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Treatment of myeloma

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https://www.readbyqxmd.com/read/28219836/donor-lymphocyte-infusion-for-relapsed-hematological-malignancies-after-unrelated-allogeneic-bone-marrow-transplantation-facilitated-by-the-japan-marrow-donor-program
#1
Toshihiro Miyamoto, Takahiro Fukuda, Marie Nakashima, Tomoko Henzan, Shinsuke Kusakabe, Naoki Kobayashi, Junichi Sugita, Takeshi Mori, Mineo Kurokawa, Shin-Ichiro Mori
To evaluate the safety and efficacy of donor lymphocyte infusion (DLI), we retrospectively analyzed 414 recipients who received unrelated DLI (UDLI) for the treatment of relapsed hematological malignancy after unrelated bone marrow transplantation (BMT). UDLI was administered for acute myelogenous leukemia (n=184), myelodysplastic syndrome (n=69), acute lymphocytic leukemia (n=57), chronic myelogenous leukemia (CML, n=36), lymphoid neoplasms (n=38), adult T-cell leukemia/lymphoma (n=18), and multiple myeloma (n=12)...
February 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28219227/-targeting-mir155-restores-chemotherapy-sensitivity-in-drug-resistant-myeloma-cell-line-rpmi8226-dox-cells
#2
C R Xiao, X L Hong, J S Hu, Y M Chen, Q Y Lu
Objective: To explore the mechanism of abnormal expression of microRNA155 (miR155) in myeloma drug-resistance to probe the possibility of inhibiting miR155 expression to restore chemotherapy sensitivity and its molecular mechanism in drug-resistant myeloma cells. Methods: Drug-resistant myeloma cell-line RPMI8226/DOX was established by culturing RPMI8226 cells with continuous low concentration and intermittent gradually increasing concentration of doxorubicin in vitro; The levels of miR155 mRNA were measured by qRT-PCR, and both proteins FOXO3a and BCL-2 expressions were detected by Western blot in cell-lines RPMI8226/S and RPMI8226/Dox...
January 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28218709/pet-imaging-for-initial-staging-and-therapy-assessment-in-multiple-myeloma-patients
#3
REVIEW
Clément Bailly, Rodolphe Leforestier, Bastien Jamet, Thomas Carlier, Mickael Bourgeois, François Guérard, Cyrille Touzeau, Philippe Moreau, Michel Chérel, Françoise Kraeber-Bodéré, Caroline Bodet-Milin
Multiple myeloma (MM) is a hematological neoplasm characterized by the clonal proliferation of malignant plasma cells in the bone marrow. MM results in diffuse or focal bone infiltration and extramedullary lesions. Over the past two decades, advances have been made with regard to the diagnosis, staging, treatment, and imaging of MM. Computed tomography (CT) and magnetic resonance imaging (MRI) are currently recommended as the most effective imaging modalities at diagnostic. Yet, recent data from the literature suggest that positron emission tomography combined with computed tomography (PET/CT) using (18)F-deoxyglucose (FDG) is a promising technique for initial staging and therapeutic monitoring in this pathology...
February 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28215056/an-analysis-of-blood-utilization-for-stem-cell-transplant-patients-in-a-tertiary-care-hospital
#4
Natasha Ali
Background and Objective: Haematopoietic stem cell transplant is a potentially curative treatment option in various benign and malignant haematological diseases. Patients undergoing stem cell transplant procedure require blood transfusion on a daily basis. Currently, there is paucity of data from developing countries on transfusion practices. This audit was undertaken to determine the consumption of packed red blood cells (PRBCs) transfusion in the bone marrow transplant unit of the Aga Khan University Hospital...
February 28, 2017: International Journal of Stem Cells
https://www.readbyqxmd.com/read/28213943/a-phase-2-safety-study-of-accelerated-elotuzumab-infusion-over-less-than-1-hour-in-combination-with-lenalidomide-and-dexamethasone-in-patients-with-multiple-myeloma
#5
James Berenson, Robert Manges, Suprith Badarinath, Alan Cartmell, Kristi McIntyre, Roger Lyons, Wael Harb, Hesham Mohamed, Ali Nourbakhsh, Robert Rifkin
Elotuzumab, an immunostimulatory SLAMF7-targeting monoclonal antibody, induces myeloma cell death with minimal effects on normal tissue. In a previous phase 3 study in patients with relapsed/refractory multiple myeloma (RRMM), elotuzumab (10 mg/kg, ∼3-hour infusion), combined with lenalidomide and dexamethasone, demonstrated durable efficacy and acceptable safety; 10% (33/321) of patients had infusion reactions (IRs; Grade 1/2: 29; Grade 3: 4). This phase 2 study (NCT02159365) investigated an accelerated infusion schedule in 70 patients with newly diagnosed multiple myeloma or RRMM...
