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acute refractory myeloid leukemia

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https://www.readbyqxmd.com/read/29787320/gemtuzumab-ozogamicin-for-the-treatment-of-acute-myeloid-leukemia
#1
Jeffrey Baron, Eunice S Wang
Gemtuzumab ozogamicin (GO) is an antibody-drug conjugate consisting of a monoclonal antibody targeting CD33 linked to a cytotoxic derivative of calicheamicin. Despite the known clinical efficacy in relapsed/refractory acute myeloid leukemia (AML), GO was withdrawn from the market in 2010 due to increased early deaths seen in newly diagnosed AML patients receiving GO + intensive chemotherapy. In 2017, new data on the clinical efficacy and safety of GO administered on a fractionated dosing schedule led to re-approval for newly diagnosed and relapsed/refractory AML...
May 22, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29785506/venetoclax-and-low-dose-cytarabine-induced-complete-remission-in-a-patient-with-high-risk-acute-myeloid-leukemia-a-case-report
#2
Bingshan Liu, Roshni Narurkar, Madhura Hanmantgad, Wahib Zafar, Yongping Song, Delong Liu
Conventional combination therapies have not resulted in considerable progress in the treatment of acute myeloid leukemia (AML). Elderly patients with AML and poor risk factors have grave prognosis. Midostaurin has been recently approved for the treatment of FLT-3-mutated AML. Venetoclax, a BCL-2 inhibitor, has been approved for the treatment of relapsed and/or refractory chronic lymphoid leukemia. Clinical trials on applying venetoclax in combination with cytarabine and other agents to treat various hematological malignancies are currently underway...
May 21, 2018: Frontiers of Medicine
https://www.readbyqxmd.com/read/29773602/clofarabine-high-dose-cytarabine-and-liposomal-daunorubicin-in-pediatric-relapsed-refractory-acute-myeloid-leukemia-a-phase-ib-study
#3
Natasha K A van Eijkelenburg, Mareike Rasche, Essam Ghazaly, Michael N Dworzak, Thomas Klingebiel, Claudia Rossig, Guy Leverger, Jan Stary, Eveline S J M de Bont, Dana A Chitu, Yves Bertrand, Benoit Brethon, Brigitte Strahm, Inge M van der Sluis, Gertjan J L Kaspers, Dirk Reinhardt, C Michel Zwaan
Survival in children with relapsed/refractory acute myeloid leukemia is unsatisfactory. Treatment consists of one course fludarabine, cytarabine and liposomal daunorubicin, followed by fludarabine and cytarabine and stem-cell transplantation. Study ITCC 020/I-BFM 2009-02 aimed to identify the recommended phase 2 dose of clofarabine replacing fludarabine in the abovementioned combination regimen (3+3 design). Escalating dose-levels of clofarabine (20-40mg/m2/day x5days) and liposomal daunorubicin (40-0mg/m2/day) were administered with cytarabine (2g/m2/day x5days)...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773601/combinatorial-targeting-of-xpo1-and-flt3-exerts-synergistic-anti-leukemia-effects-through-induction-of-differentiation-and-apoptosis-in-flt3-mutated-acute-myeloid-leukemias-from-concept-to-clinical-trial
#4
Weiguo Zhang, Charlie Ly, Jo Ishizawa, Hong Mu, Vivian Ruvolo, Sharon Shacham, Naval Daver, Michael Andreeff
Targeted therapies against FLT3-mutated acute myeloid leukemia have shown limited clinical efficacy primarily because of the acquisition of secondary mutations in FLT3 and persistent activation of downstream pro-survival pathways such as MEK/ERK, PI3K/AKT, and STAT5. Activation of these additional kinases may also result in phosphorylation of tumor suppressor proteins promoting their nuclear export. Thus, co-targeting nuclear export proteins (i.e., XPO1) and FLT3 concomitantly may be therapeutically effective...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773429/real-life-experience-with-ponatinib-in-chronic-myeloid-leukemia-a-multicenter-observational-study
#5
Adi Shacham-Abulafia, Pia Raanani, David Lavie, Yulia Volchek, Ron Ram, Ilana Helman, Liat Shargian, Anna Gourevitch, Evgeni Chubar, Roy Ratzon, Uri Rozovski
BACKGROUND: The strict recruitment criteria of patients for clinical trials often lead to reduced generalizability of the findings. We studied how ponatinib is used outside clinical trials in patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: The present retrospective study included all patients with a diagnosis of CML who had received ponatinib in 7 medical centers in Israel. RESULTS: From 2011 to 2016, we identified 37 patients with CML who had received ponatinib, 21 in the chronic phase and 16 in the advanced phase...
May 7, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29770715/enasidenib-for-the-treatment-of-acute-myeloid-leukemia
#6
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
#7
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/29752743/therapy-related-acute-myeloid-leukemia-and-myelodysplastic-syndrome-among-refractory-germ-cell-tumor-patients
#8
Yuta Inoue, Terukazu Nakamura, Hiroyuki Nakanishi, Masakatsu Oishi, Fumiya Hongo, Koji Okihara, Shinsuke Mizutani, Junya Kuroda, Osamu Ukimura
OBJECTIVES: To analyze cases of therapy-related acute myeloid leukemia and myelodysplastic syndrome diagnosed after chemotherapy for refractory testicular and extragonadal germ cell tumor in our experience. METHODS: A total of 171 consecutive patients who were diagnosed and treated as refractory germ cell tumor and had records of detailed chemotherapy doses between April 1998 and December 2015 were retrospectively reviewed. RESULTS: Four testicular tumor patients (4/171, 2...
