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https://www.readbyqxmd.com/read/28409853/a-phase-1-study-of-the-cxcr4-antagonist-plerixafor-in-combination-with-high-dose-cytarabine-and-etoposide-in-children-with-relapsed-or-refractory-acute-leukemias-or-myelodysplastic-syndrome-a-pediatric-oncology-experimental-therapeutics-investigators-consortium
#1
Todd M Cooper, Edward Allan Racela Sison, Sharyn D Baker, Lie Li, Amina Ahmed, Tanya Trippett, Lia Gore, Margaret E Macy, Aru Narendran, Keith August, Michael J Absalon, Jessica Boklan, Jessica Pollard, Daniel Magoon, Patrick A Brown
BACKGROUND: Plerixafor, a reversible CXCR4 antagonist, inhibits interactions between leukemic blasts and the bone marrow stromal microenvironment and may enhance chemosensitivity. A phase 1 trial of plerixafor in combination with intensive chemotherapy in children and young adults with relapsed or refractory acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS) was performed to determine a tolerable and biologically active dose. PROCEDURE: Plerixafor was administered daily for 5 days at four dose levels (6, 9, 12, and 15 mg/m(2) /dose) followed 4 hr later by high-dose cytarabine (every 12 hr) and etoposide (daily)...
April 14, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28396161/isolated-extramedullary-relapse-of-acute-leukemia-after-allogeneic-stem-cell-transplantation-different-kinetics-and-better-prognosis-than-systemic-relapse
#2
Noga Shem-Tov, Francesco Saraceni, Ivetta Danylesko, Roni Shouval, Ronit Yerushalmi, Arnon Nagler, Avichai Shimoni
Allogeneic stem-cell transplantation (SCT) is curative treatment in patients with acute leukemia and MDS. However, recurrent disease is the major cause of treatment failure. Isolated extramedullary-relapse (iEMR) after SCT is relatively rare and not well characterized. We performed retrospective analysis of 566 consecutive patients with AML (n=446) and ALL (n=120) following SCT to study the incidence, risk factors, treatment options and outcome of iEMR. The 5-year cumulative incidence of bone-marrow relapse (BMR) and iEMR was 41...
April 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28374162/peripheral-blood-cytogenetics-allows-treatment-monitoring-and-early-identification-of-treatment-failure-to-lenalidomide-in-mds-patients-results-of-the-le-mon-5-trial
#3
Friederike Braulke, Xenia Schulz, Ulrich Germing, Esther Schuler, Uwe Platzbecker, Florian Nolte, Wolf-Karsten Hofmann, Aristoteles Giagounidis, Katharina Götze, Michael Lübbert, Richard F Schlenk, Julie Schanz, Ulrike Bacher, Arnold Ganser, Guntram Büsche, Anne Letsch, Philippe Schafhausen, Gesine Bug, Tim H Brümmendorf, Rainer Haas, Lorenz Trümper, Katayoon Shirneshan, Detlef Haase
Transfusion-dependent patients with low- or intermediate-1-risk myelodysplastic syndrome, <5% bone marrow (BM) blasts and isolated 5q-deletion received lenalidomide within the German MDS study group phase-II clinical trial LE-MON-5 (EudraCT:2008-001866-10) of the University of Duesseldorf, Germany. Cytogenetic monitoring was performed by chromosome banding analyses (CBA) of BM cells and fluorescence in situ hybridization (FISH) analyses of peripheral blood (PB) mononuclear CD34+ cells using extended probe panels...
April 3, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28370234/enumerating-bone-marrow-blasts-from-nonerythroid-cellularity-improves-outcome-prediction-in-myelodysplastic-syndromes-and-permits-a-better-definition-of-the-intermediate-risk-category-of-the-revised-international-prognostic-scoring-system-ipss-r
#4
Xavier Calvo, Leonor Arenillas, Elisa Luño, Leonor Senent, Montserrat Arnan, Fernando Ramos, Carme Pedro, Mar Tormo, Julia Montoro, María Díez-Campelo, María Laura Blanco, Beatriz Arrizabalaga, Blanca Xicoy, Santiago Bonanad, Andrés Jerez, Meritxell Nomdedeu, Ferrer Ana, Guillermo F Sanz, Lourdes Florensa
The Revised International Prognostic Scoring System (IPSS-R) has been recognized as the score with the best outcome prediction capability in MDS, but this brought new concerns about the accurate prognostication of patients classified into the intermediate risk category. The correct enumeration of blasts is essential in prognostication of MDS. Recent data evidenced that considering blasts from nonerythroid cellularity (NECs) improves outcome prediction in the context of IPSS and WHO classification. We assessed the percentage of blasts from total nucleated cells (TNCs) and NECs in 3,924 MDS patients from the GESMD, 498 of whom were MDS with erythroid predominance (MDS-E)...
