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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/28917156/tgf%C3%AE-1-synergizes-with-flt3-ligand-to-induce-chemoresistant-quiescence-in-acute-lymphoblastic-leukemia-with-mll-gene-rearrangements
#2
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/28903567/minimal-residual-disease-assessment-in-multiple-myeloma-by-multiparametric-flow-cytometry
#3
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/28899864/early-detection-of-molecular-residual-disease-in-localized-lung-cancer-by-circulating-tumor-dna-profiling
#4
Aadel A Chaudhuri, Jacob J Chabon, Alexander F Lovejoy, Aaron M Newman, Henning Stehr, Tej D Azad, Michael S Khodadoust, Mohammad Shahrokh Esfahani, Chih Long Liu, Li Zhou, Florian Scherer, David M Kurtz, Carmen Say, Justin N Carter, David J Merriott, Jonathan C Dudley, Michael S Binkley, Leslie Modlin, Sukhmani K Padda, Michael F Gensheimer, Robert B West, Joseph B Shrager, Joel W Neal, Heather A Wakelee, Billy W Loo, Ash A Alizadeh, Maximilian Diehn
Identifying molecular residual disease (MRD) after treatment of localized lung cancer could facilitate early intervention and personalization of adjuvant therapies. Here we apply Cancer Personalized Profiling by Deep Sequencing (CAPP-Seq) circulating tumor DNA (ctDNA) analysis to 255 samples from 40 patients treated with curative intent for stage I-III lung cancer and 54 healthy adults. In 94% of evaluable patients experiencing recurrence, ctDNA was detectable in the first post-treatment blood sample, indicating reliable identification of MRD...
September 12, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28891364/an-update-on-pcr-use-for-minimal-residual-disease-monitoring-in-acute-lymphoblastic-leukemia
#5
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/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
#6
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/28865180/automated-and-simplified-identification-of-normal-and-abnormal-plasma-cells-in-multiple-myeloma-by-flow-cytometry
#7
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/28864140/donor-type-and-disease-risk-predict-the-success-of-allogeneic-hematopoietic-cell-transplantation-hct-a-single-center-analysis-of-613-adult-hct-recipients-using-a-modified-composite-endpoint
#8
Melhem Solh, Xu Zhang, Katelin Connor, Stacey Brown, Lawrence E Morris, H Kent Holland, Asad Bashey, Scott R Solomon
The composite endpoint GVHD free, relapse free survival (GRFS) has recently been developed as a tool to assess the success of allogeneic HCT and has been incorporated into recent randomized trials of GVHD prophylaxis by the Blood and Marrow Transplant Clinical Trials Network (BMTCTN). As developed, GRFS incorporates 'chronic GVHD requiring systemic immunosuppression' as a measure of clinically significant chronic GVHD (cGVHD). However, the decision to start patients on immunosuppression for chronic GVHD is subjective and physician dependent...
August 29, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28864095/minimal-residual-disease-in-chronic-lymphocytic-leukaemia
#9
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/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
#10
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
https://www.readbyqxmd.com/read/28857984/levator-aponeurosis-and-muller-muscle-plication-reinforced-with-levator-sheath-advancement-for-blepharoptosis-correction
#11
Jin Suk Byun, Kun Hwang, Sang Yun Lee, Hak Tae Kim, Kenneth Kim
The authors innovated the levator aponeurosis and Muller muscle plication reinforced with levator sheath advancement (AMPSA) for blepharoptosis correction. The orbital septum was opened 1 mm above its fusion with the levator aponeurosis. The preaponeurotic fat was retracted and the thickened part of the levator sheath was identified. Two plication sutures were made: medial suture at the medial border of the pupil and lateral between the lateral border of the pupil and the lateral limbus. A needle with 6-0 nylon thread first bit the tarsal plate approximately 1 mm below its upper border, then bit the levator aponeurosis and the Muller muscle together at 3 to 6 mm above the upper border of the tarsal plate...
