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https://www.readbyqxmd.com/read/29144985/a-phase-1-2-study-of-rigosertib-in-patients-with-myelodysplastic-syndromes-mds-and-mds-progressed-to-acute-myeloid-leukemia
#1
Shyamala C Navada, Steven M Fruchtman, Rosalie Odchimar-Reissig, Erin P Demakos, Michael E Petrone, Patrick S Zbyszewski, James F Holland, Lewis R Silverman
This Phase 1/2, dose-escalating study of rigosertib enrolled 22 patients with higher-risk myelodysplastic syndromes (MDS) (n=9) and acute myeloid leukemia (AML; n=13) who had relapsed or were refractory to standard therapy and for whom no second-line therapies were approved. Patients received 3- to 7-day continuous intravenous infusions of rigosertib, an inhibitor of Ras-effector pathways that interacts with the Ras-binding domains, common to several signaling proteins including Raf and PI3 kinase. Rigosertib was administered at doses of 650-1700mg/m(2)/day in 14-day cycles...
November 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29143282/hypomethylating-agents-for-treatment-and-prevention-of-relapse-after-allogeneic-blood-stem-cell-transplantation
#2
REVIEW
Thomas Schroeder, Christina Rautenberg, Rainer Haas, Ulrich Germing, Guido Kobbe
Despite the curative potential of allogeneic stem cell transplantation (allo-SCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), many patients will relapse. Until recently therapeutic options mainly consisted of palliative care, chemotherapy, donor lymphocyte infusions and second transplantation in selected cases. Still many patients either do not tolerate intensive therapies or do not achieve durable remissions and will finally succumb. Given this unmet medical need the hypomethylating agents (HMA), Azacitidine (Aza) and Decitabine (DAC) have been tested as salvage therapy in patients with myeloid malignancies relapsing after allo-SCT...
November 15, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29119293/asparaginase-erwinia-chrysanthemi-effectively-depletes-plasma-glutamine-in-adult-patients-with-relapsed-refractory-acute-myeloid-leukemia
#3
Ashkan Emadi, Jennie Y Law, Erin T Strovel, Rena G Lapidus, Linda J B Jeng, Myounghee Lee, Miriam G Blitzer, Brandon A Carter-Cooper, Danielle Sewell, Isabella Van Der Merwe, Sunita Philip, Mohammad Imran, Stephen L Yu, Hongxia Li, Philip C Amrein, Vu H Duong, Edward A Sausville, Maria R Baer, Amir T Fathi, Zeba Singh, Søren M Bentzen
Depletion of glutamine (Gln) has emerged as a potential therapeutic approach in the treatment of acute myeloid leukemia (AML), as neoplastic cells require Gln for synthesis of cellular components essential for survival. Asparaginases deplete Gln, and asparaginase derived from Erwinia chrysanthemi (Erwinaze) appears to have the greatest glutaminase activity of the available asparaginases. In this Phase I study, we sought to determine the dose of Erwinaze that safely and effectively depletes plasma Gln levels to ≤ 120 μmol/L in patients with relapsed or refractory (R/R) AML...
November 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29100399/oxidative-stress-induced-jnk-ap-1-signaling-is-a-major-pathway-involved-in-selective-apoptosis-of-myelodysplastic-syndrome-cells-by-withaferin-a
#4
Karine Z Oben, Sara S Alhakeem, Mary K McKenna, Jason A Brandon, Rajeswaran Mani, Sunil K Noothi, Liu Jinpeng, Shailaja Akunuru, Sanjit K Dhar, Inder P Singh, Ying Liang, Chi Wang, Ahmed Abdel-Latif, Harold F Stills, Daret K St Clair, Hartmut Geiger, Natarajan Muthusamy, Kaoru Tohyama, Ramesh C Gupta, Subbarao Bondada
Myelodysplastic syndromes (MDS) are a diverse group of malignant clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, dysplastic cell morphology in one or more hematopoietic lineages, and a risk of progression to acute myeloid leukemia (AML). Approximately 50% of MDS patients respond to current FDA-approved drug therapies but a majority of responders relapse within 2-3 years. There is therefore a compelling need to identify potential new therapies for MDS treatment. We utilized the MDS-L cell line to investigate the anticancer potential and mechanisms of action of a plant-derived compound, Withaferin A (WFA), in MDS...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100287/nedd9-an-independent-good-prognostic-factor-in-intermediate-risk-acute-myeloid-leukemia-patients
#5
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...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29098609/methods-of-detection-of-measurable-residual-disease-in-aml
#6
REVIEW
Yi Zhou, Brent L Wood
The presence of measurable ("minimal") residual disease (MRD) after induction and/or consolidation chemotherapy is a significant risk factor for relapse in patients with acute myeloid leukemia (AML). In recognition of the clinical significance of AML MRD, the European LeukemiaNet (ELN) recently recommended the establishment of CR-MRD(Negative) as a separate category of treatment response. This recommendation represents a major milestone in the integration of AML MRD testing in standard clinical practice. This review article summarizes the methodologies employed in AML MRD detection and their application in clinical studies that provide evidence supporting the clinical utility of AML MRD testing...
