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https://www.readbyqxmd.com/read/29781563/associations-between-neutrophil-recovery-time-infections-and-relapse-in-pediatric-acute-myeloid-leukemia
#1
Ditte J A Løhmann, Peter H Asdahl, Jonas Abrahamsson, Shau-Yin Ha, Ólafur G Jónsson, Gertjan J L Kaspers, Minna Koskenvuo, Birgitte Lausen, Barbara De Moerloose, Josefine Palle, Bernward Zeller, Henrik Hasle
BACKGROUND: Children with acute myeloid leukemia (AML) treated similarly show different toxicity and leukemic responses. We investigated associations between neutrophil recovery time after the first induction course, infection and relapse in children treated according to NOPHO-AML 2004 and DB AML-01. PROCEDURE: Newly diagnosed patients with AML with bone marrow blast <5% between day 15 after the start of the treatment and the start of second induction course, and in complete remission after the second induction course were included (n = 279)...
May 21, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29770715/enasidenib-for-the-treatment-of-acute-myeloid-leukemia
#2
James Dugan, Daniel Pollyea
In August 2017 the United States Federal Drug Administration (FDA) approved enasidenib (Idhifa, Celgene/Agios) for adults with relapsed and refractory acute myelogenous leukemia (AML) with an IDH2 mutation. Enasidenib targets cells with mutant copies of isocitrate dehydrogenase-2 (IDH2), inhibiting the oncometabolite 2-hydroxyglutarte (2-HG) formed by the mutant IDH2. Areas covered: We review the studies leading to enasidenib's approval, as well as common side effects and safety issues experienced during the clinical trials...
May 17, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29769206/targeting-the-idh2-pathway-in-acute-myeloid-leukemia
#3
Maria L Amaya, Daniel A Pollyea
Acute myeloid leukemia (AML) is an aggressive disease with a poor prognosis. A large percentage of patients succumb to this disease, in spite of aggressive treatments with chemotherapy. Recent advances with mutational analysis led to the discovery of isocitrate dehydrogenase (IDH) mutations in AML. IDH2 is an enzyme that catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate; its mutated version leads to the accumulation of the oncometabolite (R)-2 hydroxyglutarate, which disrupts several cell processes and leads to a blockage in differentiation...
May 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29721072/glucocorticoids-inhibit-oncogenic-runx1-eto-in-acute-myeloid-leukemia-with-chromosome-translocation-t-8-21
#4
Lianghao Lu, Yefei Wen, Yuan Yao, Fengju Chen, Guohui Wang, Fangrui Wu, Jingyu Wu, Padmini Narayanan, Michele Redell, Qianxing Mo, Yongcheng Song
Acute myeloid leukemia (AML) is a major blood cancer with poor prognosis. New therapies are needed to target oncogene-driven leukemia stem cells, which account for relapse and resistance. Chromosome translocation t(8;21), which produces RUNX1-ETO (R-E) fusion oncoprotein, is found in ~13% AML. R-E dominance negatively inhibits global gene expression regulated by RUNX1, a master transcription factor for hematopoiesis, causing increased self-renewal and blocked cell differentiation of hematopoietic progenitor cells, and eventually leukemia initiation...