March 28, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28359030/increase-of-dna-damage-and-alteration-of-the-dna-damage-response-in-myelodysplastic-syndromes-and-acute-myeloid-leukemias
#5
Henning D Popp, Nicole Naumann, Susanne Brendel, Thomas Henzler, Christel Weiss, Wolf-Karsten Hofmann, Alice Fabarius
Increased DNA damage and alteration of the DNA damage response (DDR) are critical features of genetic instability presumably implicated in pathogenesis of myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML). We used immunofluorescence staining of γH2AX and 53BP1 for analyzing DNA double-strand breaks (DSB) in MDS and AML cell lines, in CD34+ selected cells of normal and MDS bone marrow (including three cases of chronic myelomonocytic leukemias) and in blasts of AML bone marrow. In addition, we screened for activation of the DDR by immunoblotting of p-ATM, p-ATR, p-CHK1, p-CHK2 and p-TP53...
March 21, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28357685/familial-acute-myeloid-leukemia-and-myelodysplasia-in-hungary
#6
Attila Péter Király, Krisztián Kállay, Ambrus Gángó, Ádám Kellner, Miklós Egyed, Anita Szőke, Richárd Kiss, István Vályi-Nagy, Judit Csomor, András Matolcsy, Csaba Bödör
Although genetic predisposition to haematological malignancies has long been known, genetic testing is not yet the part of the routine diagnostics. In the last ten years, next generation sequencing based studies identified novel germline mutations in the background of familial aggregation of certain haematologic disorders including myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). This is supported by the fact that the myeloid neoplasms with genetic predisposition represent a new category in the revised 2016 World Health Organization classification...
March 29, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28321924/infectious-complications-in-patients-with-myelodysplastic-syndromes-a-review-of-the-literature-with-emphasis-on-patients-treated-with-5-azacitidine
#7
REVIEW
Markus Radsak, Uwe Platzbecker, Cornelia S Schmidt, Wolf-Karsten Hofmann, Florian Nolte
Myelodysplastic Syndromes are oligo-clonal stem cell disorders that are associated with cytopenias in the peripheral blood. Major causes for morbidity and mortality in myelodysplastic syndromes (MDS) patients are infections mostly due to bacteria or fungi. Beside leucopenia per se in affected patients, function of white blood cells particularly that of neutrophils seems to be impaired. Here we summarize the available data on infections in MDS patients in general and particularly those treated with 5-azacitidine...
March 21, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28296243/measurement-of-platelet-aggregation-independent-of-patient-platelet-count-a-flow-cytometric-approach
#8
Pernille Just Vinholt, Henrik Frederiksen, Anne-Mette Hvas, Ulrik Sprogøe, Christian Nielsen
BACKGROUND: Methods for testing platelet aggregation in thrombocytopenia are missing. OBJECTIVE: To establish a flow cytometric test of in vitro platelet aggregation independent of the patient platelet count and examined the association of aggregation with bleeding history in thrombocytopenic patients. PATIENTS/METHODS: We established a flow cytometric assay of platelet aggregation and measured samples from healthy individuals pre-incubated with antiplatelet drugs and samples from two patients with inherited platelet disorders...
March 15, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28260960/clinical-hematological-and-cytogenetic-profile-of-adult-myelodysplastic-syndrome-in-a-tertiary-care-center
#9
Santhosh Narayanan
BACKGROUND: Myelodysplastic syndrome (MDS), a disorder of clonal hematopoiesis, is an important clinical entity, but most of the studies available are conducted among the Western population. Its etiological factors and clinicohematological profile in the Indian population are quite diverse. The information regarding its prognostic factors and cytogenetics is very scarce. OBJECTIVES: (1) To assess the clinicohematological profile, cytogenetics, prognostic factors, and outcome of MDS and (2) to study its progression to acute myeloid leukemia (AML) in the selected patients over the study period...
2017: Journal of Blood Medicine
https://www.readbyqxmd.com/read/28259884/the-dicentric-chromosome-dic-20-22-is-a-recurrent-abnormality-in-myelodysplastic-syndromes-and-is-a-product-of-telomere-fusion
#10
Ruth N MacKinnon, Hendrika M Duivenvoorden, Lynda J Campbell, Meaghan Wall
We describe a recurrent dicentric chromosome formed by telomere fusion between chromosome 20 and chromosome 22 in 4 cases of myelodysplastic syndromes (MDS) or acute myeloid leukaemia (AML). In particular, the presence of residual telomere sequences at the site of translocation in 3 of the 4 cases makes a compelling case for telomere fusion. This is the first description of a recurrent telomere fusion event in any malignant condition. The 20q subtelomeric region was retained in all 4 examples despite deletion of the 20q12 region closer to the centromere...
