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Treatment of myeloma

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https://www.readbyqxmd.com/read/29348537/radionuclides-transform-chemotherapeutics-into-phototherapeutics-for-precise-treatment-of-disseminated-cancer
#1
Nalinikanth Kotagiri, Matthew L Cooper, Michael Rettig, Christopher Egbulefu, Julie Prior, Grace Cui, Partha Karmakar, Mingzhou Zhou, Xiaoxia Yang, Gail Sudlow, Lynne Marsala, Chantiya Chanswangphuwana, Lan Lu, LeMoyne Habimana-Griffin, Monica Shokeen, Xinming Xu, Katherine Weilbaecher, Michael Tomasson, Gregory Lanza, John F DiPersio, Samuel Achilefu
Most cancer patients succumb to disseminated disease because conventional systemic therapies lack spatiotemporal control of their toxic effects in vivo, particularly in a complicated milieu such as bone marrow where progenitor stem cells reside. Here, we demonstrate the treatment of disseminated cancer by photoactivatable drugs using radiopharmaceuticals. An orthogonal-targeting strategy and a contact-facilitated nanomicelle technology enabled highly selective delivery and co-localization of titanocene and radiolabelled fluorodeoxyglucose in disseminated multiple myeloma cells...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29345096/psychiatric-sequelae-of-corticosteroid-use-in-hematology-in-australia-a-qualitative-study
#2
Dianne Clifton, Margaret Ross, Clare O'Callaghan
Despite widespread steroid usage for treating hematological conditions, minimal attention focuses on associated psychiatric side-effects. In the present study, we examined hematology patients' experiences of high-dose steroid treatment. This was undertaken by the use of a qualitative, descriptive design, which included convenience sampling and the inductive, cyclic, and constant comparative thematic analysis of interview transcripts. Eighteen patients participated, who were diagnosed with lymphoma, myeloma, leukemia, or idiopathic thrombocytopenia purpura...
January 18, 2018: Nursing & Health Sciences
https://www.readbyqxmd.com/read/29344579/prognostic-significance-of-cytogenetic-heterogeneity-in-patients-with-newly-diagnosed-multiple-myeloma
#3
Maximilian Merz, Anna Jauch, Thomas Hielscher, Tilmann Bochtler, Stefan Olaf Schönland, Anja Seckinger, Dirk Hose, Uta Bertsch, Kai Neben, Marc Steffen Raab, Jens Hillengass, Hans Salwender, Igor Wolfgang Blau, Hans-Walter Lindemann, Ingo G H Schmidt-Wolf, Christof Scheid, Mathias Haenel, Katja C Weisel, Hartmut Goldschmidt
We investigated subclonal cytogenetic aberrations (CA) detected by interphase fluorescence in situ hybridization (iFISH) in patients with newly diagnosed multiple myeloma (MM) enrolled in the Haemato Oncology Foundation for Adults in the Netherlands (HOVON)-65/German-Speaking MM Group (GMMG)-HD4 phase 3 trial. Patients were either treated with 3 cycles of vincristine, Adriamycin, and dexamethasone or bortezomib, Adriamycin, and dexamethasone and then thalidomide or bortezomib maintenance after tandem autologous transplantation...