2018: Theranostics
https://www.readbyqxmd.com/read/29720733/adding-dasatinib-to-intensive-treatment-in-core-binding-factor-acute-myeloid-leukemia-results-of-the-amlsg-11-08-trial
#5
Peter Paschka, Richard F Schlenk, Daniela Weber, Axel Benner, Lars Bullinger, Michael Heuser, Verena I Gaidzik, Felicitas Thol, Mridul Agrawal, Veronica Teleanu, Michael Lübbert, Walter Fiedler, Markus Radsak, Jürgen Krauter, Heinz-A Horst, Richard Greil, Karin Mayer, Andrea Kündgen, Uwe Martens, Gerhard Heil, Helmut R Salih, Bernd Hertenstein, Carsten Schwänen, Gerald Wulf, Elisabeth Lange, Michael Pfreundschuh, Mark Ringhoffer, Michael Girschikofsky, Thomas Heinicke, Doris Kraemer, Gudrun Göhring, Arnold Ganser, Konstanze Döhner, Hartmut Döhner
In this phase Ib/IIa study (ClinicalTrials.gov Identifier: NCT00850382) of the German-Austrian AML Study Group (AMLSG) the multikinase inhibitor dasatinib was added to intensive induction and consolidation chemotherapy and administered as single agent for 1-year maintenance in first-line treatment of adult patients with core-binding factor (CBF) acute myeloid leukemia (AML). The primary combined end point in this study was safety and feasibility, and included the rates of early (ED) and hypoplastic (HD) deaths, pleural/pericardial effusion 3°/4° and liver toxicity 3°/4°, and the rate of refractory disease...
April 17, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29719925/prognostic-markers-in-core-binding-factor-aml-and-improved-survival-with-multiple-consolidation-cycles-of-intermediate-high-dose-cytarabine
#6
Ashvind Prabahran, Mark Tacey, Shaun Fleming, Andrew Wei, Courtney Tate, Paula Marlton, Joel Wight, Andrew Grigg, Annabel Tuckfield, Jeff Szer, David Ritchie, Lynette Chee
OBJECTIVES: Core-binding factor acute myeloid leukaemia (CBF AML) defined by t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) has a favourable prognosis, however 30-40% of patients still relapse after chemotherapy. We sought to evaluate risk factors for relapse in a de novo CBF AML cohort. PATIENTS/MATERIALS/METHODS: A retrospective review of patients from 4 Australian tertiary centres from 2001-2012, comprising 40 t(8;21) and 30 inv(16) AMLs. RESULTS: Multivariate analysis identified age (p=0...
May 2, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29705537/monitoring-of-clonal-evolution-of-double-c-kit-exon-17-mutations-by-droplet-digital-pcr-in-patients-with-core-binding-factor-acute-myeloid-leukemia
#7
Yanhong Tan, Zhuang Liu, Wenjun Wang, Guiyang Zhu, Jianli Guo, Xiuhua Chen, Chaofeng Zheng, Zhifang Xu, Jianmei Chang, Fanggang Ren, Hongwei Wang
C-KIT gene mutations result in the constitutive activation of tyrosine kinase activity, and greatly affect the pathogenesis and prognosis of core-binding factor acute myeloid leukemia (CBF-AML). C-KIT mutations are often found as single point mutations. However, the rate of double mutations has recently increased in AML patients. In this study, we detected six cases (18.8%) harboring double C-KIT exon17 mutations in 75 patients with CBF-AML. The clone composition and dynamic evolution were analyzed by sequencing and droplet digital PCR (ddPCR)...
April 22, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29704019/role-of-minimal-residual-disease-in-the-management-of-acute-myeloid-leukemia-a-case-based-discussion
#8
REVIEW
A Coltoff, J Houldsworth, A Keyzner, A S Renteria, John Mascarenhas
AML is stratified into risk-categories based on cytogenetic and molecular features that prognosticate survival and facilitate treatment algorithms, though there is still significant heterogeneity within risk groupings with regard to risk of relapse and prognosis. The ambiguity regarding prognosis is due in large part to the relatively outdated criteria used to determine response to therapy. Whereas risk assessment has evolved to adopt cytogenetic and molecular profiling, response criteria are still largely determined by bone marrow morphologic assessment and peripheral cell count recovery...
April 27, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29698793/-impact-of-an-additional-chromosome-on-the-clinical-outcomes-of-hematopoietic-stem-cell-transplantation-in-philadelphia-chromosome-positive-acute-myeloid-leukemia-in-adults
#9
Gi June Min, Hee-Je Kim, Jae-Ho Yoon, Dae-Hun Kwak, Sung-Soo Park, Young-Woo Jeon, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong Wook Lee, Woo-Sung Min
BACKGROUND: The incidence of Philadelphia chromosome (Ph) positivity in adults with acute myeloid leukemia (AML) is very low. Ph-positive AML is considered to high-risk for failure to attain remission or for early relapse after standard chemotherapy. Because of the low incidence of the disease, it has been difficult to determine the best treatment including the effects of tyrosine kinase inhibitors. METHODS: We retrospectively analyzed 29 patients with Ph-positive AML (median age 45 years; range 18 - 80) managed at our center between 2002 and 2016...
