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Relapsed acute myeloid leukemia

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https://www.readbyqxmd.com/read/29232178/rapid-decrease-in-krt14-and-tp53-mrna-expression-in-the-buccal-mucosa-of-patients-receiving-total-body-irradiation-for-allogeneic-stem-cell-transplantation
#1
J Chmara, J W L Browning, H Atkins, M Sabloff, B C McKay
The only curative treatment option for relapsed patients with acute myeloid leukemia (AML) is allogeneic stem cell transplantation. Depletion of hematopoietic stem cells and leukemic blast cells is achieved through the systemic administration of DNA damaging agents, including total-body irradiation (TBI) prior to transplantation. Since other tissues are radiosensitive, the identification of biomarkers could facilitate the management of additional toxicities. Buccal keratinocytes are readily accessible and could provide a source of cells for RNA analysis...
December 12, 2017: Radiation Research
https://www.readbyqxmd.com/read/29226854/diagnostic-and-prognostic-relevance-of-serum-mir-195-in-pediatric-acute-myeloid-leukemia
#2
Ze Hong, Rongrong Zhang, Haixiao Qi
BACKGROUND: MicroRNA-195 acts as a tumor suppressor in a variety of cancers. However, its clinical significance in pediatric acute myeloid leukemia (AML) remains largely undefined. OBJECTIVE: To investigate the diagnostic and prognostic relevance of miR-195 in this malignancy. METHODS: Expression levels of miR-195 in peripheral blood and bone marrow samples of patients with pediatric AML and normal controls were detected by real-time quantitative PCR...
November 27, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29226497/similar-outcome-of-allogeneic-stem-cell-transplantation-after-myeloablative-and-sequential-conditioning-regimen-in-patients-with-refractory-or-relapsed-acute-myeloid-leukemia-a-study-from-the-soci%C3%A3-t%C3%A3-francophone-de-greffe-de-moelle-et-de-th%C3%A3-rapie-cellulaire
#3
Justine Decroocq, Raphaël Itzykson, Stéphane Vigouroux, Mauricette Michallet, Ibrahim Yakoub-Agha, Anne Huynh, Florence Beckerich, Felipe Suarez, Patrice Chevallier, Stéphanie Nguyen-Quoc, Marie-Pierre Ledoux, Laurence Clement, Yosr Hicheri, Gaëlle Guillerm, Jérôme Cornillon, Nathalie Contentin, Martin Carre, Natacha Maillard, Mélanie Mercier, Mohamad Mohty, Yves Beguin, Jean-Henri Bourhis, Amandine Charbonnier, Charles Dauriac, Jacques-Olivier Bay, Didier Blaise, Eric Deconinck, Charlotte Jubert, Nicole Raus, Regis Peffault de Latour, Nathalie Dhedin
Patients with acute myeloid leukemia (AML) in relapse or refractory to induction therapy have a dismal prognosis. Allogeneic hematopoietic stem cell transplantation is the only curative option. In these patients, we aimed to compare the results of a myeloablative transplant versus a sequential approach consisting in a cytoreductive chemotherapy followed by a reduced intensity conditioning regimen and prophylactic donor lymphocytes infusions. We retrospectively analyzed 99 patients aged 18-50 years, transplanted for a refractory (52%) or a relapsed AML not in remission (48%)...
December 11, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29222236/how-and-when-to-decide-between-epigenetic-therapy-and-chemotherapy-in-patients-with-aml
#4
REVIEW
Hervé Dombret, Raphael Itzykson
Remission induction with chemotherapy has long been the frontline treatment of acute myeloid leukemia (AML). However, intensive therapy is limited in frail patients by its associated toxicity and higher rates of failure or relapse in patients with chemoresistant disease, such as secondary AML or poor-risk cytogenetics. Frailty and chemoresistance are more frequent in older adults with AML. In recent years, epigenetic therapies with the hypomethylating agents decitabine and azacitidine have been thoroughly explored in AML...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29219176/tet2-expression-is-a-potential-prognostic-and-predictive-biomarker-in-cytogenetically-normal-acute-myeloid-leukemia
#5
Ting-Juan Zhang, Jing-Dong Zhou, Dong-Qin Yang, Yu-Xin Wang, Xiang-Mei Wen, Hong Guo, Lei Yang, Xin-Yue Lian, Jiang Lin, Jun Qian
TET2 (Ten-Eleven Translocation 2) gene is a member of TET family that can modify DNA through catalyzing the conversion of 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC). Although TET2 mutation has been disclosed in a variety of hematopoietic malignancies, the prognostic implication of TET2 expression in acute myeloid leukemia (AML) remains largely elusive. In this study, real-time quantitative PCR was carried out to detect the level of TET2 transcript in 134 de novo AML patients and 35 healthy donors...
