for patients receiving HSCT in Taiwan. We retrospectively analyzed the data from a nationwide registry for patients receiving HSCT, which was collected by the Taiwan Society of Blood and Marrow Transplantation. The data collection period was from 2009 to 2014. A total 2345 patients were reviewed and 39 patients among them were diagnosed as having hepatic VOD...
January 21, 2019: Annals of Hematology
https://read.qxmd.com/read/30655377/optimized-ebmt-transplant-specific-risk-score-in-myelodysplastic-syndromes-after-allogeneic-stem-cell-transplantation
#9
Nico Gagelmann, Diderik-Jan Eikema, Matthias Stelljes, Dietrich Beelen, Liesbeth de Wreede, Ghulam Mufti, Nina Simone Knelange, Dietger Niederwieser, Lone S Friis, Gerhard Ehnninger, Arnon Nagler, Ibrahim Yakoub-Agha, Ellen Meijer, Per Ljungman, Johan Maertens, Lothar Kanz, Lucia Lopez-Corral, Arne Brecht, Charles Craddock, Jürgen Finke, Jan J Cornelissen, Paolo Bernasconi, Patrice Chevallier, Jorge Sierra, Marie Robin, Nicolaus Kröger
Here, we aimed to develop and validate a clinical and transplant-specific prognostic score in a large cohort of patients with myelodysplastic syndromes reported to the European Society for Blood and Marrow Transplantation registry. A Cox model was fitted to detect clinical and transplant-related variables prognostic of outcome. Then, cross-validation was assessed to evaluate the validity and consistency of the model. Seven independent risk factors for survival were identified: age ≥50 years, matched unrelated donor, Karnofsky performance status < 90%, very poor cytogenetics or monosomal karyotype, positive cytomegalovirus status of the recipient, blood blasts >1%, and platelet count ≤50 x 109/L prior to transplantation...
January 17, 2019: Haematologica
https://read.qxmd.com/read/30651926/genomic-loss-of-hla-alleles-may-affect-the-clinical-outcome-in-low-risk-myelodysplastic-syndrome-patients
#10
Paola Montes, Martin Kerick, Mónica Bernal, Francisca Hernández, Pilar Jiménez, Pilar Garrido, Ana Márquez, Manuel Jurado, Javier Martin, Federico Garrido, Francisco Ruiz-Cabello
The Revised International Prognostic Score and some somatic mutations in myelodysplastic syndrome (MDS) are independently associated with transformation to acute myeloid leukemia (AML). Immunity has also been implicated in the pathogenesis of MDS, although the underlying mechanism remains unclear. We performed a SNP array on chromosome 6 in CD34+ purified blasts from 19 patients diagnosed with advanced MDS and 8 patients with other myeloid malignancies to evaluate the presence of loss of heterozygosity (LOH) in HLA and its impact on disease progression...
December 11, 2018: Oncotarget
https://read.qxmd.com/read/30632987/what-are-the-most-promising-new-agents-in-myelodysplastic-syndromes
#11
Namrata S Chandhok, Prajwal C Boddu, Steven D Gore, Thomas Prebet
PURPOSE OF REVIEW: Myelodysplastic syndromes (MDS) are a diverse group of clonal disorders of hematopoietic stem or progenitor cells that represent the most common class of acquired bone marrow failure syndromes in adults. Despite significant improvement in the pathologic insight into this group of disorders, therapeutic options remain limited and allogeneic hematopoietic stem-cell transplantation is the only treatment that can induce long-term remission in patients with MDS. The goals of therapy for MDS are based on disease prognostication, with a focus of minimizing transfusion dependence and preserving quality of life in low-risk groups and preventing progression of disease to acute myeloid leukemia in high-risk groups...
March 2019: Current Opinion in Hematology
https://read.qxmd.com/read/30630975/total-body-irradiation-dose-escalation-decreases-risk-of-progression-and-graft-rejection-after-hematopoietic-cell-transplantation-for-myelodysplastic-syndromes-or-myeloproliferative-neoplasms
#12
Federico Monaco, Bart L Scott, Thomas R Chauncey, Finn B Petersen, Barry E Storer, Frederic Baron, Mary E Flowers, H Joachim Deeg, David G Maloney, Rainer Storb, Brenda M Sandmaier
A nonmyeloablative regimen of fludarabine and 200 cGy total body irradiation combined with post-grafting immunosuppression with mycophenolate mofetil and a calcineurin inhibitor facilitates allogeneic hematopoietic cell transplantation from HLA-matched related or unrelated donors in older patients and/or those with comorbidities. However, outcomes of prior studies have been disappointing in patients with myelodysplastic syndromes or myeloproliferative neoplasms due to high incidences of progression or graft failure (together termed hematopoietic cell transplantation-failure)...
