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https://www.readbyqxmd.com/read/28921818/blinatumomab-activity-in-a-patient-with-down-syndrome-b-precursor-acute-lymphoblastic-leukemia
#1
Aman Wadhwa, Matthew A Kutny, Ana C Xavier
Persistent minimal residual disease (MRD) after consolidation may indicate chemotherapy insensitivity in B-precursor acute lymphoblastic leukemia (BP-ALL). Given the strong association of MRD and outcome in non-Down syndrome (non-DS) BP-ALL, it is likely that MRD levels are also of prognostic significance in DS BP-ALL. We report here the successful use of blinatumomab, a bispecific T-cell engager antibody construct, in a patient with DS BP-ALL and persistent MRD at the end of consolidation. Blinatumomab has been shown to have excellent results in patients with relapsed/refractory BP-ALL...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28920959/targeting-mitochondrial-oxidative-phosphorylation-eradicates-therapy-resistant-chronic-myeloid-leukemia-stem-cells
#2
Elodie M Kuntz, Pablo Baquero, Alison M Michie, Karen Dunn, Saverio Tardito, Tessa L Holyoake, G Vignir Helgason, Eyal Gottlieb
Treatment of chronic myeloid leukemia (CML) with imatinib mesylate and other second- and/or third-generation c-Abl-specific tyrosine kinase inhibitors (TKIs) has substantially extended patient survival. However, TKIs primarily target differentiated cells and do not eliminate leukemic stem cells (LSCs). Therefore, targeting minimal residual disease to prevent acquired resistance and/or disease relapse requires identification of new LSC-selective target(s) that can be exploited therapeutically. Considering that malignant transformation involves cellular metabolic changes, which may in turn render the transformed cells susceptible to specific assaults in a selective manner, we searched for such vulnerabilities in CML LSCs...
September 18, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28919634/achievement-of-a-negative-minimal-residual-disease-state-after-hypomethylating-agent-therapy-in-older-patients-with-aml-reduces-the-risk-of-relapse
#3
P Boddu, J Jorgensen, H Kantarjian, G Borthakur, T Kadia, N Daver, Y Alvarado, N Pemmaraju, P Bose, K Naqvi, M Yilmaz, S Pierce, M Brandt, C D DiNardo, E J Jabbour, M Konopleva, G Garcia-Manero, J Cortes, F Ravandi
Leukemia accepted article preview online, 18 September 2017. doi:10.1038/leu.2017.285.
September 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28917156/tgf%C3%AE-1-synergizes-with-flt3-ligand-to-induce-chemoresistant-quiescence-in-acute-lymphoblastic-leukemia-with-mll-gene-rearrangements
#4
M Tamai, Y Furuichi, S Kasai, N Ando, D Harama, K Goi, T Inukai, K Kagami, M Abe, H Ichikawa, K Sugita
Fms-like tyrosine kinase 3 (FLT3) is highly expressed in mixed-lineage leukemia (MLL) gene-rearranged acute lymphoblastic leukemia (MLL+ALL) with a dismal prognosis. We previously reported that FLT3 ligand (FL) stimulation induced cell cycle arrest in MLL+ALL cells leading to resistance against anti-leukemic agents. Given that FL stimulation enhanced transforming growth factor (TGF)β1 mRNA levels in MLL+ALL cells, we extensively examined the effect of TGFβ1 on the cell cycle progression and chemosensitivity in MLL+ALL cells, and found that TGFβ1 stimulation induced MLL+ALL cells into cell cycle arrest resistant to arabinosyl cytosine; its effect was markedly enhanced in synergy with FL...
September 13, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28916311/lenalidomide-maintenance-after-first-line-therapy-for-high-risk-chronic-lymphocytic-leukaemia-cllm1-final-results-from-a-randomised-double-blind-phase-3-study
#5
Anna Maria Fink, Jasmin Bahlo, Sandra Robrecht, Othman Al-Sawaf, Ali Aldaoud, Holger Hebart, Kathleen Jentsch-Ullrich, Steffen Dörfel, Kirsten Fischer, Clemens-Martin Wendtner, Thomas Nösslinger, Paolo Ghia, Francesc Bosch, Arnon P Kater, Hartmut Döhner, Michael Kneba, Karl-Anton Kreuzer, Eugen Tausch, Stephan Stilgenbauer, Matthias Ritgen, Sebastian Böttcher, Barbara Eichhorst, Michael Hallek
BACKGROUND: The combined use of genetic markers and detectable minimal residual disease identifies patients with chronic lymphocytic leukaemia with poor outcome after first-line chemoimmunotherapy. We aimed to assess lenalidomide maintenance therapy in these high-risk patients. METHODS: In this randomised, double-blind, phase 3 study (CLLM1; CLL Maintenance 1 of the German CLL Study Group), patients older than 18 years and diagnosed with immunophenotypically confirmed chronic lymphocytic leukaemia with active disease, who responded to chemoimmunotherapy 2-5 months after completion of first-line therapy and who were assessed as having a high risk for an early progression with at least a partial response after four or more cycles of first-line chemoimmunotherapy, were eligible if they had high minimal residual disease levels or intermediate levels combined with an unmutated IGHV gene status or TP53 alterations...
