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https://www.readbyqxmd.com/read/29444931/complete-remission-with-reduction-of-high-risk-clones-following-haploidentical-nk-cell-therapy-against-mds-and-aml
#1
Andreas T Björklund, Mattias Carlsten, Ebba Sohlberg, Lisa L Liu, Trevor Clancy, Mohsen Karimi, Sarah Cooley, Jeffrey S Miller, Monika Klimkowska, Marie Schaffer, Emma Watz, Kristina I Wikstrom, Pontus Blomberg, Bjorn E Wahlin, Marzia Palma, Lotta Hansson, Per Ljungman, Eva Hellström-Lindberg, Hans-Gustaf Ljunggren, Karl-Johan Malmberg
PURPOSE: To evaluate the safety, efficacy and immunobiological correlates of allogeneic NK cell-based therapy in primary chemotherapy-refractory or relapsed high-risk myelodysplastic syndrome (MDS), secondary AML (MDS/AML), and de novo AML patients. EXPERIMENTAL DESIGN: Sixteen patients received fludarabine/cyclophosphamide conditioning combined with total lymphoid irradiation followed by adoptive immunotherapy with IL-2-activated haploidentical NK cells. RESULTS: NK cell infusions were well tolerated with only transient adverse events observed in the 16 patients...
February 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29435331/systematic-review-of-azacitidine-regimens-in-myelodysplastic-syndrome-and-acute-myeloid-leukemia
#2
Roman M Shapiro, Alejandro Lazo-Langner
Background: 5-Azacitidine administered as a 7-day dosing regimen (7-0-0) is approved in high risk IPSS myelodysplastic syndrome (MDS) patients. Alternative regimens such as a 5-day (5-0-0) or 7-day with a weekend break (5-2-2) are commonly used. No randomized controlled trial has been done directly comparing all three dosing regimens. The objective of this study was to compare the efficacies of the 5-0-0, 5-2-2, and 7-0-0 regimens in MDS and AML. Methods: A systematic review was conducted using MEDLINE, EMBASE and CENTRAL...
2018: BMC Hematology
https://www.readbyqxmd.com/read/29397844/-clinical-study-of-patients-with-myelodysplastic-syndrome-transformed-into-acute-myeloid-leukemia
#3
Fang Ye, Dong-Sheng Ma, Jie Wang, Zhen-Hua Qiao
OBJECTIVE: To study the biological characteristics and treatment response of patients with myelodysplastic syndrome (MDS) transformed into acute leukemia(AL). METHODS: Using WHO standard method, the clinical characteristics of patients with MDS into AML were retrospectively analyzed, the related factors influencing the MDS into AML and the treatment response of patients were analyzed. RESULTS: Twenty-six cases (17%) of MDS were transformed into AL among 153 cases of middle and high risk MDS, all of which were AML...
February 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29397193/the-poly-adp-ribose-polymerase-inhibitor-niraparib-management-of-toxicities
#4
Kathleen N Moore, Mansoor Raza Mirza, Ursula A Matulonis
Niraparib is an oral poly(ADP ribose) polymerase (PARP) inhibitor that is currently approved by the United States Food and Drug Administration (US FDA) as well as recently approved by the European Medicines Agency (EMA) for the maintenance treatment of women with recurrent ovarian cancer who are in complete or partial response to platinum-based chemotherapy. The mechanisms of action of niraparib include inhibition of PARP enzymatic activity as well as increased formation of PARP-DNA complexes through "trapping" the PARP enzyme on damaged DNA...
January 31, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29396905/transplant-related-mortality-and-survival-in-children-with-malignancies-treated-with-allogeneic-hematopoietic-stem-cell-transplantation-a-multicenter-analysis
#5
Agnieszka Zaucha-Prazmo, Jolanta Gozdzik, Robert Debski, Katarzyna Drabko, Elzbieta Sadurska, Jerzy R Kowalczyk
The aim of the study was to assess the risk of TRM in pediatric patients treated for malignant disorders with allogeneic HSCT, according to different risk factors. The treatment outcome was analyzed in 299 pediatric patients treated in pediatric transplant departments from 2006 to 2015. To compare the outcome, patients were analyzed all together and in groups according to the diagnosis, age at transplant, donor type, disease status, stem cell source, and pediatric TRM score. At the end of the observation time, 82 patients were alive, 82 died, of which 40 due to transplant-related reasons...