February 18, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28212756/the-holy-grail-solid-tumor-efficacy-by-proteasome-inhibition
#6
Mark Rolfe
Proteasome inhibitors have revolutionized the treatment of multiple myeloma but have had disappointing results when treating solid tumors. The work of Weyburne et al. (2017), published in this issue of Cell Chemical Biology, sheds some light on this conundrum and suggests a novel approach to achieve solid tumor efficacy.
February 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28211573/the-cationic-small-molecule-gw4869-is-cytotoxic-to-high-phosphatidylserine-expressing-myeloma-cells
#7
Slavica Vuckovic, Kate Vandyke, David A Rickards, Padraig McCauley Winter, Simon H J Brown, Todd W Mitchell, Jun Liu, Jun Lu, Philip W Askenase, Elizabeth Yuriev, Ben Capuano, Paul A Ramsland, Geoffrey R Hill, Andrew C W Zannettino, Andrew T Hutchinson
We have discovered that a small cationic molecule, GW4869, is cytotoxic to a subset of myeloma cell lines and primary myeloma plasma cells. Biochemical analysis revealed that GW4869 binds to anionic phospholipids such as phosphatidylserine - a lipid normally confined to the intracellular side of the cell membrane. However, interestingly, phosphatidylserine was expressed on the surface of all myeloma cell lines tested (n = 12) and 9/15 primary myeloma samples. Notably, the level of phosphatidylserine expression correlated well with sensitivity to GW4869...
February 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28211054/real-world-use-of-pomalidomide-and-dexamethasone-in-double-refractory-multiple-myeloma-suggests-benefit-in-renal-impairment-and-adverse-genetics-a-multi-centre-uk-experience
#8
Nicola Maciocia, Andrew Melville, Simon Cheesman, Faye Sharpley, Karthik Ramasamy, Matthew Streetly, Matthew Jenner, Reuben Benjamin, Steve Schey, Paul Maciocia, Rakesh Popat, Shirley D'sa, Ali Rismani, Aviva Cerner, Kwee Yong, Neil Rabin
Myeloma patients who become refractory to immunomodulatory agents (IMiDs) and bortezomib have poor survival, with limited therapeutic options. Pomalidomide has shown improved survival and good tolerability in this patient cohort in clinical trials, but real world data are scarce. We retrospectively analysed all patients treated with pomalidomide at five UK centres between 2013 and 2016. Of 85 patients identified, 70 had sufficient information for response assessments. Median age was 66 years [40-89], 96·5% were refractory to IMiDs, 72·9% were refractory to both an IMiD and bortezomib and 92·9% were refractory to their last treatment...
February 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28210014/dilemma-correlation-between-serum-level-of-hepcidin-and-il-6-in-anemic-myeloma-patients
#9
Lejla Ibricevic-Balic, Emina Icindic-Nakas, Sabaheta Hasic, Emina Kiseljakovic, Alma Sofo-Hafizovic, Sefkija Balic
INTRODUCTION: Anemia occurs in 60% to 80 % of patients with newly diagnosed myeloma multiplex (MM). The cause of anemia in MM is probably multi factorial and involved among the others hepcidin and some cytokines, especially interleukine-6. Anemia in MM is one of the risk factor used in Durie-Salmon classification for staging and prognostic score. Treatment options are set according to this score with most significant impact on survival. AIM: To estimate baseline level of serum hepcidin, IL-6 and iron metabolism markers in anemic MM patients, possible role of hepcidin and its interaction with IL-6...
December 2016: Medical Archives
https://www.readbyqxmd.com/read/28210004/monoclonal-antibody-therapy-in-multiple-myeloma
#10
REVIEW
Cyrille Touzeau, Philippe Moreau, Charles Dumontet
The therapeutic landscape of multiple myeloma (MM) has evolved spectacularly over the past decade with the discovery and validation of proteasome inhibitors and immunomodulatory agents as highly active agents, both in front-line therapy as well as in the relapse and maintenance settings. While previous attempts to apply available monoclonal antibodies (Mabs) to the treatment of patients with MM has until recently been disappointing, novel targets specifically explored in the context of MM have recently lead to the first approvals of Mabs for the treatment of patients with MM...
