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AML Treatment

Rik A Brooimans, Vincent H J van der Velden, Nancy Boeckx, Jennita Slomp, Frank Preijers, Jeroen G Te Marvelde, Ngoc M Van, Antoinette Heijs, Erik Huys, Bronno van der Holt, Georgine E de Greef, Angele Kelder, Gerrit Jan Schuurhuis
Flow-cytometric detection of now termed measurable residual disease (MRD) in acute myeloid leukemia (AML) has proven to have an independent prognostic impact. In a previous multicenter study we developed protocols to accurately define leukemia-associated immunophenotypes (LAIPs) at diagnosis. It has, however, not been demonstrated whether the use of the defined LAIPs in the same multicenter setting results in a high concordance between centers in MRD assessment. In the present paper we evaluated whether interpretation of list-mode data (LMD) files, obtained from MRD assessment of previously determined LAIPs during and after treatment, could reliably be performed in a multicenter setting...
November 27, 2018: Leukemia Research
Qun Li, Wei Song, Jianmin Wang
Increasing evidence has suggested the involvement of long non-coding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in chemoresistance of cancer treatment. However, its function and molecular mechanisms in acute myeloid leukemia (AML) chemoresistance are still not well elucidated. In the present study, we investigate the functional role of TUG1 in Adriamycin (ADR) resistance of AML and discover the underlying molecular mechanism. Our study revealed that TUG1 was up-regulated in ADR-resistant AML tissues and cells...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Anne-Sofie Skou, Steen Ø Olsen, Lars H Nielsen, Heidi Glosli, Kirsi Jahnukainen, Marianne Jarfelt, Guðmundur K Jónmundsson, Johan Malmros, Karsten Nysom, Henrik Hasle
BACKGROUND: As more children survive acute myeloid leukemia (AML) it is increasingly important to assess possible late effects of the intensive treatment. Hearing loss has only sporadically been reported in survivors of childhood AML. We assessed hearing status in survivors of childhood AML treated with chemotherapy alone according to 3 consecutive NOPHO-AML trials. PROCEDURE: A population-based cohort of children treated according to the NOPHO-AML-84, NOPHO-AML-88, and NOPHO-AML-93 trials included 137 eligible survivors among whom 101 (74%) completed a questionnaire and 99 (72%) had otologic and audiologic examination performed including otoscopy (72%), pure tone audiometry (70%), and tympanometry (60%)...
January 2019: Journal of Pediatric Hematology/oncology
Silin Zhang, Yunhe Xiong, Yixian Zhang, Hongmei Zhao
Interactions between the tumor cells and bone marrow (BM) microenvironment promote survival, growth, and chemoresistance of acute myeloid leukemia (AML). The mTOR pathway plays a key role in mediating the AML-BM microenvironment interactions. Here, we report the anti-AML activity of a natural monomer extracted from the Chinese medicinal herb Evodia rutaecarpa, dihydroevocarpine. Our results showed that dihydroevocarpine-induced cytotoxicity, apoptosis, and G0/G1 arrest in AML cells, and inhibited the tumor growth in an AML xenograft model...
December 12, 2018: Journal of Cellular Physiology
Gregory S Calip, Kellyn M Moran, Karen I Sweiss, Pritesh R Patel, Zhaoju Wu, Sruthi Adimadhyam, Todd A Lee, Naomi Y Ko, John G Quigley, Brian C-H Chiu
BACKGROUND: Granulocyte colony-stimulating factors (G-CSFs), which are used for the prevention of complications from chemotherapy-related neutropenia, are linked to the risk of developing second primary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The objective of this study was to examine the correlation between using a specific G-CSF agent and the risk of MDS/AML among older patients with non-Hodgkin lymphoma (NHL). METHODS: This was a retrospective cohort study of adults aged >65 years who were diagnosed with first primary NHL between 2001 and 2011...
