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https://www.readbyqxmd.com/read/29907552/beyond-maximum-grade-modernising-the-assessment-and-reporting-of-adverse-events-in-haematological-malignancies
#1
REVIEW
Gita Thanarajasingam, Lori M Minasian, Frederic Baron, Franco Cavalli, R Angelo De Claro, Amylou C Dueck, Tarec C El-Galaly, Neil Everest, Jan Geissler, Christian Gisselbrecht, John Gribben, Mary Horowitz, S Percy Ivy, Caron A Jacobson, Armand Keating, Paul G Kluetz, Aviva Krauss, Yok Lam Kwong, Richard F Little, Francois-Xavier Mahon, Matthew J Matasar, María-Victoria Mateos, Kristen McCullough, Robert S Miller, Mohamad Mohty, Philippe Moreau, Lindsay M Morton, Sumimasa Nagai, Simon Rule, Jeff Sloan, Pieter Sonneveld, Carrie A Thompson, Kyriaki Tzogani, Flora E van Leeuwen, Galina Velikova, Diego Villa, John R Wingard, Sophie Wintrich, John F Seymour, Thomas M Habermann
Tremendous progress in treatment and outcomes has been achieved across the whole range of haematological malignancies in the past two decades. Although cure rates for aggressive malignancies have increased, nowhere has progress been more impactful than in the management of typically incurable forms of haematological cancer. Population-based data have shown that 5-year survival for patients with chronic myelogenous and chronic lymphocytic leukaemia, indolent B-cell lymphomas, and multiple myeloma has improved markedly...
June 12, 2018: Lancet Haematology
https://www.readbyqxmd.com/read/29907380/monoclonal-gammopathies-of-unknown-significance-and-smoldering-myeloma-assessment-and-management-of-the-elderly-patients
#2
Verónica González-Calle, María Victoria Mateos
Monoclonal gammopathy of unknown significance (MGUS) is the most frequent plasma cell disorder that commonly affects elderly patients. Although it is an asymptomatic condition, as well as smoldering myeloma (SMM), the risk of progression to multiple myeloma requiring therapy or other B-cell disorders varies greatly for individual patients, remaining low for MGUS (1% per year), while higher and not uniform for SMM patients (10% per year). This scenario implies some special considerations regarding assessment and follow-up, especially in the elderly...
June 12, 2018: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/29906496/screening-and-characterization-of-a-annenix-a2-binding-aptamer-that-inhibits-the-proliferation-of-myeloma-cells
#3
Weihua Zhou, Yibin Zhang, Yayue Zeng, Minyuan Peng, Hui Li, Shuming Sun, Bianying Ma, Yanpeng Wang, Mao Ye, Jing Liu
Multiple myeloma (MM) is a malignant plasma cell disease and is considered incurable. Annexin A2 (ANXA2) is closely related to the proliferation and adhesion of MM. Using protein-SELEX, we performed a screen for aptamers that bind GST-ANXA2 from a library, and GST protein was used for negative selection. The enrichment of the ssDNA pool was monitored by filter-binding assay during selection. After nine rounds of screening and high-throughput sequencing, we obtained six candidate aptamers that bind to the ANXA2 protein...
June 12, 2018: Biochimie
https://www.readbyqxmd.com/read/29905462/the-human-biomolecular-corona-of-liposomal-doxorubicin-the-overlooked-factor-in-anticancer-drug-delivery
#4
Giulio Caracciolo, Sara Palchetti, Luca Digiacomo, Riccardo Zenezini Chiozzi, Anna Laura Capriotti, Heinz Amenitsch, Paolo Maria Tentori, Valentina Palmieri, Massimiliano Papi, Francesco Cardarelli, Daniela Pozzi, Aldo Laganà
More than twenty years after its approval by the Food and Drug Administration (FDA) liposomal doxorubicin (DOX) is still the drug of choice for the treatment of breast cancer and other conditions such as ovarian cancer and multiple myeloma. Yet, despite the efforts, liposomal DOX did not satisfy expectations at the clinical level. When liposomal drugs enter a physiological environment, their surface gets coated by a dynamic biomolecular corona (BC). The BC changes liposome's synthetic identity, providing it with a new one, referred to as 'biological identity' (size, aggregation state, and BC composition)...
