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Myelodysplastic syndromes

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https://www.readbyqxmd.com/read/29166742/-allogeneic-hematopoietic-stem-cell-transplantation-for-the-treatment-of-acute-myeloid-leukemia-with-primary-thrombocytosis-three-cases-report-and-literatures-review
#1
X P Zong, L Tang, J N Cen, S N Chen, A N Sun, D P Wu
Objective: To investigate the characteristics of the essential thrombocythemia (ET) cases transformed to the acute myeloid leukemia (AML) and the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of this disease. Methods: The clinical and laboratory characteristics of 3 ET cases before and after transformation and after allo-HSCT were retrospectively analyzed, meanwhile the related literatures were reviewed and discussed. Results: Case 1 was a male patient of 44 years old, whose PLT was 500×10(9)/L when firstly diagnosed ET...
October 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29165768/recent-perspectives-of-pediatric-leukemia-an-update
#2
Q An, C-H Fan, S-M Xu
Leukemia is defined as an aberrant hyper-proliferation of immature blood cells that do not form solid tumor masses (i.e., liquid cancer). Usually, leukemia could be either of the myeloid or lymphoid lineages, and is classified as acute or chronic in nature. Chronic leukemias tend to have more mature cells and are rare in pediatric patients. Acute leukemias, on the other hand, are typically less mature and commonly occur in patients of all ages and are potentially rapidly fatal if not readily treated. The acute lymphoblastic leukemia (ALL) is the most common childhood malignancy...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29164009/next-generation-gene-sequencing-differentiates-hypoplastic-myelodysplastic-syndrome-from-aplastic-anemia
#3
Jeffrey L Lew, Joshua L Fenderson, Mark G Carmichael
Hypoplastic Myelodysplastic Syndrome (h-MDS) comprises 15% of all MDS and has traditionally been difficult to distinguish from aplastic anemia (AA) by current testing. Accurate differentiation is important because treatment and prognosis differ. Since the publication of the 2008 World Health Organization classification of MDS, next-generation DNA sequencing has discovered novel mutations strongly associated with AA and MDS. Recent research supports the utility of identifying these mutations in the diagnosis and management of MDS; however, use of next-generation sequencing is not yet recommended in guidelines and the study is not routinely performed...
November 2017: Hawai'i Journal of Medicine & Public Health: a Journal of Asia Pacific Medicine & Public Health
https://www.readbyqxmd.com/read/29159200/analyzing-the-genotoxicity-of-retroviral-vectors-in-hematopoietic-cell-gene-therapy
#4
REVIEW
Luca Biasco, Michael Rothe, Hildegard Büning, Axel Schambach
Retroviral vectors, including those derived from gammaretroviruses and lentiviruses, have found their way into the clinical arena and demonstrated remarkable efficacy for the treatment of immunodeficiencies, leukodystrophies, and globinopathies. Despite these successes, gene therapy unfortunately also has had to face severe adverse events in the form of leukemias and myelodysplastic syndromes, related to the semi-random vector integration into the host cell genome that caused deregulation of neighboring proto-oncogenes...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29158926/acquired-elliptocytosis-as-a-manifestation-of-myelodysplastic-syndrome-with-ring-sideroblasts-and-multilineage-dysplasia
#5
Jacob D Kjelland, Denis M Dwyre, Brian A Jonas
Acquired elliptocytosis is a known but rarely described abnormality in the myelodysplastic syndromes (MDS). Here we report the case of an elderly male who was admitted to the hospital with chest pain, dyspnea, and fatigue and was found to be anemic with an elliptocytosis that had only recently been noted on peripheral smears of his blood. After bone marrow biopsy he was diagnosed with MDS with ring sideroblasts and multilineage dysplasia and acquired elliptocytosis. Here we report a rare case of acquired elliptocytosis cooccurring with MDS with ring sideroblasts and multilineage dysplasia...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/29157626/risk-association-of-congenital-anomalies-in-patients-with-ambiguous-genitalia-a-22-year-single-center-experience
#6
Jennifer M Heeley, Abby S Hollander, Paul F Austin, Diane F Merritt, Victoria G Wesevich, Ina E Amarillo
BACKGROUND: Ambiguous genitalia refers to a form of differences of sex development (DSD) wherein the appearance of the external genitalia is atypical. This rare condition presents challenges in decision-making and clinical management. Review of historical data may reveal areas for clinical research to improve care for patients with ambiguous genitalia. OBJECTIVE: This chart review was performed to identify patients with ambiguous genitalia, and to classify them as having 46,XX DSD, 46,XY DSD, or sex chromosome DSD...