December 12, 2018: Cancer
Guangjie Zhao, Wanling Wu, Xiaoqin Wang, Jingwen Gu
Acute megakaryocytic leukemia (AMKL) is a rare subtype of acute myeloid leukemia (AML), which is challenging to diagnose due to frequent myelofibrosis (MF) and a low percentage of blast cells. In the present study, clinical characteristics and experimental observations in 9 adult patients diagnosed with AMKL, who were recruited by the Sino-U.S. Shanghai Leukemia Co-operative Group, were analyzed in order to summarize the diagnostic experience and provide recommendations on diagnosing AMKL. All the patients were diagnosed according to the 2008 World Health Organization diagnostic criteria...
December 2018: Oncology Letters
Kamya Sankar, Brady L Stein
Polycythemia vera (PV) and essential thrombocythemia (ET) are Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPNs), characterized by expansion of normal blood counts, bleeding, thrombosis, and the potential for transformation to myelofibrosis (MF) or acute myeloid leukemia (AML). The primary goals of treatment for MPNs are to reduce the risk of thrombosis, alleviate systemic symptom burden (eg, fatigue, pruritus, microvascular symptoms, and symptomatic splenomegaly), and to prevent transformation to MF/AML...
December 2018: Journal of the National Comprehensive Cancer Network: JNCCN
Iris Z Uras, Barbara Maurer, Sofie Nebenfuehr, Markus Zojer, Peter Valent, Veronika Sexl
While significant progress has been made in the treatment of acute myeloid leukemia (AML), not all patients can be cured. Mutated in about 1/3 of de novo AML, the FLT3 receptor tyrosine kinase is an attractive target for drug development, activating mutations of the FLT3 map to the juxtamembrane domain (internal tandem duplications, ITD) or the tyrosine kinase domain (TKD), most frequently at codon D835. While small molecule tyrosine kinase inhibitors (TKI) effectively target ITD mutant forms, those on the TKD are not responsive...
December 11, 2018: International Journal of Molecular Sciences
Sebastian Klobuch, Tim Steinberg, Emanuele Bruni, Carina Mirbeth, Bernhard Heilmeier, Lina Ghibelli, Wolfgang Herr, Albrecht Reichle, Simone Thomas
Effective and tolerable salvage therapies for elderly patients with chemorefractory acute myeloid leukemia (AML) are limited and usually do not change the poor clinical outcome. We recently described in several chemorefractory elderly AML patients that a novel biomodulatory treatment regimen consisting of low-dose azacitidine (AZA) in combination with PPARγ agonist pioglitazone (PGZ) and all- trans retinoic acid (ATRA) induced complete remission of leukemia and also triggered myeloid differentiation with rapid increase of peripheral blood neutrophils...
2018: Frontiers in Pharmacology
Wendelien Zeijlemaker, Tim Grob, Rosa Meijer, Diana Hanekamp, Angèle Kelder, Jannemieke C Carbaat-Ham, Yvonne J M Oussoren-Brockhoff, Alexander N Snel, Dennis Veldhuizen, Willemijn J Scholten, Johan Maertens, Dimitri A Breems, Thomas Pabst, Markus G Manz, Vincent H J van der Velden, Jennichjen Slomp, Frank Preijers, Jacqueline Cloos, Arjan A van de Loosdrecht, Bob Löwenberg, Peter J M Valk, Mojca Jongen-Lavrencic, Gert J Ossenkoppele, Gerrit J Schuurhuis
Current risk algorithms are primarily based on pre-treatment factors and imperfectly predict outcome in acute myeloid leukemia (AML). We introduce and validate a post-treatment approach of leukemic stem cell (LSC) assessment for prediction of outcome. LSC containing CD34+CD38- fractions were measured using flow cytometry in an add-on study of the HOVON102/SAKK trial. Predefined cut-off levels were prospectively evaluated to assess CD34+CD38-LSC levels at diagnosis (n = 594), and, to identify LSClow /LSChigh (n = 302) and MRDlow /MRDhigh patients (n = 305) in bone marrow in morphological complete remission (CR)...