August 28, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28857648/impact-of-clinical-utility-of-mrd-assessment-with-different-techniques-on-survival-in-acute-b-lymphoblastic-leukemia
#12
Aijie Huang, Chongmei Huang, Gusheng Tang, Hui Cheng, Min Liu, Jing Ding, Shenglan Gong, Qi Chen, Weiping Zhang, Jianmin Yang, Jianmin Wang, Xiaoxia Hu
We investigated the impact of minimal residual disease (MRD) obtained from different approaches on the outcomes of 141 B lymphoblastic leukemia (B-ALL) patients. Among 169 samples with more than 5% blasts by morphology, 3.6% (6/169) were Flow-MRD negative. Of the 212 positive molecular-MRD samples from Ph+ ALL patients, 55 (25.9%) were Flow-MRD negative. Before consolidation or allogeneic stem cell transplantation (allo-HSCT), negative Flow-MRD was associated with improved survival (p = .019 and .041, respectively) for Ph- ALL patients, but not for Ph+ ALL (p = ...
August 31, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28846953/post-remissional-and-pre-transplant-role-of-minimal-residual-disease-detected-by-wt1-in-acute-myeloid-leukemia-a-retrospective-cohort-study
#13
Chiara Frairia, Semra Aydin, Ernesta Audisio, Ludovica Riera, Sabrina Aliberti, Bernardino Allione, Alessandro Busca, Stefano D'Ardia, Chiara Maria Dellacasa, Anna Demurtas, Andrea Evangelista, Giovannino Ciccone, Paola Francia di Celle, Barbara Nicolino, Alessandra Stacchini, Filippo Marmont, Umberto Vitolo
In acute myeloid leukemia (AML), the detection of minimal residual disease (MRD) is still under investigation. The aim of the present retrospective study was to assess the role of Wilms tumor gene 1 (WT1) overexpression in a large monocentric cohort of AML patients. Among 255 enrolled patients, MRD was investigated in those in complete remission (CR) with an available WT1 at baseline (>250 copies) and at two further time-points: after induction (n=117) and prior allogeneic hematopoietic cell transplantation (allo-HCT), n=65...
August 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28844499/rindopepimut-with-temozolomide-for-patients-with-newly-diagnosed-egfrviii-expressing-glioblastoma-act-iv-a-randomised-double-blind-international-phase-3-trial
#14
Michael Weller, Nicholas Butowski, David D Tran, Lawrence D Recht, Michael Lim, Hal Hirte, Lynn Ashby, Laszlo Mechtler, Samuel A Goldlust, Fabio Iwamoto, Jan Drappatz, Donald M O'Rourke, Mark Wong, Mark G Hamilton, Gaetano Finocchiaro, James Perry, Wolfgang Wick, Jennifer Green, Yi He, Christopher D Turner, Michael J Yellin, Tibor Keler, Thomas A Davis, Roger Stupp, John H Sampson
BACKGROUND: Rindopepimut (also known as CDX-110), a vaccine targeting the EGFR deletion mutation EGFRvIII, consists of an EGFRvIII-specific peptide conjugated to keyhole limpet haemocyanin. In the ACT IV study, we aimed to assess whether or not the addition of rindopepimut to standard chemotherapy is able to improve survival in patients with EGFRvIII-positive glioblastoma. METHODS: In this randomised, double-blind, phase 3 trial, we recruited patients aged 18 years and older with glioblastoma from 165 hospitals in 22 countries...
August 22, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28832354/autologous-hematopoietic-cell-transplantation-of-mantle-cell-lymphoma-emerging-trends
#15
Umberto Falcone, John Kuruvilla
PURPOSE OF REVIEW: The management of mantle cell lymphoma has changed significantly with the adoption of immunochemotherapy and dose intensive treatment strategies in specific patient populations. Randomized controlled trials have established the role of rituximab-based treatments and autologous stem cell transplantation as standards of care. Novel therapeutics are also being integrated into these treatment strategies. RECENT FINDINGS: Rituximab-based primary treatment has been shown to significantly improve complete remission rates...
August 21, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28830517/assessment-of-ibrutinib-plus-rituximab-in-front-line-cll-flair-trial-study-protocol-for-a-phase-iii-randomised-controlled-trial
#16
Laura Collett, Dena R Howard, Talha Munir, Lucy McParland, Jamie B Oughton, Andy C Rawstron, Anna Hockaday, Claire Dimbleby, David Phillips, Kathryn McMahon, Claire Hulme, David Allsup, Adrian Bloor, Peter Hillmen
BACKGROUND: Treatment of chronic lymphocytic leukaemia (CLL) has seen a substantial improvement over the last few years. Combination immunochemotherapy, such as fludarabine, cyclophosphamide and rituximab (FCR), is now standard first-line therapy. However, the majority of patients relapse and require further therapy, and so new, effective, targeted therapies that improve remission rates, reduce relapses, and have fewer side effects, are required. The FLAIR trial will assess whether ibrutinib plus rituximab (IR) is superior to FCR in terms of progression-free survival (PFS)...
