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low-risk myelodysplastic syndromes

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https://www.readbyqxmd.com/read/30108110/severe-aplastic-anemia-allogeneic-bone-marrow-transplantation-as-first-line-treatment
#1
REVIEW
George E Georges, Kris Doney, Rainer Storb
Treatment of severe aplastic anemia has improved significantly over the past 4 decades. This review will summarize the key areas of progress in the use of allogeneic hematopoietic cell transplantation and nontransplant immunosuppressive therapy (IST) for the treatment of aplastic anemia and then summarize the recommendations for first-line treatment. Based on recent data, we argue that guidelines for the initial treatment of patients with newly diagnosed severe aplastic anemia require revision. At the time of diagnosis, before beginning treatment, HLA typing should be done to identify a marrow donor among family members or in the unrelated donor registries, and a marrow transplant should be considered first-line therapy...
August 14, 2018: Blood Advances
https://www.readbyqxmd.com/read/30103018/graft-versus-host-disease-free-relapse-free-survival-after-allogeneic-stem-cell-transplantation-for-myelodysplastic-syndrome
#2
Sung-Soo Park, Young-Woo Jeon, Gi June Min, Silvia Park, Seung-Ah Yahng, Jae-Ho Yoon, Seung-Hwan Shin, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Seok Lee, Hee-Je Kim, Chang-Ki Min, Seok-Goo Cho, Jong Wook Lee, Yoo-Jin Kim
Graft-versus-host disease-free, relapse-free survival (GRFS) is a composite endpoint that measures survival free of relapse or significant morbidity following allogeneic hematopoietic stem cell transplantation (HSCT). Consecutive 324 adult patients who received HSCT with fluarabine and busulfan based conditioning for myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia evolved from MDS were retrospectively analyzed. 1-year and 3-year GRFS rates were 47.8% and 34.5%, respectively. Three fixed factors (circulating blast >3%, high cytogenetic risk, and high comorbidity index) and two factors (which is) modifiable by clinicians [myeloablative conditioning and low-dose (<7...
August 10, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/30085172/european-guidelines-for-primary-antifungal-prophylaxis-in-adult-haematology-patients-summary-of-the-updated-recommendations-from-the-european-conference-on-infections-in-leukaemia
#3
Johan A Maertens, Corrado Girmenia, Roger J Brüggemann, Rafael F Duarte, Christopher C Kibbler, Per Ljungman, Zdenek Racil, Patricia Ribaud, Monica A Slavin, Oliver A Cornely, J Peter Donnelly, Catherine Cordonnier
The European Conference on Infections in Leukaemia (ECIL) updated its guidelines on antifungal prophylaxis for adults using the grading system of IDSA. The guidelines were extended to provide recommendations for other haematological diseases besides AML and recipients of an allogeneic haematopoietic stem cell transplantation (HSCT). Posaconazole remains the drug of choice when the incidence of invasive mould diseases exceeds 8%. For patients undergoing remission-induction chemotherapy for AML and myelodysplastic syndrome (MDS), fluconazole can still offer an alternative provided it forms part of an integrated care strategy that includes screening with biomarkers and imaging...
August 1, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/30084010/predictors-of-clinical-responses-to-hypomethylating-agents-in-acute-myeloid-leukemia-or-myelodysplastic-syndromes
#4
REVIEW
Hong Wang, Yan Li, Na Lv, Yonghui Li, Lili Wang, Li Yu
Azacitidine and decitabine, two hypomethylating agents, are known to be effective in the treatment of high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients who cannot endure intensive cytotoxic chemotherapy or are not eligible for transplantation. However, the treatment response rate is low. The molecular mechanisms underlying the resistance to demethylation therapy are unclear. Though a wide range of predictors of treatment response have been investigated, no consensus has been reached...
August 6, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/30080246/effects-of-all-trans-retinoic-acid-atra-in-addition-to-chemotherapy-for-adults-with-acute-myeloid-leukaemia-aml-non-acute-promyelocytic-leukaemia-non-apl
#5
REVIEW
Yasemin Küley-Bagheri, Karl-Anton Kreuzer, Ina Monsef, Michael Lübbert, Nicole Skoetz
BACKGROUND: Acute myeloid leukaemia (AML) is the most common acute leukaemia affecting adults. Most patients diagnosed with AML are at advanced age and present with co-morbidities, so that intensive therapy such as stem cell transplantation (SCT) is impossible to provide or is accompanied by high risks for serious adverse events and treatment-related mortality. Especially for these patients, it is necessary to find out whether all-trans retinoic acid (ATRA), an intermediate of vitamin A inducing terminal differentiation of leukaemic cell lines, added to chemotherapy confers increased benefit or harm when compared with the same chemotherapy alone...