November 17, 2017: Journal of Pediatric Urology
https://www.readbyqxmd.com/read/29156198/the-evolving-role-of-genomic-testing-in-assessing-prognosis-of-patients-with-myelodysplastic-syndromes
#7
REVIEW
David P Steensma
The introduction into routine hematology-oncology clinical practice of molecular genetic testing assays based on next-generation sequencing platforms is prompting reassessment of the importance of molecular assay results in comparison to existing disease-specific risk stratification tools based on clinical assessment and light microscopy. For patients with myelodysplastic syndromes (MDS), the most commonly used tools for prognostication currently include the International Prognostic Scoring System (IPSS) and the Revised IPSS (IPSS-R), which are based on marrow blast proportion, number and degree of cytopenias, and the metaphase karyotype...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29156197/mutational-complexity-in-myelodysplasia
#8
REVIEW
R Coleman Lindsley
Myelodysplastic syndromes are characterized by genetic and clinical heterogeneity. Some mutations are able to drive clonal hematopoiesis without causing clinical consequences, while other mutations may have significant impact, including the transformation to leukemia. This review aims to describe the pathogenesis of myelodysplastic syndromes (MDS) by focusing on 3 aspects: combinatorial genetic events, environmental factors, and inherited genetic conditions.
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29156196/familial-myelodysplastic-syndrome-acute-myeloid-leukemia
#9
REVIEW
Jane E Churpek
A growing number of inherited genetic loci that contribute to myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) development in both children as well as adults are rapidly being identified. In recognition of the clinical impact of this emerging field, the World Health Organization, National Comprehensive Cancer Network, and European LeukemiaNet have all added consideration of inherited predisposition to MDS/AML classification and management. Study of these disorders is providing unique insight into the biology of both sporadic and familial MDS/AML...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29155367/predicted-indirectly-recognizable-hla-epitopes-are-not-associated-with-clinical-outcomes-after-haploidentical-hematopoietic-stem-cell-transplantation
#10
Ming-Rui Huo, Dan Li, Ying-Jun Chang, Lan-Ping Xu, Xiao-Hui Zhang, Kai-Yan Liu, Xiao-Jun Huang
Haploidentical stem cell transplantation (haplo-SCT) provides an alternative method to cure patients with malignant and nonmalignant hematologic diseases who lack a human leukocyte antigen (HLA) matched related or unrelated donor. HLA disparity between donor and patient was the main reason causing lots of clinical immune response. The aim of this study was to investigate whether indirect recognition of mismatched HLA could predict the clinical outcomes in haplo-SCT. The probability of indirect recognition was predicted by the Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) model...
November 16, 2017: Human Immunology
https://www.readbyqxmd.com/read/29155023/therapy-related-myeloid-neoplasm-in-an-18-year-old-boy-with-b-lymphoblastic-leukemia
#11
Xin Qing, Eduard Panosyan, ChangjunYue, Ping Ji, Moran Gotesman, Samuel French, Junchao Cai
BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Acute myeloid leukemia or myelodysplastic syndrome during the course of ALL is a rare entity. Some of these cases are therapy-related while the others occur due to lineage switch. The correct diagnosis relies on comparing the immunophenotypes and cytogenetic/molecular alterations of the myeloid neoplasm and the ALL. We present the clinical, pathologic and cytogenetic features of a case of an 18-year-old male with prior treatment for B-lymphoblastic leukemia (B-ALL) who developed therapy-related myeloid neoplasm (t-MN) 4-5years after his initial diagnosis of B-ALL...