January 10, 2019: Haematologica
https://read.qxmd.com/read/30618061/refractory-anemia-with-ring-sideroblasts-rars-and-rars-with-thrombocytosis-rars-t-2019-update-on-diagnosis-risk-stratification-and-management
#13
Mrinal M Patnaik, Ayalew Tefferi
DISEASE OVERVIEW: Ring sideroblasts (RS) are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation. Two myeloid neoplasms defined by the presence of RS, include refractory anemia with ring sideroblasts (RARS), now classified under myelodysplastic syndromes with RS (MDS-RS) and RARS with thrombocytosis (RARS-T); now called myelodysplastic/myeloproliferative neoplasm with RS and thrombocytosis (MDS/MPN-RS-T). DIAGNOSIS: MDS-RS is a lower risk MDS, with single or multilineage dysplasia (SLD/MLD), <5% bone marrow (BM) blasts and ≥15% BM RS (≥5% in the presence of SF3B1 mutations)...
January 7, 2019: American Journal of Hematology
https://read.qxmd.com/read/30590617/evaluation-of-sf3b1-mutation-screening-by-high-resolution-melting-analysis-and-its-clinical-utility-for-myelodysplastic-syndrome-with-ring-sideroblasts-at-the-point-of-diagnosis
#14
Shumpei Mizuta, Noriko Yamane, Takao Komai, Yusuke Koba, Naoya Ukyo, Akira Tamekane, Mitsumasa Watanabe
Background: SF3B1 (splicing factor 3B subunit-1) somatic mutation is specifically detected in myelodysplastic syndrome (MDS) with ring sideroblasts (MDS-RS). We investigated the sensitivity and utility of SF3B1 mutation analysis as a clinical laboratory test. Method: Detection limit for SF3B1 mutations by high-resolution melting (HRM) analysis was investigated by plasmid mixture. In 67 MDS patients, we examined the association between SF3B1 mutation and prognostic evaluation using the Revised International Prognostic Scoring System and revalidated MDS classifications based on the revised 4th edition of the WHO classification...
December 26, 2018: Laboratory Medicine
https://read.qxmd.com/read/30587636/presence-of-cd34-in-megakaryocytes-in-association-with-p53-expression-predicts-unfavorable-prognosis-in-low-risk-myelodysplastic-syndrome-patients
#15
Talyta Ellen DE Jesus Dos Santos, Fernando Barroso Duarte, Maritza Cavalcante Barbosa, Anna Thawanny Gadelha Moura, João Paulo Leitão DE Vasconcelos, Francisco Dário Rocha-Filho, Diego F Coutinho, Ilana Zalcberg, Paulo R L Vasconcelos, Yhasmine Delles Oliverira Garcia, Romélia Pinheiro Gonçalves Lemes
BACKGROUND/AIM: Although risk stratification using the Prognostic Scores Systems (IPSS, WPSS and IPSS-R) incorporate key information about prognosis of patients with Myelodysplastic syndromes (MDS), patients classified as low-risk may evolve rapidly and aggressively, despite a "favorable" prognostic stratification. The aim of this study was to identify biomarkers for predicting prognosis, and for better stratification and management of these patients. MATERIALS AND METHODS: Expression of CD34 and p53 in megakaryocytes was examined by immunohistochemistry in 71 MDS patients classified as low-risk...
January 2019: In Vivo
https://read.qxmd.com/read/30555165/randomized-comparison-of-low-dose-cytarabine-with-or-without-glasdegib-in-patients-with-newly-diagnosed-acute-myeloid-leukemia-or-high-risk-myelodysplastic-syndrome
#16
Jorge E Cortes, Florian H Heidel, Andrzej Hellmann, Walter Fiedler, B Douglas Smith, Tadeusz Robak, Pau Montesinos, Daniel A Pollyea, Pierre DesJardins, Oliver Ottmann, Weidong Wendy Ma, M Naveed Shaik, A Douglas Laird, Mirjana Zeremski, Ashleigh O'Connell, Geoffrey Chan, Michael Heuser
Glasdegib is a Hedgehog pathway inhibitor. This phase II, randomized, open-label, multicenter study (ClinicalTrials.gov, NCT01546038) evaluated the efficacy of glasdegib plus low-dose cytarabine (LDAC) in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome unsuitable for intensive chemotherapy. Glasdegib 100 mg (oral, QD) was administered continuously in 28-day cycles; LDAC 20 mg (subcutaneous, BID) was administered for 10 per 28 days. Patients (stratified by cytogenetic risk) were randomized (2:1) to receive glasdegib/LDAC or LDAC...
