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https://www.readbyqxmd.com/read/29925044/a-systematic-review-of-patient-reported-outcomes-in-phase-ii-or-iii-clinical-trials-of-myelodysplastic-syndromes-and-acute-myeloid-leukemia
#1
REVIEW
Ashley Leak Bryant, Sarah W Drier, Sejin Lee, Antonia V Bennett
The purpose of this systematic literature review was to identify clinical trials of MDS and AML that included patient-reported outcome (PRO) instruments, and to summarize the symptom and other health related quality of life (HRQOL) concepts most frequently assessed and the PRO instruments that were used. Sixteen manuscripts describing 14 distinct trials met all criteria (i.e., phase 2 or 3 clinical trial for MDS or AML which included PRO assessment) and were published between 1996-2017. In trials evaluating anemia, PRO scores showed significant improvement in relevant domains (e...
June 7, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29891567/clonal-dynamics-of-donor-derived-mds-after-unrelated-hct-for-high-risk-pediatric-b-lymphoblastic-leukemia
#2
Jason R Schwartz, Michael P Walsh, Jing Ma, Tamara Lamprecht, Shuoguo Wang, Gang Wu, Susana Raimondi, Brandon Triplett, Jeffery Klco
Donor-derived hematologic malignancies are rare complications of hematopoietic cell transplantation (HCT). Although these are commonly either a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), in general, they are a heterogeneous group of diseases and a unified mechanism for their development has remained elusive. Here we report next generation sequencing, including whole exome sequencing (WES), whole genome sequencing (WGS), and targeted sequencing, of a case of donor-derived MDS (dMDS) following HCT for high-risk B-lymphoblastic leukemia (B-ALL) in an adolescent...
June 11, 2018: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/29883054/genetic-compensation-of-runx-family-transcription-factors-in-leukemia
#3
REVIEW
Yasuhiko Kamikubo
RUNX1 is a transcription factor belonging to the Core Binding Factor (CBF) family. It is considered to be a master regulator of hematopoiesis and has been regarded as a tumor suppressor because it is essential for definitive hematopoiesis in vertebrates. It is one of the most frequent target genes of chromosomal translocation in leukemia, and germ line mutation of RUNX1 causes familial platelet disorder with associated myeloid malignancies (FPDMM). Somatic cell mutations and chromosomal abnormalities, including those of RUNX1, are observed in myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myelomonocytic leukemia (CMML) at a high frequency...
June 8, 2018: Cancer Science
https://www.readbyqxmd.com/read/29880247/development-and-current-use-of-in-hematopoietic-stem-cell-transplantation-in-children-and-adolescents-in-poland-report-of-the-polish-pediatric-study-group-for-hematopoietic-stem-cell-transplantation-of-the-polish-society-for-pediatric-oncology-and-hematology
#4
REVIEW
Jacek Wachowiak, Alicja Chybicka, Jerzy R Kowalczyk, Mariusz Wysocki, Jolanta Goździk, Ewa Gorczyńska, Krzysztof Kałwak, Jan Styczyński, Katarzyna Drabko, Anna Pieczonka
The purpose of the survey was to evaluate the development and current use of hematopoietic stem cell transplantation (HSCT) in Poland between 1989-2016. The data for analysis (indication, number of performed HSCT, HSCT type, donor type, and stem cell source, year) have been collected annually using a standardized form. In Poland, between 1989-2016, the number of pediatric transplant beds grew from one to 40 and number and rate of transplants increased annually from 1/year (0.8/10 million) to 186/year (248/10 million)...
May 16, 2018: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/29795386/myelodysplastic-syndromes-current-treatment-algorithm-2018
#5
David P Steensma
Myelodysplastic syndromes (MDS) include a group of clonal myeloid neoplasms characterized by cytopenias due to ineffective hematopoiesis, abnormal blood and marrow cell morphology, and a risk of clonal evolution and progression to acute myeloid leukemia (AML). Because outcomes for patients with MDS are heterogeneous, individual risk stratification using tools such as the revised International Prognostic Scoring System (IPSS-R) is important in managing patients-including selecting candidates for allogeneic hematopoietic stem cell transplantation (ASCT), the only potentially curative therapy for MDS...
