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https://www.readbyqxmd.com/read/29348856/prognostic-value-of-diametrically-polarized-tumor-associated-macrophages-in-multiple-myeloma
#1
Xinyi Chen, Jin Chen, Wenyan Zhang, Ruixue Sun, Ting Liu, Yuhuan Zheng, Yu Wu
Tumor-associated macrophages (TAMs) are correlated with the prognosis of different types of solid tumors and lymphoma, according to many clinical studies. In vitro experiments have demonstrated the roles of these cells in myeloma cell survival, angiogenesis, immunomodulation, drug resistance, and the interaction between malignant myeloma cells and the microenvironment. Here, we investigated the prognostic significance of TAMs in patients with multiple myeloma (MM). We evaluated the polarized functional status of bone marrow infiltrated by TAMs by immunohistochemical staining of CD68, iNOS, and CD163 in 240 patients with MM from January 2009 to December 2014...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29344579/prognostic-significance-of-cytogenetic-heterogeneity-in-patients-with-newly-diagnosed-multiple-myeloma
#2
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/29339642/significance-of-salvage-autologous-stem-cell-transplantation-for-relapsed-multiple-myeloma-a-nationwide-retrospective-study-in-japan
#3
Tsuyoshi Muta, Toshihiro Miyamoto, Tomohiko Kamimura, Yoshinobu Kanda, Masaharu Nohgawa, Yasunori Ueda, Koji Iwato, Osamu Sasaki, Takehiko Mori, Naoyuki Uchida, Shinsuke Iida, Takahiro Fukuda, Yoshiko Atsuta, Kazutaka Sunami
Autologous stem cell transplantation (ASCT) has been employed for patients with relapsed multiple myeloma (MM) after up-front ASCT. The present retrospective study aimed to examine the survival benefit from salvage ASCT. Among 446 patients with relapsed MM after up-front single ASCT, 70 patients received salvage ASCT, the employment of which reduced the risk of mortality after relapse (p = 0.041). Using the parameters before initial ASCT, the advantage of salvage ASCT compared to standard therapy was confirmed in the subgroup with an international staging system stage of I or II (p = 0...
January 17, 2018: Acta Haematologica
https://www.readbyqxmd.com/read/29334316/potential-therapeutic-and-economic-value-of-risk-stratified-treatment-as-initial-treatment-of-multiple-myeloma-in-europe
#4
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/29333406/stat3-expression-is-associated-with-poor-survival-in-non-elderly-adult-patients-with-newly-diagnosed-multiple-myeloma
#5
Sung-Hoon Jung, Seo-Yeon Ahn, Hyun-Woo Choi, Myung-Geun Shin, Seung-Shin Lee, Deok-Hwan Yang, Jae-Sook Ahn, Yeo-Kyeoung Kim, Hyeoung-Joon Kim, Je-Jung Lee
Background: Signal transducer and activator of transcription 3 (STAT3) is not only a key signaling molecule in the regulation of growth but is also involved in malignant transformation. We investigated the prognostic significance of STAT3 expression in 94 non-elderly adult patients (aged 38 to 65 yr) with newly diagnosed multiple myeloma (MM). Methods: Tumor cell-specific phosphotyrosine-STAT3 (PY-STAT3) expression at the time of diagnosis was evaluated with dual immunohistochemical (IHC) staining for PY-STAT3 and CD138...
December 2017: Blood Research
https://www.readbyqxmd.com/read/29330561/salvage-therapy-post-pomalidomide-based-regimen-in-relapsed-refractory-myeloma
#6
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/29318955/case-report-of-igm-multiple-myeloma-diagnosing-a-rare-hematologic-entity
#7
Fernando Javier Bonilla-Valentín, Javier Cerra, William Cáceres-Perkins, Melissa Alsina
IgM multiple myeloma is an exceedingly rare hematologic entity comprising only less than 0.5% of multiple myeloma cases. Given the rarity of this disorder, it makes it a challenge to differentiate from other more prevalent hematologic disorders like Waldenstrom macroglobulinemia. These 2 diseases have the common finding of an IgM monoclonal gammopathy and distinguishing between these 2 diagnoses is of great importance given that therapy and prognosis differ significantly. This report illustrates the case of a 64-year-old man who presented with IgM lambda monoclonal gammopathy in whom signs, symptoms, laboratories, and imaging were initially thought to be consistent with Waldenstrom macroglobulinemia...