September 12, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28905508/tandem-thiotepa-with-autologous-hematopoietic-cell-rescue-in-patients-with-recurrent-refractory-or-poor-prognosis-solid-tumor-malignancies
#6
Diana S Osorio, Ira J Dunkel, Kelly Ann Cervone, Rakesh K Goyal, K M Steve Lo, Jonathan L Finlay, Sharon L Gardner
BACKGROUND: The purpose of this study was to determine the feasibility and tolerability of tandem courses of high-dose thiotepa with autologous hematopoietic cell rescue (AHCR) in patients with recurrent, refractory solid tumors who were ineligible for a single course of high-dose therapy due to greater than minimal residual disease. Patients with decreased hearing or poor renal function were eligible. PROCEDURE: Thiotepa was administered intravenously at a dose of 200 mg/m(2) /day (6...
September 14, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28903574/whole-exome-sequencing-of-aberrant-plasma-cells-in-a-patient-with-multiple-myeloma-minimal-residual-disease
#7
M Zatopkova, J Filipová, T Jelínek, P Vojta, T Sevcikova, M Simicek, L Rihova, R Bezdekova, K Growkova, Z Kufová, J Smejkalová, M Hajdúch, L Pour, J Minárik, A Jungová, V Maisnar, F Kryukov, R Hájek
Multiple myeloma is a plasma cell dyscrasia. It is the second most common hematological malignancy which is characterized by proliferation of clonal plasma cells producing harmful monoclonal immunoglobulin. Despite treatment modalities greatly evolved during the last decade, small amount of aberrant residual cells reside in patients after therapy and can cause relapse of the disease. Characterization of the residual, resistant clones can help to reveal important therapeutic targets for application of effective and precious treatment...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28903567/minimal-residual-disease-assessment-in-multiple-myeloma-by-multiparametric-flow-cytometry
#8
L Rihova, P Vsianska, R Bezdekova, R Kralova, M Penka, M Krejci, L Pour, R Hájek
BACKGROUND: Progress in treatment of multiple myeloma extensively increased patient remission rates, so minimal residual disease (MRD) detection becomes essential to assess the effectivity of treatment and depth of complete response. Nowadays, multiparametric flow cytometry (MFC) is the most used method for monitoring of MRD presence in the bone marrow of multiple myeloma patients; however, detection on molecular level can be used as well. It is evident that choice of protocol used for MFC-MRD assessment can significantly affect required results; nevertheless, standardized and highly sensitive approach of "next generation flow" is already available...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28903566/biobanking-the-first-step-to-successful-liquid-biopsy-experiments
#9
M Almasi, S Sevcikova, M Penka, M Krejci, Z Adam, P Vrublova, T Jelínek, R Hájek
BACKGROUND: Archiving of biological materials in biobanks is considered to be the initial crucial part of research activities. Most often, biobanks are founded for research purposes since they allow collection of sufficient material for analysis of new or testing of previously identified biomarkers. Biobanking needs to quickly react to current needs of researchers as well as clinicians, it is not a rigid system. Laboratory analyses of monoclonal gammopathies are based on separation of plasma cells from bone marrow of patients...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28903565/liquid-biopsies-the-clinics-and-the-molecules
#10
V Kubaczková, L Sedlarikova, B Bollová, V Sandecká, M Stork, L Pour, S Sevcikova
Unlike bone marrow biopsies, liquid biopsies represent a gentler, more accessible, less painful, repeatable and more comprehensive approach to get biologically relevant information about the entire tumor but also about treatment response and level of minimal residual disease. This is all possible since peripheral blood contains not only circulating tumor cells but also many circulating molecules of nucleic acids (microRNA, cell-free DNA, long non-coding RNA etc.). Multiple myeloma is a genetically heterogeneous disease characterized by multifocal tumor deposits in the bone marrow but also focal lesions elsewhere...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28891364/an-update-on-pcr-use-for-minimal-residual-disease-monitoring-in-acute-lymphoblastic-leukemia
#11
Vittorio Nunes, Gianni Cazzaniga, A Biondi
Acute lymphoblastic leukemia (ALL) is the first neoplasm where the assessment of early response to therapy by minimal residual disease (MRD) monitoring has proven to be a fundamental tool for guiding therapeutic choices. In recent years, thanks to real-time quantitative PCR (qPCR), MRD monitoring has further achieved higher levels of sensitivity and standardization. However, some outstanding issues still remain to be addressed and emerging technologies hold the promise of improving MRD detection in ALL patients...