February 3, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29367710/the-japan-marrow-donor-program-25-years-of-experience-in-achieving-20-000-bone-marrow-transplantations-organization-structure-activity-and-financial-basis
#6
Hidehiko Saito, Masaharu Ito, Shunichi Kato, Yoshihisa Kodera, Shinichiro Okamoto, Shuichi Taniguchi, Minoko Takanashi, Heiwa Kanamori, Toru Masaoka, Fumimaro Takaku
The Japan Marrow Donor Program (JMDP), established in 1991, has continued to grow in its capacity to facilitate unrelated bone marrow (BMT) and peripheral blood stem cell transplantation (PBSCT) for the past 25 years in Japan. The current donor pool is 463,465 (as of 31 December 2016) and 20,237 transplants were performed with the help of the Japanese Red Cross, government, and supporters. As JMDP introduced PBSCT in 2010, the vast majority of transplants are BMT. All donors are fully typed for HLA-A, B, C, and DR...
January 24, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29344089/bone-marrow-failure-may-be-caused-by-chromosome-anomalies-exerting-effects-on-runx1t1-gene
#7
R Valli, L Vinti, A Frattini, M Fabbri, G Montalbano, C Olivieri, A Minelli, F Locatelli, F Pasquali, E Maserati
Background: The majority of the cases of bone marrow failure syndromes/aplastic anaemias (BMFS/AA) are non-hereditary and considered idiopathic (80-85%). The peripheral blood picture is variable, with anaemia, neutropenia and/or thrombocytopenia, and the patients with idiopathic BMFS/AA may have a risk of transformation into a myelodysplastic syndrome (MDS) and/or an acute myeloid leukaemia (AML), as ascertained for all inherited BMFS. We already reported four patients with different forms of BMFS/AA with chromosome anomalies as primary etiologic event: the chromosome changes exerted an effect on specific genes, namely RUNX1, MPL, and FLI1, leading to the disease...
2018: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29311715/the-bone-marrow-niche-in-mds-and-mgus-implications-for-aml-and-mm
#8
REVIEW
Irene M Ghobrial, Alexandre Detappe, Kenneth C Anderson, David P Steensma
Several haematological malignancies, including multiple myeloma (MM) and acute myeloid leukaemia (AML), have well-defined precursor states that precede the development of overt cancer. MM is almost always preceded by monoclonal gammopathy of undetermined significance (MGUS), and at least a quarter of all patients with myelodysplastic syndromes (MDS) have disease that evolves into AML. In turn, MDS are frequently anteceded by clonal haematopoiesis of indeterminate potential (CHIP). The acquisition of additional genetic and epigenetic alterations over time clearly influences the increasingly unstable and aggressive behaviour of neoplastic haematopoietic clones; however, perturbations in the bone-marrow microenvironment are increasingly recognized to have key roles in initiating and supporting oncogenesis...
January 9, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29307747/the-u2af-homology-motif-kinase-1-uhmk1-is-upregulated-upon-hematopoietic-cell-differentiation
#9
Isabella Barbutti, João Agostinho Machado-Neto, Vanessa Cristina Arfelli, Paula de Melo Campos, Fabiola Traina, Sara Teresinha Olalla Saad, Leticia Fröhlich Archangelo
UHMK1 (KIS) is a nuclear serine/threonine kinase that possesses a U2AF homology motif and phosphorylates and regulates the activity of the splicing factors SF1 and SF3b155. Mutations in these components of the spliceosome machinery have been recently implicated in leukemogenesis. The fact that UHMK1 regulates these factors suggests that UHMK1 might be involved in RNA processing and perhaps leukemogenesis. Here we analyzed UHMK1 expression in normal hematopoietic and leukemic cells as well as its function in leukemia cell line...
January 4, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29296959/somatic-mutations-in-children-with-gata2-associated-myelodysplastic-syndrome-who-lack-other-features-of-gata2-deficiency
#10
Kevin E Fisher, Amy P Hsu, Christopher L Williams, Hadi Sayeed, Brian Y Merritt, M Tarek Elghetany, Steven M Holland, Alison A Bertuch, Maria Monica Gramatges
Approximately 10% of children with primary myelodysplastic syndrome (MDS) have germ line GATA2 mutations, leading to the proposal that all children with primary MDS and certain cytogenetic findings, including monosomy 7, be tested for germ line GATA2 mutations regardless of family history or other clinical features associated with GATA2 deficiency. In adults with familial GATA2-MDS, those with somatic mutations in ASXL1 experience rapid disease progression to acute myeloid leukemia (AML) and poor prognosis after stem cell transplantation; however, the prevalence of somatic mutations in primary pediatric GATA2-MDS is unclear...
February 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296797/patient-derived-antibody-recognizes-a-unique-cd43-epitope-expressed-on-all-aml-and-has-antileukemia-activity-in-mice
#11
Marijn A Gillissen, Greta de Jong, Martijn Kedde, Etsuko Yasuda, Sophie E Levie, Gemma Moiset, Paul J Hensbergen, Arjen Q Bakker, Koen Wagner, Jullien Villaudy, Pauline M van Helden, Hergen Spits, Mette D Hazenberg
Immunotherapy has proven beneficial in many hematologic and nonhematologic malignancies, but immunotherapy for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is hampered by the lack of tumor-specific targets. We took advantage of the tumor-immunotherapeutic effect of allogeneic hematopoietic stem cell transplantation and searched the B-cell repertoire of a patient with a lasting and potent graft-versus-AML response for the presence of AML-specific antibodies. We identified an antibody, AT1413, that was of donor origin and that specifically recognizes a novel sialylated epitope on CD43 (CD43s)...
