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https://www.readbyqxmd.com/read/28655093/-long-term-follow-up-of-multiple-myeloma-after-autologous-hematopoietic-stem-cell-transplantation-a-single-center-results
#1
W W Sui, D H Zou, G An, S H Yi, S H Deng, W Y Huang, T Y Wang, J Li, H Liu, M W Fu, R Lyu, W Liu, Y Xu, Z J Li, Y Z Zhao, L G Qiu
Objective: To evaluate the efficacy and long-term outcome of a combined protocol for multiple myeloma (MM) , including induction therapy, autologous hematopoietic stem cell transplantation (ASCT) and consolidation and maintenance therapy. Methods: Clinical records of 144 patients with MM from January 1, 2005 to February 1, 2016 were retrospectively analyzed. Results: The overall response rate (ORR) after ASCT was 100.0%, in which the complete remission (CR) was 64.1% and the best treatment response rate of superior to PR was 89...
June 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28655091/-outcomes-of-lenalidomide-based-treatment-for-57-patients-of-relapsed-or-refractory-multiple-myeloma
#2
S H Deng, Y Xu, W W Sui, G An, X H Mao, Z J Li, D H Zou, L G Qiu
Objective: To investigate the clinical efficacy and safety of lenalidomide (Revlimid, R) -based chemotherapy in the treatment of relapsed/refractory multiple myeloma (MM) patients. Methods: 57 consecutively relapsed/refractory MM patients were retrospectively analyzed from June 2013 to February 2016. All the patients received lenalidomide-based chemotherapy. Results: ① 60.4% patients had international staging system (ISS) stage Ⅲ, 37.9% patients had revised international staging system (R-ISS) stage Ⅲ, and 53...
June 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28655090/-molecular-mechanisms-and-relationship-of-m2-polarized-macrophages-with-early-response-in-multiple-myeloma
#3
X Y Chen, R X Sun, W Y Zhang, T Liu, Y H Zheng, Y Wu
Objective: To investigate the relationship between M2-polarized macrophages and early response in multiple myeloma and its molecular mechanism. Methods: Two hundred and forty bone marrow biopsy tissue were collected and M2-polarized macrophages were stained by anti-CD163 monoclonal antibody. In vitro M2-polarized macrophages were derived from human peripheral blood mononuclear cell or THP-1 cells and identified by flow cytometry. Two myeloma cell lines RPMI 8226 and U266 were co-cultured with M2 macrophages using a transwell system...
June 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28655089/-prognostic-value-of-the-revised-international-staging-system-for-newly-diagnosed-multiple-myeloma-patients
#4
J Lu, J Du, W J Fu, H Y He, L Li, R Li, L L Zhou, H Jiang, J Hou
Objective: To assess the prognostic value of revised international staging system (R-ISS) for multiple myeloma (MM) in real world. Methods: A total of 202 newly diagnosis symptomatic MM patients were enrolled from May 2010 to April 2015 and the clinical data were retrospectively analyzed. All the patients received at least four courses of bortezomib-based or thalidomide-based induction therapy. Results: With a median follow-up of 31 months, the cohort included 56 cases in R-ISSⅠ, 108 in R-ISS Ⅱ, and 38 in R-ISS Ⅲ, and the median OS was not reached/61/38 months, respectively (P=0...
June 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28653942/torsade-de-pointes-in-a-patient-with-severe-hypercalcaemia-and-multiple-myeloma
#5
D Fuchs, D Voskova, K J Krenosz, T Lambert, M A Fridrik
We report a case of a 48-year-old female patient with newly diagnosed multiple myeloma. She developed recurrent torsade de pointes and required cardiopulmonary resuscitation and defibrillation. Atrial arrhythmias in patients with multiple myeloma and hypercalcaemia have been described, but, to the best of our knowledge, this is the first report of torsade de pointes in this setting.