January 9, 2018: Blood Advances
https://www.readbyqxmd.com/read/29344169/bortezomib-overcomes-the-negative-prognostic-impact-of-renal-impairment-in-a-newly-diagnosed-elderly-patient-with-multiple-myeloma-a-case-report
#4
Tao Wu, Jinmao Zhou, Cunbang Wang, Binbin Wang, Shuting Zhang, Hai Bai
Multiple myeloma (MM) is a common B-cell hematological malignancy in the clinic. Bortezomib is the first-in-class proteasome inhibitor that has been approved for the treatment of patients with MM in the bone marrow. The present study report the case of an 83-year-old man who showed marked weakness, fatigue and a poor appetite. The patient was admitted to the Department of Nephrology due to severe renal impairment (RI). Immunofixation electrophoresis indicated a λ light chain-positive status. There were 19...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29342125/induction-of-pro-apoptotic-endoplasmic-reticulum-stress-in-multiple-myeloma-cells-by-neo214-perillyl-alcohol-conjugated-to-rolipram
#5
Thomas C Chen, Nymph Chan, Shirin Labib, Jiali Yu, Hee-Yeon Cho, Florence M Hofman, Axel H Schönthal
Despite the introduction of new therapies for multiple myeloma (MM), many patients are still dying from this disease and novel treatments are urgently needed. We have designed a novel hybrid molecule, called NEO214, that was generated by covalent conjugation of the natural monoterpene perillyl alcohol (POH), an inducer of endoplasmic reticulum (ER) stress, to rolipram (Rp), an inhibitor of phosphodiesterase-4 (PDE4). Its potential anticancer effects were investigated in a panel of MM cell lines. We found that NEO214 effectively killed MM cells in vitro with a potency that was over an order of magnitude stronger than that of its individual components, either alone or in combination...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29341834/improvement-in-overall-survival-with-carfilzomib-lenalidomide-and-dexamethasone-in-patients-with-relapsed-or-refractory-multiple-myeloma
#6
David S Siegel, Meletios A Dimopoulos, Heinz Ludwig, Thierry Facon, Hartmut Goldschmidt, Andrzej Jakubowiak, Jesus San-Miguel, Mihaela Obreja, Julie Blaedel, A Keith Stewart
Purpose In the ASPIRE study of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide plus dexamethasone (Rd) in patients with relapsed or refractory multiple myeloma, progression-free survival was significantly improved in the carfilzomib group (hazard ratio, 0.69; two-sided P < .001). This prespecified analysis reports final overall survival (OS) data and updated safety results. Patients and Methods Adults with relapsed multiple myeloma (one to three prior lines of therapy) were eligible and randomly assigned at a one-to-one ratio to receive KRd or Rd in 28-day cycles until withdrawal of consent, disease progression, or occurrence of unacceptable toxicity...
January 17, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29341831/role-of-bone-modifying-agents-in-multiple-myeloma-american-society-of-clinical-oncology-clinical-practice-guideline-update
#7
Kenneth Anderson, Nofisat Ismaila, Patrick J Flynn, Susan Halabi, Sundar Jagannath, Mohammed S Ogaily, Jim Omel, Noopur Raje, G David Roodman, Gary C Yee, Robert A Kyle
Purpose To update guideline recommendations on the role of bone-modifying agents in multiple myeloma. Methods An update panel conducted a targeted systematic literature review by searching PubMed and the Cochrane Library for randomized controlled trials, systematic reviews, meta-analyses, clinical practice guidelines, and observational studies. Results Thirty-five relevant studies were identified, and updated evidence supports the current recommendations. Recommendations For patients with active symptomatic multiple myeloma that requires systemic therapy with or without evidence of lytic destruction of bone or compression fracture of the spine from osteopenia on plain radiograph(s) or other imaging studies, intravenous administration of pamidronate 90 mg over at least 2 hours or zoledronic acid 4 mg over at least 15 minutes every 3 to 4 weeks is recommended...