June 15, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29903988/oncolytic-viruses-for-multiple-myeloma-therapy
#5
REVIEW
Christine M Calton, Kevin R Kelly, Faiz Anwer, Jennifer S Carew, Steffan T Nawrocki
Although recent treatment advances have improved outcomes for patients with multiple myeloma (MM), the disease frequently becomes refractory to current therapies. MM thus remains incurable for most patients and new therapies are urgently needed. Oncolytic viruses are a promising new class of therapeutics that provide tumor-targeted therapy by specifically infecting and replicating within cancerous cells. Oncolytic therapy yields results from both direct killing of malignant cells and induction of an anti-tumor immune response...
June 14, 2018: Cancers
https://www.readbyqxmd.com/read/29898899/linking-transcriptional-and-genetic-tumor-heterogeneity-through-allele-analysis-of-single-cell-rna-seq-data
#6
Jean Fan, Hae-Ock Lee, Soohyun Lee, Da-Eun Ryu, Semin Lee, Catherine Xue, Seok Jin Kim, Kihyun Kim, Nikolas Barkas, Peter J Park, Woong-Yang Park, Peter V Kharchenko
Characterization of intratumoral heterogeneity is critical to cancer therapy, as presence of phenotypically diverse cell populations commonly fuels relapse and resistance to treatment. Although genetic variation is a well-studied source of intratumoral heterogeneity, the functional impact of most genetic alterations remains unclear. Even less understood is the relative importance of other factors influencing heterogeneity, such as epigenetic state or tumor microenvironment. To investigate the relationship between genetic and transcriptional heterogeneity in a context of cancer progression, we devised a computational approach called HoneyBADGER to identify copy number variation and loss-of-heterozygosity in individual cells from single-cell RNA-sequencing data...
June 13, 2018: Genome Research
https://www.readbyqxmd.com/read/29897481/association-between-autologous-stem-cell-transplant-and-survival-among-californians-with-multiple-myeloma
#7
Aaron S Rosenberg, Ann Brunson, Brian A Jonas, Theresa H M Keegan, Ted Wun
Background: Autologous hematopoietic stem cell transplant (aHSCT) is an efficacious treatment for newly diagnosed multiple myeloma patients. However, as rapid advances have resulted in other highly efficacious and less intensive therapies, the role of aHSCT has been questioned. Methods: We utilized population-based data to identify 13 494 newly diagnosed patients younger than age 80 years between 1998 and 2012. Patient characteristics of aHSCT and non-aHSCT groups were balanced using inverse probability weighting of a propensity score predicting aHSCT use...
June 11, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29895955/multiple-myeloma-clonal-evolution-in-homogeneously-treated-patients
#8
Jill Corre, Alice Cleynen, Sébastien Robiou du Pont, Laure Buisson, Niccolo Bolli, Michel Attal, Nikhil Munshi, Hervé Avet-Loiseau
Clonal evolution drives tumor progression, chemoresistance and relapse in cancer. Little is known about clonal selection induced by therapeutic pressure in multiple myeloma. To address this issue, we performed large targeted sequencing of bone marrow plasma cells in 43 multiple myeloma patients at diagnosis and at relapse from exactly the same intensive treatment. The most frequently mutated genes at diagnosis were KRAS (35%), NRAS (28%), DIS3 (16%), BRAF, and LRP1B (12% each). At relapse, the mutational burden was unchanged...