August 6, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/30076178/effects-of-erythropoiesis-stimulating-agents-on-overall-survival-of-ipss-low-int-1-risk-transfusion-independent-myelodysplastic-syndrome-patients-a-cohort-study
#6
Emanuela Messa, Daniela Gioia, Elisa Masiera, Anna Castiglione, Manuela Ceccarelli, Flavia Salvi, Paolo Danise, Alessandro Sanna, Bernardino Allione, Enrico Balleari, Antonella Poloni, Giovanni Cametti, Dario Ferrero, Rodolfo Tassara, Carlo Finelli, Margherita Bonferroni, Pellegrino Musto, Giuseppe Saglio, Alessandro Levis, Valeria Santini
No abstract text is available yet for this article.
August 3, 2018: Haematologica
https://www.readbyqxmd.com/read/30073392/response-to-hypomethylating-agents-improves-long-term-outcomes-for-lower-risk-patients-with-myelodysplastic-syndrome-in-case-matched-cohorts
#7
Dong Won Baek, Yoo Jin Lee, Hyunjeong Kim, Seo Yeon Ahn, Jae Sook Ahn, Ho Jin Shin, Won Sik Lee, Sang Min Lee, Ik Chan Song, Ho Sup Lee, Sung Woo Park, Yunsuk Choi, Yoon Young Cho, Sung Hwa Bae, Hyeoung Joon Kim, Sang Kyun Sohn, Joon Ho Moon
Predictive factors for initiating hypomethylating agents' (HMAs) treatment and the survival benefit of HMAs for lower-risk myelodysplastic syndrome (LR-MDS) are still unknown. This study evaluated the factors affecting the use of HMAs and compared long-term outcomes between best supportive care (BSC) and HMA groups after matching baseline clinical factors. Data of 353 patients diagnosed with LR-MDS by International Prognostic Scoring System between October 1992 and July 2013 were retrospectively analyzed. HMAs were administered continuously until a clinical response or progression...
August 2, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/30058088/recommendations-for-the-diagnosis-and-treatment-of-patients-with-polycythaemia-vera
#8
Antonia Hatalova, Jiri Schwarz, Mirjana Gotic, Miroslav Penka, Mikulas Hrubisko, Rajko Kusec, Miklós Egyed, Martin Griesshammer, Maria Podolak-Dawidziak, Andrzej Hellmann, Sergiy Klymenko, Emilia Niculescu-Mizil, Petro E Petrides, Sebastian Grosicki, Matjaz Sever, Nathan Cantoni, Jürgen Thiele, Dominik Wolf, Heinz Gisslinger
OBJECTIVES: To present the Central European Myeloproliferative Neoplasm Organisation (CEMPO) treatment recommendations for polycythaemia vera (PV). METHODS: During meetings held from 2015 through 2017, CEMPO discussed PV, and its treatment and recent data. RESULTS: PV is associated with increased risks of thrombosis/thrombo-haemorrhagic complications, fibrotic progression, and leukaemic transformation. Presence of Janus kinase (JAK)-2 gene mutations is a diagnostic marker and standard diagnostic criterion...
July 30, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/30045276/gastric-carcinoma-subsequent-to-myelodysplastic-syndrome-with-t-1-19-chromosome-translocation-a-rare-case-report-and-its-potential-mechanisms
#9
Wenqing Yu, Gaoyang Chen, Yunpeng Sun, Sujun Gao, Wei Li, Jiuwei Cui, Jingnan Sun
RATIONALE: Myelodysplastic syndrome (MDS) is a heterogeneous malignant hematologic disease with median overall survival ranging from six months to more than ten years. Solid tumor rarely occurs in combination with MDS and the underlying pathogenesis and prognostic significance still remain controversial. PATIENT CONCERNS: Here we report a relative low risk myelodysplastic syndrome-refractory cytopenia with multilineage dysplasia (MDS-RCMD) patient, with a rare t(1; 19)chromosome translocation...
July 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/30034245/health-care-utilization-and-outcomes-of-patients-at-high-risk-of-invasive-fungal-infection
#10
Rao Fu, Jake Gundrum, Anita H Sung
Purpose: The objectives of this study were to present trends in posaconazole use over time and describe selected outcomes among patients at high risk of invasive fungal infections (IFIs) by use and type of antifungal medicine. Methods: A retrospective observational study using data from the Premier Healthcare Database between January 2007 and March 2016 was conducted. Inpatient use of posaconazole by formulation and year is described. Separately, four cohorts of patients at high risk of IFI - those with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), hematopoietic stem-cell transplantation (HSCT), and graft-vs-host disease (GVHD) - but without a diagnosis code for IFI during the index encounter were identified as potential candidates for antifungal prophylaxis...