September 11, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28890671/current-management-of-peritoneal-carcinomatosis-from-colorectal-cancer-the-role-of-cytoreductive-surgery-and-hyperthermic-peritoneal-chemoperfusion
#12
Ibrahim Nassour, Patricio M Polanco
Peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is a disease with a poor prognosis, often thought to be a terminal illness with no hope except for palliative treatment. New therapeutic modalities combining cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have shown favorable outcomes and may provide a significant survival benefit in a selected group of patients. The main rational for CRS is to remove all visible tumor burden to allow for the chemotherapeutic agent (HIPEC) to eradicate any microscopic residual disease...
April 2017: Current Colorectal Cancer Reports
https://www.readbyqxmd.com/read/28888074/early-recovery-of-circulating-immature-b-cells-in-b-lymphoblastic-leukemia-patients-after-cd19-targeted-car-t-cell-therapy-a-pitfall-for-minimal-residual-disease-detection
#13
Wenbin Xiao, Dalia Salem, Catherine McCoy, Daniel Lee, Nirali N Shah, Maryalice Stetler-Stevenson, Constance M Yuan
BACKGROUND: CD19-targeted chimeric-antigen receptor-modified T-cells (CAR-T) are promising in the treatment of refractory B-lymphoblastic leukemia (B-ALL). Minimal residual disease (MRD) detection by multicolor flow cytometry (FCM) is critical to distinguish B-ALL MRD from regenerating, non-neoplastic B-cell populations. METHODS: FCM was performed on samples from 9 patients with B-ALL treated with CAR-T. RESULTS: All 9 patients showed response to CAR-T...
September 9, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28884236/identification-of-a-serotype-independent-linear-epitope-of-foot-and-mouth-disease-virus
#14
Baolin Yang, Mingxia Wang, Wenming Liu, Zhiqiang Xu, Haiwei Wang, Decheng Yang, Wenge Ma, Guohui Zhou, Li Yu
Foot-and-mouth disease (FMD), caused by foot-and-mouth disease virus (FMDV), is a highly contagious infectious disease that affects domestic and wild cloven-hoofed animals worldwide. VP2 is a structural protein of FMDV. In this study, an FMDV serotype-independent monoclonal antibody (MAb), 10B10, against the viral capsid protein VP2 was generated, and a series of GST fusion proteins expressing a truncated peptide of VP2 was subjected to Western blot analysis using MAb 10B10. Their results indicated that the peptide (8)TLLEDRILT(16) of VP2 is the minimal requirement of the epitope recognized by MAb 10B10...
September 7, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28874751/disease-mutations-reveal-residues-critical-to-the-interaction-of-p4-atpases-with-lipid-substrates
#15
Rasmus H Gantzel, Louise S Mogensen, Stine A Mikkelsen, Bente Vilsen, Robert S Molday, Anna L Vestergaard, Jens P Andersen
Phospholipid flippases (P4-ATPases) translocate specific phospholipids from the exoplasmic to the cytoplasmic leaflet of membranes. While there is good evidence that the overall molecular structure of flippases is similar to that of P-type ATPase ion-pumps, the transport pathway for the "giant" lipid substrate has not been determined. ATP8A2 is a flippase with selectivity toward phosphatidylserine (PS), possessing a net negatively charged head group, whereas ATP8B1 exhibits selectivity toward the electrically neutral phosphatidylcholine (PC)...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28874686/targeted-error-suppressed-quantification-of-circulating-tumor-dna-using-semi-degenerate-barcoded-adapters-and-biotinylated-baits
#16
Miguel Alcaide, Stephen Yu, Jordan Davidson, Marco Albuquerque, Kevin Bushell, Daniel Fornika, Sarah Arthur, Bruno M Grande, Suzan McNamara, Mathilde Couetoux du Tertre, Gerald Batist, David G Huntsman, Luca Cavallone, Adriana Aguilar, Mark Basik, Nathalie A Johnson, Rebecca J Deyell, S Rod Rassekh, Ryan D Morin