April 23, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29690909/targeting-chemotherapy-resistant-leukemia-by-combining-dnt-cellular-therapy-with-conventional-chemotherapy
#10
Branson Chen, Jong Bok Lee, Hyeonjeong Kang, Mark D Minden, Li Zhang
BACKGROUND: While conventional chemotherapy is effective at eliminating the bulk of leukemic cells, chemotherapy resistance in acute myeloid leukemia (AML) is a prevalent problem that hinders conventional therapies and contributes to disease relapse, and ultimately patient death. We have recently shown that allogeneic double negative T cells (DNTs) are able to target the majority of primary AML blasts in vitro and in patient-derived xenograft models. However, some primary AML blast samples are resistant to DNT cell therapy...
April 24, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29685952/hypomethylating-agents-in-relapsed-and-refractory-aml-outcomes-and-their-predictors-in-a-large-international-patient-cohort
#11
Maximilian Stahl, Michelle DeVeaux, Pau Montesinos, Raphael Itzykson, Ellen K Ritchie, Mikkael A Sekeres, John D Barnard, Nikolai A Podoltsev, Andrew M Brunner, Rami S Komrokji, Vijaya R Bhatt, Aref Al-Kali, Thomas Cluzeau, Valeria Santini, Amir T Fathi, Gail J Roboz, Pierre Fenaux, Mark R Litzow, Sarah Perreault, Tae Kon Kim, Thomas Prebet, Norbert Vey, Vivek Verma, Ulrich Germing, Juan Miguel Bergua, Josefina Serrano, Steven D Gore, Amer M Zeidan
Although hypomethylating agents (HMAs) are frequently used in the frontline treatment of older acute myeloid leukemia (AML) patients, little is known about their effectiveness in relapsed or primary treatment-refractory (RR)-AML. Using an international multicenter retrospective database, we studied the effectiveness of HMAs in RR-AML and evaluated for predictors of response and overall survival (OS). A total of 655 patients from 12 centers received azacitidine (57%) or decitabine (43%), including 290 refractory (44%) and 365 relapsed (56%) patients...
April 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/29682375/myeloid-sarcoma-after-allogenic-stem-cell-transplantation-for-acute-myeloid-leukemia-successful-consolidation-treatment-approaches-in-two-patients
#12
Silje Johansen, Hilde Kollsete Gjelberg, Aymen Bushra Ahmed, Øystein Bruserud, Håkon Reikvam
Myeloid sarcoma is an extramedullary (EM) manifestation (i.e., manifestation outside the bone marrow) of acute myeloid leukemia (AML); it is assumed to be relatively uncommon and can be the only manifestation of leukemia relapse after allogenic stem cell transplantation (allo-SCT). An EM sarcoma can manifest in any part of the body, although preferentially manifesting in immunological sanctuary sites as a single or multiple tumors. The development of myeloid sarcoma after allo-SCT is associated with certain cytogenetic abnormalities, developing of graft versus host disease (GVHD), and treatment with donor lymphocytes infusion (DLI)...
