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t(4:14) multiple myeloma

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https://www.readbyqxmd.com/read/29779345/-role-of-minimal-residual-disease-detection-by-multiparameter-flow-cytometry-in-newly-diagnosed-multiple-myeloma-an-analysis-of-106-patients
#1
S H Deng, Y Xu, W W Sui, H J Wang, Z J Li, T Y Wang, W Liu, W Y Huang, R Lyu, J Li, M W Fu, D H Zou, G An, L G Qiu
Objective: To assess the feasibility and prognostic value of the minimal residual disease (MRD) evaluated by multiparameter flow cytometry (MFC) in the newly diagnosed multiple myeloma (MM) patients of China. Methods: Clinical data of 106 consecutively newly diagnosed MM patients with MRD data were retrospectively analyzed in a single center in China from June 2013 to June 2015. Results: ① Of 106 patients, 48 (45.3%) achieved MRD negativity. The median time to MRD-negative was 3 months. More patients undergoing autologous stem cell transplantation (ASCT) achieved MRD negativity compared with non-ASCT patients (62...
May 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29720731/front-line-therapies-for-elderly-patients-with-transplant-ineligible-multiple-myeloma-and-high-risk-cytogenetics-in-the-era-of-novel-agents
#2
REVIEW
Herve Avet-Loiseau, Thierry Facon
In multiple myeloma, certain cytogenetic abnormalities, such as t(4;14), t(14;16), and del(17p), are considered high risk and are associated with worse prognosis. Patients with these high-risk cytogenetic abnormalities, as well as those who are elderly and transplant ineligible, have not experienced the same degree of improved survival outcomes that other patients have seen with recent advances in the treatment of multiple myeloma. To date, no treatment regimen has demonstrated sustained and consistent survival benefits in elderly, transplant-ineligible patients with high-risk cytogenetic abnormalities and newly diagnosed multiple myeloma...
March 28, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29531651/elotuzumab-for-the-treatment-of-relapsed-or-refractory-multiple-myeloma-with-special-reference-to-its-modes-of-action-and-slamf7-signaling
#3
REVIEW
Masafumi Taniwaki, Mihoko Yoshida, Yosuke Matsumoto, Kazuho Shimura, Junya Kuroda, Hiroto Kaneko
Elotuzumab, targeting signaling lymphocytic activation molecule family 7 (SLAMF7), has been approved in combination with lenalidomide and dexamethasone (ELd) for relapsed/refractory multiple myeloma (MM) based on the findings of the phase III randomized trial ELOQUENT-2 (NCT01239797). Four-year follow-up analyses of ELOQUENT-2 have demonstrated that progression-free survival was 21% in ELd versus 14% in Ld. Elotuzumab binds a unique epitope on the membrane IgC2 domain of SLAMF7, exhibiting a dual mechanism of action: natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and enhancement of NK cell activity...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29453220/identification-of-novel-fusion-transcripts-in-multiple-myeloma
#4
Mingxuan Lin, Peak Ling Lee, Lily Chiu, Constance Chua, Kenneth H K Ban, Adeline H F Lin, Zit Liang Chan, Tae-Hoon Chung, Benedict Yan, Wee-Joo Chng
AIMS: Multiple myeloma (MM) is a heterogeneous disease characterised by genetically complex abnormalities. The classical mutational spectrum includes recurrent chromosomal aberrations and gene-level mutations. Recurrent translocations involving the IGH gene such as t(11;14), t(4;14) and t(14;16) are well known. However, the presence of complex genetic abnormalities raises the possibility that fusions other than the recurrent IGH translocations exist. We therefore employed a targeted RNA-sequencing panel to identify novel putative fusions in a local cohort of MM...
February 16, 2018: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29401553/clinical-utility-of-a-diagnostic-approach-to-detect-genetic-abnormalities-in-multiple-myeloma-a-single-institution-experience
#5
Hyun Ae Jung, Mi Ae Jang, Kihyun Kim, Sun Hee Kim
BACKGROUND: The identification of genetic abnormalities in patients with multiple myeloma (MM) has gained emphasis because genetics-based risk stratification significantly affects overall survival (OS). We investigated genetic abnormalities using conventional cytogenetics and FISH and analyzed the prognostic significance of the identified additional abnormalities in MM. METHODS: In total, 267 bone marrow samples were collected from February 2006 to November 2013 from patients who were newly diagnosed as having MM in a tertiary-care hospital in Korea...