December 16, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30552652/the-role-of-real-world-evidence-in-uk-reimbursement-case-study-of-lenalidomide-in-myelodysplastic-syndrome-deletion-5q
#17
Dawn Lee, Nic Brereton, Sujith Dhanasiri, Austin Kulasekararaj
BACKGROUND: Uncertainty within cost-effectiveness analysis, often driven by lack of mature data from large clinical trials, plays a key role in decisions made by the National Institute for Health and Care Excellence (NICE), particularly for early access medicines and orphan drugs. OBJECTIVES: In this case study, we used real-world evidence to address the uncertainty in the cost-effectiveness case for lenalidomide in transfusion-dependent low- and intermediate-1-risk myelodysplastic syndrome (MDS) deletion 5q [del(5q)], affecting a small but unique subpopulation with an orphan disease...
December 14, 2018: PharmacoEconomics Open
https://read.qxmd.com/read/30549002/clinical-effectiveness-and-safety-of-erythropoietin-stimulating-agents-for-the-treatment-of-low-and-intermediate-1-risk-myelodysplastic-syndrome-a-systematic-literature-review
#18
REVIEW
Sophie Park, Peter Greenberg, Aylin Yucel, Caroline Farmer, Frank O'Neill, Cisio De Oliveira Brandao, Pierre Fenaux
Many patients with lower-risk myelodysplastic syndrome (MDS) experience anaemia, which has negative consequences. Erythropoiesis-stimulating agents (ESAs) and their biosimilars are used to treat anaemia in MDS and, currently, epoetin alfa and darbepoetin alfa are commonly used and recommended by clinical guidelines. To better understand the evidence available on the use of ESAs for anaemia in lower-risk MDS, we conducted a systematic literature review to identify randomized and nonrandomized prospective studies reporting on clinical efficacy/effectiveness, patient-reported quality of life (QoL), and safety...
December 13, 2018: British Journal of Haematology
https://read.qxmd.com/read/30545923/azacitidine-with-or-without-lenalidomide-in-higher-risk-myelodysplastic-syndrome-low-blast-acute-myeloid-leukemia
#19
Melita Kenealy, Mark Hertzberg, Warwick Benson, Kerry Taylor, Ilona Cunningham, Will Stevenson, Devendra Hiwase, Richard Eek, Daniela Zantomio, Steve Jong, Meaghan Wall, Piers Blombery, Tracey Gerber, Marlyse Debrincat, Diana Zannino, John F Seymour
Standard treatment for higher risk myelodysplastic syndromes, chronic myelomonocytic leukemia and low blast acute myeloid leukemia is azacitidine. In single arm studies, adding lenalidomide had been suggested to improve outcomes. The ALLG MDS4 phase II trial randomized such patients to standard azacitidine or combination azacitidine (75mg/m2/d days 1 to 5) with lenalidomide (10mg days 1-21 of 28-day cycle from cycle 3) to assess clinical benefit (alive without progressive disease) at 12 months. A total 160 patients were enrolled; median age 70...
December 13, 2018: Haematologica
https://read.qxmd.com/read/30531303/malignancies-in-adults-living-with-hiv-in-asia
#20
Awachana Jiamsakul, Mark Polizzotto, Stephane Wen-Wei Ku, Junko Tanuma, Eugenie Hui, Romanee Chaiwarith, Sasisopin Kiertiburanakul, Anchalee Avihingasanon, Evy Yunihastuti, Nagalingeswaran Kumarasamy, Penh Sun Ly, Sanjay Pujari, Rossana Ditangco, Cuong Duy Do, Tuti Parwati Merati, Pacharee Kantipong, Fujie Zhang, Kinh Van Nguyen, Adeeba Kamarulzaman, Jun Yong Choi, Benedict Lh Sim, Oon Tek Ng, Jeremy Ross, Wingwai Wong
BackgroundHaematological malignancies have continued to be highly prevalent among people living with HIV (PLHIV). This study assessed the occurrence, risk factors for, and outcomes of haematological and non-haematological malignancies in PLHIV in Asia.MethodsIncidence of malignancy after cohort enrolment was evaluated. Factors associated with development of haematological and non-haematological malignancy were analysed using competing risk regression and survival time using Kaplan-Meier.ResultsOf 7455 patients, 107 patients (1%) developed a malignancy: 34 (0...
November 29, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
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