November 2, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29091870/immunotherapy-for-acute-myeloid-leukemia-aml-a-potent-alternative-therapy
#7
REVIEW
Desmond O Acheampong, Christian K Adokoh, Du-Bois Asante, Ernest A Asiamah, Prince A Barnie, Dan O M Bonsu, Foster Kyei
The standard therapy of AML for many years has been chemotherapy with or without stem transplantation. However, there has not been any tangible improvement in this treatment beyond induction through chemotherapy and consolidation with allogeneic stem cell transplantation or chemotherapy. Residual AML cells which later cause relapse mostly persist even after rigorous standard therapy. It is imperative therefore to find an alternative therapy that can take care of the residual AML cells. With a better understanding of how the immune system works to destroy tumor cells and inhibit their growth, another therapeutic option immunotherapy has emerged to address the difficulties associated with the standard therapy...
October 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29090473/results-of-a-phase-1-study-of-quizartinib-as-maintenance-therapy-in-subjects-with-acute-myeloid-leukemia-in-remission-following-allogeneic-hematopoietic-stem-cell-transplant
#8
Brenda M Sandmaier, Samer Khaled, Betül Oran, Guy Gammon, Denise Trone, Olga Frankfurt
FLT3-ITD-mutated acute myeloid leukemia (AML) has very high risk of relapse and is associated with poor outcome following allogeneic hematopoietic-cell transplant (allo-HCT). This two-part, phase 1, multicenter, open-label, sequential-group, dose-escalation study aimed to determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and safety/tolerability of quizartinib, a selective and highly potent FLT3 inhibitor, when administered as maintenance therapy after allo-HCT. Thirteen subjects with documented FLT3-ITD-mutated AML in morphological remission following allo-HCT received one of two quizartinib dihydrochloride dose levels (DL): 40 mg/d (DL1; n=7) and 60 mg/d (DL2; n=6), administered orally in 28-day cycles for up to 24 cycles...
November 1, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29090344/the-role-of-mutant-idh1-and-idh2-inhibitors-in-the-treatment-of-acute-myeloid-leukemia
#9
REVIEW
Samah Nassereddine, Coen J Lap, Faysal Haroun, Imad Tabbara
For decades, researchers have looked into the pathophysiology of acute myeloid leukemia (AML). With the advances in molecular techniques, the two-hit hypothesis was replaced by a multi-hit model, which also emphasizes the importance of aberrant epigenetic regulation in the pathogenesis of AML. IDH1 and IDH2 are two isoforms of isocitrate dehydrogenase that perform crucial roles in cellular metabolism. Somatic mutations in either of these two genes impart a neomorphic enzymatic activity upon the encoded enzymes resulting in the ability to convert α-ketoglutarate (αKG) into the oncometabolite R2-hydroxyglutarate (R2-HG), which can competitively inhibit multiple αKG-dependent dioxygenases...
October 31, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29080982/the-progress-and-current-status-of-immunotherapy-in-acute-myeloid-leukemia
#10
REVIEW
Dan Yang, Xiuqun Zhang, Xuezhong Zhang, Yanli Xu
Recently, there has been remarkable progress in basic and preclinical studies of acute myeloid leukemia (AML). The improved outcomes of AML can largely be attributed to advances in supportive care and hematopoietic cell transplantation as opposed to conventional chemotherapy. However, as the 5-year survival rate remains low due to a high incidence of relapse, novel and effective treatments are urgently needed. Increasing attention is focusing on identifying suitable immunotherapeutic strategies for AML. Here, we describe the immunological features, mechanisms of immune escape, and recent progress in immunotherapy for AML...