2018: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/30026010/leukaemia-and-myeloid-malignancy-among-people-exposed-to-low-doses-100-msv-of-ionising-radiation-during-childhood-a-pooled-analysis-of-nine-historical-cohort-studies
#11
Mark P Little, Richard Wakeford, David Borrego, Benjamin French, Lydia B Zablotska, M Jacob Adams, Rodrigue Allodji, Florent de Vathaire, Choonsik Lee, Alina V Brenner, Jeremy S Miller, David Campbell, Mark S Pearce, Michele M Doody, Erik Holmberg, Marie Lundell, Siegal Sadetzki, Martha S Linet, Amy Berrington de González
BACKGROUND: Substantial evidence links exposure to moderate or high doses of ionising radiation, particularly in childhood, with increased risk of leukaemia. The association of leukaemia with exposure to low-dose (<100 mSv) radiation is less certain, although this is the dose range most relevant to the general population. We aimed to estimate the risk of leukaemia associated with low-dose radiation exposure in childhood (age <21 years). METHODS: In this analysis of historical cohort studies, we pooled eligible cohorts reported up to June 30, 2014...
August 2018: Lancet Haematology
https://www.readbyqxmd.com/read/30025278/outcomes-and-mutational-analysis-of-patients-with-lower-risk-non-del5q-myelodysplastic-syndrome-treated-with-antithymocyte-globulin-with-or-without-ciclosporine-a
#12
C Kelaidi, T Braun, R Arana, A Marceau-Renaut, G Lazarian, J Soret, S Cereja, R Letestu, V Eclache, D Lusina, F Baran-Marszak, L Ades, C Preudhomme, A Martin, P Fenaux, C Gardin
Immunosuppressive treatment is a disease-modifying therapy for lower-risk myelodysplastic syndromes (MDS). However, IST is relatively rarely used and long-term outcomes of patients are seldom reported. We retrospectively studied outcomes of 20 patients with lower-risk non del 5q MDS with transfusion dependency, with horse or rabbit antithymocyte globulin ± ciclosporine A, and frontline eltrombopag in two of them. IPSS-R was low, intermediate and high in 30%, 55% and 10% of the patients, respectively. Fifty-five percent of the patients had hypocellular bone marrow (BM)...
August 2018: Leukemia Research
https://www.readbyqxmd.com/read/30020493/radiation-exposure-from-pediatric-ct-scans-and-subsequent-cancer-risk-in-the-netherlands
#13
Johanna M Meulepas, Cécile M Ronckers, Anne M J B Smets, Rutger A J Nievelstein, Patrycja Gradowska, Choonsik Lee, Andreas Jahnen, Marcel van Straten, Marie-Claire Y de Wit, Bernard Zonnenberg, Willemijn M Klein, Johannes H Merks, Otto Visser, Flora E van Leeuwen, Michael Hauptmann
Background: Computed tomography (CT), a strong diagnostic tool, delivers higher radiation doses than most imaging modalities. As CT use has increased rapidly, radiation protection is important, particularly among children. We evaluate leukemia and brain tumor risk following exposure to low-dose ionizing radiation from CT scans in childhood. Methods: For a nationwide retrospective cohort of 168 394 children who received one or more CT scans in a Dutch hospital between 1979 and 2012 who were younger than age 18 years, we obtained cancer incidence, vital status, and confounder information by record linkage with external registries...
July 18, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/30002802/thrombocytopenia-in-patients-with-myelodysplastic-syndromes-still-an-unsolved-problem
#14
REVIEW
May Basood, Howard S Oster, Moshe Mittelman
The myelodysplastic syndromes (MDS) are a group of clonal bone marrow (BM) stem cell disorders, characterized by ineffective hematopoiesis, peripheral cytopenias, and hematologic cellular dysfunction, as well as potential transformation to acute leukemia. Thrombocytopenia is common in MDS and is associated with bleeding complications, occasionally life-threatening. Low platelet count (PLT), as well declining PLT also serves as a prognostic marker. Understanding thrombopoiesis led to the cloning of thrombopoietin, resulting in the development of platelet stimulating agents, thrombomimetics, romiplostim and eltrombopag...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29967380/modeling-asxl1-mutation-revealed-impaired-hematopoiesis-caused-by-derepression-of-p16ink4a-through-aberrant-prc1-mediated-histone-modification
#15
Masahiro Uni, Yosuke Masamoto, Tomohiko Sato, Yasuhiko Kamikubo, Shunya Arai, Eiji Hara, Mineo Kurokawa
In spite of distinct clinical importance, the molecular mechanisms how Additional sex combs-like 1 (ASXL1) mutation contributes to the pathogenesis of premalignant conditions are largely unknown. Here, with newly generated knock-in mice, we investigated the biological effects of the mutant. Asxl1G643fs heterozygous (Asxl1G643fs/+ ) mice developed phenotypes recapitulating human low-risk myelodysplastic syndromes (MDS), and some of them developed MDS/myeloproliferative neoplasm-like disease after long latency...