June 2017: Netherlands Journal of Medicine
https://www.readbyqxmd.com/read/28653881/effects-of-dtx3l-on-the-cell-proliferation-adhesion-and-drug-resistance-of-multiple-myeloma-cells
#6
Yaodong Shen, Yuxiang Sun, Linlin Zhang, Hong Liu
Cell adhesion-mediated drug resistance is an important factor that influences the effects of chemotherapy in multiple myeloma. DTX3L, a ubiquitin ligase, plays a key role in cell-cycle-related process. Here, we found that the expression of DTX3L gradually increased during the proliferation of myeloma cells, which resulted in arrest of the cell cycle in the G1 phase and promoted the adherence of myeloma cells to fibronectin or bone marrow stromal cells. In addition, silencing of DTX3L improved sensitivity to chemotherapy drugs in multiple myeloma cell lines adherent to bone marrow stromal cells and increased the expression of caspase-3 and poly-adenosine diphosphate-ribose polymerase, two markers of apoptosis...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28653421/comparison-of-biosimilar-filgrastim-originator-filgrastim-and-lenograstim-for-autologous-stem-cell-mobilization-in-patients-with-multiple-myeloma
#7
Katharina Lisenko, Marc-Andrea Baertsch, Renate Meiser, Petra Pavel, Thomas Bruckner, Mark Kriegsmann, Anita Schmitt, Mathias Witzens-Harig, Anthony D Ho, Jens Hillengass, Patrick Wuchter
BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) originators such as filgrastim (Neupogen) and lenograstim (Granocyte) are widely used for peripheral blood stem cell (PBSC) mobilization. In recent years, biosimilar agents have been approved for the same indications. The aim of this retrospective study was to compare the mobilization efficiency of the three G-CSF variants originator filgrastim, lenograstim, and the biosimilar Filgrastim Hexal in a homogeneous group of multiple myeloma (MM) patients in first-line therapy...
June 26, 2017: Transfusion
https://www.readbyqxmd.com/read/28653400/panobinostat-plus-bortezomib-and-dexamethasone-impact-of-dose-intensity-and-administration-frequency-on-safety-in-the-panorama-1-trial
#8
Jesús F San-Miguel, Vania T M Hungria, Sung-Soo Yoon, Meral Beksac, Meletios A Dimopoulos, Ashraf Elghandour, Wieslaw W Jedrzejczak, Andreas Guenther, Thanyaphong Na Nakorn, Noppadol Siritanaratkul, Robert L Schlossman, Jian Hou, Philippe Moreau, Sagar Lonial, Jae-Hoon Lee, Hermann Einsele, Hans Salwender, Monika Sopala, Suman Redhu, Sofia Paul, Claudia Corrado, Paul G Richardson
Panobinostat in combination with bortezomib and dexamethasone demonstrated a significant and clinically meaningful progression-free survival benefit compared with placebo, bortezomib and dexamethasone in the phase 3 PANORAMA 1 (Panobinostat Oral in Multiple Myeloma 1) trial. Despite this benefit, patients in the panobinostat arm experienced higher rates of adverse events (AEs) and higher rates of discontinuation due to AEs. This PANORAMA 1 subanalysis examined AEs between 2 treatment phases of the study (TP1 and TP2), in which administration frequency of bortezomib and dexamethasone differed per protocol...
June 27, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28653323/increased-fracture-risk-in-plasma-cell-dyscrasias-is-associated-with-poorer-overall-survival
#9
Graham McIlroy, Jemma Mytton, Felicity Evison, Punit Yadav, Mark T Drayson, Mark Cook, Guy Pratt, Paul Cockwell, Jennifer H Pinney
Pathological fractures are a common complication of plasma cell dyscrasias (PCD) and are associated with significant morbidity. Routine use of bisphosphonates over the past decade has aimed to reduce the risk of fractures in patients with multiple myeloma, but despite this, fractures continue to represent a significant burden of disease. In this study we report the fracture rate of hospital in-patients with PCD in England. Data from the national registry Hospital Episode Statistics between 2001 and 2015 were used to determine fracture rate and its effect on overall survival...
June 27, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28651310/clinicopathological-characteristics-of-extremely-young-korean-multiple-myeloma-patients-therapeutic-implications
#10
Junghoon Shin, Youngil Koh, Jeonghwan Youk, Miso Kim, Byung Soo Kim, Chul Won Choi, Hwa Jung Sung, Yong Park, Sung-Soo Yoon, Inho Kim
Background/Aims: Although multiple myeloma (MM) is typically a disease of the elderly, a certain subset of extremely young patients exists. It is necessary to establish clinicopathological characteristics for this population. Methods: We reviewed the medical records of MM patients whose age was 40 years or younger at diagnosis. Results: A total of 32 patients were analyzed (male to female ratio 19:13, median age 37 years). According to International Staging System, 29%, 48%, and 16% were in stage I, II, and III, respectively...