May 2018: Annals of Laboratory Medicine
https://www.readbyqxmd.com/read/29397346/single-center-experience-in-treating-patients-with-t-4-14-multiple-myeloma-with-and-without-planned-frontline-autologous-stem-cell-transplantation
#6
Henry Chan, Madeline Phillips, Manjula Maganti, Sophia Farooki, Giovanni Piza Rodriguez, Esther Masih-Khan, Christine Chen, Anca Prica, Donna Reece, Rodger Tiedemann, Suzanne Trudel, Vishal Kukreti
BACKGROUND: Translocation t(4;14) has traditionally been classified as a high-risk cytogenetic feature in patients with multiple myeloma with shortened progression-free (PFS) and overall survival (OS) despite initial response to treatment. Recent data have shown an improved long-term survival in these patients treated with novel agents, such as bortezomib. PATIENTS AND METHODS: We conducted a retrospective study on our patients with t(4;14) multiple myeloma treated with bortezomib-based induction between July 1, 2006 and June 30, 2014 to assess the real-world outcomes of these patients in a tertiary center...
March 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29381435/selective-inhibition-of-nuclear-export-with-oral-selinexor-for-treatment-of-relapsed-or-refractory-multiple-myeloma
#7
Dan T Vogl, David Dingli, Robert Frank Cornell, Carol Ann Huff, Sundar Jagannath, Divaya Bhutani, Jeffrey Zonder, Rachid Baz, Ajay Nooka, Joshua Richter, Craig Cole, Ravi Vij, Andrzej Jakubowiak, Rafat Abonour, Gary Schiller, Terri L Parker, Luciano J Costa, David Kaminetzky, James E Hoffman, Andrew J Yee, Ajai Chari, David Siegel, Rafael Fonseca, Scott Van Wier, Gregory Ahmann, Ilsel Lopez, Michael Kauffman, Sharon Shacham, Jean-Richard Saint-Martin, Carla D Picklesimer, Cassandra Choe-Juliak, A Keith Stewart
Purpose Selinexor, a first-in-class, oral, selective exportin 1 (XPO1) inhibitor, induces apoptosis in cancer cells through nuclear retention of tumor suppressor proteins and the glucocorticoid receptor, along with inhibition of translation of oncoprotein mRNAs. We studied selinexor in combination with low-dose dexamethasone in patients with multiple myeloma refractory to the most active available agents. Patients and Methods This phase II trial evaluated selinexor 80 mg and dexamethasone 20 mg, both orally and twice weekly, in patients with myeloma refractory to bortezomib, carfilzomib, lenalidomide, and pomalidomide (quad-refractory disease), with a subset also refractory to an anti-CD38 antibody (penta-refractory disease)...
March 20, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29380550/distinct-predictive-impact-of-fish-abnormality-in-proteasome-inhibitors-and-immunomodulatory-agents-response-redefining-high-risk-multiple-myeloma-in-asian-patients
#8
Ja Min Byun, Dong-Yeop Shin, Junshik Hong, Inho Kim, Hyun Kyung Kim, Dong Soon Lee, Youngil Koh, Sung-Soo Yoon
For risk-adaptive therapeutic approaches in multiple myeloma (MM) treatment, we analyzed treatment outcome according to in situ hybridization (FISH) profiles to investigate the prognostic and predictive values of structural variations in a large series of Asian population. A total of 565 newly diagnosed patients with multiple myeloma between January 2005 and June 2015 were evaluated. FISH results showed del(17p13) in 8.8% (29/331), del(13q14) in 35.5% (184/519), t(14;16) in 2.5% (8/326), t(4;14) in 27.9% (109/390), IgH rearrangement in 47...
March 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29200420/the-effect-of-novel-therapies-in-high-molecular-risk-multiple-myeloma
#9
Guido Lancman, Douglas Tremblay, Kevin Barley, Bart Barlogie, Hearn Jay Cho, Sundar Jagannath, Deepu Madduri, Erin Moshier, Samir Parekh, Ajai Chari
Multiple myeloma is a heterogeneous disease with a prognosis that varies with patient factors, disease burden, tumor biology, and treatments. Certain molecular abnormalities confer a worse prognosis and thus are considered high-risk. These include t(4;14), del(17p), t(14;16), t(14;20), hypodiploidy, and gain(1q)/del(1p). In our previous review in 2013, we discussed the effect of available therapies on prognosis in these high-risk patients. Since then, seven phase 3 clinical trials in relapsed myeloma with 1 to 3 lines of therapy have been conducted, resulting in the approval of panobinostat, ixazomib, daratumumab, and elotuzumab, as well as additional data on carfilzomib...
November 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29166734/-a-retrospective-study-of-the-bird-regimen-in-the-treatment-of-relapsed-refractory-multiple-myeloma
#10
X L Liu, L Li, Q L Shi, L J Chen, X X Cao, J Li, A J Liao, D H Zou, J N Sun, S J Gao, W Li, J Hou, F Y Jin
Objective: To evaluate efficacy of the BiRd regimen, a combination of clarithromycin, lenalidomide, and dexamethasone, in the treatment of patients with relapsed/refractory multiple myeloma (RRMM) . Methods: Patients with RRMM treated with BiRd between September 11, 2013 and August 1, 2016 at six centers were included to evaluate overall survival rate (ORR) , clinical benefit rate (CBR) , progression-free survival (PFS) , overall survival (OS) , as well as adverse events. Results: Of 30 patients with RRMM, 27 patients were evaluable, and ORR and CBR were 51...