February 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28208828/ginkgolic-acid-c-17-1-derived-from-ginkgo-biloba-leaves-suppresses-constitutive-and-inducible-stat3-activation-through-induction-of-pten-and-shp-1-tyrosine-phosphatase
#11
Seung Ho Baek, Jong Hyun Lee, Chulwon Kim, Jeong-Hyeon Ko, Seung-Hee Ryu, Seok-Geun Lee, Woong Mo Yang, Jae-Young Um, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Gautam Sethi, Kwang Seok Ahn
Ginkgolic acid C 17:1 (GAC 17:1) extracted from Ginkgo biloba leaves, has been previously reported to exhibit diverse antitumor effect(s) through modulation of several molecular targets in tumor cells, however the detailed mechanism(s) of its actions still remains to be elucidated. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that regulates various critical functions involved in progression of diverse hematological malignancies, including multiple myeloma, therefore attenuating STAT3 activation may have a potential in cancer therapy...
February 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28208219/impact-of-induction-treatment-before-autologous-stem-cell-transplantation-on-long-term-outcome-in-patients-with-newly-diagnosed-multiple-myeloma
#12
Susanna Gassiot, Cristina Motlló, Inuska Llombart, Mireia Morgades, Yolanda González, Montse Garcia-Caro, Josep-Maria Ribera, Albert Oriol
OBJECTIVE: Clinical trials for multiple myeloma patients using novel agent-based regimens before autologous stem cell transplantation (SCT) have shown improvement in response rates and progression-free survival (PFS), however they have failed to identify a significant overall survival (OS) benefit. The aim of this study was to analyze the potential impact of initial induction on the feasibility and outcome of subsequent treatment lines in a real clinical practice setting. METHODS: Consecutive multiple myeloma patients less than 70 years of age diagnosed between 1999 and 2009 were prospectively registered and classified as having received conventional chemotherapy induction regimens with new agents available at relapse (CC cohort, 89 patients) or as treated with novel agents upfront (NA cohort, 65 patients)...
February 16, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28208215/nanoparticle-delivery-systems-general-approaches-and-their-implementation-in-multiple-myeloma
#13
REVIEW
Pilar de la Puente, Abdel Kareem Azab
Multiple myeloma (MM) is a hematological malignancy that remains incurable, with relapse rates greater than 90%. The main limiting factor for the effective use of chemotherapies in MM is the serious side effects caused by these drugs. The emphasis in cancer treatment has shifted from cytotoxic, non-specific chemotherapies to molecularly targeted and rationally designed therapies showing greater efficacy and fewer side effects. Traditional chemotherapy has shown several disadvantages such as lack of targeting capabilities, systemic toxicity and side effects; low therapeutic index, as well as, most anticancer drugs have poor water solubility...
February 16, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28205262/modern-multiple-myeloma-therapy-deep-sustained-treatment-response-and-good-clinical-outcomes
#14
REVIEW
O Landgren, K Iskander
In the USA at the beginning of this century, the average overall survival in patients with multiple myeloma was about 3 years. Around that time, three drugs (bortezomib, lenalidomide and thalidomide) were introduced for the treatment of multiple myeloma and, in 2012, carfilzomib received accelerated approval by the US Food and Drug Administration (FDA). Driven by access to better drugs, median overall survival in younger patients (aged <50 years) was >10 years by 2014. The FDA approved 14 new drugs for the treatment of cancer in 2015; four of these were approved for the treatment of myeloma (panobinostat, daratumumab, elotuzumab and ixazomib)...
February 16, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28205024/immunomodulatory-drugs-in-multiple-myeloma-mechanisms-of-action-and-clinical-experience
#15
REVIEW
Sarah A Holstein, Philip L McCarthy
Over the last two decades, the outcomes for patients with multiple myeloma, a plasma cell malignancy, have dramatically improved. The development of the immunomodulatory drugs (IMiDs), which include thalidomide, lenalidomide, and pomalidomide, has contributed significantly to these improved outcomes. While thalidomide is now less commonly prescribed, lenalidomide is widely used in the treatment of newly diagnosed transplant-eligible and transplant-ineligible patients, in the maintenance setting post-transplant and in the relapsed/refractory setting, while pomalidomide is currently utilized in the relapsed/refractory setting...