June 26, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28650454/analysis-of-hematopoietic-recovery-after-autologous-transplantation-as-method-of-quality-control-for-long-term-progenitor-cell-cryopreservation
#11
J Pavlů, H W Auner, R M Szydlo, B Sevillano, R Palani, F O'Boyle, A Chaidos, C Jakob, E Kanfer, D MacDonald, D Milojkovic, A Rahemtulla, A Bradshaw, E Olavarria, J F Apperley, O M Pello
Hematopoietic precursor cells (HPC) are able to restore hematopoiesis after high-dose chemotherapy and their cryopreservation is routinely employed prior to the autologous hematopoietic cell transplantation (AHCT). Although previous studies showed feasibility of long-term HPC storage, concerns remain about possible negative effects on their potency. To study the effects of long-term cryopreservation, we compared time to neutrophil and platelet recovery in 50 patients receiving two AHCT for multiple myeloma at least 2 years apart between 2006 and 2016, using HPC obtained from one mobilization and collection attempt before the first transplant...
June 26, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28647402/autologous-stem-cell-transplantation-in-patients-with-multiple-myeloma-an-activity-based-costing-analysis-comparing-a-total-inpatient-model-versus-an-early-discharge-model
#12
Massimo Martino, Giuseppe Console, Letteria Russo, Antonella Meliado', Nicola Meliambro, Tiziana Moscato, Giuseppe Irrera, Giuseppe Messina, Antonella Pontari, Fortunato Morabito
BACKGROUND: Activity-based costing (ABC) was developed and advocated as a means of overcoming the systematic distortions of traditional cost accounting. MATERIALS AND METHODS: We calculated the cost of high-dose chemotherapy and autologous stem cell transplantation (ASCT) in patients with multiple myeloma using the ABC method, through 2 different care models: the total inpatient model (TIM) and the early-discharge outpatient model (EDOM) and compared this with the approved diagnosis related-groups (DRG) Italian tariffs...
June 6, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28647392/a-novel-dual-inhibitor-of-microtubule-and-bruton-s-tyrosine-kinase-inhibits-survival-of-multiple-myeloma-and-osteoclastogenesis
#13
Manoj K Pandey, Krishne Gowda, Shen-Shu Sung, Thomas Abraham, Tulin Budak-Alpdogan, Giampolo Talamo, Sinisa Dovat, Shantu Amin
Bruton's tyrosine kinase (BTK) regulates many vital signaling pathways and play critical role in cell proliferation, survival, migration, and resistance. Earlier we reported that a small molecule KS99 is an inhibitor of tubulin polymerization. In the present study we explored that whether KS99 is a dual inhibitor of BTK and tubulin polymerization. While it is known that BTK is required for clonogenic growth, and resistance; and microtubules are essential for cancer cell growth; dual targeting of these two components has not been explored...
June 21, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28645562/anti-myeloma-effects-of-ruxolitinib-combined-with-bortezomib-and-lenalidomide-a-rationale-for-jak-stat-pathway-inhibition-in-myeloma-patients
#14
Mariana B de Oliveira, Veruska L Fook-Alves, Angela I P Eugenio, Rodrigo C Fernando, Luiz Felipe G Sanson, Mariana F de Carvalho, Walter M T Braga, Faith E Davies, Gisele W B Colleoni
JAK proteins have been linked with survival and proliferation of multiple myeloma (MM) cells; therefore, JAK inhibition could be a therapeutic strategy for MM. We evaluated JAK1 and JAK2 expression in MM patients and the effects of JAK/STAT pathway inhibition on apoptosis, cell cycle, gene and protein expression in RPMI-8226 and U266 MM cell lines. 57% of patients presented overexpression of JAK2 and 27%, of JAK1. After treatment with ruxolitinib and bortezomib, RPMI-8226 and U266 presented 50% of cells in late apoptosis, reduction of anti-apoptotic genes expression and higher number of cells in SubG0 phase...
June 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28645097/raman-spectroscopy-differentiates-between-sensitive-and-resistant-multiple-myeloma-cell-lines
#15
Domenico Franco, Sebastiano Trusso, Enza Fazio, Alessandro Allegra, Caterina Musolino, Antonio Speciale, Francesco Cimino, Antonella Saija, Fortunato Neri, Marco S Nicolò, Salvatore P P Guglielmino
Current methods for identifying neoplastic cells and discerning them from their normal counterparts are often nonspecific and biologically perturbing. Here, we show that single-cell micro-Raman spectroscopy can be used to discriminate between resistant and sensitive multiple myeloma cell lines based on their highly reproducible biomolecular spectral signatures. In order to demonstrate robustness of the proposed approach, we used two different cell lines of multiple myeloma, namely MM.1S and U266B1, and their counterparts MM...