December 12, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Minervo Perez, John Blankenhorn, Kevin Jason Murray, Laurie L Parker
Acute myeloid leukemia (AML) is an aggressive disease that is characterized by abnormal increase of immature myeloblasts in blood and bone marrow. The FLT3 receptor tyrosine kinase plays an integral role in haematopoiesis, and one third of AML diagnoses exhibit gain-of-function mutations in FLT3, with the juxtamembrane domain internal tandem duplication (ITD) and the kinase domain D835Y variants observed most frequently. Few FLT3 substrates or phosphorylation sites are known, which limits insight into FLT3's substrate preferences and makes assay design particularly challenging...
December 12, 2018: Molecular & Cellular Proteomics: MCP
Aviva C Krauss, Xin Gao, Liang Li, Michael L Manning, Paresma Patel, Wentao Fu, Kumar G Janoria, Gerlie Gieser, David A Bateman, Donna Przepiorka, Yuan Li Shen, Stacy Shifflett Shord, Christopher M Sheth, Anamitro Banerjee, Jiang Liu, Kirsten B Goldberg, Ann T Farrell, Gideon M Blumenthal, Richard Pazdur
On August 3, 2017, the Food and Drug Administration (FDA) granted regular approval to Vyxeos (also known as CPX-351), a liposomal formulation of daunorubicin and cytarabine in a fixed combination, for the treatment of adults with newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). Approval was based on data from Study CLTR0310-301, a randomized, multicenter, open-label, active-controlled trial comparing Vyxeos to a standard combination of daunorubicin and cytarabine ("7+3") in 309 patients 60-75 years of age with newly-diagnosed t-AML or AML-MRC...
December 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Kentaro Minagawa, Mustafa Al-Obaidi, Antonio Di Stasi
Chimeric antigen receptor (CAR)-redirected T-cells are a powerful tool for the treatment of several type of cancers; however, they can cause several adverse effects including cytokine release syndrome, off-target effects resulting in potentially fatal organ damage or even death. Particularly, for CAR T-cells redirected toward acute myeloid leukemia (AML) antigens myelosuppression can be a challenge. The previously validated inducible Caspase9 (iC9) suicide gene system is one of the approaches to control the infused cells in vivo through its activation with a nontherapeutic chemical inducer of dimerizer (CID)...
2019: Methods in Molecular Biology
Anna Maria Ierardi, Mario Petrillo, Andrea Coppola, Salvatore Alessio Angileri, Andrea Galassi, Barbara Padovano, Angela Volpi, Mario Cozzolino, Gianpaolo Carrafiello
AIM: To evaluate efficacy, safety and quality of life of the patients with renal angiomyolipomas (AMLs) associated with tuberous sclerosis complex (TSC) treated with percutaneous microwave ablation (MWA). MATERIALS AND METHODS: Nine patients (7 females and 2 males; mean age 27.6 years, range 23-34), with 10 renal AMLs with a mean size of 6.3 cm (range 4.5-8.5) were treated with image-guided percutaneous MWA. Indications for treatment were the risk of rupture/hemorrhage due to size greater than 4 cm and symptomatology; in one case, a previous hemorrhage was the indication for treatment...
December 11, 2018: La Radiologia Medica
Yang Yang, Gang Wang, Wenjun Wu, Shunnan Yao, Xiaoyan Han, Donghua He, Jingsong He, Gaofeng Zheng, Yi Zhao, Zhen Cai, Rui Yu
Camalexin is a phytoalexin that accumulates in various cruciferous plants upon exposure to environmental stress and plant pathogens. It was shown that camalexin has potent antitumor properties, but its underlying mechanisms are still elusive. In the present study, we evaluated the effects of camalexin on human leukemic cells and normal polymorph nuclear cells. CCK-8 assay was used to determine cell viability after camalexin treatment. Apoptosis, intracellular reactive oxygen species (ROS) levels, and loss of mitochondrial membrane potential (MMP) were measured by flow cytometry...