June 12, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29893485/treatment-of-pediatric-plasma-cell-myeloma-type-post-transplant-lymphoproliferative-disorder-with-modern-risk-directed-therapy
#9
Rebecca Epperly, John Ozolek, Kyle Soltys, Debra Cohen, Rakesh Goyal, Erika Friehling
Post-transplant lymphoproliferative disorder (PTLD) related plasma cell neoplasms are rare in pediatric patients. We report a pediatric liver transplant recipient with plasma cell myeloma type PTLD. Cytogenetics included 1q duplication, associated with poor prognosis in adult multiple myeloma, and t(8;14). High-risk cytogenetics has not been reported in pediatric plasma cell myeloma type PTLD. The patient was treated with bortezomib, dexamethasone, and lenalidomide with subsequent autologous stem cell transplant...
June 12, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29886833/arterial-hypertension-and-multiple-myeloma-physiopathology-and-cardiovascular-risk-and-practical-indications-in-patients-receiving-carfilzomib
#10
Alberto Milan, Giulia Bruno, Ilaria Maffei, Andrea Iannaccone, Agnese Ravera, Domenica Schiavone, Franco Veglio
The introduction of carfilzomib in the treatment of relapsing and refractory multiple myeloma has allowed a significant increase in survival. The most frequent adverse effect of Carfilzomib treatment is arterial hypertension, even thought the exact physiopathological mechanism are still unclear. MM patients, on the other hand, often present significant cardiovascular risk factors and comorbidities. Uncontrolled hypertension is frequently the cause of cardiovascular complications. It has been estimated that up to 50% of subjects in the general population are unaware of their hypertensive condition and only half of those who are aware of this risk factor present good control of blood pressure...
June 10, 2018: Current Hypertension Reviews
https://www.readbyqxmd.com/read/29885947/a-transcriptomic-signature-predicting-septic-outcome-in-patients-undergoing-autologous-stem-cell-transplantation
#11
Labiad Yasmine, Venton Geoffroy, Farnault Laure, Baier Céline, Colle Julien, Mercier Cedric, Ivanov Vadim, Nicolino Corinne, Loriod Béatrice, Fernandez-Nunez Nicolas, Torres Magali, Mattei Jean-Camille, Rihet Pascal, Nguyen Catherine, Costello Régis
Autologous hematopoietic stem cell transplantation (auto-HSCT) is a standard treatment in multiple myeloma and relapsed or refractory lymphomas. After auto-HSCT, hematologic reconstitution and infectious complications are the main two critical issues. Though many patients develop infectious complications after therapeutic intensification, it remains impossible to predict infection for each individual. The goal of this work was to determine and identify a predictive transcriptomic signature of systemic inflammatory response syndrome (SIRS) and/or sepsis in patients receiving auto-HSCT...
June 7, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29885924/clinical-course-of-a-patient-with-kidney-failure-due-to-isolated-bilateral-renal-extramedullary-plasmacytomas
#12
Braden J Lawrence, Emily L Petersen, Wayne G Riches, David C Pfeiffer
Plasmacytomas are rare immunoproliferative monoclonal plasma cell diseases of lymphoid lineage that may present in an isolated or systemic manner. Systemic involvement is much more common than occurrences isolated to a particular organ, and for this reason, it is imperative to rule out systemic involvement for osseous and nonosseous isolated neoplasms. These neoplasms present unique challenges due to their location, extent of involvement, vague presentation, and dearth of treatment protocol. We report the case of a 69-year-old man who developed chronic kidney disease stage 4 between 2009 and 2012...
