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Aml relapse treatment

Kavin Fatehchand, Elizabeth L McMichael, Brenda F Reader, Huiqing Fang, Ramasamy Santhanam, Shalini Gautam, Saranya Elavazhagan, Payal Mehta, Nathaniel J Buteyn, Giovanna Merchand-Reyes, Sumithira Vasu, Xiaokui Mo, Don M Benson, James S Blachly, William E Carson, John C Byrd, Jonathan P Butchar, Susheela Tridandapani
Acute Myeloid Leukemia (AML) is characterized by the proliferation of immature myeloid-lineage blasts. Due to its heterogeneity and to the high rate of acquired drug resistance and relapse, new treatment strategies are needed. Here, we demonstrate that IFNγ promotes AML blasts to act as effector cells within the context of antibody therapy. Treatment with IFNγ drove AML blasts toward a more differentiated state, wherein they showed increased expression of the M1-related markers HLA-DR and CD86, as well as of FcγRI, which mediates effector responses to therapeutic antibodies...
October 25, 2016: Journal of Biological Chemistry
Maximilian Fleischmann, Ulf Schnetzke, Karin G Schrenk, Volker Schmidt, Herbert G Sayer, Inken Hilgendorf, Andreas Hochhaus, Sebastian Scholl
BACKGROUND: Activating mutations of the receptor tyrosine kinase FLT3 (fms-related tyrosine kinase 3) reflect the most frequent molecular aberration in acute myeloid leukemia (AML). In particular, FLT3 internal tandem duplications (FLT3-ITD) are characterized by an unfavorable prognosis and allogeneic stem cell transplantation (allogeneic SCT) in first complete remission is recommended. In case of imminent or frank relapse following allogeneic SCT, treatment with FLT3 tyrosine kinase inhibitors (TKI) constitutes a promising clinical approach to induce hematologic remission without conventional chemotherapy...
October 24, 2016: Journal of Cancer Research and Clinical Oncology
Jundi Hou, Tao Luo, Ka Lam Ng, Raymond Liang, Anskar Y H Leung, Dong Sun
One of the greatest challenges in acute myeloid leukemia (AML) treatment is preventing relapse. Leukemia cells can hide in bone marrow niche or vascular niche. Hence, many chemical drugs cannot kill these cells. To characterize migration and adhesion properties of leukemia cells in specific niches, CXCR4/SDF-1α signal pathway has been widely used for investigation. AMD3100 is treated as one of the most common chemical drugs that can inhibit this signal. In the current study, we particularly investigate the effect of AMD3100 on the adhesion property of leukemia cells on stromal cells by using engineering tools, namely, optical tweezers (OT) and dielectrophoresis (DEP), to probe single cell property...
October 19, 2016: IEEE Transactions on Nanobioscience
Irina A Tikhonova, Martin W Hoyle, Tristan M Snowsill, Chris Cooper, Joanna L Varley-Campbell, Claudius E Rudin, Ruben E Mujica Mota
The National Institute for Health and Care Excellence (NICE) invited the manufacturer of azacitidine (Celgene) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of acute myeloid leukaemia with more than 30 % bone marrow blasts in adults who are not eligible for haematopoietic stem cell transplantation, as part of the NICE's Single Technology Appraisal process. The Peninsula Technology Assessment Group was commissioned to act as the Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company's submission to NICE...
October 17, 2016: PharmacoEconomics
Michael Medinger, Claudia Lengerke, Jakob Passweg
Acute myeloid leukemia (AML) is a biologically complex and molecularly and clinically heterogeneous disease, and its incidence is increasing as the population ages. Cytogenetic anomalies and mutation testing remain important prognostic tools for tailoring treatment after induction therapy. Despite major advances in understanding the genetic landscape of AML and its impact on the pathophysiology and biology of the disease, as well as the rapid development of new drugs, standard treatment options have not experienced major changes during the past three decades...
