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AML

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https://www.readbyqxmd.com/read/29318584/treatment-of-relapsed-refractory-acute-myeloid-leukaemia-in-adults
#1
REVIEW
Armin Rashidi, Daniel J Weisdorf, Nelli Bejanyan
The prognosis of relapsed acute myeloid leukaemia (AML) is poor and treatment is challenging. While the most potent treatment modality for patients who achieve a complete remission after relapse is still allogeneic haematopoietic cell transplantation (allo-HCT), both transplant-related mortality and relapse rates are high and many patients are not candidates for this approach. After a few decades of relative stasis in this field, a large number of novel approaches have become available to tackle this highly fatal disease...
January 9, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29241762/eltrombopag-for-advanced-myelodysplastic-syndromes-or-acute-myeloid-leukaemia-and-severe-thrombocytopenia-aspire-a-randomised-placebo-controlled-phase-2-trial
#2
Moshe Mittelman, Uwe Platzbecker, Boris Afanasyev, Sebastian Grosicki, Raymond S M Wong, Achilles Anagnostopoulos, Benjamin Brenner, Claudio Denzlinger, Giuseppe Rossi, Arnon Nagler, Regina Garcia-Delgado, Maria Socorro O Portella, Zewen Zhu, Dominik Selleslag
BACKGROUND: Thrombocytopenia is a life-threatening complication in patients with advanced myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). In this study (ASPIRE), we aimed to assess eltrombopag, an oral thrombopoietin receptor agonist, for thrombocytopenia (grade 4) treatment in adult patients with advanced MDS or AML. METHODS: ASPIRE consisted of an open-label, double-blind phase for 8 weeks and a randomised, double-blind phase (parts 1 and 2, reported here) for 12 weeks, and an open-label extension (part 3)...
December 11, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28658204/tracing-the-origins-of-relapse-in-acute-myeloid-leukaemia-to-stem-cells
#3
Liran I Shlush, Amanda Mitchell, Lawrence Heisler, Sagi Abelson, Stanley W K Ng, Aaron Trotman-Grant, Jessie J F Medeiros, Abilasha Rao-Bhatia, Ivana Jaciw-Zurakowsky, Rene Marke, Jessica L McLeod, Monica Doedens, Gary Bader, Veronique Voisin, ChangJiang Xu, John D McPherson, Thomas J Hudson, Jean C Y Wang, Mark D Minden, John E Dick
In acute myeloid leukaemia, long-term survival is poor as most patients relapse despite achieving remission. Historically, the failure of therapy has been thought to be due to mutations that produce drug resistance, possibly arising as a consequence of the mutagenic properties of chemotherapy drugs. However, other lines of evidence have pointed to the pre-existence of drug-resistant cells. For example, deep sequencing of paired diagnosis and relapse acute myeloid leukaemia samples has provided direct evidence that relapse in some cases is generated from minor genetic subclones present at diagnosis that survive chemotherapy, suggesting that resistant cells are generated by evolutionary processes before treatment and are selected by therapy...
July 6, 2017: Nature
https://www.readbyqxmd.com/read/29316944/car-t-cells-targeting-cll-1-as-an-approach-to-treat-acute-myeloid-leukemia
#4
Jinghua Wang, Siyu Chen, Wei Xiao, Wende Li, Liang Wang, Shuo Yang, Weida Wang, Liping Xu, Shuangye Liao, Wenjian Liu, Yang Wang, Nawei Liu, Jianeng Zhang, Xiaojun Xia, Tiebang Kang, Gong Chen, Xiuyu Cai, Han Yang, Xing Zhang, Yue Lu, Penghui Zhou
BACKGROUND: Acute myeloid leukemia (AML) is one of the most common types of adult acute leukemia. Standard chemotherapies can induce complete remission in selected patients; however, a majority of patients eventually relapse and succumb to the disease. Thus, the development of novel therapeutics for AML is urgently needed. Human C-type lectin-like molecule-1 (CLL-1) is a type II transmembrane glycoprotein, and its expression is restricted to myeloid cells and the majority of AML blasts...