June 6, 2018: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/29884741/identification-of-novel-mutational-drivers-reveals-oncogene-dependencies-in-multiple-myeloma
#13
Brian A Walker, Konstantinos Mavrommatis, Christopher P Wardell, T Cody Ashby, Michael Bauer, Faith E Davies, Adam Rosenthal, Hongwei Wang, Pingping Qu, Antje Hoering, Mehmet Samur, Fadi Towfic, Maria Ortiz, Erin Flynt, Zhinuan Yu, Zhihong Yang, Dan Rozelle, John Obenauer, Matthew Trotter, Daniel Auclair, Jonathan Keats, Niccolo Bolli, Mariateresa Fulciniti, Raphael Szalat, Philippe Moreau, Brian Durie, A Keith Stewart, Hartmut Goldschmidt, Marc S Raab, Hermann Einsele, Pieter Sonneveld, Jesus San Miguel, Sagar Lonial, Graham H Jackson, Kenneth C Anderson, Herve Avet-Loiseau, Nikhil Munshi, Anjan Thakurta, Gareth J Morgan
Understanding the profile of oncogene and tumor suppressor gene mutations with their interactions and impact on the prognosis of multiple myeloma (MM) can improve the definition of disease subsets and identify pathways important in disease pathobiology. Using integrated genomics of 1,273 newly diagnosed patients with multiple myeloma we identify 63 driver genes, some of which are novel including IDH1 , IDH2 , HUWE1 , KLHL6 , and PTPN11 Oncogene mutations are significantly more clonal than tumor suppressor mutations, indicating they may exert a bigger selective pressure...
June 8, 2018: Blood
https://www.readbyqxmd.com/read/29882602/the-efficacy-and-safety-of-pomalidomide-in-relapsed-refractory-multiple-myeloma-in-a-real-world-study-polish-myeloma-group-experience
#14
Grzegorz Charlinski, Norbert Grzasko, Artur Jurczyszyn, Mariusz Janczarski, Agnieszka Szeremet, Anna Waszczuk-Gajda, Paweł Bernatowicz, Alina Swiderska, Renata Guzicka-Kazimierczak, Ewa Lech-Maranda, Andrzej Szczepaniak, Ryszard Wichary, Anna Dmoszynska
BACKGROUND: Patients with relapsed/refractory multiple myeloma (RRMM) have poor prognosis. Pomalidomide is an immunomodulatory compound that has demonstrated activity in MM patients with disease refractory to lanlidomide and bortezomib. OBJECTIVES: Participants of clinical trials are highly selected populations; therefore, the aim of this study was to present observations from real practice that might provide important information for practitioners. PATIENTS AND METHODS: We analyzed retrospectively 50 patients treated with pomalidomide in 12 Polish sites between 2014 and 2017...
June 8, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29880892/patient-centered-practice-in-elderly-myeloma-patients-an-overview-and-consensus-from-the-european-myeloma-network-emn
#15
REVIEW
Alessandra Larocca, Sandra Maria Dold, Sonja Zweegman, Evangelos Terpos, Ralph Wäsch, Mattia D'Agostino, Sophia Scheubeck, Hartmut Goldschmidt, Francesca Gay, Michele Cavo, Heinz Ludwig, Christian Straka, Sara Bringhen, Holger W Auner, Jo Caers, Martin Gramatzki, Massimo Offidani, Meletios A Dimopoulos, Hermann Einsele, Mario Boccadoro, Pieter Sonneveld, Monika Engelhardt
Multiple myeloma is a disease typical of the elderly, and, because of the increase in life expectancy of the general population, its incidence is expected to grow in the future. Elderly patients represent a particular challenge due to their marked heterogeneity. Many new and highly effective drugs have been introduced in the last few years and results from clinical trials are promising. Besides the availability of novel agents, a careful evaluation of elderly patients showed to be a key factor for the success of therapy...
April 25, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29880611/impaired-mitochondrial-activity-explains-platelet-dysfunction-in-thrombocytopenic-cancer-patients-undergoing-chemotherapy
#16
Constance C F M J Baaten, Floor C J I Moenen, Yvonne M C Henskens, Frauke Swieringa, Rick J H Wetzels, René van Oerle, Harry F G Heijnen, Hugo Ten Cate, Graham P Holloway, Erik A M Beckers, Johan W M Heemskerk, Paola E J van der Meijden
Severe thrombocytopenia (≤50x109 platelets/L) due to hematological malignancy and intensive chemotherapy is associated with an increased risk of clinically significant bleeding. Since the bleeding risk is not linked to the platelet count only, other hemostatic factors must be involved. In 77 patients with acute leukemia, multiple myeloma or malignant lymphoma, who experienced chemotherapy-induced thrombocytopenia, we studied platelet function. Platelets from all patients - independent of disease or treatment type - were to a variable extent compromised in Ca2+ flux, integrin αIIbβ3 activation and P-selectin expression, when stimulated with a panel of agonists...