May 24, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29753157/treosulfan-fludarabine-and-low-dose-total-body-irradiation-for-children-and-young-adults-with-acute-myeloid-leukemia-or-myelodysplastic-syndrome-undergoing-allogeneic-hematopoietic-cell-transplantation-prospective-phase-ii-trial-of-the-pediatric-blood-and-marrow
#6
Eneida R Nemecek, Ralf A Hilger, Alexia Adams, Bronwen E Shaw, Deidre Kiefer, Jennifer Le-Rademacher, John E Levine, Gregory Yanik, Wing Leung, Julie-An Talano, Paul Haut, David Delgado, Neena Kapoor, Aleksandra Petrovic, Roberta Adams, Rabi Hanna, Hemalatha Rangarajan, Jignesh Dalal, Joseph Chewning, Michael R Verneris, Stacy Epstein, Lauri Burroughs, Evelio D Perez-Albuerne, Michael A Pulsipher, Colleen Delaney
This multicenter study evaluated a treosulfan-based regimen in children and young adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplant (HCT). Forty patients with median age 11 years (range, 1 to 19) underwent allogeneic HCT for AML in first (n = 18), second (n = 11), and third or greater remission (n = 3) or MDS (n = 8) using bone marrow (n = 25), peripheral blood stem cells (n = 5), or cord blood (n = 9). The regimen consisted of body surface area (BSA)-based treosulfan 10 g/m2 /day (BSA ≤ ...
May 9, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29705535/associations-of-myeloid-hematological-diseases-of-the-elderly-with-osteoporosis-a-longitudinal-analysis-of-routine-health-care-data
#7
Thomas Datzmann, Freya Trautmann, Falko Tesch, Anna Mies, Lorenz C Hofbauer, Uwe Platzbecker, Jochen Schmitt
BACKGROUND: Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML) are hematological stem cell diseases mainly of the elderly. Studies indicate a close relationship between bone metabolism and hematopoietic stem cells within the osteo-hematopoietic niche. However, it remains unclear how the disturbed interaction within the osteo-hematopoietic niche affects bone homeostasis in MDS and AML patients. METHODS: We utilized data of a large German statutory health insurance of approximately 2 million persons living in the German federal state of Saxony...
June 2018: Leukemia Research
https://www.readbyqxmd.com/read/29673771/posaconazole-vs-voriconazole-in-the-prevention-of-invasive-fungal-diseases-in-patients-with-haematological-malignancies-a-retrospective-study
#8
L Tang, X-F Yang, M Qiao, L Zhang, X-W Tang, H-Y Qiu, D-P Wu, A-N Sun
BACKGROUND: Posaconazole is superior to fluconazole or itraconazole in preventing invasive fungal diseases (IFDs) in patients with haematological malignancies; however, there have been reports of the comparing posaconazole and voriconazole. METHODS: This single-centre, retrospective study in China enrolled AML, ALL and MDS patients, among others. Prophylaxis with posaconazole or voriconazole was administered for patients recovering from neutropenia or who had achieved complete remission...
April 16, 2018: Journal de Mycologie Médicale
https://www.readbyqxmd.com/read/29668073/sequential-systematic-anti-mold-prophylaxis-with-micafungin-and-voriconazole-results-in-very-low-incidence-of-invasive-mold-infections-in-patients-undergoing-allogeneic-hematopoietic-stem-cell-transplantation
#9
Claudia Rosillo, Ana Maria Avila, Yao-Ting Huang, Sean Devlin, Christina Cho, Juan Montoro, Molly A Maloy, Genovefa A Papanicolaou, Pere Barba, Miguel-Angel Perales
Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at high risk for invasive mold infections (IMI). The goal of the study is to describe the incidence and outcome of IMI in patients after allo-HSCT in a large cohort of patients receiving anti-mold prophylaxis. We conducted a retrospective review of 988 consecutive adults who underwent allo-HSCT in our center from 2008 through 2014. Standard prophylaxis consisted of micafungin 150 mg IV daily from admission to day +7 ± 3 followed by voriconazole until day +75 to +100...
April 18, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/29659040/the-prognostic-value-of-monosomal-karyotype-mk-in-higher-risk-patients-with-myelodysplastic-syndromes-treated-with-5-azacitidine-a-retrospective-analysis-of-the-hellenic-greek-myelodysplastic-syndromes-study-group
#10
Sotirios G Papageorgiou, Diamantina Vasilatou, Christos K Kontos, Ioannis Kotsianidis, Argiris Symeonidis, Athanasios G Galanopoulos, Eleftheria Hatzimichael, Aekaterini Megalakaki, Elias Poulakidas, Panagiotis Diamantopoulos, Theodoros P Vassilakopoulos, Panagiotis Zikos, Helen Papadaki, Despoina Mparmparousi, Eleni Bouronikou, Panayiotis Panayiotidis, Nora-Athina Viniou, Vassiliki Pappa
In this study, we investigated the incidence and prognostic impact of monosomal karyotype (MK) in 405 higher-risk Myelodysplastic Syndromes (MDS) patients treated with 5-AZA. The MK was present in 66 out of 405 (16.3%) patients, most of whom had complex karyotype (CK). MK was strongly associated with CK and the cytogenetic risk defined according to IPSS-R, as well as with high-risk disease, according to IPSS (P = .029), IPSS-R (P < .001), and WPSS (P < .001) classification systems. The overall response rate (ORR) was not different between MK+ and MK- patients (46...
