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https://www.readbyqxmd.com/read/28636531/nedd9-an-independent-good-prognostic-factor-in-intermediaterisk-acute-myeloid-leukemia-patients
#1
Victor Pallarès, Montserrat Hoyos, M Carmen Chillón, Eva Barragán, M Isabel Prieto Conde, Marta Llop, María Virtudes Céspedes, Josep F Nomdedeu, Salut Brunet, Miguel Ángel Sanz, Marcos González-Díaz, Jorge Sierra, Isolda Casanova, Ramon Mangues
Intermediate-risk acute myeloid leukemia (IR-AML) is the largest subgroup of AML patients and is highly heterogeneous. Whereas adverse and favourable risk patients have well-established treatment protocols, IR-AML patients have not. It is, therefore, crucial to find novel factors that stratify this subgroup to implement risk-adapted strategies. The CAS (Crk-associated substrate) adaptor protein family regulates cell proliferation, survival, migration and adhesion. Despite its association with metastatic dissemination and prognosis of different solid tumors, the role of these proteins in hematological malignancies has been scarcely evaluated...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28632487/prospective-randomized-comparison-of-idarubicin-and-high-dose-daunorubicin-in-induction-chemotherapy-for-newly-diagnosed-acute-myeloid-leukemia
#2
Je-Hwan Lee, Hawk Kim, Young-Don Joo, Won-Sik Lee, Sung Hwa Bae, Dae Young Zang, Jihyun Kwon, Min Kyoung Kim, Junglim Lee, Gyeong Won Lee, Jung-Hee Lee, Yunsuk Choi, Dae-Young Kim, Eun-Hye Hur, Sung-Nam Lim, Sang-Min Lee, Hun Mo Ryoo, Hyo Jung Kim, Myung Soo Hyun, Kyoo-Hyung Lee
Purpose We compared two induction regimens, idarubicin (12 mg/m(2)/d for 3 days) versus high-dose daunorubicin (90 mg/m(2)/d for 3 days), in young adults with newly diagnosed acute myeloid leukemia (AML). Patients and Methods A total of 299 patients (149 randomly assigned to cytarabine plus idarubicin [AI] and 150 assigned to cytarabine plus high-dose daunorubicin [AD]) were analyzed. All patients received cytarabine (200 mg/m(2)/d for 7 days). Results Complete remission (CR) was induced in 232 patients (77...
June 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28628276/acute-myeloid-leukaemia-relapsing-after-allogeneic-haematopoietic-stem-cell-transplantation-prognostic-factors-and-impact-of-initial-therapy-of-relapse
#3
Andrew B M Lim, Cameron Curley, Chun Yew Fong, Ian Bilmon, Ashanka Beligaswatte, Duncan Purtill, Bartlomiej Getta, Anne Maree Johnston, Tasman Armytage, Marnie Collins, Kate Mason, Katherine Fielding, Matthew Greenwood, John Gibson, Mark Hertzberg, Matthew Wright, Ian Lewis, John Moore, David Curtis, Jeff Szer, Glen Kennedy, David Ritchie
AIMS: We sought to determine factors associated with overall survival from relapse (OSR) of acute myeloid leukaemia (AML) after allogeneic haematopoietic stem cell transplantation (alloHSCT), and the effect of first salvage therapy and subsequent GVHD on OSR. METHODS: Data on 386 patients from nine Australian centres with relapsed AML post-alloHSCT were collected retrospectively. OSR was calculated using the Kaplan-Meier method. Univariate and multivariate analyses were conducted using the logrank test and proportional hazards modelling respectively, and a prognostic index for OSR was derived from multivariate modelling...
June 19, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28625976/a-genome-wide-crispr-screen-identifies-genes-critical-for-resistance-to-flt3-inhibitor-ac220
#4
Panpan Hou, Chao Wu, Yuchen Wang, Rui Qi, Dheeraj Bhavanasi, Zhixiang Zuo, Cedric Dos Santos, Shuliang Chen, Yu Chen, Hong Zheng, Hong Wang, Alexander E Perl, Deyin Guo, Jian Huang
Acute myeloid leukemia (AML) is a malignant hematopoietic disease and the most common type of acute leukemia in adults. The mechanisms underlying drug resistance in AML are poorly understood. Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are the most common molecular abnormality in AML. Quizartinib (AC220) is a potent and selective second-generation inhibitor of FLT3. It is in clinical trials for the treatment of relapsed or refractory FLT3-ITD-positive and -negative AML patients and as maintenance therapy...