2018: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/29682194/a-novel-dual-pan-pim-flt3-inhibitor-sel24-exhibits-broad-therapeutic-potential-in-acute-myeloid-leukemia
#13
Wojciech Czardybon, Renata Windak, Aniela Gołas, Michał Gałęzowski, Aleksandra Sabiniarz, Izabela Dolata, Magdalena Salwińska, Paweł Guzik, Magdalena Zawadzka, Ewelina Gabor-Worwa, Bożena Winnik, Małgorzata Żurawska, Ewa Kolasińska, Ewelina Wincza, Marta Bugaj, Monika Danielewicz, Eliza Majewska, Milena Mazan, Grzegorz Dubin, Monika Noyszewska-Kania, Ewa Jabłońska, Maciej Szydłowski, Tomasz Sewastianik, Bartosz Puła, Anna Szumera-Ciećkiewicz, Monika Prochorec-Sobieszek, Elżbieta Mądro, Ewa Lech-Marańda, Krzysztof Warzocha, Jerome Tamburini, Przemysław Juszczyński, Krzysztof Brzózka
Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is one of the most common genetic lesions in acute myeloid leukemia patients (AML). Although FLT3 tyrosine kinase inhibitors initially exhibit clinical activity, resistance to treatment inevitably occurs within months. PIM kinases are thought to be major drivers of the resistance phenotype and their inhibition in relapsed samples restores cell sensitivity to FLT3 inhibitors. Thus, simultaneous PIM and FLT3 inhibition represents a promising strategy in AML therapy...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29680875/salvage-regimens-using-conventional-chemotherapy-agents-for-relapsed-refractory-adult-aml-patients-a-systematic-literature-review
#14
REVIEW
Juan Eduardo Megías-Vericat, David Martínez-Cuadrón, Miguel Ángel Sanz, Pau Montesinos
Prognosis in relapsed and refractory acute myeloid leukemia (R/R AML) patients is dismal, with no satisfactory and standard salvage chemotherapy regimen. We performed a systematic review in order to analyze the clinical outcomes reported with conventional chemotherapy schemes in adult patients with R/R AML. To have a better understanding of the R/R ground, we included studies in R/R AML adult population at any disease stage (i.e., primary refractory as well as first relapse or beyond). Study selection included a total number of 157 out of 850 records, with a wide variety of schedules...
April 21, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29670208/allohsct-for-inv-3-q21-q26-t-3-3-q21-q26-aml-a-report-from-the-acute-leukemia-working-party-of-the-european-society-for-blood-and-marrow-transplantation
#15
Kazimierz Halaburda, Myriam Labopin, Mohamed Houhou, Dietger Niederwieser, Jürgen Finke, Liisa Volin, Johan Maertens, Jan J Cornelissen, Noel Milpied, Gernot Stuhler, Nicolaus Kröger, Jordi Esteve, Mohamad Mohty, Arnon Nagler
Acute myeloid leukemia with inv(3)(q21;q26.2)/t(3;3)(q21;q26.2) (3q26 AML) is a rare disease with poor prognosis and median survival of <1 year. To evaluate allogeneic stem cell transplantation (alloHSCT) in the treatment of 3q26 AML, we studied 98 patients reported to the European Society for Blood and Marrow Transplantation between 1995 and 2013. Majority of patients were transplanted using peripheral blood, from unrelated donors and after myeloablative conditioning. Fifty-three patients were transplanted with active disease and 45 in complete remission...
April 18, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29669568/social-preferences-for-health-states-associated-with-acute-myeloid-leukemia-for-patients-undergoing-treatment-in-the-united-kingdom
#16
Nacho Castejón, Joseph C Cappelleri, Jesús Cuervo, Kathryn Lang, Priyanka Mehta, Ruth Mokgokong, Carla Mamolo
BACKGROUND: Health state (HS) utility values for patients with acute myeloid leukemia (AML), a hematological malignancy, are not available in the United Kingdom (UK). This study aims to develop clinically sound HSs for previously untreated patients with AML and to assign utility values based on preferences of the general UK population. METHODS: This study was conducted in the UK and comprised 2 stages. During the first stage, AML HSs were drafted based on evidence from a literature review of AML clinical and health-related quality-of-life studies (published January 2000-June 2016) and patient-reported outcome measures previously used in this population...