January 17, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29340073/ym155-exerts-potent-cytotoxic-activity-against-quiescent-g0-g1-multiple-myeloma-and-bortezomib-resistant-cells-via-inhibition-of-survivin-and-mcl-1
#8
Miyuki Ookura, Tatsuya Fujii, Hideki Yagi, Takuya Ogawa, Shinji Kishi, Naoko Hosono, Hiroko Shigemi, Takahiro Yamauchi, Takanori Ueda, Akira Yoshida
YM155, a novel small molecule inhibitor of survivin, shows broad anticancer activity. Here, we have focused on the cytotoxic activity of YM155 against multiple myeloma (MM) including cytokinetically quiescent (G0/G1) cells and bortezomib resistant cells. YM155 strongly inhibited the growth of MM cell lines with the IC50 value of below 10 nM. YM155 also showed potent anti-myeloma activity in mouse xenograft model. YM155 suppressed the expression of survivin and rapidly directed Mcl-1 protein for proteasome degradation...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340048/alteration-of-mitochondrial-biogenesis-promotes-disease-progression-in-multiple-myeloma
#9
Xin Zhan, Wenjie Yu, Reinaldo Franqui-Machin, Melissa L Bates, Kalyan Nadiminti, Huojun Cao, Brad A Amendt, Yogesh Jethava, Ivana Frech, Fenghuang Zhan, Guido Tricot
Many cancers, including multiple myeloma (MM), retain more cytosolic iron to promote tumor cell growth and drug resistance. Higher cytosolic iron promotes oxidative damage due to its interaction with reactive oxygen species generated by mitochondria. The variation of mitochondrial biogenesis in different stages of MM disease was evaluated using gene expression profiles in a large clinical dataset. Sixteen of 18mitochondrial biogenesis related gene sets, including mitochondrial biogenesis signature and oxidative phosphorylation, were increased in myeloma cells compared with normal plasma cells and high expression was associated with an inferior patient outcome...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339269/phase-2-study-of-an-intravenous-busulfan-and-melphalan-conditioning-regimen-for-autologous-stem-cell-transplantation-in-patients-with-multiple-myeloma-kmm150
#10
Sung-Hoon Jung, Je-Jung Lee, Jin Seok Kim, Chang-Ki Min, Kihyun Kim, Yunsuk Choi, Hyeon-Seok Eom, Young Don Joo, Sung-Hyun Kim, Jae-Yong Kwak, Hye Jin Kang, Jae Hoon Lee, Ho Sup Lee, Yeung-Chul Mun, Joon Ho Moon, Sang Kyun Sohn, Seong Kyu Park, Yong Park, Ho-Jin Shin, Sung-Soo Yoon
This prospective study evaluated the efficacy and toxicity of intravenous busulfan and melphalan as a conditioning regimen for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). A total of 99 patients with MM, enrolled between January 2013 and March 2016, received intravenous busulfan (9.6 mg/kg) and melphalan (140 mg/m2) prior to ASCT. The median time to transplant was 6.2 months, and 90 patients (90.9%) underwent ASCT within 12 months of the diagnosis. The overall response rate after ASCT was 94...
January 12, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29338789/diagnosis-treatment-and-response-assessment-in-solitary-plasmacytoma-updated-recommendations-from-a-european-expert-panel
#11
REVIEW
J Caers, B Paiva, E Zamagni, X Leleu, J Bladé, S Y Kristinsson, C Touzeau, N Abildgaard, E Terpos, R Heusschen, E Ocio, M Delforge, O Sezer, M Beksac, H Ludwig, G Merlini, P Moreau, S Zweegman, M Engelhardt, L Rosiñol
Solitary plasmacytoma is an infrequent form of plasma cell dyscrasia that presents as a single mass of monoclonal plasma cells, located either extramedullary or intraosseous. In some patients, a bone marrow aspiration can detect a low monoclonal plasma cell infiltration which indicates a high risk of early progression to an overt myeloma disease. Before treatment initiation, whole body positron emission tomography-computed tomography or magnetic resonance imaging should be performed to exclude the presence of additional malignant lesions...
January 16, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29336950/daratumumab-therapeutic-asset-biological-trap
#12
V Deneys, C Thiry, A Frelik, C Debry, B Martin, C Doyen
OBJECTIVES: Recently, daratumumab has been included in the therapeutic strategies for myeloma patients. This molecule is an antibody directed against CD38, strongly expressed on plasma cells. Nevertheless, as CD38 is also present on erythrocyte membrane, daratumumab interferes with immunohaematological tests, complicating the selection of compatible blood. METHODS: A total of 14 patients treated by daratumumab have been followed in our transfusion laboratory. Among them, 11 have been transfused...