January 2018: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/29305553/preclinical-efficacy-of-daratumumab-in-t-cell-acute-lymphoblastic-leukemia-t-all
#8
Karen L Bride, Tiffaney L Vincent, Soo-Yeon Im, Richard Aplenc, David M Barrett, William L Carroll, Robin Carson, Yunfeng Dai, Meenakshi Devidas, Kimberly P Dunsmore, Tori Fuller, Tina Glisovic-Aplenc, Terzah M Horton, Stephen P Hunger, Mignon L Loh, Shannon L Maude, Elizabeth A Raetz, Stuart S Winter, Stephan A Grupp, Michelle L Hermiston, Brent L Wood, David T Teachey
As a consequence of acquired or intrinsic disease resistance, the prognosis for patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) is dismal. Novel, less toxic drugs are clearly needed. One of the most promising emerging therapeutic strategies for cancer treatment is targeted immunotherapy. Immune therapies have improved outcomes for patients with other hematologic malignancies including B-ALL, however no immune therapy has been successfully developed for T-ALL. We hypothesize targeting CD38 will be effective against T-ALL...
January 5, 2018: Blood
https://www.readbyqxmd.com/read/29296896/maintenance-of-telomere-length-in-aml
#9
REVIEW
Peter M Lansdorp
The importance of telomere length to human health, aging, and cancer continues to be underappreciated. This review examines some basics of telomere biology and relates how telomere function, telomerase activity, and mutations in TERC or TERT are involved in bone marrow failure, leukemias, and other cancers. Given the challenge to obtain accurate data on telomerase activity and telomere length in specific cell types, the situation in acute myeloid leukemia (AML) remains puzzling. In most cancers, telomerase levels are increased after cells have encountered a "telomere crisis," which is typically associated with poor prognosis...
November 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296880/cd86-regulates-myeloma-cell-survival
#10
Catherine M Gavile, Benjamin G Barwick, Scott Newman, Paola Neri, Ajay K Nooka, Sagar Lonial, Kelvin P Lee, Lawrence H Boise
Although prognosis for patients with multiple myeloma has improved over the past decade, research toward discovery of new therapeutic avenues is important and could lead to a cure for this plasma cell malignancy. Here we show that blocking the CD28-CD86 pathway via silencing of either CD28 or CD86 leads to myeloma cell death. Inhibiting this pathway leads to downregulation of integrins and IRF4, a known myeloma survival factor. Our data also indicate that CD86, the canonical ligand in this pathway, has prosurvival activity that is dependent on its cytosolic domain...
November 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296751/a-novel-cxcr4-antagonist-igg1-antibody-pf-06747143-for-the-treatment-of-hematologic-malignancies
#11
Shu-Hui Liu, Yin Gu, Bernadette Pascual, Zhengming Yan, Max Hallin, Cathy Zhang, Conglin Fan, Wenlian Wang, Justine Lam, Mary E Spilker, Rolla Yafawi, Eileen Blasi, Brett Simmons, Nanni Huser, Wei-Hsien Ho, Kevin Lindquist, Thomas-Toan Tran, Jyothirmayee Kudaravalli, Jing-Tyan Ma, Gretchen Jimenez, Ishita Barman, Colleen Brown, Sherman Michael Chin, Maria J Costa, David Shelton, Tod Smeal, Valeria R Fantin, Flavia Pernasetti
The chemokine receptor CXCR4 is highly expressed and associated with poor prognosis in multiple malignancies. Upon engagement by its ligand, CXCL12, CXCR4 triggers intracellular signaling pathways that control trafficking of cells to tissues where the ligand is expressed, such as the bone marrow (BM). In hematologic cancers, CXCR4-driven homing of malignant cells to the BM protective niche is a key mechanism driving disease and therapy resistance. We developed a humanized CXCR4 immunoglobulin G1 (IgG1) antibody (Ab), PF-06747143, which binds to CXCR4 and inhibits CXCL12-mediated signaling pathways, as well as cell migration...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296748/immune-signatures-associated-with-improved-progression-free-and-overall-survival-for-myeloma-patients-treated-with-ahsct