August 22, 2017: Trials
https://www.readbyqxmd.com/read/28821454/low-dose-antithymocyte-globulin-for-graft-versus-host-disease-prophylaxis-in-matched-unrelated-allogeneic-hematopoietic-stem-cell-transplantation
#17
Adam Bryant, Ranjeeta Mallick, Lothar Huebsch, David Allan, Harold Atkins, Grizel Anstee, Mitchell Sabloff, Nicholas Scrivens, Dawn Maze, Chris Bredeson, Natasha Kekre
Graft-versus-host disease (GVHD) is a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (alloHCT). Prophylactic in vivo T cell depletion with antithymocyte globulin (ATG) has been associated with decreased GVHD rates in many alloHCT settings. Despite decades of clinical study, optimal ATG dosing has not been established. Understanding that higher rates of GVHD are observed with matched unrelated donor (MUD) versus matched related donor (MRD) alloHCT, at our institution MUD alloHSCT recipients have historically had low-dose Thymoglobulin (total dose, 2...
August 15, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28815990/trade-patterns-facilitating-highly-pathogenic-avian-influenza-virus-dissemination-in-the-free-grazing-layer-duck-system-in-vietnam
#18
A Meyer, T X Dinh, T A Han, D V Do, T V Nhu, L T Pham, T T T Nguyen, S Newman, B Häsler, D U Pfeiffer, T Vergne
Highly pathogenic avian influenza (HPAI) viruses continue to threaten smallholder poultry producers in several South-east Asian countries, including Vietnam. In particular, the free-grazing duck system has been repeatedly highlighted as a major risk factor for HPAI outbreaks. Free-grazing ducks, which scavenge on rice paddies after the harvest, account for a large proportion of the duck population in Vietnam and the wider South-east Asian region. However, the structure and dynamics of the free-grazing duck production from farm to consumption has not been described for Vietnam...
August 16, 2017: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/28810324/-minimal-residual-disease-level-predicts-outcomes-in-the-non-favorable-risk-patients-with-acute-myeloid-leukemia
#19
X Ren, T Zhao, J Wang, H H Zhu, H Jiang, J S Jia, S M Yang, B Jiang, D B Wang, X J Huang, Q Jiang
Objective: To explore impact of minimal residual leukemia (MRD) on outcomes in the non-favorable risk adults with de novo acute myeloid leukemia (AML) . Methods: From January 2008 to February 2016, data of consecutive newly-diagnosed non-favorable risk adults with AML (non-APL) according to SWOG criteria who achieved morphologic leukemia-free state (MLFS) and received continuous chemotherapy were assessed retrospectively. Results: 292 AML patients were enrolled, 150 (51.4%) were male. Median age was 46 years (range, 18-65 years) ...
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28801986/persistent-detection-of-alternatively-spliced-bcr-abl-variant-results-in-a-failure-to-achieve-deep-molecular-response
#20
Junichiro Yuda, Toshihiro Miyamoto, Jun Odawara, Yasuyuki Ohkawa, Yuichiro Semba, Masayasu Hayashi, Koichi Miyamura, Mitsune Tanimoto, Kazuhito Yamamoto, Masafumi Taniwaki, Koichi Akashi
Treatment with tyrosine kinase inhibitors (TKIs) may sequentially induce TKI-resistant BCR-ABL mutants in chronic myeloid leukemia (CML). Conventional polymerase chain reaction (PCR) monitoring of BCR-ABL is an important indicator to determine therapeutic intervention for preventing disease progression. However, PCR cannot quantify separately amounts of BCR-ABL and its mutants, including alternatively spliced BCR-ABL with an insertion of 35 intronic nucleotides (BCR-ABL(I)(ns35bp) ) between ABL exons 8 and 9 which introduces the premature termination and loss of kinase activity...
August 12, 2017: Cancer Science
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