December 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29218851/clinical-experience-with-the-bcl2-inhibitor-venetoclax-in-combination-therapy-for-relapsed-and-refractory-acute-myeloid-leukemia-and-related-myeloid-malignancies
#6
Courtney D DiNardo, Caitlin R Rausch, Christopher Benton, Tapan Kadia, Nitin Jain, Naveen Pemmaraju, Naval Daver, Wendy Covert, Kayleigh R Marx, Morgan Mace, Elias Jabbour, Jorge Cortes, Guillermo Garcia-Manero, Farhad Ravandi, Kapil N Bhalla, Hagop Kantarjian, Marina Konopleva
INTRODUCTION: Venetoclax (VEN), a selective BCL2 inhibitor, has single-agent activity in relapsed and refractory (R/R) acute myeloid leukemia (AML) and efficacy in lower-intensity combinations for treatment-naïve elderly AML patients. VEN treatment combinations in R/R AML have not been previously reported. METHODS: All R/R myeloid patients (including AML, myelodysplastic syndrome (MDS), and blastic plasmacytoid dendritic cell neoplasm (BPDCN)) treated with VEN combinations in the salvage setting were reviewed...
December 8, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29214689/distinct-factors-determine-the-kinetics-of-disease-relapse-in-adults-transplanted-for-acute-myeloid-leukaemia
#7
C Craddock, J Versluis, M Labopin, G Socie, A Huynh, E Deconinck, L Volin, N Milpied, J H Bourhis, A Rambaldi, P Chevallier, D Blaise, M Manz, E Vellenga, M-C Vekemans, J Maertens, J Passweg, P Vyas, C Schmid, B Löwenberg, G Ossenkoppele, M Mohty, J J Cornelissen, A Nagler
Disease recurrence remains the major cause of death in adults with acute myeloid leukemia (AML) treated using either intensive chemotherapy (IC) or allogenic stem cell transplantation (allo-SCT). The timely delivery of maintenance drug or cellular therapies represent emerging strategies with the potential to reduce relapse after both treatment modalities, but whilst the determinants of overall relapse risk have been extensively characterized the factors determining the timing of disease recurrence have not been characterized...
December 7, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29212263/combination-of-betulinic-acid-and-chidamide-inhibits-acute-myeloid-leukemia-by-suppression-of-the-hif1%C3%AE-pathway-and-generation-of-reactive-oxygen-species
#8
Hongyu Zhang, Ling Li, Min Li, Xiaodong Huang, Weiguo Xie, Wei Xiang, Paul Yao
Acute myeloid leukemia (AML) is a heterogeneous disorder of the hematopoietic system with no common genetic "Achilles heel" that can be targeted. Most patients respond well to standard therapy, while a majority relapse, and development of an effective therapy for AML patients is still urgently needed. In this study, we demonstrated that betulinic acid (BA) significantly increased Aryl hydrocarbon receptor (AHR) expression through demethylation on the AHR promoter in AML cells, and the increased AHR expression interacts with and sequesters ARNT, subsequently suppressing hypoxia-inducible factor-1α (HIF1α) pathway...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212250/histone-deacetylase-inhibitors-reduce-differentiating-osteoblast-mediated-protection-of-acute-myeloid-leukemia-cells-from-cytarabine
#9
Rosalie M Sterner, Kimberly N Kremer, Aref Al-Kali, Mrinal M Patnaik, Naseema Gangat, Mark R Litzow, Scott H Kaufmann, Jennifer J Westendorf, Andre J van Wijnen, Karen E Hedin