2018: Oxidative Medicine and Cellular Longevity
Pamela C Egan, John L Reagan
Through the years gemtuzumab ozogamicin (GO) has moved from a panacea in the treatment of acute myeloid leukemia (AML) to a pariah and back again. Early promise of targeted therapy with accelerated approval in the United States in 2000 gave way to fear over increased toxicity in the absence of efficacy, which subsequently resulted in the drug manufacturer voluntarily withdrawing GO from the market in 2010. We outline the history of GO in terms of initial drug development and early clinical trials that ultimately led the way to GO frontline use in AML based on a series of Phase III studies...
2018: OncoTargets and Therapy
Wangda Zhou, Dolly A Parasrampuria, Sepideh Nemat, Susumu Nakahara, Italo Poggesi, Joseph Massarella, Liping Zhang, Carlos Appiani
Dacogen, the formulated product of the pharmaceutically active agent decitabine (5 aza-2'-deoxycytidine), is approved for treatment of myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML). The current analysis was performed to characterize the pharmacokinetics of decitabine in pediatric patients with AML and evaluate their consistency with the PK in adult patients. A population pharmacokinetic model was developed by pooling decitabine concentration-time data from 5 adult (AML and MDS) and 2 pediatric (AML) studies...
December 11, 2018: Journal of Clinical Pharmacology
Maurizio Gianni, Mineko Terao, Mami Kurosaki, Gabriela Paroni, Laura Brunelli, Roberta Pastorelli, Adriana Zanetti, Monica Lupi, Andrea Acquavita, Marco Bolis, Maddalena Fratelli, Cecile Rochette-Egly, Enrico Garattini
All trans-retinoic acid (ATRA) is used in the treatment of acute promyelocytic leukemia (APL) and it is a promising agent also in solid tumors. The pharmacological activity of ATRA is mediated by the ligand-activated RAR and RXR transcription factors. In the present study, we define the basal and ATRA dependent RARα interactome in a RARα-overexpressing breast cancer cellular model, identifying 28 nuclear proteins. We focus our attention on the S100A3 calcium-binding protein, which interacts with RARα constitutively...
December 7, 2018: Oncogene
Carla Filì, Anna Candoni, Maria Elena Zannier, Jacopo Olivieri, Silvia Imbergamo, Manuela Caizzi, Gianpaolo Nadali, Eros Di Bona, Anna Ermacora, Michele Gottardi, Davide Facchinelli, Rosanna Ciancia, Davide Lazzarotto, Maria Vittoria Dubbini, Gianluca Festini, Filippo Gherlinzoni, Maria Grazia Michieli, Gianpietro Semenzato, Renato Fanin
BACKGROUND: The hypomethylating agent Decitabine (DAC) is a valuable treatment option in acute myeloid leukemia (AML), particularly in elderly patients (pts) not suitable for intensive chemotherapy (CHT). However, limited data are available about efficacy and safety of DAC in clinical practice. PATIENTS AND METHODS: We retrospectively reviewed data of 104 AML pts treated with DAC in eight Italian Hematological Centers from 2015 to 2017. The objective of this study was to evaluate the efficacy and safety of DAC in older AML pts outside of clinical trial...
November 28, 2018: Leukemia Research
Beatrice U Mueller, Katja Seipel, Thomas Pabst
Most patients above 60 years with acute myeloid leukemia (AML) will die from their disease. Nevertheless, the treatment concepts in elderly patients with myelodysplastic syndromes (MDS) and AML are rapidly evolving. A number of recent reports have identified better survival rates with intensive induction chemotherapy for patients up to 80 years, with the exception of patients with unfavorable genomic risk abnormalities or with major co-morbidities. Gemtuzumab ozogamicin is increasingly added to induction therapy for AML patients up to 70 years with favorable or intermediate risk profile, and Midostaurin for patients with a FLT3 mutation...
December 2018: European Journal of Internal Medicine
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