May 11, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/29721667/the-influence-of-mutational-status-and-biological-characteristics-of-acute-myeloid-leukemia-on-xenotransplantation-outcomes-in-nod-scid-gamma-mice
#9
Martin Culen, Zdenka Kosarova, Ivana Jeziskova, Adam Folta, Jana Chovancova, Tomas Loja, Nikola Tom, Vojtech Bystry, Veronika Janeckova, Dana Dvorakova, Jiri Mayer, Zdenek Racil
PURPOSE: This study aimed at analyzing the association of gene mutations and other acute myeloid leukemia (AML) characteristics with engraftment outcomes in immunodeficient mice and to select the engraftment outcomes that best reflect patient survival. METHODS: Mutations in 19 genes as well as leukemia- and patient-related characteristics were analyzed for a group of 47 de novo AML samples with respect to three engraftment outcomes: engraftment ability, engraftment intensity (percentage of hCD45+ cells) and engraftment latency...
May 2, 2018: Journal of Cancer Research and Clinical Oncology
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
#10
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/29703727/nkg2d-based-chimeric-antigen-receptor-therapy-induced-remission-in-a-relapsed-refractory-acute-myeloid-leukemia-patient
#11
David A Sallman, Jason Brayer, Elizabeth M Sagatys, Caroline Lonez, Eytan Breman, Sophie Agaugué, Bikash Verma, David E Gilham, Frédéric F Lehmann, Marco L Davila
No abstract text is available yet for this article.
April 27, 2018: Haematologica
https://www.readbyqxmd.com/read/29702970/a-new-intensive-conditioning-regimen-for-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-refractory-or-relapsed-acute-myeloid-leukemia
#12
Jingbo Wang, Jie Zhao, Xinhong Fei, Yuming Yin, Haoyu Cheng, Weijie Zhang, Jiangying Gu, Fan Yang, Yixin Yang, Song Xue, Zhengqin Tian, Junbao He, Shuqin Zhang, Xiaocan Wang
To explore the efficacy, and safety of the intensive conditioning regimen consisting of cladribine, cytarabine (Ara-C), and granulocyte colony-stimulating factor (G-CSF) plus modified busulfan (Bu) combined with cytoxan (Cy) (BuCy), prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with refractory, or relapsed acute myeloid leukemia (R/R AML).Thirty-Six R/R AML patients scheduled to receive allo-HSCT were consecutively, enrolled in this prospective study, and treated using intensive conditioning regimen consisting of CLAG plus modified BuCy...
April 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29685952/hypomethylating-agents-in-relapsed-and-refractory-aml-outcomes-and-their-predictors-in-a-large-international-patient-cohort
#13
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/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/29669568/social-preferences-for-health-states-associated-with-acute-myeloid-leukemia-for-patients-undergoing-treatment-in-the-united-kingdom
#15
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
#16
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/29665944/-current-status-and-challenges-of-car-t-immunotherapy-in-hematologic-malignancies-review
#17
Xin Cheng, Ya-Jie Wang, Shuai Feng, Ya-Yun Wu, Tong-Hua Yang, Xun Lai
The chimeric antigen receptor (CAR) T cell therapy has gradually became a new trend in the treatment of refractory and relapsed hematologic malignancies by developing for 30 years. With the exciting development of genetic engineering, CAR-T technology has subjected to 4 generations of innovation. Structure of CAR-T started from a single signal molecule to 2 or more than 2 co-stimulatory molecules, and then coding the CAR gene or promoter. CAR-T can specifically recognize tumor antigens, and does not be restricted by major histocompatibility complex (MHC), thus making a breakthrough in clinical treatment...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665938/-research-and-applications-progress-of-lenalidomide-in-relapsed-refractory-blood-system-diseases-review
#18
Wen-Jing Fan, Zhi-Qiao Fan, Tao Wu, Hai Bai
Lenalidomide, a novel immunomodulatory agent, is a kind of thalidomide derivatives, which shows a good efficacy and safety for hematological system diseases. This review is aimed to evaluate the efficacy and safety of lenalidomide in treatment of patients with multiple myeloma, chronic lymphocytic leukemia, acute myeloid leukemia, non-Hodgkin's lymphoma, classical Hodgkin's lymphoma and POEMS syndrome at their replased or refractory state. At the same time, this review focuses on the newest clinical research and the latest application progress of lenalidomide for relapsed or refractory hematological system diseases...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29661880/refractory-hypokalemia-from-syndrome-of-apparent-mineralocorticoid-excess-on-low-dose-posaconazole
#19
Travis Wassermann, Eleanor K Reimer, Marie McKinnon, Wendy Stock
A 67-year-old woman with acute myeloid leukemia experienced refractory hypokalemia while taking low-dose posaconazole.….
April 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29661755/a-cd123-targeting-antibody-drug-conjugate-imgn632-designed-to-eradicate-aml-while-sparing-normal-bone-marrow-cells
#20
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
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