February 16, 2017: Drugs
https://www.readbyqxmd.com/read/28203342/optimizing-current-and-emerging-therapies-in-multiple-myeloma-a-guide-for-the-hematologist
#16
REVIEW
Shahzad Raza, Rachael A Safyan, Evan Rosenbaum, Alex S Bowman, Suzanne Lentzsch
Multiple myeloma (MM) is the second most common hematologic malignancy. The diagnosis of MM requires ⩾10% clonal plasma cells in the bone marrow or biopsy-proven plasmacytoma, plus evidence of end-organ damage (hypercalcemia, renal failure, anemia, and lytic bone lesions). The definition of MM has recently been expanded to include a ⩾60% clonal plasma cell burden in the bone marrow, serum involved/uninvolved light chain ratio of ⩾100, or more than one focal lesion on magnetic resonance imaging ⩾5 mm in the absence of end-organ damage...
February 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28203341/new-monoclonal-antibodies-on-the-horizon-in-multiple-myeloma
#17
REVIEW
Elizabeth K O'Donnell, Noopur S Raje
Across all cancers, monoclonal antibodies have emerged as a potential strategy for cancer therapy. Monoclonal antibodies target antigens expressed on the surface of cancer cells and accessory cells. This targeted approach uses the host's immune system to promote the killing of cancer cells. Multiple myeloma (MM) is the second most common hematologic malignancy that remains incurable in the majority of patients. The treatment of MM has evolved dramatically over the past decade and continues to evolve with the approval of four new drugs in 2015...
February 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28203307/epigenetic-strategies-to-reverse-drug-resistance-in-heterogeneous-multiple-myeloma
#18
REVIEW
Mark E Issa, Farnaz Sedigheh Takhsha, Chandra Sekhar Chirumamilla, Claudina Perez-Novo, Wim Vanden Berghe, Muriel Cuendet
Multiple myeloma (MM) is a hematological malignancy, which remains incurable because most patients eventually relapse or become refractory to current treatments. Due to heterogeneity within the cancer cell microenvironment, cancer cell populations employ a dynamic survival strategy to chemotherapeutic treatments, which frequently results in a rapid acquisition of therapy resistance. Besides resistance-conferring genetic alterations within a tumor cell population selected during drug treatment, recent findings also reveal non-mutational mechanisms of drug resistance, involving a small population of "cancer stem cells" (CSCs) which are intrinsically more refractory to the effects of a variety of anticancer drugs...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28203295/management-of-anaemia-in-oncohaematological-patients-treated-with-biosimilar-epoetin-alfa-results-of-an-italian-observational-retrospective-study
#19
Giovanni Rosti, Mario Petrini, Alberto Bosi, Piero Galieni, Daniele Bernardi, Gianfranco Giglio, Laura Dorotea, Brunangelo Falini, Elvira Scelzi, Enzo Veltri, Roberto Castelli, Chiara Longagnani, Tommaso Raggi, Federico Simonetti
BACKGROUND: Many patients with solid tumours or nonmyeloid haematopoietic tumours develop symptomatic anaemia, which has a major impact on quality of life (QoL). The efficacy of erythropoiesis-stimulating agents (ESAs) in improving QoL and reducing blood transfusions has been widely demonstrated. Binocrit® (biosimilar epoetin alfa) is an ESA indicated in the European Union for treating chemotherapy-induced anaemia. The aim of this study was to investigate the effect of Binocrit® on haemoglobin (Hb) levels in anaemic cancer patients in Italian clinical practice...
January 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28201978/multiple-myeloma-and-the-immune-microenvironment
#20
Yawara Kawano, Aldo M Roccaro, Jamil Azzi, Irene M Ghobrial
One of the great advances in the field of cancer therapy in recent years is the emergence of immune therapies. Immune therapies, especially immune checkpoint inhibitors, have shown promising results in pre-clinical models and clinical trials of solid tumors, such as melanoma, breast cancer and lung cancer. Therapeutic strategies targeting the immune microenvironment have also been applied to hematological malignancies such as multiple myeloma (MM), a plasma cell neoplasia characterized by clonal expansion of malignant plasma cells mainly in the bone marrow (BM)...
February 13, 2017: Current Cancer Drug Targets
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