April 16, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29656609/monocyte-function-in-patients-with-myelodysplastic-syndrome
#11
Daniel A Pollyea, Brenna R Hedin, Brian P O'Connor, Scott Alper
Myelodysplastic syndrome (MDS) is a malignant hematopoietic stem cell disorder that frequently evolves into acute myeloid leukemia (AML). Patients with MDS are prone to infectious complications, in part due to the presence of severe neutropenia and/or neutrophil dysfunction. However, not all patients with neutropenia become infected, suggesting that other immune cells may compensate in these patients. Monocytes are also integral to immunologic defense; however, much less is known about monocyte function in patients with MDS...
April 14, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29614393/lenalidomide-treatment-in-lower-risk-myelodysplastic-syndromes-the-experience-of-a-czech-hematology-center-positive-effect-of-erythropoietin-%C3%A2-prednisone-addition-to-lenalidomide-in-refractory-or-relapsed-patients
#12
Anna Jonasova, Radana Neuwirtova, Helena Polackova, Magda Siskova, Tomas Stopka, Eduard Cmunt, Monika Belickova, Alena Moudra, Lubomir Minarik, Ota Fuchs, Kyra Michalova, Zuzana Zemanova
Lenalidomide therapy represents meaningful progress in the treatment of anemic patients with myelodysplastic syndromes with del(5q). We present our initial lenalidomide experience and the positive effect of combining erythropoietin and steroids with lenalidomide in refractory and relapsed patients. We treated by lenalidomide 55 (42 female; 13 male; median age 69) chronically transfused lower risk MDS patients with del(5q) (45) and non-del(5q) (10). Response, meaning transfusion independence (TI) lasting ≥ eight weeks, was achieved in 38 (90%) of analyzed patients with del(5q), of whom three achieved TI only by adding erythropoietin ± prednisone...
March 27, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29610366/exome-chip-analyses-identify-genes-affecting-mortality-after-hla-matched-unrelated-donor-blood-and-marrow-transplantation
#13
Qianqian Zhu, Li Yan, Qian Liu, Chi Zhang, Lei Wei, Qiang Hu, Leah Preus, Alyssa I Clay-Gilmour, Kenan Onel, Daniel O Stram, Loreall Pooler, Xin Sheng, Christopher A Haiman, Xiaochun Zhu, Stephen R Spellman, Marcelo Pasquini, Philip L McCarthy, Song Liu, Theresa Hahn, Lara E Sucheston-Campbell
Although survival outcomes have significantly improved, up to 40% of patients die within 1 year of HLA-matched unrelated-donor blood and marrow transplantation (BMT). To identify non-HLA genetic contributors to mortality after BMT, we performed the first exome-wide association study in the DISCOVeRY-BMT cohorts using the Illumina HumanExome BeadChip. This study includes 2473 patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome and 2221 10/10 HLA-matched donors treated from 2000 to 2011...
May 31, 2018: Blood
https://www.readbyqxmd.com/read/29569278/lenalidomide-treatment-of-myelodysplastic-syndromes-with-chromosome-5q-deletion-results-from-the-national-registry-of-the-italian-drug-agency
#14
Francesco Arcioni, Andrea Roncadori, Valeria Di Battista, Sante Tura, Anna Covezzoli, Sante Cundari, Cristina Mecucci
OBJECTIVE: The most typical cytogenetic aberration in myelodysplastic syndromes is del(5q), which, when isolated, is associated with refractory anaemia and good prognosis. Based on high rates of erythroid response and transfusion independence, Lenalidomide (LEN) became the standard treatment. This multi-centre study was designed to supplement Italian Registry data on LEN by addressing prescription, administration appropriateness, haematological and cytogenetic responses and disease evolution...
March 22, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29555313/a-comparison-of-the-myeloablative-conditioning-regimen-fludarabine-busulfan-with-cyclophosphamide-total-body-irradiation-for-allogeneic-stem-cell-transplantation-in-the-modern-era-a-cohort-analysis
#15
Mahasweta Gooptu, Haesook T Kim, Vincent T Ho, Edwin P Alyea, John Koreth, Philippe Armand, Jerome Ritz, Sarah Nikiforow, Brett E Glotzbecker, Prashant Nageshwar, Robert J Soiffer, Joseph H Antin, Corey S Cutler
With improvement in transplantation practices in the modern era, nonrelapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (HSCT) has improved, while disease relapse rates have remained unchanged. Survival outcomes are therefore driven by NRM in the modern era. Myeloablative conditioning (MAC) regimens are used to maximize disease control and facilitate engraftment; however, their use is often limited by toxicity. The commonly used MAC regimens incorporate either chemotherapy plus total body irradiation (TBI) or combination chemotherapy...