January 10, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29301553/precision-therapy-for-acute-myeloid-leukemia
#5
REVIEW
Xue Yang, Jianxiang Wang
Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous disease. Despite advances in understanding the pathogenesis of AML, the standard therapy remained nearly unchanged over the past three decades. With the poor survival for older patients and high relapse rate, multiple studies are ongoing to address this important issue. Novel therapies for AML, including the refinements of conventional cytotoxic chemotherapies and genetic and epigenetic targeted drugs, as well as immunotherapies, have been developed in recent years...
January 5, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28987821/low-dose-lenalidomide-plus-cytarabine-in-very-elderly-unfit-acute-myeloid-leukemia-patients-final-result-of-a-phase-ii-study
#6
MULTICENTER STUDY
Giuseppe Visani, Felicetto Ferrara, Francesco Di Raimondo, Federica Loscocco, Fabio Fuligni, Stefania Paolini, Valentina Zammit, Eleonora Spina, Marco Rocchi, Axel Visani, Pier Paolo Piccaluga, Alessandro Isidori
Outcome for elderly patients with acute myeloid leukemia (AML) is extremely poor. Intensive induction chemotherapy is often unsuitable. Sixty-six newly diagnosed AML patients (median age: 76years), ineligible for standard therapy, were consecutively treated with low-dose lenalidomide (10mg/day orally, days 1-21) plus 10mg/m2 low-dose cytarabine, subcutaneously, twice a day (days 1-15) every six weeks, up to 6 cycles. Complete remission (CR) rate was 36.3% according to intention-to-treat. Responding patients had a longer median overall survival than non-responders (517 vs...
November 2017: Leukemia Research
https://www.readbyqxmd.com/read/29102721/cellular-immunotherapy-for-hematologic-malignancies-beyond-bone-marrow-transplantation
#7
REVIEW
Melita Cirillo, Peter Tan, Marian Sturm, Catherine Cole
Immunotherapy has changed treatment practices for many hematologic malignancies. Even in the current era of targeted therapy, chemotherapy remains the backbone of treatment for many hematologic malignancies, especially in acute leukemias, where relapse remains the major cause of mortality. Application of novel immunotherapies in hematology attempts to harness the killing power of the immune system against leukemia and lymphoma. Cellular immunotherapy is evolving rapidly for high-risk hematologic disorders. Recent advances include chimeric antigen-receptor T cells, mesenchymal stromal/stem cells, dendritic cell tumor vaccines, cytokine-induced killer cells, and virus-specific T cells...
November 26, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28776567/retinoic-acid-and-arsenic-trioxide-sensitize-acute-promyelocytic-leukemia-cells-to-er-stress
#8
S Masciarelli, E Capuano, T Ottone, M Divona, S De Panfilis, C Banella, N I Noguera, A Picardi, G Fontemaggi, G Blandino, F Lo-Coco, F Fazi
Retinoic acid (RA) in association with chemotherapy or with arsenic trioxide (ATO) results in high cure rates of acute promyelocytic leukemia (APL). We show that RA-induced differentiation of human leukemic cell lines and primary blasts dramatically increases their sensitivity to endoplasmic reticulum (ER) stress-inducing drugs at doses that are not toxic in the absence of RA. In addition, we demonstrate that the PERK pathway, triggered in response to ER stress, has a major protective role. Moreover, low amounts of pharmacologically induced ER stress are sufficient to strongly increase ATO toxicity...
August 4, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28743264/recent-developments-in-immunotherapy-of-acute-myeloid-leukemia
#9
REVIEW
Felix S Lichtenegger, Christina Krupka, Sascha Haubner, Thomas Köhnke, Marion Subklewe
The advent of new immunotherapeutic agents in clinical practice has revolutionized cancer treatment in the past decade, both in oncology and hematology. The transfer of the immunotherapeutic concepts to the treatment of acute myeloid leukemia (AML) is hampered by various characteristics of the disease, including non-leukemia-restricted target antigen expression profile, low endogenous immune responses, and intrinsic resistance mechanisms of the leukemic blasts against immune responses. However, considerable progress has been made in this field in the past few years...