The bone marrow microenvironment protects acute myeloid leukemia (AML) cells during chemotherapy and is a major factor in relapse. Here, we examined which type(s) of bone marrow cells are responsible for the relapse of AML following treatment with cytarabine (Ara-C), and we identified a means to inhibit this protection. To determine the protective cell type(s), AML cells were treated with Ara-C, and AML cell survival in the presence or absence of osteoblast lineage cells was assessed. Cultured AML cells and patient bone marrow isolates were each significantly protected from Ara-C-induced apoptosis by co-culture with differentiating osteoblasts...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29211308/dose-schedule-safety-and-efficacy-of-guadecitabine-in-relapsed-or-refractory-acute-myeloid-leukemia
#10
Gail J Roboz, Hagop M Kantarjian, Karen W L Yee, Patricia L Kropf, Casey L O'Connell, Elizabeth A Griffiths, Wendy Stock, Naval G Daver, Elias Jabbour, Ellen K Ritchie, Katherine J Walsh, David Rizzieri, Scott D Lunin, Tania Curio, Woonbok Chung, Yong Hao, James N Lowder, Mohammad Azab, Jean-Pierre J Issa
BACKGROUND: Outcomes for patients with relapsed or refractory acute myeloid leukemia (AML) are poor. Guadecitabine, a next-generation hypomethylating agent, could be useful in treating such patients. METHODS: In this multicenter, open-label, phase 2 dose-expansion study, AML patients from 10 North American medical centers were first randomized (1:1) to receive subcutaneous guadecitabine at 60 or 90 mg/m2 on 5 consecutive days in each 28-day cycle (5-day regimen)...
December 6, 2017: Cancer
https://www.readbyqxmd.com/read/29209600/targeting-flt3-signaling-in-childhood-acute-myeloid-leukemia
#11
REVIEW
Amy N Sexauer, Sarah K Tasian
Acute myeloid leukemia (AML) is the second most common leukemia of childhood and is associated with high rates of chemotherapy resistance and relapse. Clinical outcomes for children with AML treated with maximally intensive multi-agent chemotherapy lag far behind those of children with the more common acute lymphoblastic leukemia, demonstrating continued need for new therapeutic approaches to decrease relapse risk and improve long-term survival. Mutations in the FMS-like tyrosine kinase-3 receptor gene (FLT3) occur in approximately 25% of children and adults with AML and are associated with particularly poor prognoses...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/29197675/japanese-recipients-who-receive-hla-matched-hematopoietic-cell-transplantation-for-their-myeloid-leukemia-have-an-advantage-to-prevent-recurrence-if-they-have-homozygous-hla-c1
#12
Nobuyoshi Arima, Junya Kanda, Junji Tanaka, Toshio Yabe, Yasuo Morishima, Sung-Won Kim, Yuho Najima, Yukiyasu Ozawa, Tetsuya Eto, Heiwa Kanamori, Takehiko Mori, Naoki Kobayashi, Tadakazu Kondo, Hirohisa Nakamae, Naoyuki Uchida, Masami Inoue, Takahiro Fukuda, Tatsuo Ichinohe, Yoshiko Atsuta, Yoshinobu Kanda
Natural killer (NK) cells assume graft-versus-leukemia alloreactivity after hematopoietic stem-cell transplantation (HSCT) through their inhibitory killer cell immunoglobulin-like receptors (KIRs). KIR2D family members recognize human leukocyte antigen (HLA)-C alleles with Asn80 (HLA-C1) or Lys80 (HLA-C2). The predominance of HLA-C1 over HLA-C2 and a frequent KIR2DL1 possession are characteristic of Japanese people. We compared clinical outcomes among homozygous HLA-C1 (HLA-C1/C1) patients and heterozygous HLA-C1/C2 patients who underwent HLA-matched HSCT for hematological malignancies by assessing the data of 10,638 patients from the Japanese national registry...