June 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28619982/jak1-2-and-bcl2-inhibitors-synergize-to-counteract-bone-marrow-stromal-cell-induced-protection-of-aml
#5
Riikka Karjalainen, Tea Pemovska, Mihaela Popa, Minxia Liu, Komal K Javarappa, Muntasir M Majumder, Bhagwan Yadav, David Tamborero, Jing Tang, Dmitrii Bychkov, Mika Kontro, Alun Parsons, Minna Suvela, Mireia Mayoral Safont, Kimmo Porkka, Tero Aittokallio, Olli Kallioniemi, Emmet McCormack, Bjørn T Gjertsen, Krister Wennerberg, Jonathan Knowles, Caroline A Heckman
The bone marrow (BM) provides a protective microenvironment to support the survival of leukemic cells and influence their response to therapeutic agents. In acute myeloid leukemia (AML), the high rate of relapse may in part be due to the inability of current treatment to effectively overcome the protective influence of the BM niche. To better understand the impact of the BM microenvironment on drug responses in AML, we conducted a comprehensive evaluation of 304 inhibitors, including approved and investigational agents, comparing ex vivo responses of primary AML cells in BM stroma-derived and standard culture conditions...
June 15, 2017: Blood
https://www.readbyqxmd.com/read/28619754/antitumor-effect-of-the-atypical-retinoid-st1926-in-acute-myeloid-leukemia-and-nanoparticle-formulation-prolongs-lifespan-and-reduces-tumor-burden-of-xenograft-mice
#6
Leeanna El-Houjeiri, Walid Saad, Berthe Hayar, Patrick Aouad, Nadim Tawil, Rana Abdel-Samad, Rita Hleihel, Maguy Hamie, Angelo Mancinelli, Claudio Pisano, Hiba El Hajj, Nadine Darwiche
Acute myeloid leukemia (AML) is one of the most frequent types of blood malignancies. It is a complex disorder of undifferentiated hematopoietic progenitor cells. The majority of patients generally respond to intensive therapy. Nevertheless, relapse is the major cause of death in AML, warranting the need for novel treatment strategies. Retinoids have demonstrated potent differentiation and growth regulatory effects in normal, transformed and hematopoietic progenitor cells. All-trans retinoic acid (ATRA) is the paradigm of treatment in acute promyelocytic leukemia, an AML subtype...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28616699/flt3-itd-with-dnmt3a-r882-double-mutation-is-a-poor-prognostic-factor-in-chinese-patients-with-acute-myeloid-leukemia-after-chemotherapy-or-allogeneic-hematopoietic-stem-cell-transplantation
#7
Shanhao Tang, Hongjie Shen, Xinliang Mao, Haiping Dai, Xiaming Zhu, Shengli Xue, Zixuan Ding, Jing Lu, Depei Wu, Xiaowen Tang
To investigate clinical characteristics and outcomes of transplantation in AML patients with FLT3-ITD/DNMT3A double mutation, we retrospectively analyzed 206 Chinese patients with AML after Sanger sequencing. Our analysis showed that AML patients with FLT3-ITD and DNMT3A R882 mutations had a higher white blood cell count and a lower complete remission (CR) rate after first induction chemotherapy. All 206 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in status of CR. These results indicate that AML patients with FLT3-ITD and DNMT3A R882 double mutation show a higher 2-year cumulative incidence of relapse (CIR), lower 2-year overall survival (OS) rate, and lower 2-year leukocyte-free survival (LFS) after allo-HSCT...