October 28, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29076145/durable-graft-versus-leukaemia-effects-without-donor-lymphocyte-infusions-results-of-a-phase-ii-study-of-sequential-t-replete-allogeneic-transplantation-for-high-risk-acute-myeloid-leukaemia-and-myelodysplasia
#11
Jeff K Davies, Sandra Hassan, Shah-Jalal Sarker, Caroline Besley, Heather Oakervee, Matthew Smith, David Taussig, John G Gribben, Jamie D Cavenagh
Allogeneic haematopoietic stem-cell transplantation remains the only curative treatment for relapsed/refractory acute myeloid leukaemia (AML) and high-risk myelodysplasia but has previously been limited to patients who achieve remission before transplant. New sequential approaches employing T-cell depleted transplantation directly after chemotherapy show promise but are burdened by viral infection and require donor lymphocyte infusions (DLI) to augment donor chimerism and graft-versus-leukaemia effects. T-replete transplantation in sequential approaches could reduce both viral infection and DLI usage...
October 26, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29070128/-clinical-observation-of-therapeutic-regimen-consisted-of-decitabine-combined-with-low-dose-ia-regimen-for-myelodysplastic-syndrome-eb
#12
Di Wu, Jin-Xia Hao, Jing Li, Mei Zhang
OBJECTIVE: To investigate the clinical efficacy of decitabine combined with low-dose IA for treating patients with myelodysplastic syndrome-EB. METHODS: Thirty-seven cases of myelodysplastic syndrome-EB patients diagnosed in the First Affiliated Hospital of Xi'an Jiaotong University from June 2015 to January 2017 were analyzed retrospectively. These patients accepted DAC+IA(19 cases) and DAC(18 cases) treatment separately, and the differences of clinical efficacy between them were compared...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29068783/microrna-expression-based-model-indicates-event-free-survival-in-pediatric-acute-myeloid-leukemia
#13
Emilia L Lim, Diane L Trinh, Rhonda E Ries, Jim Wang, Robert B Gerbing, Yussanne Ma, James Topham, Maya Hughes, Erin Pleasance, Andrew J Mungall, Richard Moore, Yongjun Zhao, Richard Aplenc, Lillian Sung, E Anders Kolb, Alan Gamis, Malcolm Smith, Daniela S Gerhard, Todd A Alonzo, Soheil Meshinchi, Marco A Marra
Purpose Children with acute myeloid leukemia (AML) whose disease is refractory to standard induction chemotherapy therapy or who experience relapse after initial response have dismal outcomes. We sought to comprehensively profile pediatric AML microRNA (miRNA) samples to identify dysregulated genes and assess the utility of miRNAs for improved outcome prediction. Patients and Methods To identify miRNA biomarkers that are associated with treatment failure, we performed a comprehensive sequence-based characterization of the pediatric AML miRNA landscape...
October 25, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29067925/3q26-chromosomal-anomalies-in-acute-myeloid-leukemia-first-descriptions-from-india
#14
A Gupta, L Kumar
Cytogenetic anomalies involving the 3q26 chromosomal region are rare in acute myeloid leukemia (AML). There is no such description of these anomalies from the Indian sub-continent. A total of 174 AML patients were admitted to our hospital for therapy between January 2001 and January 2008. Cytogenetic studies could be done in 115 patients; which revealed three cases with 3q26 anomalies. All were males. In the first two cases, the anomaly was detected in all the metaphases. The common features seen were the presence of only mild thrombocytopenia (relatively high platelet counts when assessed against the background of AML with high blast percentages), monosomy 7, myeloperoxidase positive blasts, mild eosinophilia, and poor therapeutic response...
October 23, 2017: Journal of Postgraduate Medicine
https://www.readbyqxmd.com/read/29067751/monitoring-of-fusion-gene-transcripts-to-predict-relapses-in-pediatric-acute-myeloid-leukemia
#15
Hidemasa Matsuo, Yuka Iijima-Yamashita, Miho Yamada, Takao Deguchi, Nobutaka Kiyokawa, Akira Shimada, Akio Tawa, Daisuke Tomizawa, Takashi Taga, Akitoshi Kinoshita, Souichi Adachi, Keizo Horibe
BACKGROUND: In acute myeloid leukemia (AML), accurate detection of minimal residual disease (MRD) enables better risk-stratified therapy. However, there are few studies monitoring multiple fusion transcripts and evaluating their accuracy as MRDs at multiple timepoints. METHODS: We retrospectively examined RNA obtained from 82 pediatric AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 study. The expression of six important fusion transcripts (AML1(RUNX1)-ETO, CBFB-MYH11, MLL(KMT2A)-AF9, MLL-ELL, MLL-AF6, and FUS-ERG) was analyzed at five timepoints 30-40 days apart following diagnosis...