August 22, 2017: Blood Advances
https://www.readbyqxmd.com/read/29285795/ataluren-driven-restoration-of-shwachman-bodian-diamond-syndrome-protein-function-in-shwachman-diamond-syndrome-bone-marrow-cells
#12
Valentino Bezzerri, Donatella Bardelli, Jacopo Morini, Antonio Vella, Simone Cesaro, Claudio Sorio, Andrea Biondi, Cesare Danesino, Piero Farruggia, Baroukh Maurice Assael, Giovanna D'Amico, Marco Cipolli
Shwachman-Diamond syndrome (SDS) is a rare inherited recessive disease mainly caused by mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene, which encodes for the homonymous protein SBDS, whose function still remains to be fully established. SDS affects several organs causing bone marrow failure, exocrine pancreatic insufficiency, skeletal malformations, and cognitive disorders. About 15% of SDS patients develop myelodysplastic syndromes (MDS) and are at higher risk of developing acute myeloid leukemia (AML)...
December 29, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29274396/transplant-conditioning-with-treosulfan-fludarabine-with-or-without-tbi-a-randomized-phase-ii-trial-in-patients-with-mds-and-aml
#13
H Joachim Deeg, Emily A Stevens, Rachel B Salit, Ralph P Ermoian, Min Fang, Boglarka Gyurkocza, Mohamed L Sorror, Giancarlo Fatobene, Joachim Baumgart, Lauri M Burroughs, Colleen Delaney, Kris Doney, Daniel N Egan, Mary E D Flowers, Filippo Milano, Jerry P Radich, Bart L Scott, Eileen J Sickle, Brent L Wood, Cecilia Yeung, Barry E Storer
In this prospective randomized phase II "pick the winner" trial we assessed the efficacy of transplant conditioning with treosulfan/fludarabine ± 2 Gy total body irradiation (TBI) in reducing post-transplant relapse in 100 patients, 2-70 (median 57) years of age, with myelodysplastic syndrome/chronic myelomonocytic leukemia (MDS/CMML; n=51) or acute myeloid leukemia (AML; n=49). Patients received intravenous (IV) treosulfan, 14 g/m2/day on days -6 to -4 and IV fludarabine, 30 mg/m2/day on days -6 to -2, alone or combined with 2 Gy TBI (day 0)...
December 20, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29239497/clinical-outcomes-of-unrelated-cord-blood-transplantation-in-children-with-malignant-and-non-malignant-diseases-multicenter-experience-in-china
#14
Xiangfeng Tang, Jianpei Fang, Jie Yu, Zhiguang Li, Jing Chen, Xin Sun, Yiping Zhu, Shaoyan Hu, Maoquan Qin, Yongmin Tang, Zuo Luan
This multicenter retrospective study included 184 children with malignant and non-malignant diseases who underwent UCBT between January 1998 and August 2012. The malignant disease group included 101 children with ALL, AML, CML, JMML, and MDS, and the non-malignant disease group included 83 children with PID, β-thalassemia, IMD BMF, and HLH. The median duration to neutrophil and platelet engraftment was 16 and 35 days in the malignant disease group vs 15 and 38 days in the non-malignant disease group. The cumulative incidence of grade II-IV aGVHD and cGVHD was 25...
December 14, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/29236294/acute-myeloid-leukemia-and-myelodysplastic-syndrome-after-adjuvant-chemotherapy-a-population-based-study-among-older-breast-cancer-patients
#15
Aron S Rosenstock, Jiangong Niu, Sharon H Giordano, Hui Zhao, Antonio C Wolff, Mariana Chavez-MacGregor
BACKGROUND: Chemotherapy for early breast cancer is associated with a small risk of developing myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). The aim of this study was to determine the risk of developing AML or MDS after modern adjuvant chemotherapy in older breast cancer patients and to further define the risk of individual chemotherapy regimens. METHODS: Patients diagnosed with stage I to III breast cancer from 2003 to 2009 were identified in the Surveillance, Epidemiology, and End Results-Medicare and Texas Cancer Registry-Medicare linked databases...