June 14, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28600031/hematopoietic-cell-transplantation-in-myelodysplastic-syndromes-after-treatment-with-hypomethylating-agents
#8
Moreno Festuccia, Kelsey Baker, Theodore A Gooley, Brenda M Sandmaier, H Joachim Deeg, Bart L Scott
The prognosis of patients with myelodysplastic syndromes (MDS) following failure of hypomethylating agent (HMA) therapy is poor. Allogeneic hematopoietic cell transplantation (HCT) can be effective in curing patients who have failed therapy with HMA. However, published results have not addressed the outcomes with HCT in this setting. We identified 125 MDS patients who had been treated with HMA and underwent subsequent HCT. Among these, 68 were considered HMA failures, and 57 responders. Failure was defined as progression to higher grade MDS or acute myeloid leukemia (AML), lack of hematological improvement after at least 4 HMA cycles, or loss of response after initial improvement...
June 6, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28592126/autologous-hematopoietic-stem-cell-transplantation-for-acute-myeloid-leukemia-single-center-experience
#9
I Simancikova, E Bojtarova, M Hrubisko, F Farkas, D Horvathova, L Sopko, A Batorova, M Mistrik
We aimed to determine the effect of autologous hematopoietic stem cell transplantation (auto-HSCT) on acute myeloid leukemia (AML) patients as a valid alternative therapeutic option for patients without HLA-compatible donor. This retrospective single center study included 79 patients with AML older than 18 years. In this report, we describe the patient characteristics, engraftment, toxicity of treatment, complications, overall survival, and relapse incidence of 79 patients treated chemotherapy and followed by auto-HSCT...
June 8, 2017: Neoplasma
https://www.readbyqxmd.com/read/28589431/bone-marrow-fibrosis-at-diagnosis-predicts-survival-for-primary-acute-myeloid-leukemia
#10
Z Wu, R Chen, L Wu, L Zou, F Ding, M Wang, X Liu
PURPOSE: As a desmoplastic reaction, tissue fibrosis played crucial roles in solid tumor progression, chemo-resistance, and consequently heralded poor clinical outcome. Previous studies implied the effects of marrow fibrosis on prognosis for acute lymphoblastic leukemia were disputable. In this study, we aimed to investigate the potential role of bone marrow fibrosis on clinical survival in acute myeloid leukemia (AML) patients. METHODS: Bone marrow fibrosis (evaluated as reticulin fiber density, RFD) in bone marrow sections was evaluated at diagnosis via computer technology...
June 6, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28588617/outcomes-of-six-dose-high-dose-cytarabine-as-a-salvage-regimen-for-patients-with-relapsed-refractory-acute-myeloid-leukemia
#11
Brandi Anders, Lauren Veltri, Abraham S Kanate, Alexandra Shillingburg, Nilay Shah, Michael Craig, Aaron Cumpston
Relapsed/refractory acute myeloid leukemia (RR-AML) is associated with poor prognosis and long-term disease-free survival requires allogeneic hematopoietic cell transplantation (allo-HCT). Limited data exists, regarding the optimal regimen to obtain remission prior to allo-HCT. Single agent high-dose cytarabine (10-12 doses administered every 12 hours) has been previously used as induction therapy. Six-dose high-dose cytarabine (HiDAC-6), commonly used as a consolidation regimen, has never been evaluated as induction therapy...
2017: Advances in Hematology
https://www.readbyqxmd.com/read/28588020/enasidenib-in-mutant-idh2-relapsed-or-refractory-acute-myeloid-leukemia
#12
Eytan M Stein, Courtney D DiNardo, Daniel A Pollyea, Amir T Fathi, Gail J Roboz, Jessica K Altman, Richard M Stone, Daniel J DeAngelo, Ross L Levine, Ian W Flinn, Hagop M Kantarjian, Robert Collins, Manish R Patel, Arthur E Frankel, Anthony Stein, Mikkael A Sekeres, Ronan T Swords, Bruno C Medeiros, Christophe Willekens, Paresh Vyas, Alessandra Tosolini, Qiang Xu, Robert D Knight, Katharine E Yen, Sam Agresta, Stéphane de Botton, Martin S Tallman
Recurrent mutations in isocitrate dehydrogenase 2 (IDH2) occur in ~12% of patients with acute myeloid leukemia (AML). Mutated IDH2 proteins neomorphically synthesize 2-hydroxyglutarate resulting in DNA and histone hypermethylation, leading to blocked cellular differentiation. Enasidenib (AG-221/CC-90007) is a first-in-class, oral, selective inhibitor of mutant-IDH2 enzymes. This first-in-human, phase 1/2 study assessed the maximum tolerated dose (MTD), pharmacokinetic and pharmacodynamic profiles, safety, and clinical activity of enasidenib in patients with mutant-IDH2 advanced myeloid malignancies...
