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https://www.readbyqxmd.com/read/27930944/high-throughput-sequencing-in-acute-lymphoblastic-leukemia-follow-up-of-minimal-residual-disease-and-emergence-of-new-clones
#1
Mikaël Salson, Mathieu Giraud, Aurélie Caillault, Nathalie Grardel, Nicolas Duployez, Yann Ferret, Marc Duez, Ryan Herbert, Tatiana Rocher, Shéhérazade Sebda, Sabine Quief, Céline Villenet, Martin Figeac, Claude Preudhomme
Minimal residual disease (MRD) is known to be an independent prognostic factor in patients with acute lymphoblastic leukemia (ALL). High-throughput sequencing (HTS) is currently used in routine practice for the diagnosis and follow-up of patients with hematological neoplasms. In this retrospective study, we examined the role of immunoglobulin/T-cell receptor-based MRD in patients with ALL by HTS analysis of immunoglobulin H and/or T-cell receptor gamma chain loci in bone marrow samples from 11 patients with ALL, at diagnosis and during follow-up...
November 21, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27930388/should-patients-with-acute-myeloid-leukemia-and-measurable-residual-disease-be-transplanted-in-first-complete-remission
#2
Francesco Buccisano, Roland B Walter
PURPOSE OF REVIEW: Measurable ('minimal') residual disease in acute myeloid leukemia during first complete morphologic remission (MRD CR1) identifies patients with particularly high relapse risk and short survival. Here, we examine the evidence regarding optimal postremission treatment strategy for such patients. RECENT FINDINGS: With chemotherapy alone or chemotherapy/autologous hematopoietic cell transplantation (HCT), disease recurrence appears inevitable in patients with MRD CR1...
December 7, 2016: Current Opinion in Hematology
https://www.readbyqxmd.com/read/27920559/e2a-pbx1-exhibited-a-promising-prognosis-in-pediatric-acute-lymphoblastic-leukemia-treated-with-the-cclg-all2008-protocol
#3
Yixin Hu, Hailong He, Jun Lu, Yi Wang, Peifang Xiao, Jianqin Li, Jie Li, Yina Sun, Hui Lv, Junjie Fan, Yanhua Yao, Yihuan Chai, Shaoyan Hu
OBJECTIVE: The objective of this study was to observe the prognosis of pediatric patients with E2A-PBX1-positive acute lymphoblastic leukemia (ALL) from the treatment with the CCLG-ALL2008 protocol. DESIGN AND METHODS: Three hundred and forty-nine Chinese pediatric patients with pre-B-cell ALL were enrolled in this study from December 2008 to September 2013. Of these, 20 patients with E2A-PBX1 expression and 223 without the gene expression were stratified into two cohorts...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27916615/characterization-of-rare-dormant-and-therapy-resistant-cells-in-acute-lymphoblastic-leukemia
#4
Sarah Ebinger, Erbey Ziya Özdemir, Christoph Ziegenhain, Sebastian Tiedt, Catarina Castro Alves, Michaela Grunert, Michael Dworzak, Christoph Lutz, Virginia A Turati, Tariq Enver, Hans-Peter Horny, Karl Sotlar, Swati Parekh, Karsten Spiekermann, Wolfgang Hiddemann, Aloys Schepers, Bernhard Polzer, Stefan Kirsch, Martin Hoffmann, Bettina Knapp, Jan Hasenauer, Heike Pfeifer, Renate Panzer-Grümayer, Wolfgang Enard, Olivier Gires, Irmela Jeremias
Tumor relapse is associated with dismal prognosis, but responsible biological principles remain incompletely understood. To isolate and characterize relapse-inducing cells, we used genetic engineering and proliferation-sensitive dyes in patient-derived xenografts of acute lymphoblastic leukemia (ALL). We identified a rare subpopulation that resembled relapse-inducing cells with combined properties of long-term dormancy, treatment resistance, and stemness. Single-cell and bulk expression profiling revealed their similarity to primary ALL cells isolated from pediatric and adult patients at minimal residual disease (MRD)...
November 18, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27913601/calorespirometry-reveals-that-goldfish-prioritize-aerobic-metabolism-over-metabolic-rate-depression-in-all-but-near-anoxic-environments
#5
Matthew D Regan, Ivan Gill, Jeffrey G Richards
Metabolic rate depression (MRD) has long been proposed as the key metabolic strategy of hypoxic survival, but surprisingly the effects of changes in hypoxic O2 tensions (PwO2) on MRD are largely unexplored. We simultaneously measured the O2 consumption rate (ṀO2) and metabolic heat of goldfish using calorespirometry to test the hypothesis that MRD is employed at hypoxic PwO2s and initiated just below Pcrit, the PwO2 below which ṀO2 is forced to progressively decline as the fish oxyconforms to decreasing PwO2 Specifically, we used closed-chamber and flow-through calorespirometry together with terminal sampling experiments to examine the effects of PwO2 and time on ṀO2, metabolic heat and anaerobic metabolism (lactate and ethanol production)...