March 16, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29549983/setbp1-mutations-in-chinese-patients-with-acute-myeloid-leukemia-and-myelodysplastic-syndrome
#16
Xin-Yu Yao, Jing-Dong Zhou, Jing Yang, Wei Zhang, Ji-Chun Ma, Xiang-Mei Wen, Dong-Ming Yao, Zi-Jun Xu, De-Hong Wu, Pin-Fang He, Jun Qian, Jiang Lin
BACKGROUND: Somatic mutations in SETBP1 gene have recently been detected in hematologic malignancies. The present study aimed to explore the frequency and clinical correlations of SETBP1 mutations in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). METHODS: In this study, we used high-resolution melting analysis (HRMA) to detect the SETBP1 mutations in a cohort of 363 patients with AML or MDS. RESULTS: A total of 1...
May 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29544131/similar-incidence-of-typhlitis-in-patients-receiving-various-doses-of-daunorubicin-or-idarubicin-as-induction-for-acute-myeloid-leukemia
#17
Amanda N Seddon, Joshua Chaim, Oguz Akin, Esther Drill, Angela G Michael, Nelly Adel, Martin S Tallman
BACKGROUND: The current standard of care for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) is an anthracycline plus cytarabine. Both anthracyclines and cytarabine have been associated with the development of typhlitis, a serious adverse event characterized by inflammation of the bowel wall in patients with profound neutropenia, diagnosed by abdominal CT imaging and clinical symptoms. Given the paucity of available data, the aim of our study was to determine the incidence of typhlitis among AML patients receiving induction chemotherapy with idarubicin 12 mg/m2 (IDA), daunorubicin 60 mg/m2 (DNA60), or daunorubicin 90 mg/m2 (DNA90)...
May 2018: Leukemia Research
https://www.readbyqxmd.com/read/29483711/universal-genetic-testing-for-inherited-susceptibility-in-children-and-adults-with-myelodysplastic-syndrome-and-acute-myeloid-leukemia-are-we-there-yet
#18
REVIEW
Kiran Tawana, Michael W Drazer, Jane E Churpek
Comprehensive genomic profiling of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) cases have enabled the detection and differentiation of driver and subclonal mutations, informed risk prognostication, and defined targeted therapies. These insights into disease biology, and management have made multigene-acquired mutation testing a critical part of the diagnostic assessment of patients with sporadic MDS and AML. More recently, our understanding of the role of an increasing number of inherited genetic factors on MDS/AML risk and management has rapidly progressed...
February 27, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29463550/phase-ib-study-of-glasdegib-a-hedgehog-pathway-inhibitor-in-combination-with-standard-chemotherapy-in-patients-with-aml-or-high-risk-mds
#19
Michael R Savona, Daniel A Pollyea, Wendy Stock, Vivian G Oehler, Mark A Schroeder, Jeffrey Lancet, James McCloskey, Hagop M Kantarjian, Weidong Wendy Ma, M Naveed Shaik, A Douglas Laird, Mirjana Zeremski, Ashleigh O'Connell, Geoffrey Chan, Jorge E Cortes
Purpose: This open-label, multicenter, dose-finding, phase Ib study (NCT01546038) evaluated the safety, pharmacokinetics, pharmacodynamics, and clinical activity of the novel Hedgehog pathway Smoothened inhibitor glasdegib (PF-04449913) in patients ( N = 52) with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). Experimental Design: Glasdegib 100 or 200 mg was administered orally, once daily in 28-day cycles, in combination with low-dose cytarabine (arm A) or decitabine (arm B) to newly diagnosed patients considered not suitable for standard induction chemotherapy, and in combination with cytarabine/daunorubicin (arm C) to fit patients...
February 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29460654/cumulative-experience-and-long-term-follow-up-of-pentostatin-based-chemoimmunotherapy-trials-for-patients-with-chronic-lymphocytic-leukemia
#20
Neil E Kay, Betsy R LaPlant, Adam M Pettinger, Timothy G Call, Jose F Leis, Wei Ding, Sameer A Parikh, Michael J Conte, Deborah A Bowen, Tait D Shanafelt
BACKGROUND: 7 regimens of pentostatin based chemoimmunotherapy (CIT) for progressive previously untreated CLL primarily with long term follow-up to update both efficacy and toxicity. RESEARCH DESIGN AND METHODS: Prognostic markers including assessment of IGVH and FISH status were done on all. Response rates and 95% binomial confidence intervals were calculated for each regimen and in the combined cohort. Overall survival and treatment-free survival were evaluated using Kaplan-Meier methods...
April 2018: Expert Review of Hematology
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