June 6, 2017: Blood
https://www.readbyqxmd.com/read/28588019/enasidenib-induces-acute-myeloid-leukemia-cell-differentiation-to-promote-clinical-response
#13
Michael D Amatangelo, Lynn Quek, Alan Shih, Eytan M Stein, Mikhail Roshal, Muriel D David, Benoit Marteyn, Noushin Rahnamay Farnoud, Stephane de Botton, Olivier A Bernard, Bin Wu, Katharine E Yen, Martin S Tallman, Elli Papaemmanuil, Virginie Penard-Lacronique, Anjan Thakurta, Paresh Vyas, Ross L Levine
Recurrent mutations at R140 and R172 in isocitrate dehydrogenase 2 (IDH2) occur in many cancers, including ~12% of acute myeloid leukemia (AML). In preclinical models these mutations cause accumulation of the oncogenic metabolite R-2-hydroxyglutarate (2-HG) and induce hematopoietic differentiation block. Single-agent enasidenib (AG-221/CC-90007), a selective mutant IDH2 (mIDH2) inhibitor, produced an overall response rate of 40.3% in relapsed/refractory AML patients with mIDH2 in a phase 1 trial. However, its mechanism of action and biomarkers associated with response remain unclear...
June 6, 2017: Blood
https://www.readbyqxmd.com/read/28567238/vosaroxin-in-relapsed-refractory-acute-myeloid-leukemia-efficacy-and-safety-in-the-context-of-the-current-treatment-landscape
#14
REVIEW
Valeriy Sedov, Robert K Stuart
Treatment for acute myeloid leukemia (AML) generally consists of a combination of cytarabine and an anthracycline. Although induction therapy leads to complete remission (CR) for most patients, refractoriness to chemotherapy or relapse after initial response is associated with poor outcomes. The 1-year survival rates after first relapse have been reported at 29%, declining to 11% at 5 years. Prognosis is particularly poor among older patients whose higher prevalence of unfavorable cytogenetics and high frequency of comorbidities diminish their ability to tolerate intensive chemotherapy...
June 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28562519/epigenetic-combination-therapy-for-children-with-secondary-myelodysplastic-syndrome-mds-acute-myeloid-leukemia-aml-and-concurrent-solid-tumor-relapse
#15
Chana L Glasser, Alice Lee, Don Eslin, Lianna Marks, Shakeel Modak, Julia L Glade Bender
Secondary myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) is a rare but devastating complication of solid tumor treatment involving high-dose topoisomerase II inhibitor and alkylator chemotherapy. For relapsed or elderly MDS and AML patients ineligible for hematopoietic stem cell transplantation, epigenetic therapies, including DNA methyltransferase inhibitors and histone deacetylase inhibitors, have been utilized as palliative therapy, offering a well-tolerated approach to disease stabilization, prolonged survival, and quality of life...
May 29, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28556917/decreased-relapsed-rate-and-treatment-related-mortality-contribute-to-improved-outcomes-for-pediatric-acute-myeloid-leukemia-in-successive-clinical-trials
#16
Thomas B Alexander, Lei Wang, Hiroto Inaba, Brandon M Triplett, Stanley Pounds, Raul C Ribeiro, Ching-Hon Pui, Jeffrey E Rubnitz
BACKGROUND: Outcomes for children with acute myeloid leukemia (AML) have improved over the past 20 years even though the medications used for induction therapy have not changed. METHODS: This study analyzed data from patients with AML who were enrolled in successive protocols (AML97 and AML02) to determine the contributors to the improved outcomes of the latter clinical trial. RESULTS: There were significant improvements in 5-year overall survival (48...