#12
Christine M Ho, Philip L McCarthy, Paul K Wallace, Yali Zhang, Ahmad Fora, Patrick Mellors, Joseph D Tario, Benjamin L S McCarthy, George L Chen, Sarah A Holstein, Sophia R Balderman, Xuefang Cao, Bruno Paiva, Theresa Hahn
Multiple therapeutic options exist for multiple myeloma (MM), including autologous hematopoietic stem cell transplantation (AHSCT). Measurement of minimal residual disease (MRD) and immune reconstitution is rapidly becoming an integral part of the care of MM patients. We investigated comprehensive immune profiling (IP) associated with progression-free survival (PFS) and overall survival (OS). From August 2007 to January 2014, 101 consecutive MM patients underwent peripheral blood IP and marrow MRD testing before and approximately 100 days after AHSCT...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29259009/loss-of-rassf4-expression-in-multiple-myeloma-promotes-ras-driven-malignant-progression
#13
Eva De Smedt, Ken Maes, Stefaan Verhulst, Hui Liu, Alboukadel Kassambara, Anke Maes, Nicolas Robert, Carlo Heirman, Andrew Cakana, Dirk Hose, Karine Breckpot, Leo A van Grunsven, Kim De Veirman, Eline Menu, Karin Vanderkerken, Jerome Moreaux, Elke De Bruyne
RAS mutations occur frequently in multiple myeloma (MM), but apart from driving progression they can also stimulate antitumor effects by activating tumor suppressive RASSF proteins. While this family of death effector molecules are often silenced in cancers, functional data about RASSF proteins in MM are lacking. Here we report that RASSF4 is downregulated during MM progression and correlates with a poor prognosis. Promoter methylation analysis in human cell lines revealed an inverse correlation between RASSF4 mRNA levels and methylation status...
December 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/29245977/the-cancer-testis-antigen-sperm-protein-17-a-new-biomarker-and-immunological-target-in-head-and-neck-squamous-cell-carcinoma
#14
Christopher A Schutt, Leonardo Mirandola, Jose A Figueroa, Diane D Nguyen, Joehassin Cordero, Klauss Bumm, Benjamin L Judson, Maurizio Chiriva-Internati
Head and Neck Squamous Cell Carcinoma is a deadly and locally aggressive malignancy that frequently portends a poor prognosis. Since current treatment modalities including surgery, chemotherapy and radiation are heavily debilitating and often result in recurrence intense efforts have been put into the development of novel less toxic and more lasting treatment strategies. Recently, immunotherapy has been proposed as a promising alternative that could potentially meet these requirements. SP17 is a validated cancer-testis antigen in multiple myeloma, ovarian cancer and non-small cell lung cancer...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29241222/flavopiridol-enhances-abt-199-sensitivity-in-unfavourable-risk-multiple-myeloma-cells-in-vitro-and-in-vivo
#15
Liang Zhou, Yu Zhang, Deepak Sampath, Joel Leverson, Yun Dai, Maciej Kmieciak, Matthew Nguyen, Robert Z Orlowski, Steven Grant
BACKGROUND: The BCL-2-specific BH3-mimetic ABT-199 (venetoclax) has been reported to be principally active against favourable-risk multiple myeloma (MM) cells, prompting efforts to extend its activity to include more resistant, higher-risk MM subsets. METHODS: Effects of the CDK9 inhibitor flavopiridol (FP; alvocidib) on responses to ABT-199 were examined in MM cells. Cell death and protein expression were evaluated by western blot and immunofluorescence. Xenograft models were used to study combination effects in vivo...