November 16, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29151133/treatment-of-relapsed-aml-and-mds-after-allogeneic-stem-cell-transplantation-with-decitabine-and-dli-a-retrospective-multicenter-analysis-on-behalf-of-the-german-cooperative-transplant-study-group
#12
Thomas Schroeder, Christina Rautenberg, William Krüger, Uwe Platzbecker, Gesine Bug, Juliane Steinmann, Stefan Klein, Olaf Hopfer, Kathrin Nachtkamp, Mustafa Kondakci, Stefanie Geyh, Rainer Haas, Ulrich Germing, Martin Bornhäuser, Guido Kobbe
In contrast to the evidence regarding azacitidine (Aza), there is limited knowledge about the combination of decitabine (DAC) and donor lymphocyte infusions as salvage therapy for relapse after allogeneic stem cell transplantation (allo-SCT) so far. We retrospectively analyzed data of 36 patients with hematological (n = 35) or molecular relapse (n = 1) of acute myeloid leukemia (AML, n = 29) or myelodysplastic syndrome (MDS, n = 7) collected from 6 German transplant centers. Patients were treated with a median of 2 cycles DAC (range, 1 to 11)...
November 18, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29149650/iron-chelation-therapy-in-lower-ipss-risk-myelodysplastic-syndromes-which-subtypes-benefit
#13
Shannon A Wong, Heather A Leitch
BACKGROUND: Analyses suggest MDS patients with higher serum ferritin levels (SF) have inferior overall survival (OS), in one study across MDS subtypes. Multiple analyses suggest those with high SF receiving iron chelation therapy (ICT) have superior OS, but which MDS subtypes benefit from ICT remains undefined. METHODS: We performed survival analyses of MDS subtypes by receipt of ICT. RESULTS: 182 MDS were lower IPSS risk and received red blood cell (RBC) transfusions; 63 received ICT...
November 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29147080/effect-of-the-ginger-derivative-6-shogaol-on-ferritin-levels-in-patients-with-low-to-intermediate-1-risk-myelodysplastic-syndrome-a-small-investigative-study
#14
Terry Golombick, Terrence H Diamond, Arumugam Manoharan, Rajeev Ramakrishna, Vladimir Badmaev
Background: Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal stem cell disorders characterized by dysplastic and ineffective hematopoiesis and peripheral cytopenias. Elevated serum ferritin (SF) is often observed in nontransfused, lower risk MDS. It has been reported that ineffective erythropoiesis enhances iron absorption in MDS through downregulation of hepcidin and its prohormones such that SF rises. Aim: To determine the effect of 6-shogaol, a dehydration derivative of ginger, known to have hepatoprotective and chemotherapeutic activity, on 6 early-stage, transfusion-independent patients with MDS, 3 of whom had raised levels of SF...
2017: Clinical Medicine Insights. Blood Disorders
https://www.readbyqxmd.com/read/29146900/the-genomic-landscape-of-pediatric-myelodysplastic-syndromes
#15
Jason R Schwartz, Jing Ma, Tamara Lamprecht, Michael Walsh, Shuoguo Wang, Victoria Bryant, Guangchun Song, Gang Wu, John Easton, Chimene Kesserwan, Kim E Nichols, Charles G Mullighan, Raul C Ribeiro, Jeffery M Klco
Myelodysplastic syndromes (MDS) are uncommon in children and have a poor prognosis. In contrast to adult MDS, little is known about the genomic landscape of pediatric MDS. Here, we describe the somatic and germline changes of pediatric MDS using whole exome sequencing, targeted amplicon sequencing, and/or RNA-sequencing of 46 pediatric primary MDS patients. Our data show that, in contrast to adult MDS, Ras/MAPK pathway mutations are common in pediatric MDS (45% of primary cohort), while mutations in RNA splicing genes are rare (2% of primary cohort)...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146882/physiological-srsf2-p95h-expression-causes-impaired-hematopoietic-stem-cell-functions-and-aberrant-rna-splicing-in-mice
#16
Ayana Kon, Satoshi Yamazaki, Yasuhito Nannya, Keisuke Kataoka, Yasunori Ota, Masahiro Marshall Nakagawa, Kenichi Yoshida, Yusuke Shiozawa, Maiko Morita, Tetsuichi Yoshizato, Masashi Sanada, Manabu Nakayama, Haruhiko Koseki, Hiromitsu Nakauchi, Seishi Ogawa
Splicing factor (SF) mutations are characteristic of myelodysplastic syndromes (MDS) and related myeloid neoplasms and implicated in their pathogenesis, but their roles in the development of MDS have not fully been elucidated. Here, we investigated the consequence of mutant Srsf2 expression using newly generated Vav1-Cre-mediated conditional knock-in mice. Mice carrying a heterozygous Srsf2 P95H mutation showed significantly reduced numbers of hematopoietic stem and progenitor cells (HSPCs) and differentiation defects both in the steady-state condition and transplant settings...