November 29, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29196987/underweight-status-at-diagnosis-is-associated-with-poorer-outcomes-in-adult-patients-with-acute-myeloid-leukemia-a-retrospective-study-of-jalsg-aml-201
#13
Kaito Harada, Noriko Doki, Takeshi Hagino, Shuichi Miyawaki, Shigeki Ohtake, Hitoshi Kiyoi, Yasushi Miyazaki, Hiroyuki Fujita, Noriko Usui, Hirokazu Okumura, Koichi Miyamura, Chiaki Nakaseko, Atsushi Fujieda, Tadashi Nagai, Takahisa Yamane, Hisashi Sakamaki, Kazunori Ohnishi, Tomoki Naoe, Ryuzo Ohno, Kazuteru Ohashi
Recent studies have described various impacts of obesity and being overweight on acute myeloid leukemia (AML) outcomes in adult patients, but little is known about the impact of being underweight. We compared the outcomes of underweight patients to those of normal weight and overweight patients. Adult patients with AML who registered in the JALSG AML201 study (n = 1057) were classified into three groups: underweight (body mass index [BMI] < 18.5, n = 92), normal weight (BMI 18.5-25, n = 746), and overweight (BMI ≥ 25, n = 219)...
December 2, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29196412/a-phase-1-trial-of-vadastuximab-talirine-as-monotherapy-in-patients-with-cd33-positive-acute-myeloid-leukemia-aml
#14
Eytan M Stein, Roland B Walter, Harry P Erba, Amir T Fathi, Anjali S Advani, Jeffrey E Lancet, Farhad Ravandi, Tibor Kovacsovics, Daniel J DeAngelo, Dale Bixby, Stefan Faderl, Anand P Jillella, Phoenix Ho, Megan M O'Meara, Baiteng Zhao, Charles Biddle-Snead, Anthony S Stein
Vadastuximab talirine (SGN-CD33A, 33A) is an antibody-drug conjugate consisting of pyrrolobenzodiazepine dimers linked to a monoclonal antibody targeting CD33, which is expressed in the majority of acute myeloid leukemia (AML) patients. This phase 1 study (clinicaltrials.gov NCT01902329) evaluated the safety, pharmacokinetics, and preliminary activity of vadastuximab talirine and determined the recommended monotherapy dose in patients with relapsed or refractory AML. Additional expansion cohorts tested vadastuximab talirine in specific subpopulations of relapsed AML, and in a cohort of older, treatment-naïve patients...
December 1, 2017: Blood
https://www.readbyqxmd.com/read/29196178/long-term-remissions-of-patients-with-follicular-lymphoma-grade-3-treated-with-r-chop
#15
Paolo Strati, Nathan Fowler, Sergio Pina-Oviedo, L Jeffrey Medeiros, Michael J Overman, Jorge E Romaguera, Loretta Nastoupil, Michael Wang, Fredrick B Hagemeister, Alma Rodriguez, Yasuhiro Oki, Jason Westin, Francesco Turturro, Sattva S Neelapu, Luis Fayad
BACKGROUND: The optimal management of patients with follicular lymphoma Grade 3 (FLG3) is controversial. PATIENTS AND METHODS: This is a case series of 45 patients with FLG3 treated with first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and observed for an extended time interval. RESULTS: The overall response rate was 100% and the median progression-free survival (PFS) has not been reached, with a 3-year PFS of 70%; 14 (31%) patients relapsed, nearly all within 3 years...