May 30, 2017: Cancer
https://www.readbyqxmd.com/read/28555084/mitoxantrone-etoposide-and-cytarabine-mec-following-epigenetic-priming-with-decitabine-in-adults-with-relapsed-refractory-acute-myeloid-leukemia-or-other-high-grade-myeloid-neoplasms-a-phase-1-2-study
#17
A B Halpern, M Othus, E M Huebner, S A Buckley, E L Pogosova-Agadjanyan, K F Orlowski, B L Scott, P S Becker, P C Hendrie, T L Chen, M-Em Percival, E H Estey, D L Stirewalt, R B Walter
DNA methyltransferase inhibitors sensitize leukemia cells to chemotherapeutics. We therefore conducted a phase 1/2 study of mitoxantrone, etoposide, and cytarabine following 'priming' with 5-10 days of decitabine (dec/MEC) in 52 adults (median age 55 [range: 19-72] years) with relapsed/refractory acute myeloid leukemia (AML) or other high-grade myeloid neoplasms. During dose escalation in cohorts of 6-12 patients, all dose levels were well-tolerated. As response rates appeared similar with 7 and 10-days of decitabine, a 7-day course was defined as the recommended phase 2 dose (RP2D)...
May 30, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28541716/investigational-bet-bromodomain-protein-inhibitors-in-early-stage-clinical-trials-for-acute-myelogenous-leukemia-aml
#18
Thorsten Braun, Claude Gardin
Acute myelogenous leukemia (AML) is a heterogeneous group of malignancies driven by genetic mutations and deregulated epigenetic control. Relapse/refractory disease remains frequent in younger patients and even more so in older patients, including treatment with epigenetic drugs in this age group, mainly with hypomethylating agents. New treatment strategies are urgently needed. The recent discovery that epigenetic readers of the bromodomain (BRD) and extraterminal (BET) protein family, are crucial for AML maintenance by transcription of oncogenic c-MYC lead to rapid development of BET inhibitors entering clinical trials...
June 9, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28541603/comparison-of-first-line-chemotherapy-including-escalated-beacopp-versus-chemotherapy-including-abvd-for-people-with-early-unfavourable-or-advanced-stage-hodgkin-lymphoma
#19
REVIEW
Nicole Skoetz, Andrea Will, Ina Monsef, Corinne Brillant, Andreas Engert, Bastian von Tresckow
BACKGROUND: There are two different international standards for the treatment of early unfavourable and advanced stage Hodgkin lymphoma (HL): chemotherapy with escalated BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone) regimen and chemotherapy with ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) regimen. OBJECTIVES: To determine the advantages and disadvantages of chemotherapy including escalated BEACOPP compared to chemotherapy including ABVD in the treatment of early unfavourable or advanced stage HL as first-line treatment...
May 25, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28527985/long-term-follow-up-and-impact-of-comorbidity-prior-to-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-relapsed-or-refractory-aml-lessons-learned-from-the-prospective-bridge-trial-clofarabine-salvage-therapy-prior-to-allogeneic-transplantation
#20
Jan Moritz Middeke, Regina Herbst, Stefani Parmentier, Gesine Bug, Mathias Hänel, Gernot Stuhler, Kerstin Schäfer-Eckart, Wolf Rösler, Stefan Klein, Wolfgang Bethge, Ulrich Bitz, Bozena Büttner, Holger Knoth, Nael Alakel, Markus Schaich, Anke Morgner, Michael Kramer, Katja Sockel, Malte von Bonin, Friedrich Stölzel, Uwe Platzbecker, Christoph Röllig, Christian Thiede, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig
In patients with relapsed or refractory (r/r) AML, allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is considered to be the only treatment providing long-term disease control. The BRIDGE trial studied the safety and efficacy of a clofarabine-based salvage therapy prior to HSCT in patients with r/r AML. Here, we report the long-term follow up of this Phase II, multi-center trial and exploratory analyses on the impact of comorbidity on outcome. Eighty-four patients with a median age of 61 years (range 40 - 75) were enrolled...
May 17, 2017: Biology of Blood and Marrow Transplantation
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