December 13, 2017: Cancer
https://www.readbyqxmd.com/read/29232940/no-benefit-of-hypomethylating-agents-compared-to-supportive-care-for-higher-risk-myelodysplastic-syndrome
#16
Sang Kyun Sohn, Joon Ho Moon, In Hee Lee, Jae Sook Ahn, Hyeoung Joon Kim, Joo Seop Chung, Ho Jin Shin, Sung Woo Park, Won Sik Lee, Sang Min Lee, Hawk Kim, Ho Sup Lee, Yang Soo Kim, Yoon Young Cho, Sung Hwa Bae, Ji Hyun Lee, Sung Hyun Kim, Ik Chan Song, Ji Hyun Kwon, Yoo Jin Lee
Background/Aims: This study evaluated the role of hypomethylating agents (HMA) compared to best supportive care (BSC) for patients with high or very-high (H/VH) risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System. Methods: A total of 279 H/VH risk MDS patients registered in the Korean MDS Working Party database were retrospectively analyzed. Results: HMA therapy was administered to 205 patients (73...
December 15, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29218851/clinical-experience-with-the-bcl2-inhibitor-venetoclax-in-combination-therapy-for-relapsed-and-refractory-acute-myeloid-leukemia-and-related-myeloid-malignancies
#17
Courtney D DiNardo, Caitlin R Rausch, Christopher Benton, Tapan Kadia, Nitin Jain, Naveen Pemmaraju, Naval Daver, Wendy Covert, Kayleigh R Marx, Morgan Mace, Elias Jabbour, Jorge Cortes, Guillermo Garcia-Manero, Farhad Ravandi, Kapil N Bhalla, Hagop Kantarjian, Marina Konopleva
INTRODUCTION: Venetoclax (VEN), a selective BCL2 inhibitor, has single-agent activity in relapsed and refractory (R/R) acute myeloid leukemia (AML) and efficacy in lower-intensity combinations for treatment-naïve elderly AML patients. VEN treatment combinations in R/R AML have not been previously reported. METHODS: All R/R myeloid patients (including AML, myelodysplastic syndrome (MDS), and blastic plasmacytoid dendritic cell neoplasm (BPDCN)) treated with VEN combinations in the salvage setting were reviewed...
December 8, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29218389/primary-prophylaxis-of-invasive-fungal-infections-in-patients-with-haematological-malignancies-2017-update-of-the-recommendations-of-the-infectious-diseases-working-party-agiho-of-the-german-society-for-haematology-and-medical-oncology-dgho
#18
REVIEW
Sibylle C Mellinghoff, Jens Panse, Nael Alakel, Gerhard Behre, Dieter Buchheidt, Maximilian Christopeit, Justin Hasenkamp, Michael Kiehl, Michael Koldehoff, Stefan W Krause, Nicola Lehners, Marie von Lilienfeld-Toal, Annika Y Löhnert, Georg Maschmeyer, Daniel Teschner, Andrew J Ullmann, Olaf Penack, Markus Ruhnke, Karin Mayer, Helmut Ostermann, Hans-H Wolf, Oliver A Cornely
Immunocompromised patients are at high risk of invasive fungal infections (IFI), in particular those with haematological malignancies undergoing remission-induction chemotherapy for acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) and recipients of allogeneic haematopoietic stem cell transplants (HSCT). Despite the development of new treatment options in the past decades, IFI remains a concern due to substantial morbidity and mortality in these patient populations. In addition, the increasing use of new immune modulating drugs in cancer therapy has opened an entirely new spectrum of at risk periods...
December 7, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29214694/myelodysplastic-syndromes-2018-update-on-diagnosis-risk-stratification-and-management
#19
Guillermo Montalban-Bravo, Guillermo Garcia-Manero
DISEASE OVERVIEW: The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy. DIAGNOSIS: Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry or molecular genetics is usually complementary and may help refine diagnosis...
January 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29179894/-preventative-and-therapeutic-relapse-strategies-after-allogeneic-hematopoietic-stem-cell-transplantation-guidelines-from-the-francophone-society-of-bone-marrow-transplantation-and-cellular-therapy-sfgm-tc
#20
Nabil Yafour, Florence Beckerich, Claude Eric Bulabois, Patrice Chevallier, Étienne Daguindau, Cécile Dumesnil, Thierry Guillaume, Anne Huynh, Stavroula Masouridi Levrat, Anne-Lise Menard, Mauricette Michallet, Cécile Pautas, Xavier Poiré, Aurelie Ravinet, Ibrahim Yakoub-Agha, Ali Bazarbachi
Disease relapse remains the first cause of mortality of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT). The risk of recurrence is elevated in patients with high-risk cytogenetic or molecular abnormalities, as well as when allo-HCT is performed in patients with refractory disease or with persistent molecular or radiological (PET-CT scan) residual disease. Within the frame of the 7th annual workshops of the francophone society for bone marrow transplantation and cellular therapy, the working group reviewed the literature in order to elaborate unified guidelines for the prevention and treatment of relapse after allo-HCT...
December 2017: Bulletin du Cancer
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