Ultrasensitive methods for rare allele detection are critical to leverage the full potential offered by liquid biopsies. Here, we describe a novel molecular barcoding method for the precise detection and quantification of circulating tumor DNA (ctDNA). The major benefits of our design include straightforward and cost-effective production of barcoded adapters to tag individual DNA molecules before PCR and sequencing, and better control over cross-contamination between experiments. We validated our approach in a cohort of 24 patients with a broad spectrum of cancer diagnoses by targeting and quantifying single-nucleotide variants (SNVs), indels and genomic rearrangements in plasma samples...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28865180/automated-and-simplified-identification-of-normal-and-abnormal-plasma-cells-in-multiple-myeloma-by-flow-cytometry
#17
Elina Alaterre, Sébastien Raimbault, Jean-Michel Garcia, Thierry Rème, Guilhem Requirand, Bernard Klein, Jérôme Moreaux
BACKGROUND: Multiple myeloma (MM) is an incurable disease characterized by clonal plasma cell (PC) proliferation within the bone marrow (BM). Next-generation flow cytometry has become the reference tool to follow minimal residual disease (MRD). We developed a new simpler and cheaper flow cytometry method to analyze bone marrow samples in patients with MM. METHODS: To identify and characterize abnormal PC, we designed a simple panel composed of anti-CD38, anti-kappa and anti-lambda light chain antibodies, combined with two antibody pools with the same fluorophore (anti-CD19 and anti-CD27 for the negative pool, and anti-CD56, anti-CD117 and anti-CD200 antibodies for the positive pool)...
September 2, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28864095/minimal-residual-disease-in-chronic-lymphocytic-leukaemia
#18
REVIEW
José Antonio García Vela, José Antonio García Marco
Minimal residual disease (MRD) assessment is an important endpoint in the treatment of chronic lymphocytic leukaemia (CLL). It is highly predictive of prolonged progression-free survival (PFS) and overall survival and could be considered a surrogate for PFS in the context of chemoimmunotherapy based treatment. Evaluation of MRD level by flow cytometry or molecular techniques in the era of the new BCR and Bcl-2 targeted inhibitors could identify the most cost-effective and durable treatment sequencing. A therapeutic approach guided by the level of MRD might also determine which patients would benefit from an early stop or consolidation therapy...
August 29, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28862553/transorbital-endoscopic-eyelid-approach-for-resection-of-sphenoorbital-meningiomas-with-predominant-hyperostosis-report-of-2-cases
#19
João Paulo Almeida, Sacit B Omay, Sathwik R Shetty, Yu-Ning Chen, Armando S Ruiz-Treviño, Buqing Liang, Vijay K Anand, Benjamin Levine, Theodore H Schwartz
Sphenoorbital meningiomas (SOMs) are slow-growing tumors that originate from the sphenoidal wing and are associated with visual deterioration, extrinsic ocular movement disorders, and proptosis caused by hyperostosis of the lateral wall of the orbit. In some cases, the intracranial component is quite small or "en plaque," and the majority of the symptoms arise from adjacent hyperostosis. Craniotomy has traditionally been the standard of care, but new minimally invasive multiportal endoscopic approaches offer an alternative...
September 1, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28859185/salvage-chemoimmunotherapy-with-inotuzumab-ozogamicin-combined-with-mini-hyper-cvd-for-patients-with-relapsed-or-refractory-philadelphia-chromosome-negative-acute-lymphoblastic-leukemia-a-phase-2-clinical-trial
#20
Elias Jabbour, Farhad Ravandi, Partow Kebriaei, Xuelin Huang, Nicholas J Short, Deborah Thomas, Koji Sasaki, Michael Rytting, Nitin Jain, Marina Konopleva, Guillermo Garcia-Manero, Richard Champlin, David Marin, Tapan Kadia, Jorge Cortes, Zeev Estrov, Koichi Takahashi, Yogin Patel, Maria R Khouri, Jovitta Jacob, Rebecca Garris, Susan O'Brien, Hagop Kantarjian
Importance: The outcome of patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) is poor. Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to calicheamicin, has single-agent activity in R/R ALL. Objective: To evaluate the efficacy and safety of inotuzumab ozogamicin plus low-intensity chemotherapy in patients with R/R ALL. Design, Setting, and Participants: A single-arm, phase 2 study of adults with R/R B-cell ALL conducted at The University of Texas MD Anderson Cancer Center, Houston...
August 31, 2017: JAMA Oncology
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