2016: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28249294/coexpression-of-nup98-top1-and-top1-nup98-in-de-novo-acute-myeloid-leukemia-with-t-11-20-p15-q12-and-t-2-5-q33-q31
#11
Katsuya Yamamoto, Yosuke Minami, Kimikazu Yakushijin, Yu Mizutani, Yumiko Inui, Shinichiro Kawamoto, Keiji Matsui, Yuji Nakamachi, Seiji Kawano, Hiroshi Matsuoka, Hironobu Minami
The t(11;20)(p15;q11∼12) translocation is a very rare but recurrent cytogenetic aberration that occurs in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). This translocation was shown to form a fusion gene between NUP98 at 11p15 and TOP1 at 20q12. Here, we describe a new case of de novo AML M2 with t(11;20) which was associated with another balanced translocation. An 81-year-old man was admitted to undergo salvage therapy for relapsed AML. G-banding and spectral karyotyping showed 46,XY,t(2;5)(q33;q31),t(11;20)(p15;q12)[20]...
2016: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28196450/a-review-of-therapy-related-myelodysplastic-syndromes-and-acute-myeloid-leukaemia-t-mds-aml-in-irish-patients-a-single-centre-experience
#12
Su W Maung, Cathie Burke, Jennifer Hayde, Janice Walshe, Ray McDermott, Ronan Desmond, Johnny McHugh, Helen Enright
OBJECTIVES: To demonstrate the incidence, characteristics, treatment and outcomes of patients with therapy-related myelodysplastic syndromes and therapy-related acute myeloid leukaemia (t-MDS/AML) in a tertiary referral centre. METHODS: Patients meeting the diagnostic criteria for t-MDS/AML from 2003 to 2014 were reviewed to analyse their diagnostic features, details of antecedent disorder and treatment, approach to management and survival. RESULTS: 39 patients who developed t-MDS/AML were identified with incidence of 8...
February 15, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28179279/role-of-runx1-in-hematological-malignancies
#13
REVIEW
Raman Sood, Yasuhiko Kamikubo, Paul Liu
RUNX1 is a member of the core-binding factor family of transcription factors and is indispensable for the establishment of definitive hematopoiesis in vertebrates. RUNX1 is one of the most frequently mutated genes in a variety of hematological malignancies. Germ line mutations in RUNX1 cause familial platelet disorder with associated myeloid malignancies. Somatic mutations and chromosomal rearrangements involving RUNX1 are frequently observed in myelodysplastic syndrome and leukemias of myeloid and lymphoid lineages, that is, acute myeloid leukemia, acute lymphoblastic leukemia, and chronic myelomonocytic leukemia...
April 13, 2017: Blood
https://www.readbyqxmd.com/read/28119224/clinical-significance-of-isolated-del-7p-in-myeloid-neoplasms
#14
Hatice Deniz Gur, Sa A Wang, Zhenya Tang, Shimin Hu, Shaoying Li, L Jeffrey Medeiros, Guilin Tang
Sole del(7p) is a rare finding in myeloid neoplasms and its clinical significance is largely unknown. Here we report 10 patients with isolated del(7p), 4 had acute myeloid leukemia (AML), 2 myelodysplastic syndromes (MDS), 1 chronic myelomonocytic leukemia (CMML), 1 primary myelofibrosis (PMF), and 2 AML in remission. Seven patients had large and 3 had small del(7p) clone. For patients with AML, 3 acquired del(7p) either at disease relapse or disease progression, then became refractory to therapy and died shortly thereafter (median 5 months)...