July 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29963245/efficacy-of-azacitidine-is-independent-of-molecular-and-clinical-characteristics-an-analysis-of-128-patients-with-myelodysplastic-syndromes-or-acute-myeloid-leukemia-and-a-review-of-the-literature
#16
REVIEW
Andrea Kuendgen, Catharina Müller-Thomas, Michael Lauseker, Torsten Haferlach, Petra Urbaniak, Thomas Schroeder, Carolin Brings, Michael Wulfert, Manja Meggendorfer, Barbara Hildebrandt, Beate Betz, Brigitte Royer-Pokora, Norbert Gattermann, Rainer Haas, Ulrich Germing, Katharina S Götze
Azacitidine is the first drug to demonstrate a survival benefit for patients with MDS. However, only half of patients respond and almost all patients eventually relapse. Limited and conflicting data are available on predictive factors influencing response. We analyzed 128 patients from two institutions with MDS or AML treated with azacitidine to identify prognostic indicators. Genetic mutations in ASXL1, RUNX1, DNMT3A, IDH1, IDH2, TET2, TP53, NRAS, KRAS, FLT3, KMT2A-PTD, EZH2, SF3B1, and SRSF2 were assessed by next-generation sequencing...
June 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29950231/-expression-of-insulin-like-growth-factor-recepter-type-i-in-cd34-cells-of-patients-with-myelodysplastic-syndromes
#17
Qing-Xia Zhang, Qi He, Juan Guo, Feng Xu, Zheng Zhang, Lian-Ping Yang, Chun-Kang Chang
OBJECTIVE: To explore the expression level of insulin-like growth facter (IGF-IR) in CD34+ cells of patients with myelodysplastic syndromes(MDS). METHODS: Flow cytometry was used to detect the expression of IGF-IR in the CD34+ cells of 100 MDS patients and 18 normal controls. RESULTS: The average IGF-IR expression level in the CD34+ cells of 100 MDS patients (41.0±28.1)% was statistically and significantly elevated in comparison with the corresponding level in normal controls(4...
June 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29934935/disordered-immune-regulation-and-its-therapeutic-targeting-in-myelodysplastic-syndromes
#18
REVIEW
Kathryn S Ivy, P Brent Ferrell
PURPOSE OF REVIEW: Immune dysregulation is a defining feature of myelodysplastic syndromes (MDS). Recently, several studies have further defined the complex role of immune alterations within MDS. Herein, we will summarize some of these findings and discuss the therapeutic strategies currently in development. RECENT FINDINGS: Immune alterations in MDS are complex, heterogeneous, and intertwined with clonal hematopoiesis and stromal cell dysfunction. Inflammation in MDS proceeds as a vicious cycle, mediated in large part by secreted factors, which induce cell death and activate innate immune signaling...
June 22, 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29878489/chronic-myelomonocytic-leukemia-2018-update-on-diagnosis-risk-stratification-and-management
#19
Mrinal M Patnaik, Ayalew Tefferi
DISEASE OVERVIEW: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms, with an inherent risk for leukemic transformation (∼15%-20% over 3-5 years). DIAGNOSIS: Diagnosis is based on the presence of sustained (>3 months) peripheral blood monocytosis (≥1 × 109 /L; monocytes ≥10%), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ∼ 30% of patients, while >90% have gene mutations...
June 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29877251/-biomarkers-predicting-the-efficacy-of-dna-hypomethylating-agents-in-the-treatment-of-myelodysplastic-syndromes-and-acute-myeloid-leukemia-tet-enzymes
#20
Shigeru Chiba
Azacitidine (AZA), a hypomethylating agent, is widely used in patients with high-risk (HR) myelodysplastic syndromes (MDS). AZA is also believed to aid in the treatment of acute myeloid leukemia (AML). In randomized clinical trials for MDS, major and overall response rates for AZA alone were 16-33% and 38-60%, respectively. In the AZA-001 trial, the median overall survival (OS) for the AZA group was >24 months compared to 15 months for the control. However, other clinical trials have reported OS periods of 15-21 months, while population-based studies have reported OS rates much shorter than 20 months...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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