November 14, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29192243/autonomous-feedback-loop-of-runx1-p53-cbfb-in-acute-myeloid-leukemia-cells
#16
Ken Morita, Mina Noura, Chieko Tokushige, Shintaro Maeda, Hiroki Kiyose, Gengo Kashiwazaki, Junichi Taniguchi, Toshikazu Bando, Kenichi Yoshida, Toshifumi Ozaki, Hidemasa Matsuo, Seishi Ogawa, Pu Paul Liu, Tatsutoshi Nakahata, Hiroshi Sugiyama, Souichi Adachi, Yasuhiko Kamikubo
Although runt-related transcription factor 1 (RUNX1) and its associating core binding factor-β (CBFB) play pivotal roles in leukemogenesis, and inhibition of RUNX1 has now been widely recognized as a novel strategy for anti-leukemic therapies, it has been elusive how leukemic cells could acquire the serious resistance against RUNX1-inhibition therapies and also whether CBFB could participate in this process. Here, we show evidence that p53 (TP53) and CBFB are sequentially up-regulated in response to RUNX1 depletion, and their mutual interaction causes the physiological resistance against chemotherapy for acute myeloid leukemia (AML) cells...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29191655/q482h-mutation-of-procaspase-8-in-acute-myeloid-leukemia-abolishes-caspase-8-mediated-apoptosis-by-impairing-procaspase-8-dimerization
#17
Ming Li, Jianfeng Yao, Xiangxi Zhang, Xuan Chen, Juan Chen, Yingying Guan, Xiaoyu Yang
INTRODUCTION: Certain procaspase-8 mutations are reported to be associated with the progression and prognosis of multiple tumors. However, it remains unclear whether the poor chemotherapy response and frequent relapse after complete remission of patients with acute myeloid leukemia (AML) is also related to procaspase-8 abnormalities. METHODS: Polymerase chain reaction (PCR) amplification and Sanger sequencing of the procaspase-8 gene (CASP8) were performed. Apoptotic rates were analyzed with Annexin V-FITC staining in cells expressing wild-type (WT) procaspase-8, the Q482H or C360S mutant, or control vector after treatment with or without tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)...
November 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29190891/high-bone-marrow-id2-expression-predicts-poor-chemotherapy-response-and-prognosis-in-acute-myeloid-leukemia
#18
Jing-Dong Zhou, Ji-Chun Ma, Ting-Juan Zhang, Xi-Xi Li, Wei Zhang, De-Hong Wu, Xiang-Mei Wen, Zi-Jun Xu, Jiang Lin, Jun Qian
Dysregulation of ID proteins is a frequent event in various human cancers and has a direct role in cancer initiation, maintenance, progression and drug resistance. Our previous study has revealed ID1 expression and its prognostic value in acute myeloid leukemia (AML). Herein, we further reported ID2 expression and its clinical significance in AML. Real-time quantitative PCR was performed to detect ID2 transcript level in bone marrow mononuclear cells of 145 de novo AML patients. ID2 expression was significantly up-regulated in AML patients compared with controls...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29190182/checkpoint-inhibition-in-pediatric-hematologic-malignancies
#19
Kara L Davis, Archana M Agarwal, Anupam R Verma
Immune surveillance comprising of adaptive and innate immune systems is naturally designed to eliminate cancer development; overexpression of inhibitory receptors and their ligands prevent this check and lead to evasion and hence cancer progression and metastasis. The use of tumor-specific monoclonal antibodies (MAbs) targeting these checkpoint regulators is promising and has led to this novel field of cancer immunotherapy. The first antibody directed against cytotoxic T-lymphocyte associated protein 4 (CTLA-4), ipilimumab, showed promising results in clinical trials and was approved by the US Food and Drug Administration (FDA) for the treatment of metastatic melanoma in 2011...
November 30, 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29189507/acute-myeloid-leukemia-with-central-nervous-system-involvement-in-children-experience-from-the-french-protocol-analysis-elam02
#20
Arthur Felix, Thierry Leblanc, Arnaud Petit, Brigitte Nelkem, Yves Bertrand, Virginie Gandemer, Anne Sirvent, Catherine Paillard, Claudine Schmitt, Pierre Simon Rohrlich, Odile Fenneteau, Christine Ragu, Gerard Michel, Anne Auvrignon, André Baruchel, Guy Leverger
Central nervous system (CNS) involvement at diagnosis of pediatric acute myeloid leukemia (AML) is not considered as an independent prognostic factor. This study describes the prognostic value of pediatric AML with CNS involvement at diagnosis. Pediatric patients were treated for de novo AML in the French multicenter trial ELAM02. Lumbar puncture was carried out in the first week, and the treatment was adapted to the CNS status. No patient received CNS radiotherapy. The patients were classified into 2 groups: CNS+ and CNS-...
November 17, 2017: Journal of Pediatric Hematology/oncology
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