November 16, 2017: Blood
https://www.readbyqxmd.com/read/29144985/a-phase-1-2-study-of-rigosertib-in-patients-with-myelodysplastic-syndromes-mds-and-mds-progressed-to-acute-myeloid-leukemia
#17
Shyamala C Navada, Steven M Fruchtman, Rosalie Odchimar-Reissig, Erin P Demakos, Michael E Petrone, Patrick S Zbyszewski, James F Holland, Lewis R Silverman
This Phase 1/2, dose-escalating study of rigosertib enrolled 22 patients with higher-risk myelodysplastic syndromes (MDS) (n=9) and acute myeloid leukemia (AML; n=13) who had relapsed or were refractory to standard therapy and for whom no second-line therapies were approved. Patients received 3- to 7-day continuous intravenous infusions of rigosertib, an inhibitor of Ras-effector pathways that interacts with the Ras-binding domains, common to several signaling proteins including Raf and PI3 kinase. Rigosertib was administered at doses of 650-1700mg/m(2)/day in 14-day cycles...
November 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29144072/relapse-and-cytogenetic-evolution-in-myeloid-neoplasms
#18
Natalie Ertz-Archambault, Katalin Kelemen
Based on the current WHO Classification of Myeloid Neoplasms, cytogenetic findings play a central role in the diagnostic classification of the myeloid malignancies. Cytogenetic abnormalities detected at primary diagnosis may change over time. Karyotype changes can be characterized as cytogenetic evolution, cytogenetic regression or a combination of both. While the exact mechanism of cytogenetic evolution is not completely understood, the process of cytogenetic evolution is not random, but follows different, and often disease-specific patterns during progression and relapse of myeloid neoplasms...
December 2017: Panminerva Medica
https://www.readbyqxmd.com/read/29143282/hypomethylating-agents-for-treatment-and-prevention-of-relapse-after-allogeneic-blood-stem-cell-transplantation
#19
REVIEW
Thomas Schroeder, Christina Rautenberg, Rainer Haas, Ulrich Germing, Guido Kobbe
Despite the curative potential of allogeneic stem cell transplantation (allo-SCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), many patients will relapse. Until recently therapeutic options mainly consisted of palliative care, chemotherapy, donor lymphocyte infusions and second transplantation in selected cases. Still many patients either do not tolerate intensive therapies or do not achieve durable remissions and will finally succumb. Given this unmet medical need the hypomethylating agents (HMA), Azacitidine (Aza) and Decitabine (DAC) have been tested as salvage therapy in patients with myeloid malignancies relapsing after allo-SCT...
November 15, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29141943/anemia-at-older-age-etiologies-clinical-implications-and-management
#20
Reinhard Stauder, Peter Valent, Igor Theurl
Anemia is quite frequently diagnosed in older individuals and is a key indicator of various reactive and clonal conditions. Many underlying diseases, like the myelodysplastic syndromes (MDS), develop preferentially in elderly individuals. The prevalence of anemia at older age is increasing, and this is mainly due to more frequently applied diagnostics and demographic changes in our societies. The etiology of anemia at older age is complex and ranges from bone marrow failure syndromes to chronic kidney disease, and from nutritional deficiencies to inflammatory processes including inflammaging in immunosenescence...
November 15, 2017: Blood
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