January 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28106288/nuclear-inositide-signaling-via-phospholipase-c
#15
Stefano Ratti, Sara Mongiorgi, Giulia Ramazzotti, Matilde Y Follo, Giulia A Mariani, Pann-Ghill Suh, James A McCubrey, Lucio Cocco, Lucia Manzoli
The existence of an independent nuclear inositide pathway distinct from the cytoplasmic one has been demonstrated in different physiological systems and in diseases. In this prospect we analyze the role of PI-PLCβ1 nuclear isoform in relation to the cell cycle regulation, the cell differentiation and different physiopathological pathways focusing on the importance of the nuclear localization from both molecular and clinical point of view. PI-PLCβ1 is essential for G1/S transition through DAG and Cyclin D3 and plays also a central role in G2/M progression through Cyclin B1 and PKCα...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28103645/prognostic-impact-of-lymphocyte-subpopulations-in-peripheral-blood-after-hematopoietic-stem-cell-transplantation-for-hematologic-malignancies
#16
Sang Hyuk Park, Chan-Jeoung Park, Borae G Park, Mi-Hyun Bae, Bo-Hyun Kim, Young-Uk Cho, Seongsoo Jang, Ae-Ja Park, Dae-Young Kim, Jung-Hee Lee, Je-Hwan Lee, Kyoo-Hyung Lee
BACKGROUND: We prospectively evaluated prognostic value of lymphocyte subpopulations in peripheral blood of allogeneic hematopoietic stem cell transplant (HSCT) recipients. METHODS: 113 allogeneic HSCT (47 sibling matched, 37 unrelated matched, 29 haploidentical)-performed patients diagnosed as AML (n = 66), ALL (n = 28), and MDS (n = 19) were prospectively enrolled. 14 lymphocyte subpopulations were quantified by flow cytometry of PB at specific time-points after HSCT, and their prognostic impacts were analyzed...
January 19, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28054397/conventional-cytogenetics-for-myeloid-neoplasms-in-the-era-of-next-generation-sequencing
#17
Frank C Kuo, David P Steensma, Paola Dal Cin
No abstract text is available yet for this article.
March 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28052028/establishment-and-characterization-of-hypomethylating-agent-resistant-cell-lines-molm-aza-1-and-molm-dec-5
#18
Eun-Hye Hur, Seung-Hyun Jung, Bon-Kwan Goo, Juhyun Moon, Yunsuk Choi, Dae Ro Choi, Yeun-Jun Chung, Je-Hwan Lee
Two hypomethylating agents (HMAs), azacitidine and decitabine, have demonstrated clinical activities in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML); however, potential problems include development of acquired resistance. HMA-resistant patients have very poor prognosis and this cohort of patients constitutes an important area of research. To understand the mechanisms underlying HMA-resistance and to overcome it, we established an azacitidine-resistant cell line, MOLM/AZA-1 and a decitabine-resistant cell line, MOLM/DEC-5 using MOLM-13...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28013106/cpx-351-exhibits-potent-and-direct-ex-vivo-cytotoxicity-against-aml-blasts-with-enhanced-efficacy-for-cells-harboring-the-flt3-itd-mutation
#19
Max J Gordon, Paul Tardi, Marc M Loriaux, Stephen E Spurgeon, Elie Traer, Tibor Kovacsovics, Lawrence D Mayer, Jeffrey W Tyner
PURPOSE: Identify AML patients most likely to respond to CPX-351, a nano-scale liposome formulation containing cytarabine and daunorubicin co-encapsulated at a 5:1 molar ratio. METHODS: We examined the ex vivo cytotoxic activity of CPX-351 against leukemic cells isolated from 53 AML patients and an additional 127 samples including acute lymphoblastic leukemia, myelodysplastic syndrome/myeloproliferative neoplasms, or chronic lymphocytic leukemia/lymphoma. We assessed activity with respect to common molecular lesions and used flow cytometry to assess CPX-351 cellular uptake...
December 12, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27923552/preleukaemic-clonal-haemopoiesis-and-risk-of-therapy-related-myeloid-neoplasms-a-case-control-study
#20
Koichi Takahashi, Feng Wang, Hagop Kantarjian, Denaha Doss, Kanhav Khanna, Erika Thompson, Li Zhao, Keyur Patel, Sattva Neelapu, Curtis Gumbs, Carlos Bueso-Ramos, Courtney D DiNardo, Simona Colla, Farhad Ravandi, Jianhua Zhang, Xuelin Huang, Xifeng Wu, Felipe Samaniego, Guillermo Garcia-Manero, P Andrew Futreal
BACKGROUND: Therapy-related myeloid neoplasms are secondary malignancies that are often fatal, but their risk factors are not well understood. Evidence suggests that individuals with clonal haemopoiesis have increased risk of developing haematological malignancies. We aimed to identify whether patients with cancer who have clonal haemopoiesis are at an increased risk of developing therapy-related myeloid neoplasms. METHODS: We did this retrospective case-control study to compare the prevalence of clonal haemopoiesis between patients treated for cancer who later developed therapy-related myeloid neoplasms (cases) and patients who did not develop these neoplasms (controls)...
January 2017: Lancet Oncology
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