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Relapsed acute myeloid leukemia

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https://www.readbyqxmd.com/read/28632487/prospective-randomized-comparison-of-idarubicin-and-high-dose-daunorubicin-in-induction-chemotherapy-for-newly-diagnosed-acute-myeloid-leukemia
#1
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/28625976/a-genome-wide-crispr-screen-identifies-genes-critical-for-resistance-to-flt3-inhibitor-ac220
#2
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
#3
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
#4
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/28618016/abcg2-and-cd200-define-patients-at-high-risk-of-relapse-in-enl-favorable-subgroup-of-aml
#5
Mario Tiribelli, Antonella Geromin, Margherita Cavallin, Sara Di Giusto, Erica Simeone, Renato Fanin, Daniela Damiani
OBJECTIVE: overexpression of ABCG2 and CD200 have been independently associated with poor outcome in acute myeloid leukemia (AML). However, no data are available on the role of these two factors in patients with core binding factor (CBF) positive or FLT3-negative / NPM1-mutated cytogenetically normal (CN) AML. METHODS: we analyzed 65 adult AML patients with CBF+ (n=16) or FLT3-/NPM1+ CN (n=49), evaluating clinical and biological factors associated with complete remission attainment, leukemia-free survival (LFS) and overall survival (OS)...
June 15, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28617445/acquired-cross-linker-resistance-associated-with-a-novel-spliced-brca2-protein-variant-for-molecular-phenotyping-of-brca2-disruption
#6
Stefan Meyer, Adam Stevens, Roberto Paredes, Marion Schneider, Michael J Walker, Andrew J K Williamson, Maria-Belen Gonzalez-Sanchez, Stephanie Smetsers, Vineet Dalal, Hsiang Ying Teng, Daniel J White, Sam Taylor, Joanne Muter, Andrew Pierce, Chiara de Leonibus, Davy A P Rockx, Martin A Rooimans, Elaine Spooncer, Stacey Stauffer, Kajal Biswas, Barbara Godthelp, Josephine Dorsman, Peter E Clayton, Shyam K Sharan, Anthony D Whetton
BRCA2 encodes a protein with a fundamental role in homologous recombination that is essential for normal development. Carrier status of mutations in BRCA2 is associated with familial breast and ovarian cancer, while bi-allelic BRCA2 mutations can cause Fanconi anemia (FA), a cancer predisposition syndrome with cellular cross-linker hypersensitivity. Cancers associated with BRCA2 mutations can acquire chemo-resistance on relapse. We modeled acquired cross-linker resistance with an FA-derived BRCA2-mutated acute myeloid leukemia (AML) platform...
June 15, 2017: Cell Death & Disease
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/28612220/individual-outcome-prediction-for-myelodysplastic-syndrome-mds-and-secondary-acute-myeloid-leukemia-from-mds-after-allogeneic-hematopoietic-cell-transplantation
#8
Michael Heuser, Razif Gabdoulline, Patrick Löffeld, Vera Dobbernack, Henriette Kreimeyer, Mira Pankratz, Madita Flintrop, Alessandro Liebich, Sabrina Klesse, Victoria Panagiota, Michael Stadler, Martin Wichmann, Rabia Shahswar, Uwe Platzbecker, Christian Thiede, Thomas Schroeder, Guido Kobbe, Robert Geffers, Brigitte Schlegelberger, Gudrun Göhring, Hans-Heinrich Kreipe, Ulrich Germing, Arnold Ganser, Nicolaus Kröger, Christian Koenecke, Felicitas Thol
We integrated molecular data with available prognostic factors in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) for myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia (sAML) from MDS to evaluate their impact on prognosis. Three hundred four patients were sequenced for mutations in 54 genes. We used a Cox multivariate model and competing risk analysis with internal and cross validation to identify factors prognostic of overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM)...