2016: Leukemia Research Reports
G L Uy, E J Duncavage, G S Chang, M A Jacoby, C A Miller, J Shao, S Heath, K Elliott, T Reinick, R S Fulton, C C Fronick, M O'Laughlin, L Ganel, C N Abboud, A F Cashen, J F DiPersio, R K Wilson, D C Link, J S Welch, T J Ley, T A Graubert, P Westervelt, M J Walter
Traditional response criteria in MDS and AML are based on bone marrow morphology and may not accurately reflect clonal tumor burden in patients treated with non-cytotoxic chemotherapy. We used next-generation sequencing of serial bone marrow samples to monitor MDS and AML tumor burden during treatment with epigenetic therapy (decitabine and panobinostat). Serial bone marrow samples (and skin as a source of normal DNA) from 25 MDS and AML patients were sequenced (exome or 285 gene panel). We observed that responders, including those in complete remission (CR), can have persistent measurable tumor burden (i...
October 14, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Marianne Jarfelt, Niels H Andersen, Henrik Hasle
Since cardiotoxicity is a life threatening late effect, a reduction of cardiotoxicity in the treatment of acute myeloid leukaemia (AML) is essential. This review is a compilation of the current knowledge about cardiotoxicity after AML treatment and of how future directions in treatment may affect its incidence. A total of six studies concerning AML and cardiotoxicity were identified. The incidence of late subclinical cardiotoxicity varied between 1·3 and 15·3%, and late clinical cardiotoxicity varied between 1·3 and 9·3%...
October 14, 2016: British Journal of Haematology
Savitha Varatharajan, John C Panetta, Ajay Abraham, Sreeja Karathedath, Ezhilpavai Mohanan, Kavitha M Lakshmi, Nancy Arthur, Vivi M Srivastava, Sandeep Nemani, Biju George, Alok Srivastava, Vikram Mathews, Poonkuzhali Balasubramanian
PURPOSE: Chemotherapy drug resistance and relapse of the disease have been the major factors limiting the success of acute myeloid leukemia (AML) therapy. Several factors, including the pharmacokinetics (PK) of Cytarabine (Ara-C) and Daunorubicin (Dnr), could contribute to difference in treatment outcome in AML. METHODS: In the present study, we evaluated the plasma PK of Dnr, the influence of genetic polymorphisms of genes involved in transport and metabolism of Dnr on the PK, and also the influence of these factors on clinical outcome...
October 13, 2016: Cancer Chemotherapy and Pharmacology
Chantal Fridle, Michael Medinger, Matthias C Wilk, Katja Seipel, Jakob Passweg, Markus G Manz, Thomas Pabst
BACKGROUND: The prognosis for relapsing AML patients is disappointing and the preferred salvage chemotherapy is unclear. Among other regimens, cladribine, cytarabine, and idarubicin (CLA-Ida) is used. METHODS: We analyzed relapsing AML patients receiving CLA-Ida chemotherapy between July 2012 and April 2015 at three academic centers in Switzerland. RESULTS: Thirty-four patients underwent at least one cycle of CLA-Ida chemotherapy, with 6 patients having two cycles...
October 13, 2016: Leukemia & Lymphoma
Takahiro Yamauchi
Standard induction chemotherapy regimens achieve complete remission rates of 80% in younger adult patients with acute myeloid leukemia (AML). However, because of disease relapse only 40-50% of patients achieve long-term survival. Five-year survival rates in older patients are only one third of those achieved in younger cases. The adverse prognostic impact of advanced age is attributable to the chemotherapy-resistant nature of the blasts and the limited tolerability these patients have for intensive chemotherapy...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Stephen S Y Lam, Eric S K Ho, Bai-Liang He, Wui-Wing Wong, Chae-Yin Cher, Nelson K L Ng, Cheuk-Him Man, Harinder Gill, Alice M S Cheung, Ho-Wan Ip, Chi-Chiu So, Jerome Tamburini, Chi Wai Eric So, Dona N Ho, Chun-Hang Au, Tsun-Leung Chan, Edmond S K Ma, Raymond Liang, Yok-Lam Kwong, Anskar Y H Leung
An in vitro drug-screening platform on patient samples was developed and validated to design personalized treatment for relapsed/refractory acute myeloid leukemia (AML). Unbiased clustering and correlation showed that homoharringtonine (HHT), also known as omacetaxine mepesuccinate, exhibited preferential antileukemia effect against AML carrying internal tandem duplication of fms-like tyrosine kinase 3 (FLT3-ITD). It worked synergistically with FLT3 inhibitors to suppress leukemia growth in vitro and in xenograft mouse models...