December 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29235380/pharmacokinetic-drug-evaluation-of-ixazomib-citrate-for-the-treatment-of-multiple-myeloma
#16
REVIEW
Marco Salvini, Rossella Troia, Davide Giudice, Chiara Pautasso, Mario Boccadoro, Alessandra Larocca
multiple myeloma (MM) is a plasma cell disorder that represents the second most frequent hematologic cancer. Although MM is still an incurable disease, prognosis has improved in the last decades thanks to the introduction of novel agents such as proteasome inhibitors (PIs), immunomodulatory drugs, monoclonal antibodies, and histone deacetylase inhibitors. Areas covered: ixazomib is the first oral PI recently approved by Food and Drug Administration (FDA) and European Medicine Agency (EMA) in combination with lenalidomide and dexamethasone as salvage therapy in MM patients...
January 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29226427/case-report-treatment-of-light-chain-amyloidosis-with-daratumumab-monotherapy-in-two-patients
#17
Charlotte Gran, Gösta Gahrton, Evren Alici, Hareth Nahi
Immunoglobulin light-chain amyloidosis (AL) affects multiple organs, most prominently the kidney and the heart. Renal and cardiac impairment are both associated with poor prognosis.(1) Typical treatment regimens for AL include proteasome inhibitors, alkylating agents, and steroids as well as autologous stem cell transplantation (ASCT) for younger, fit patients. Complete response after treatment is associated with a better outcome and can be measured by free light chain (FLC) reduction.(2, 3) Monoclonal antibodies such as daratumumab (Dara, human IgG1 anti-CD38) have shown promising efficacy for the treatment of relapsed and refractory multiple myeloma...
December 11, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29222258/fixed-duration-vs-continuous-therapy-in-multiple-myeloma
#18
REVIEW
Heinz Ludwig, Niklas Zojer
The introduction of new drugs with less severe toxicity profiles than those of conventional antimyeloma agents allowed the evaluation of continuous therapy compared with fixed duration therapy. In transplant-eligible patients, consolidation therapy with bortezomib or bortezomib-based regimens showed significant progression-free survival (PFS) benefit in cytogenetic standard-risk patients and to a lesser extent, high-risk patients. Continuous therapy with lenalidomide maintenance treatment after autologous stem cell transplantation resulted in a significant survival gain...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29220877/increased-circulating-plasma-cells-detected-by-flow-cytometry-predicts-poor-prognosis-in-patients-with-plasma-cell-myeloma
#19
Mi Hyun Bae, Chan-Jeoung Park, Bo Hyun Kim, Young-Uk Cho, Seongsoo Jang, Dong-Hyun Lee, Eul-Ju Seo, Dok Hyun Yoon, Jung-Hee Lee, Cheolwon Suh
BACKGROUND: Flow cytometry (FC) is a reliable tool for diagnosing and monitoring of plasma cell myeloma (PCM). Recent studies used FC for quantifying plasma cells (PCs) in peripheral blood (PB) using various panels, and an adverse prognostic effect of circulating PCs (cPCs) has been reported. We investigated the prognostic implication of cPCs quantified using a simple panel in patients with PCM. METHODS: Bone marrow (BM) and PB of 85 patients with PCM were analyzed by five-color FC at time of diagnosis...
December 8, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/29217780/from-transplant-to-novel-cellular-therapies-in-multiple-myeloma-emn-guidelines-and-future-perspectives
#20
Francesca Gay, Monika Engelhardt, Evangelos Terpos, Ralph Wäsch, Luisa Giaccone, Holger W Auner, Jo Caers, Martin Gramatzki, Niels van de Donk, Stefania Oliva, Elena Zamagni, Laurent Garderet, Christian Straka, Roman Hajek, Heinz Ludwig, Hermann Einsele, Meletios Dimopoulos, Mario Boccadoro, Nicolaus Kröger, Michele Cavo, Hartmut Goldschmidt, Benedetto Bruno, Pieter Sonneveld
Survival of myeloma patients has greatly improved with the use of autologous stem cell transplantation and novel agents, such as proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. Compared to bortezomib- and lenalidomide-based regimens alone, the addition of high-dose melphalan followed by autologous transplantation significantly improves progression-free survival; although an overall survival benefit was not observed in all trials. Moreover, follow-up of recent trials is still too short to show any difference in survival...
December 7, 2017: Haematologica
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