December 2, 2016: Journal of Experimental Biology
https://www.readbyqxmd.com/read/27913532/t-cell-acute-lymphoblastic-leukemia
#6
Elizabeth A Raetz, David T Teachey
T-cell acute lymphoblastic leukemia (T-ALL) is biologically distinct from its B lymphoblastic (B-ALL) counterpart and shows different kinetic patterns of disease response. Although very similar regimens are used to treat T-ALL and B-ALL, distinctions in response to different elements of therapy have been observed. Similar to B-ALL, the key prognostic determinant in T-ALL is minimal residual disease (MRD) response. Unlike B-ALL, other factors including age, white blood cell count at diagnosis, and genetics of the ALL blasts are not independently prognostic when MRD response is included...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913513/minimal-residual-disease-in-mantle-cell-lymphoma-insights-into-biology-and-impact-on-treatment
#7
Eva Hoster, Christiane Pott
Despite the recent substantial improvement of clinical outcome in mantle cell lymphoma (MCL), resistance to immunochemotherapy and common relapses are challenges for long-term tumor control. The assessment of minimal residual disease (MRD) by real-time quantitative polymerase chain reaction has emerged as a widely feasible and standardized tool for direct assessment of therapy-induced reduction of tumor burden and regrowth after cytotoxic treatment in MCL, with much improved sensitivity compared with conventional staging procedures...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913502/mrd-in-aml-does-it-already-guide-therapy-decision-making
#8
Gert Ossenkoppele, Gerrit Jan Schuurhuis
Prognostic factors determined at diagnosis are predictive for outcome whereas achievement of morphological complete remission (CR) is still an important end point during treatment. Residual disease after therapy may reflect the sum of all diagnosis and postdiagnosis resistance mechanisms/factors; its measurement could hypothetically be very instrumental for guiding treatment. The possibility of defining residual disease (minimal residual disease [MRD]) far below the level of 5% blast cells is changing the landscape of risk classification...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27905338/the-utility-of-margin-reflex-distance-in-determining-the-type-of-surgical-intervention-for-congenital-blepharoptosis
#9
Ozlem Ural, Mehmet Cem Mocan, Anıl Dolgun, Ugur Erdener
AIMS: To evaluate the utility of margin-reflex distance (MRD) as an alternative to levator function (LF) in choosing the appropriate surgical procedure for congenital blepharoptosis. SETTINGS AND DESIGN: This was a retrospective, observational study. SUBJECTS AND METHODS: Records of patients with simple (dystrophic) congenital ptosis who were operated and followed for ≥6 months postoperatively and whose outcomes were deemed as successful were evaluated in the study...
October 2016: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/27903527/standardized-flow-cytometry-for-highly-sensitive-mrd-measurements-in-b-cell-acute-lymphoblastic-leukemia
#10
Prisca Theunissen, Ester Mejstrikova, Lukasz Sedek, Alita J van der Sluijs-Gelling, Giuseppe Gaipa, Marius Bartels, Elaine Sobral da Costa, Michaela Kotrova, Michaela Novakova, Edwin Sonneveld, Chiara Buracchi, Paola Bonaccorso, Elen Oliviera, Jeroen G Te Marvelde, Tomasz Szczepanski, Ludovic Lhermitte, Ondrej Hrusak, Quentin Lecrevisse, Georgiana Emilia Grigore, Eva Fronkova, Jan Trka, Monika Brüggemann, Alberto Orfao, Jacques J M van Dongen, Vincent H J van der Velden
A fully-standardized EuroFlow 8-color antibody panel and laboratory procedure was stepwise designed to measure minimal residual disease (MRD) in B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) patients with a sensitivity of ≤10(-5), comparable to real-time quantitative (RQ)-PCR-based MRD detection via antigen-receptor rearrangements. Leukocyte markers and the corresponding antibodies and fluorochromes were selected based on their contribution in separating BCP-ALL cells from normal/regenerating BCP cells in multidimensional principal component analyses...