October 5, 2016: Science Translational Medicine
Mixue Xie, Qi Jiang, Li Li, Jingjing Zhu, Lixia Zhu, De Zhou, Yanlong Zheng, Xiudi Yang, Mingyu Zhu, Jianai Sun, Wanzhuo Xie, Xiujin Ye
BACKGROUND: In China, the combination of homoharringtonine, cytarabine, and G-CSF (HAG) has been extensively applied for treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). METHODS: We performed a meta-analysis of 2,314 patients (AML, n = 1754; MDS, n = 560) to determine the overall safety and efficacy of this regimen. RESULTS: The complete response (CR) rate of AML patients (53%) was significantly higher than that of MDS/transformed-AML patients (45%; P = 0...
2016: PloS One
Ruiqi Li, Xiaoxia Hu, Libing Wang, Hui Cheng, Shuqing Lv, Weiping Zhang, Jianmin Wang, Jianmin Yang, Xianmin Song
Acute myeloid leukemia (AML) patients with t(8;21) aberration often have favorable outcomes, however, relapse still occurs in 30-40% patients, with only 50-60% of patients with t(8;21) AML cured with regimens containing high-dose cytarabine (HD-Ara-C). To evaluate the effects of fludarabine and cytarabine (FA) consolidation therapy for t(8;21) AML patients, a prospective randomized study was performed. A total of 45 patients with t(8;21) AML after achieving complete remission (CR) were randomly assigned to receive four course consolidation with FA (n = 23) or HD-Ara-C (n = 22)...
September 27, 2016: American Journal of Hematology
Xiaoyu An, Jinping Liu, Na Wang, Di Wang, Liang Huang, Likun Zhang, Jie Cai, Jean-Pierre Wery, Demin Zhou, Jianfeng Zhou, Qi-Xiang Li
Engrafting a M5-AML patient bone marrow (BM) cells into immunocompromised mice (AM7577) achieved serially transferrable stable AML and eventual mortality. The disease starts at BM followed by expansion to peripherals, typical of M5 leukemogenesis, where high leukemic burden in blood is coincident with symptoms/mortality. The leukemic cells in mice have similar myeloid morphology, phenotypes and genotypes (including FLT3-ITD) as the original patient. Autocrine mechanisms of human GM-CSF/IL-3 likely support AM7577 growth in mice...
September 23, 2016: Experimental Hematology
Shyam A Patel
Acute myeloid leukemia (AML) involvement of the central nervous system is relatively rare, and detection of leptomeningeal disease typically occurs only after a patient presents with neurological symptoms. The case herein describes a 48-year-old man with relapsed/refractory AML of the mixed lineage leukemia rearrangement subtype, who presents with monocular vision loss due to leukemic eye infiltration. MRI revealed right optic nerve sheath enhancement and restricted diffusion concerning for nerve ischemia and infarct from hypercellularity...
2016: Case Reports in Hematology
Yahui Ding, Huier Gao, Yu Zhang, Ye Li, Neil Vasdev, Yingdai Gao, Yue Chen, Quan Zhang
BACKGROUND: The poor outcomes for patients diagnosed with acute myeloid leukemia (AML) are largely attributed to leukemia stem cells (LSCs) which are difficult to eliminate with conventional therapy and responsible for relapse. Thus, new therapeutic strategies which could selectively target LSCs in clinical leukemia treatment and avoid drug resistance are urgently needed. However, only a few small molecules have been reported to show anti-LSCs activity. METHODS: The aim of the present study was to identify alantolactone as novel agent that can ablate acute myeloid leukemia stem and progenitor cells from AML patient specimens and evaluate the anticancer activity of alantolactone in vitro and in vivo...