June 15, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28643680/-towards-precision-medicine-in-myeloma-new-evidence-and-challenges
#16
Verónica González-Calle, Rafael Fonseca
In the last few years, next-generation sequencing studies have provided insights into the mutational landscape of multiple myeloma. The identification of actionable mutations might give a precious opportunity for exploring new targeted therapies. Thus, the implementation of promising precision medicine strategies seems to be closer than ever. Throughout this review we describe the main challenges that should to be dealt with in this new era, in order to achieve the main goal of precision medicine, namely matching patients with their right drug...
2017: Medicina
https://www.readbyqxmd.com/read/28643330/muc1-c-is-a-target-in-lenalidomide-resistant-multiple-myeloma
#17
Li Yin, Ashujit Tagde, Reddy Gali, Yu-Tzu Tai, Teru Hideshima, Kenneth Anderson, David Avigan, Donald Kufe
Lenalidomide (LEN) acts directly on multiple myeloma (MM) cells by inducing cereblon-mediated degradation of interferon regulatory factor 4, Ikaros (IKZF)1 and IKZF3, transcription factors that are essential for MM cell survival. The mucin 1 (MUC1) C-terminal transmembrane subunit (MUC1-C) oncoprotein is aberrantly expressed by MM cells and protects against reactive oxygen species (ROS)-mediated MM cell death. The present studies demonstrate that targeting MUC1-C with GO-203, a cell-penetrating peptide inhibitor of MUC1-C homodimerization, is more than additive with LEN in downregulating the WNT/β-catenin pathway, suppressing MYC, and inducing late apoptosis/necrosis...
June 23, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28643017/safety-and-efficacy-of-daratumumab-in-japanese-patients-with-relapsed-or-refractory-multiple-myeloma-a-multicenter-phase-1-dose-escalation-study
#18
Shinsuke Iida, Kenshi Suzuki, Shigeru Kusumoto, Masaki Ri, Nobuhiro Tsukada, Yu Abe, Masayuki Aoki, Mitsuo Inagaki
Safety, efficacy, and pharmacokinetics (PK) of daratumumab as a monotherapy were investigated in Japanese patients with relapsed/refractory multiple myeloma (MM). This multicenter, dose-escalation study included patients (age ≥20 years) with ≥2 prior therapies. Daratumumab was administered intravenously: 8 mg/kg (n = 4) and 16 mg/kg (n = 5). The primary endpoint was safety. Secondary endpoints included objective response, overall response rate (ORR), progression-free survival (PFS), PK, and immunogenicity...
June 22, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28642620/pomalidomide-bortezomib-and-low-dose-dexamethasone-in-lenalidomide-refractory-and-proteasome-inhibitor-exposed-myeloma
#19
P G Richardson, C C Hofmeister, N S Raje, D S Siegel, S Lonial, J Laubach, Y A Efebera, D H Vesole, A K Nooka, J Rosenblatt, D Doss, M H Zaki, A Bensmaine, J Herring, Y Li, L Watkins, M S Chen, K C Anderson
This phase 1 dose-escalation study evaluated pomalidomide, bortezomib (subcutaneous (SC) or intravenous (IV)) and low-dose dexamethasone (LoDEX) in lenalidomide-refractory and proteasome inhibitor-exposed relapsed or relapsed and refractory multiple myeloma (RRMM). In 21-day cycles, patients received pomalidomide (1-4 mg days 1-14), bortezomib (1-1.3 mg/m(2) days 1, 4, 8 and 11 for cycles 1-8; days 1 and 8 for cycle ⩾9) and LoDEX. Primary endpoint was to determine the maximum tolerated dose (MTD). Thirty-four patients enrolled: 12 during escalation, 10 in the MTD IV bortezomib cohort and 12 in the MTD SC bortezomib cohort...
June 2, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28642592/integrative-network-analysis-identifies-novel-drivers-of-pathogenesis-and-progression-in-newly-diagnosed-multiple-myeloma
#20
A Laganà, D Perumal, D Melnekoff, B Readhead, B A Kidd, V Leshchenko, P-Y Kuo, J Keats, M DeRome, J Yesil, D Auclair, S Lonial, A Chari, H J Cho, B Barlogie, S Jagannath, J T Dudley, S Parekh
Multiple Myeloma (MM) is an incurable malignancy of bone marrow plasma cells characterized by wide clinical and molecular heterogeneity. In this study we applied an integrative network biology approach to molecular and clinical data measured from 450 patients with newly diagnosed MM from the MMRF CoMMpass study. A novel network model of myeloma (MMNet) was constructed, revealing complex molecular disease patterns and novel associations between clinical traits and genomic markers. Genomic alterations and groups of co-expressed genes correlate with disease stage, tumor clonality, and early progression...
June 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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