November 30, 2016: Blood
https://www.readbyqxmd.com/read/27902457/tfdp3-confers-chemoresistance-in-minimal-residual-disease-within-childhood-t-cell-acute-lymphoblastic-leukemia
#11
Ming Chu, Kailin Yin, Yujun Dong, Pingzhang Wang, Yun Xue, Peng Zhou, Yuqi Wang, Yuedan Wang
Acquired drug resistance in childhood T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. In this study, a novel gene therapy target for childhood T-ALL to overcome chemoresistance was discovered: TFDP3 increased in the minimal residual disease (MRD) positive childhood T-ALL patients. Then, we established a preclinical model of resistance to induction therapy to examine the functional relevance of TFDP3 to chemoresistance in MRD derived from Jurkat/E6-1. Jurkat xenografts in NOD/SCID mice were exposed to a four drug combination (VXLD) of vincristine (VCR), dexamethasone (DEX), L-asparaginase (L-asp) and daunorubicin (DNR)...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27890255/chimeric-antigen-receptor-t-cell-therapy-in-aml-how-close-are-we
#12
REVIEW
Saar Gill
The majority of patients presenting with acute myeloid leukemia (AML) initially respond to chemotherapy but post-remission therapy is required to consolidate this response and achieve long-term disease-free survival. The most effective form of post-remission therapy relies on T cell immunotherapy in the form of allogeneic hematopoietic cell transplantation (HCT). However, patients with active disease cannot usually expect to be cured with HCT. This inherent dichotomy implies that traditional T cell-based immunotherapy in the form of allogeneic HCT stops being efficacious somewhere between the measurable residual disease (MRD) and the morphologically obvious range...
December 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27890252/aml-in-2016-where-we-are-now
#13
REVIEW
Jacob M Rowe
A high relapse rate for patients with acute myeloid leukemia (AML) is still a major barrier to the long-term survival of these patients. Nevertheless, considerable progress has been made both in the biology and therapy of the disease. Specifically, progress has been made in the areas of integrated genomic analysis for prognosis, the widening application of minimal residual disease (MRD) monitoring in clinical practice, the development of new agents, and the increasing use of drugs, such as IDH and FLT3 inhibitors, as a bridge to transplant...
December 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27889709/role-of-mid-induction-peripheral-blood-minimal-residual-disease-detection-in-pediatric-b-lineage-acute-lymphoblastic-leukemia
#14
Karthik Bommannan, Man Updesh Singh Sachdeva, Neelam Varma, Parveen Bose, Deepak Bansal
OBJECTIVE: To study the role of mid-induction (day 15) peripheral blood minimal residual disease (PBMRD) detection in pediatric B- lineage acute lymphoblastic leukemia (B-ALL). DESIGN: Prospective. SETTING: Tertiary care center. PATIENTS: Forty consecutively diagnosed treatment naive, pediatric B-ALL patients. INTERVENTION: National Cancer Institute (NCI) standard risk patients were given three drug induction regimen comprising vincristine, L-asparginase and prednisolone; NCI high risk patients were supplemented with daunorubicin...
November 5, 2016: Indian Pediatrics
https://www.readbyqxmd.com/read/27882357/the-influence-of-delta-formation-mechanism-on-geotechnical-property-sequence-of-the-late-pleistocene-holocene-sediments-in-the-mekong-river-delta
#15
Truong Minh Hoang, Nguyen van Lap, Ta Thi Kim Oanh, Takemura Jiro
The aim of the study was to characterize a variety of microstructure development-levels and geotechnical property sequences of the late Pleistocene-Holocene deposits in the Mekong River delta (MRD), and the paper furthermore discusses the influences of delta formation mechanisms on them. The survey associated the geotechnical engineering and the sedimentary geology of the late Pleistocene-Holocene deposits at five sites and also undifferentiated Pleistocene sediments. A cross-section which was rebuilt in the delta progradation-direction and between the Mekong and Bassac rivers represents the stratigraphy...
November 2016: Heliyon
https://www.readbyqxmd.com/read/27881874/acute-myeloid-leukemia-derived-from-lympho-myeloid-clonal-hematopoiesis
#16
F Thol, S Klesse, L Köhler, R Gabdoulline, A Kloos, A Liebich, M Wichman, A Chaturvedi, J Fabisch, V I Gaidzik, P Paschka, L Bullinger, G Bug, H Serve, G Göhring, B Schlegelberger, M Lübbert, H Kirchner, M Wattad, D Kraemer, B Hertenstein, G Heil, W Fiedler, J Krauter, R Schlenk, K Döhner, H Döhner, A Ganser, M Heuser
We studied acute myeloid leukemia (AML) patients with lympho-myeloid clonal hematopoiesis (LM-CH), defined by the presence of DNA methyltransferase 3A (DNMT3A) mutations in both the myeloid and lymphoid T-cell compartment. Diagnostic, CR and relapse samples were sequenced for 34 leukemia-related genes in 171 DNMT3A mutated adult AML patients. AML with LM-CH was found in 40 patients (23%) and was associated with clonal haematopoiesis of indeterminate potential (CHIP) years prior to AML, older age, secondary AML, and more frequent MDS-type co-mutations (TET2, RUNX1 and EZH2)...