2016: Journal of Hematology & Oncology
María Facenda-Lorenzo, Ana Sánchez-Quintana, Alejandro Quijada-Fumero, Ana Laynez-Carnicero, Joaquín Breña-Atienza, Francisco J Poncela-Mireles, Juan M Llanos-Gómez, Ana I Cabello-Rodríguez, María Ramos-López
Secondary or metastatic cardiac tumors are much more common than primary benign or malignant cardiac tumors. Any tumor can cause myocardial or pericardial metastasis, although isolated or combined tumor invasion of the pericardium is more common. Types of neoplasia with the highest rates of cardiac or pericardial involvement are melanoma, lung cancer, and breast and mediastinal carcinomas. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Initial treatment involves chemotherapy followed by consolidation treatment to reduce the risk of relapse...
2016: Case Reports in Oncological Medicine
Nirali N Shah, David M Loeb, Hahn Khuu, David Stroncek, Tolu Ariyo, Mark Raffeld, Cindy Delbrook, Crystal L Mackall, Alan S Wayne, Terry J Fry
Relapse of hematologic malignancies is the primary cause of treatment failure after allogeneic hematopoietic stem cell transplantation (HCT). Treatment for post-HCT relapse using donor lymphocyte infusion (DLI) has limited utility, particularly in the setting of acute leukemia, and can result in the development of graft-versus-host disease (GVHD). The Wilms' tumor 1 (WT1) gene product is a tumor-associated antigen that is expressed in acute leukemia and other hematologic malignancies, with limited expression in normal tissues...
September 12, 2016: Biology of Blood and Marrow Transplantation
Laure David, Anne Fernandez-Vidal, Sarah Bertoli, Srdana Grgurevic, Benoît Lepage, Dominique Deshaies, Naïs Prade, Maëlle Cartel, Clément Larrue, Jean-Emmanuel Sarry, Eric Delabesse, Christophe Cazaux, Christine Didier, Christian Récher, Stéphane Manenti, Jean-Sébastien Hoffmann
The nucleoside analog cytarabine, an inhibitor of DNA replication fork progression that results in DNA damage, is currently used in the treatment of acute myeloid leukemia (AML). We explored the prognostic value of the expression of 72 genes involved in various aspects of DNA replication in a set of 198 AML patients treated by cytarabine-based chemotherapy. We unveiled that high expression of the DNA replication checkpoint gene CHEK1 is a prognostic marker associated with shorter overall, event-free, and relapse-free survivals and determined that the expression of CHEK1 can predict more frequent and earlier postremission relapse...
2016: Science Signaling
Lucia Silla, Frederico Dulley, Rosaura Saboya, Fabio Kerbauy, Adriano de Moraes Arantes, Annelise Pezzi, Luisa Grave Gross, Eduardo Paton, Nelson Hamerschlak
INTRODUCTION/OBJECTIVES: Acute myeloid leukemia (AML) accounts for 90% of all cases of acute leukemia in adults. In Brazil, the mortality from myeloid leukemia is 1.74/100 000 men and 1.37/100 000 women. Our aim was to review and update guidelines of the Brazilian Society of Bone Marrow Transplantation on indications of hematopoietic stem cell transplantation (HSCT) for the treatment AML. CONCLUSIONS: (i) Allo-HSCT is recommended for high-risk AML (IA); (ii) allo-HSCT is recommended for AML of intermediate risk (IA); (iii) allo-HSCT is recommended for AML relapsed/refractory (C4); (iv) auto-HSCT is recommended for AML after 1 consolidation (C4); (v) auto-HSCT is recommended for AML in CR1 (higher than QT in the Brazilian experience) (C4); (vi) auto-HSCT is accepted for AML M3 in second molecular complete remission (2B); (vii) peripheral blood instead of Bone Marrow HSC for advanced disease (2A); (viii) recommended conditioning protocols: Bu-Cy/Bu-Mel, Bu-Flu, TBI-Cy...
September 13, 2016: European Journal of Haematology
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