January 11, 2018: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
https://www.readbyqxmd.com/read/29334938/therapeutic-plasma-exchange-in-a-tertiary-care-center-185-patients-undergoing-912-treatments-a-one-year-retrospective-analysis
#13
Julius J Schmidt, Firas Asper, Gunilla Einecke, Gabriele Eden, Carsten Hafer, Jan T Kielstein
BACKGROUND: Therapeutic plasma exchange (TPE) is increasingly used throughout the world. Although the procedure itself is fairly standardized, it is yet unknown how the underlying disease entities influence the key coordinates of the treatment. METHODS: Retrospective chart review. The treatment indications were clustered into four categories. Data are presented as median and interquartile (25-75%) range [IQR]. RESULTS: Within 1 year, 912 TPE treatments were performed in 185 patients (90 female, 48...
January 15, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29334316/potential-therapeutic-and-economic-value-of-risk-stratified-treatment-as-initial-treatment-of-multiple-myeloma-in-europe
#14
Jennifer G Gaultney, Therese W Ng, Carin A Uyl-de Groot, Pieter Sonneveld, Erik H van Beers, Martin H van Vliet, William K Redekop
Biomarkers associated with prognosis in multiple myeloma (MM) can be used to stratify patients into risk categories. An attractive alternative to uniform treatment (UT), risk-stratified treatment (RST) is proposed where high-risk patients receive bortezomib-based regimens while standard-risk patients receive alternative less costly regimens. An early Markov-type decision analytic model evaluated the potential therapeutic and economic value of different RST strategies compared with UT in MM patients in key European countries...
January 15, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29333597/tp53-polymorphism-in-plasma-cell-myeloma
#15
Szymon Andrzej Zmorzynski, Iwona Korszen-Pilecka, Magdalena Wojcierowska-Litwin, Barbara Kwiatkowska-Drabik, Malgorzata Luterek, Sylwia Chocholska, Dorota Koczkodaj, Sylwia Popek, Malgorzata Michalak-Wojnowska, Grazyna Swiderska-Kolacz, Joanna Januszewska, Iwona Surowiec, Waldemar Tomczak, Marek Hus, Anna Dmoszynska, Marcin Pasiarski, Katarzyna Poniewierska-Jasak, Katarzyna Cieplinska, Olga Jankowska-Lecka, Agata Anna Filip
INTRODUCTION: Significant and accessible predictive factors for bortezomib treatment in plasma cell myeloma (PCM) are still lacking. TP53 codon 72 polymorphism (P72R) results in proline (P) or arginine (R) at 72 amino acid position, which causes synthesis of proteins with distinct functions. The aims of our study were to: 1) analyze whether this polymorphism is associated with an increased risk of PCM; 2) study whether the P72R polymorphism affects overall survival (OS) among PCM patients; 3) assess the possible association of the P72R polymorphism with sensitivity to bortezomib in cell cultures derived from PCM patients...
January 15, 2018: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/29333596/risk-of-adverse-events-associated-with-front-line-anti-myeloma-treatment-in-medicare-patients-with-multiple-myeloma
#16
Ying Chen, David R Lairson, Wenyaw Chan, Xianglin L Du
This study aims to examine the risks of adverse events associated with anti-multiple myeloma (MM) therapies in a large population-based cohort of elderly patients with MM. Patients diagnosed with advanced MM from 2005 through 2009 and receiving anti-MM therapy were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked data. We compared safety outcomes between novel agents (proteasome inhibitor (PI) and immunomodulatory drugs (IMiD)) and other therapies and between PI- or IMiD-based regimens and PI plus IMiD combination regimens...