July 25, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27159408/acute-myeloid-leukaemia
#10
REVIEW
Asim Khwaja, Magnus Bjorkholm, Rosemary E Gale, Ross L Levine, Craig T Jordan, Gerhard Ehninger, Clara D Bloomfield, Eli Estey, Alan Burnett, Jan J Cornelissen, David A Scheinberg, Didier Bouscary, David C Linch
Acute myeloid leukaemia (AML) is a disorder characterized by a clonal proliferation derived from primitive haematopoietic stem cells or progenitor cells. Abnormal differentiation of myeloid cells results in a high level of immature malignant cells and fewer differentiated red blood cells, platelets and white blood cells. The disease occurs at all ages, but predominantly occurs in older people (>60 years of age). AML typically presents with a rapid onset of symptoms that are attributable to bone marrow failure and may be fatal within weeks or months when left untreated...
March 10, 2016: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28496177/targeting-flt3-by-chimeric-antigen-receptor-t-cells-for-the-treatment-of-acute-myeloid-leukemia
#11
L Chen, H Mao, J Zhang, J Chu, S Devine, M A Caligiuri, J Yu
No abstract text is available yet for this article.
August 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28420416/emerging-therapies-for-acute-myeloid-leukemia
#12
REVIEW
Caner Saygin, Hetty E Carraway
Acute myeloid leukemia (AML) is characterized by clinical and biological heterogeneity. Despite the advances in our understanding of its pathobiology, the chemotherapy-directed management has remained largely unchanged in the past 40 years. However, various novel agents have demonstrated clinical activity, either as single agents (e.g., isocitrate dehydrogenase (IDH) inhibitors, vadastuximab) or in combination with standard induction/consolidation at diagnosis and with salvage regimens at relapse. The classes of agents described in this review include novel cytotoxic chemotherapies (CPX-351 and vosaroxin), epigenetic modifiers (guadecitabine, IDH inhibitors, histone deacetylase (HDAC) inhibitors, bromodomain and extraterminal (BET) inhibitors), FMS-like tyrosine kinase receptor 3 (FLT3) inhibitors, and antibody-drug conjugates (vadastuximab), as well as cell cycle inhibitors (volasertib), B-cell lymphoma 2 (BCL-2) inhibitors, and aminopeptidase inhibitors...
April 18, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28205134/minimal-residual-disease-in-acute-lymphoblastic-leukemia-how-to-recognize-and-treat-it
#13
REVIEW
Nicholas J Short, Elias Jabbour
In recent years, the identification of minimal residual disease (MRD) that persists after chemotherapy has emerged as the most powerful tool in determining the prognosis of patients with ALL, often superseding historically relevant prognostic factors. Multiple methods to detect MRD exist, each with their own advantages and disadvantages. Multiparameter flow cytometry and quantitative polymerase chain reaction are the most commonly used methods of MRD detection in clinical practice, although there is promise in the use of more sensitive assays utilizing next-generation sequencing that may be able to further refine MRD-based risk stratification...
January 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/27417880/acute-myeloid-leukemia-2016-update-on-risk-stratification-and-management
#14
REVIEW
Elihu Estey
Evidence suggest that even patients aged 70 or above benefit from specific AML therapy. The fundamental decision in AML then becomes whether to recommend standard or investigational treatment. This decision must rest on the likely outcome of standard treatment. Hence we review factors that predict treatment related mortality and resistance to therapy, the latter the principal cause of failure even in patients aged 70 or above. We emphasize the limitations of prediction of resistance based only on pre- treatment factors and stress the need to incorporate post-treatment factors, for example indicators of minimal residual disease...
August 2016: American Journal of Hematology
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