April 18, 2018: Health and Quality of Life Outcomes
https://www.readbyqxmd.com/read/29668549/epigenetic-therapy-in-a-patient-with-down-syndrome-and-refractory-acute-myeloid-leukemia
#17
Kerri Becktell, Kerri Houser, Michael J Burke
Acute myeloid leukemia (AML) associated with Down syndrome (DS-AML) is a unique entity of AML with superior treatment response and overall survival compared with children with non-DS-AML. Despite good outcomes in DS-AML, those who relapse or have refractory disease have poor survival. Successful treatment of these patients is challenged by increased incidence of treatment-related toxicities often encountered with high-dose chemotherapy. Here we report the experience of epigenetic modifying agents (decitabine and vorinostat) followed by fludarabine, cytarabine, and granulocyte colony stimulating growth factor for a child with refractory DS-AML...
April 17, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29661755/a-cd123-targeting-antibody-drug-conjugate-imgn632-designed-to-eradicate-aml-while-sparing-normal-bone-marrow-cells
#18
Yelena Kovtun, Gregory E Jones, Sharlene Adams, Lauren Harvey, Charlene A Audette, Alan Wilhelm, Chen Bai, Lingyun Rui, Rassol Laleau, Fenghua Liu, Olga Ab, Yulius Setiady, Nicholas C Yoder, Victor S Goldmacher, Ravi V J Chari, Jan Pinkas, Thomas Chittenden
The outlook for patients with refractory/relapsed acute myeloid leukemia (AML) remains poor, with conventional chemotherapeutic treatments often associated with unacceptable toxicities, including severe infections due to profound myelosuppression. Thus there exists an urgent need for more effective agents to treat AML that confer high therapeutic indices and favorable tolerability profiles. Because of its high expression on leukemic blast and stem cells compared with normal hematopoietic stem cells and progenitors, CD123 has emerged as a rational candidate for molecularly targeted therapeutic approaches in this disease...
April 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/29661208/unmanipulated-haploidentical-in-comparison-with-matched-unrelated-donor-stem-cell-transplantation-in-patients-60-years-and-older-with-acute-myeloid-leukemia-a-comparative-study-on-behalf-of-the-alwp-of-the-ebmt
#19
Nicole Santoro, Myriam Labopin, Federica Giannotti, Gerard Ehninger, Dietger Niederwieser, Arne Brecht, Matthias Stelljes, Nicolaus Kröger, Herman Einsele, Matthias Eder, Michael Hallek, Bertram Glass, Jürgen Finke, Fabio Ciceri, Mohamad Mohty, Annalisa Ruggeri, Arnon Nagler
BACKGROUND: Acute myeloid leukemia (AML) is both more common and with more biologically aggressive phenotype in the elderly. Allogenic stem cell transplantation (allo-SCT) is the best treatment option in fit patients. Either HLA-matched unrelated donor (MUD) or haploidentical (Haplo) donor are possible alternative for patients in need. METHODS: We retrospectively compared non-T-cell-depleted Haplo (n = 250) to 10/10 MUD (n = 2589) in AML patients ≥ 60 years...
April 16, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29650683/fda-approval-summary-mylotarg-for-treatment-of-patients-with-relapsed-or-refractory-cd33-positive-acute-myeloid-leukemia
#20
Kelly J Norsworthy, Chia-Wen Ko, Jee Eun Lee, Jiang Liu, Christy S John, Donna Przepiorka, Ann T Farrell, Richard Pazdur
On September 2, 2017, the U.S. Food and Drug Administration approved gemtuzumab ozogamicin (GO; Mylotarg; Pfizer, New York City, NY) for treatment of relapsed or refractory (R/R) CD33-positive acute myeloid leukemia (AML) in patients 2 years of age and older. GO is a CD33-directed antibody drug conjugate linked to the cytotoxic antibiotic calicheamicin. It originally received accelerated approval for treatment of older patients with relapsed CD33-positive AML in 2000, but it was withdrawn from the market in 2010 when the confirmatory trial failed to demonstrate clinical benefit among safety concerns, such as a higher rate of induction fatalities on the GO combination arm compared with chemotherapy alone...
April 12, 2018: Oncologist
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