October 25, 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/29064024/measurement-of-residual-disease-in-acute-myeloid-leukemia
#16
REVIEW
Rahul S Vedula, R Coleman Lindsley
PURPOSE OF REVIEW: Assessment of measurable residual disease (MRD) after treatment can identify patients with acute myeloid leukemia (AML) that are at high risk of poor outcomes. However, there is no consensus yet regarding a standardized approach to measuring MRD that is most clinically meaningful. We review multiparameter flow cytometry (MFC) and reverse transcriptase polymerase chain reaction (RT-PCR), and discuss a framework for assessing remission MRD using next-generation sequencing (NGS)...
October 24, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29055209/long-term-survival-of-sorafenib-treated-flt3-itd-positive-acute-myeloid-leukaemia-patients-relapsing%C3%A2-after-allogeneic-stem-cell-transplantation
#17
S K Metzelder, T Schroeder, M Lübbert, M Ditschkowski, K Götze, S Scholl, R G Meyer, P Dreger, N Basara, M F Fey, H R Salih, A Finck, T Pabst, A Giagounidis, G Kobbe, E Wollmer, J Finke, A Neubauer, A Burchert
BACKGROUND: Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD)-positive acute myeloid leukaemia (AML) relapsing after allogeneic stem cell transplantation (allo-SCT) has a dismal prognosis with limited therapeutic options. FLT3-ITD kinase inhibition is a reasonable but palliative experimental treatment alternative in this situation. Information on long-term outcome is not available. METHODS: We performed a long-term follow-up analysis of a previously reported cohort of 29 FLT3-ITD-positive AML patients, which were treated in relapse after allo-SCT with sorafenib monotherapy...
October 18, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29021230/gemtuzumab-ozogamicin-for-acute-myeloid-leukemia
#18
Frederick R Appelbaum, Irwin D Bernstein
On September 1, 2017, the U.S. Food and Drug Administration (FDA) approved gemtuzumab ozogamicin for the treatment of adults with newly diagnosed CD33+ acute myeloid leukemia and for patients aged 2 years and older with CD33+ AML who have experienced a relapse or who have not responded to initial treatment. This signals a new chapter in the long and unusual story of gemtuzumab ozogamicin (GO), which was the first antibody-drug conjugate approved for human use by the FDA.
October 11, 2017: Blood
https://www.readbyqxmd.com/read/29017371/cytarabine-and-daunorubicin-for-the-treatment-of-acute-myeloid-leukemia
#19
Tracy Murphy, Karen W L Yee
Acute myeloid leukemia (AML) is the most common acute forms of leukemia in adults. It has a poor long-term survival with a high relapse rate and at relapse, is commonly resistant to available therapies. The current combination of daunorubicin (DNR) for three days and cytarabine (Ara-C) as a continuous infusion for seven days, more commonly known as '3 + 7' has remained essentially unaltered over the last forty-four years and remains the standard induction regimen internationally. Areas covered: This paper will briefly review clinically important trials related to '3 + 7'...
October 20, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28994485/modified-risk-stratification-grouping-using-standard-clinical-and-biopsy-information-for-patients-undergoing-radical-prostatectomy-results-from-search
#20
MULTICENTER STUDY
Zachary S Zumsteg, Zinan Chen, Lauren E Howard, Christopher L Amling, William J Aronson, Matthew R Cooperberg, Christopher J Kane, Martha K Terris, Daniel E Spratt, Howard M Sandler, Stephen J Freedland
INTRODUCTION: Prostate cancer is a heterogeneous disease, and risk stratification systems have been proposed to guide treatment decisions. However, significant heterogeneity remains for those with unfavorable-risk disease. METHODS: This study included 3335 patients undergoing radical prostatectomy without adjuvant radiotherapy in the SEARCH database. High-risk patients were dichotomized into standard and very high-risk (VHR) groups based on primary Gleason pattern, percentage of positive biopsy cores (PPBC), number of NCCN high-risk factors, and stage T3b-T4 disease...
December 2017: Prostate
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