November 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27876058/a-novel-non-hodgkin-lymphoma-murine-model-closer-to-the-standard-clinical-scenario
#17
Thais Bascuas, María Moreno, Amy Mónaco, Laura Reyes, Andrea Paolino, Patricia Oliver, María G Kramer, Henry Engler, José P Pacheco, Sofía Grille, José A Chabalgoity
BACKGROUND: Non-Hodgkin lymphomas (NHL) are the most frequent hemato-oncological malignancies. Despite recent major advances in treatment, a substantial proportion of patients relapses highlighting the need for new therapeutic modalities. Promissory results obtained in pre-clinical studies are usually not translated when moving into clinical trials. Pre-clinical studies are mainly conducted in animals with high tumor burden; instead patients undergo chemotherapy as first line of treatment and most likely are under remission when immunotherapies are applied...
November 22, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27872732/minimal-residual-disease-in-acute-myeloid-leukemia-of-adults-determination-prognostic-impact-and-clinical-applications
#18
REVIEW
Maria Ilaria Del Principe, Francesco Buccisano, Luca Maurillo, Giuseppe Sconocchia, Mariagiovanna Cefalo, Maria Irno Consalvo, Chiara Sarlo, Consuelo Conti, Giovanna De Santis, Eleonora De Bellis, Ambra Di Veroli, Patrizia Palomba, Cristina Attrotto, Annagiulia Zizzari, Giovangiacinto Paterno, Maria Teresa Voso, Giovanni Del Poeta, Francesco Lo-Coco, William Arcese, Sergio Amadori, Adriano Venditti
Pretreatment assessment of cytogenetic/genetic signature of acute myeloid leukemia (AML) has been consistently shown to play a major prognostic role but also to fail at predicting outcome on individual basis, even in low-risk AML. Therefore, we are in need of further accurate methods to refine the patients' risk allocation process, distinguishing more adequately those who are likely to recur from those who are not. In this view, there is now evidence that the submicroscopic amounts of leukemic cells (called minimal residual disease, MRD), measured during the course of treatment, indicate the quality of response to therapy...
2016: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/27864604/the-long-term-outcome-of-reduced-intensity-allogeneic-stem-cell-transplantation-from-a-matched-related-or-unrelated-donor-or-haploidentical-family-donor-in-patients-with-leukemia-a-retrospective-analysis-of-data-from-the-china-ric-cooperative-group
#19
Chang-Lin Yu, Zheng-Dong, Zhen-Hua Qiao, Jian-Min Wang, Huang-He, Ying-Min Liang, De-Pei Wu, Bao-An Chen, Bai-Hai, Bao-Fu Shi, Wan-Jun Sun, Jun-Xiao Qiao, Mei Guo, Jian-Hui Qiao, Qi-Yun Sun, Kai-Xun Hu, Ya-Jing Huang, Hong-Li Zuo, Xiao-Jun Huang, Hui-Sheng Ai
This study compared 6-year follow-up data from patients undergoing reduced-intensity conditioning (RIC) transplantation with an HLA-matched related donor (MRD), an HLA-matched unrelated donor (MUD), or an HLA-haploidentical donor (HID) for leukemia. Four hundred and twenty-seven patients from the China RIC Cooperative Group were enrolled, including 301 in the MRD, 79 in the HID, and 47 in the MUD groups. The conditioning regimen involved fludarabine combined with anti-lymphocyte globulin and cyclophosphamide...
November 18, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27862308/alemtuzumab-consolidation-in-chronic-lymphocytic-leukaemia-a-phase-i-ii-multicentre-trial
#20
Othman Al-Sawaf, Kirsten Fischer, Carmen D Herling, Matthias Ritgen, Sebastian Böttcher, Jasmin Bahlo, Thomas Elter, Stephan Stilgenbauer, Barbara F Eichhorst, Raymonde Busch, Ute Elberskirch, Wolfgang Abenhardt, Michael Kneba, Michael Hallek, Clemens-Martin Wendtner
OBJECTIVE: Despite high rates of long-lasting remissions in patients with chronic lymphocytic leukaemia (CLL) treated with chemoimmunotherapy, none of the current therapeutic approaches is curative with the exception of allogeneic transplantation. One strategy to extend progression-free survival and long-term survival might be the establishment of consolidation therapies. METHODS: In this trial, patients with complete or partial second remission after fludarabine-based treatment received consolidation therapy with alemtuzumab...
November 9, 2016: European Journal of Haematology
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