June 13, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28611767/natural-killer-defective-maturation-is-associated-with-adverse-clinical-outcome-in-patients-with-acute-myeloid-leukemia
#9
Anne-Sophie Chretien, Cyril Fauriat, Florence Orlanducci, Claire Galseran, Jerome Rey, Gaelle Bouvier Borg, Emmanuel Gautherot, Samuel Granjeaud, Jean-François Hamel-Broza, Clemence Demerle, Norbert Ifrah, Catherine Lacombe, Pascale Cornillet-Lefebvre, Jacques Delaunay, Antoine Toubert, Emilie Gregori, Herve Luche, Marie Malissen, Christine Arnoulet, Jacques A Nunes, Norbert Vey, Daniel Olive
Accumulating evidence highlights natural killer (NK) cell parameters as potential prognostic factors in cancer patients, which provides a strong rationale for developing therapeutic strategies aiming at restoring NK cell. However, reaching this point warrants better characterization of tumor-induced NK cell alterations. Our group recently reported heterogeneous NK maturation in acute myeloid leukemia (AML) patients. However, the clinical significance of such observations remained to be assessed on a larger cohort of patients...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28603070/clinical-utility-of-quantitative-pcr-for-chimerism-and-engraftment-monitoring-after-allogeneic-stem-cell-transplantation-for-hematologic-malignancies
#10
Müberra Ahci, Karin Stempelmann, Ulrike Buttkereit, Pietro Crivello, Mirko Trilling, Andreas Heinold, Nina Kristin Steckel, Michael Koldehoff, Peter A Horn, Dietrich W Beelen, Katharina Fleischhauer
Although quantitative PCR (qPCR) has been explored for chimerism monitoring after allogeneic stem cell transplantation (SCT), evidence regarding its clinical utility compared to standard short tandem repeat (STR) is still limited. We retrospectively studied commercial qPCR and STR chimerism with respective positivity thresholds of 0.1% and 1%, in 359 peripheral blood (PB) and 95 bone marrow (BM) samples from 30 adult patients after first HLA-matched SCT for myeloid malignancies or acute lymphatic leukemia. Concordance between the two methods was 79...
June 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28600031/hematopoietic-cell-transplantation-in-myelodysplastic-syndromes-after-treatment-with-hypomethylating-agents
#11
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/28598536/characteristics-and-outcome-in-patients-with-central-nervous-system-involvement-treated-in-european-pediatric-acute-myeloid-leukemia-study-groups
#12
Ursula Creutzig, Michael N Dworzak, Martin Zimmermann, Dirk Reinhardt, Lucie Sramkova, Jan Pierre Bourquin, Henrik Hasle, Jonas Abrahamsson, Gertjan Kaspers, Mary M van den Heuvel, Ardine M J Reedijk, Barbara De Moerloose, Franco Locatelli, Riccardo Masetti
BACKGROUND: There is no consensus on the treatment for pediatric patients with acute myeloid leukemia and initial central nervous system (CNS) involvement. METHODS: To evaluate different CNS-directed treatment options (intrathecal [IT] therapy, CNS irradiation, hematopoietic stem cell transplantation [HSCT]), 261 patients (excluding acute promyelocytic leukemia) with initial CNS involvement treated in trials with similar intensive chemotherapy by four cooperative European study groups (1998-2013) were studied and compared with CNS-negative patients from the Berlin-Frankfurt-Münster group...
June 9, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28592126/autologous-hematopoietic-stem-cell-transplantation-for-acute-myeloid-leukemia-single-center-experience
#13
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
#14
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
#15
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
#16
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
#17
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/28584756/disseminated-cutaneous-trichosporonosis-in-an-adult-bone-marrow-transplant-patient
#18
A M Y Yong, S S Yang, K B Tan, S A Ho
The Trichosporon species are yeast-like opportunistic pathogens in immunocompromised patients. Trichosporon asahii infections have been reported in pediatric bone marrow transplant (BMT) patients. However, its incidence is low in the adult literature. A 52-year-old Chinese woman who was diagnosed with acute myeloid leukemia received induction chemotherapy and underwent allogenic bone marrow transplant, which was complicated by a relapse and required salvage chemotherapy. She developed persistent non-neutropenic fever secondary to presumed hepatosplenic candidiasis...
May 2017: Indian Dermatology Online Journal
https://www.readbyqxmd.com/read/28584213/e-26-transformation-specific-related-gene-expression-and-outcomes-in-cytogenetically-normal-acute-myeloid-leukemia-a-meta-analysis
#19
Jian-Fei Fang, Hai-Ning Yuan, Yong-Fei Song, Pei-Bei Sun, Xiao-Liang Zheng, Xiao-Ju Wang
BACKGROUND: The E-26 transformation-specific related gene (ERG) is frequently expressed in cytogenetically normal acute myeloid leukemia (CN-AML). Herein, we performed a meta-analysis to investigate the relationship between the prognostic significance of ERG expression and CN-AML. METHODS: A systematic review of PubMed database and other search engines were used to identify the studies between January 2005 and November 2016. A total of 667 CN-AML patients were collected from seven published studies...
June 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28576946/flt3-inhibitors-in-acute-myeloid-leukemia-current-status-and-future-directions
#20
REVIEW
Maria Larrosa-Garcia, Maria R Baer
The receptor tyrosine kinase fms-like tyrosine kinase 3 (FLT3), involved in regulating survival, proliferation, and differentiation of hematopoietic stem/progenitor cells, is expressed on acute myeloid leukemia (AML) cells in most patients. Mutations of FLT3 resulting in constitutive signaling are common in AML, including internal tandem duplication (ITD) in the juxtamembrane domain in 25% of patients and point mutations in the tyrosine kinase domain in 5%. Patients with AML with FLT3-ITD have a high relapse rate and short relapse-free and overall survival after chemotherapy and after transplant...
June 2017: Molecular Cancer Therapeutics
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