January 15, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29333030/multiple-myeloma-presenting-as-thyroid-plasmacytoma
#17
Kaalindi Singh, Pankaj Kumar, Ritesh Pruthy, Gautam Goyal
Thyroid gland and thyroid cartilage infiltration in multiple myeloma (MM) are rare. Here, we discuss a patient who presented with hoarseness of voice and was found to have a hypodense lesion in right lobe of thyroid involving thyroid and cricoid cartilage. Fine-needle aspiration cytology with immunohistochemistry revealed extramedullary plasmacytoma of thyroid. MM was ruled out initially by serum protein electrophoresis, immunofixation, and bone marrow biopsy. Later, lytic lesions were found in multiple bones on radiation planning scan and he was finally diagnosed as case of MM with thyroid involvement...
October 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29330561/salvage-therapy-post-pomalidomide-based-regimen-in-relapsed-refractory-myeloma
#18
Guillemette Fouquet, Lionel Karlin, Margaret Macro, Denis Caillot, Murielle Roussel, Bertrand Arnulf, Brigitte Pegourie, Marie Odile Petillon, Claire Mathiot, Cyrille Hulin, Brigitte Kolb, Anne-Marie Stoppa, Sabine Brechiniac, Philippe Rodon, Mamoun Dib, Mourad Tiab, Valentine Richez, Carla Araujo, Marc Wetterwald, Laurent Garderet, Bruno Royer, Aurore Perrot, Lotfi Benboubker, Olivier Decaux, Martine Escoffre-Barbe, Jean Paul Fermand, Philippe Moreau, Hervé Avet-Loiseau, Michel Attal, Thierry Facon, Xavier Leleu
The combination of pomalidomide and low-dose dexamethasone (Pom-Dex) has proved effective and safe in patients with end-stage relapsed/refractory multiple myeloma (RRMM), otherwise characterized by a very poor outcome. MM remains an incurable disease with unavoidable relapses, and the outcome after pomalidomide is still dismal. However, some patients demonstrate prolonged survival even beyond pomalidomide therapy.We sought to analyze the treatment of RRMM patients following Pom-Dex therapy and the response and survival after this next treatment line...
January 12, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29329658/novel-compounds-with-potent-cdk9-inhibitory-activity-for-the-treatment-of-myeloma
#19
Zsófia Czudor, Mária Balogh, Péter Bánhegyi, Sándor Boros, Nóra Breza, Judit Dobos, Márk Fábián, Zoltán Horváth, Eszter Illyés, Péter Markó, Anna Sipos, Csaba Szántai-Kis, Bálint Szokol, László Őrfi
Cyclin-dependent kinases (CDKs) and Polo-like kinases (PLKs) play key role in the regulation of the cell cycle. The aim of our study was originally the further development of our recently discovered polo-like kinase 1 (PLK1) inhibitors. A series of new 2,4-disubstituted pyrimidine derivatives were synthesized around the original hit, but their PLK1 inhibitory activity was very poor. However the novel compounds showed nanomolar CDK9 inhibitory activity and very good antiproliferative effect on multiple myeloma cell lines (RPMI-8226)...
January 2, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29324245/heavy-light-chain-assay-as-a-biomarker-for-diagnosis-and-follow-up-of-multiple-myeloma
#20
Hyojin Chae, Eunhee Han, Jaeeun Yoo, Jaewoong Lee, Jeong Joong Lee, Kyoungho Cha, Myungshin Kim, Yonggoo Kim, Sung-Eun Lee, Chang-Ki Min
BACKGROUND: The heavy-light chain (HLC) assay enables the accurate measurement of each isotype-specific heavy and light chain (i.e., IgGĸ, IgGλ, IgAĸ, and IgAλ) and the derivation of an HLC-pair ratio. However, to date, only limited data have validated the usefulness of serial HLC measurements in the routine follow-up of intact immunoglobulin multiple myeloma (MM) patients. METHODS: A total of 36 diagnostic and 671 post-treatment sera from 115 IgG and 61 IgA MM patients were assessed with capillary zone electrophoresis, immunosubtraction electrophoresis, total immunoglobulin measurement, free light chain, and HLC assay...
January 8, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
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