June 7, 2018: Haematologica
https://www.readbyqxmd.com/read/29879938/a-patient-with-plasmablastic-lymphoma-achieving-long-term-complete-remission-after-thalidomide-dexamethasone-induction-and-double-autologous-stem-cell-transplantation-a-case-report
#17
Alessandro Broccoli, Laura Nanni, Vittorio Stefoni, Claudio Agostinelli, Lisa Argnani, Michele Cavo, Pier Luigi Zinzani
BACKGROUND: No standard of care is established for plasmablastic lymphoma (PBL) and prognosis remains extremely poor, given that patients relapse early after chemotherapy and display resistance to commonly applied cytostatic drugs. CASE PRESENTATION: We report a case of nodal, HIV-unrelated PBL in a patient who achieved and maintained a very long lasting complete remission after an intensive therapy consisting consisting of thalidomide plus dexamethasone followed by a consolidation with double autologous stem cell transplantation...
June 8, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29877243/-multiple-myeloma-update-on-pathophysiology-and-management
#18
Ichiro Hanamura, Shinsuke Iida
Proteasome inhibitors and immunomodulatory drugs have substantially improved the clinical outcomes in patients with multiple myeloma (MM) since 2000. In 2015, the new monoclonal antibodies, daratumumab and elotuzumab, were approved for treating relapsed and/or refractory MM (RRMM). Furthermore, venetoclax, a selective BCL-2 inhibitor, and chimeric antigen receptor (CAR) T-cell therapy that work against B-cell maturation antigen (BCMA) have reportedly shown great efficacy in phase 1 studies. The efficacy of venetoclax has been observed in RRMM with t (11;14) and higher BCL-2/BCL-XL expression...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29876158/disease-milestones-through-bibliometric-analysis-of-the-top-100-cited-articles-in-multiple-myeloma
#19
REVIEW
Azka Latif, Vikas Kapoor, Qurat Ul Ain Riaz Sipra, Saad Ullah Malik, Jawad Bilal, Irbaz Bin Riaz, Faiz Anwer
Multiple myeloma (MM) accounts for 1.6% of all cancers and 5%-10% of all hematologic malignancies in the United States (US). Despite marked progress in disease management, it remains incurable with high rates of relapse. We conducted a bibliographic analysis on the Web of Science (WOS) from July 25, 2017 and July 29, 2017. Among the top 100 most-cited articles (1901-2012), the most cited article received 2404 citations and least cited article received 336 citations. Forty-four of 100 articles were published in journals with impact factors greater than 20...
April 5, 2018: Curēus
https://www.readbyqxmd.com/read/29876006/selinexor-synergizes-with-dexamethasone-to-repress-mtorc1-signaling-and-induce-multiple-myeloma-cell-death
#20
Christian Argueta, Trinayan Kashyap, Boris Klebanov, Thaddeus J Unger, Cathy Guo, Susie Harrington, Erkan Baloglu, Margaret Lee, William Senapedis, Sharon Shacham, Yosef Landesman
Multiple myeloma (MM) is a plasma cell neoplasm that results in over 11,000 deaths in the United States annually. The backbone therapy for the treatment of MM patients almost always includes combinations with corticosteroids such as dexamethasone (DEX). We found that DEX in combination with selinexor, an inhibitor of exportin-1 (XPO1) activity, synergistically inhibits the mTOR pathway and subsequently promotes cell death in MM cells. Specifically, we show that selinexor induces the expression of the glucocorticoid receptor (GR) and when combined with dexamethasone increases GR transcriptional activity...
May 22, 2018: Oncotarget
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