October 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29156688/frequency-of-expression-and-generation-of-t-cell-responses-against-antigens-on-multiple-myeloma-cells-in-patients-included-in-the-gmmg-mm5-trial
#11
Michael Schmitt, Angela G Hückelhoven, Michael Hundemer, Anita Schmitt, Susanne Lipp, Martina Emde, Hans Salwender, Mathias Hänel, Katja Weisel, Uta Bertsch, Jan Dürig, Anthony D Ho, Igor Wolfgang Blau, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose
Background: Raising T-cell response against antigens either expressed on normal and malignant plasma cells (e.g. HM1.24) or aberrantly on myeloma cells only (e.g. cancer testis antigens, CTA) by vaccination is a potential treatment approach for multiple myeloma. Results: Expression by GEP is found for HM1.24 in all, HMMR in 318/458 (69.4%), MAGE-A3 in 209/458 (45.6%), NY-ESO-1/2 in 40/458 (8.7%), and WT-1 in 4/458 (0.8%) of samples with the pattern being confirmed by RNA-sequencing...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29105343/racial-disparity-in-utilization-of-therapeutic-modalities-among-multiple-myeloma-patients-a-seer-medicare-analysis
#12
COMPARATIVE STUDY
Sikander Ailawadhi, Ryan D Frank, Pooja Advani, Abhisek Swaika, M'hamed Temkit, Richa Menghani, Mayank Sharma, Zahara Meghji, Shumail Paulus, Nandita Khera, Shahrukh K Hashmi, Aneel Paulus, Tanya S Kakar, David O Hodge, Dorin T Colibaseanu, Michael R Vizzini, Vivek Roy, Gerardo Colon-Otero, Asher A Chanan-Khan
Outcomes have improved considerably in multiple myeloma (MM), but disparities among racial-ethnic groups exist. Differences in utilization of novel therapeutics are likely contributing factors. We explored such differences from the SEER-Medicare database. A utilization analysis of lenalidomide, thalidomide, bortezomib, and stem cell transplant (SCT) was performed for patients diagnosed with MM between 2007 and 2009, including use over time, use by race, time-dependent trends for each racial subgroup, and survival analysis...
December 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29081188/-cytogenetic-abnormalities-and-prognosis-of-532-patients-with-multiple-myeloma
#13
H Wu, H Zhang, H Y He, H Jiang, Y Y Zhao, R An, J He, R Li, J Lu, J Hou
Objective: To explore the effect of 6 common cytogenetic abnormalities on the prognosis of multiple myeloma (MM). Methods: Myeloma cells from a cohort of 532 newly-diagnosed MM patients enrolled were enriched by CD138 immunomagnetic beads, then detected 13q-, 17p-, 1q+, t (4;14), t (11;14) and t (14;16) and other common genetic abnormalities in MM by using interphase fluorescence in situ hybridization (FISH) technique to compare the influence of different genetic abnormalities on their prognoses. Results: The rate of cytogenetic abnormalities was 78...
September 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29054911/ixazomib-significantly-prolongs-progression-free-survival-in-high-risk-relapsed-refractory-myeloma-patients
#14
RANDOMIZED CONTROLLED TRIAL
Hervé Avet-Loiseau, Nizar J Bahlis, Wee-Joo Chng, Tamas Masszi, Luisa Viterbo, Ludek Pour, Peter Ganly, Antonio Palumbo, Michele Cavo, Christian Langer, Andrzej Pluta, Arnon Nagler, Shaji Kumar, Dina Ben-Yehuda, S Vincent Rajkumar, Jesus San-Miguel, Deborah Berg, Jianchang Lin, Helgi van de Velde, Dixie-Lee Esseltine, Alessandra di Bacco, Philippe Moreau, Paul G Richardson
Certain cytogenetic abnormalities are known to adversely impact outcomes in patients with multiple myeloma (MM). The phase 3 TOURMALINE-MM1 study demonstrated a significant improvement in progression-free survival (PFS) with ixazomib-lenalidomide-dexamethasone (IRd) compared with placebo-lenalidomide-dexamethasone (placebo-Rd). This preplanned analysis assessed the efficacy and safety of IRd vs placebo-Rd according to cytogenetic risk, as assessed using fluorescence in situ hybridization. High-risk cytogenetic abnormalities were defined as del(17p), t(4;14), and/or t(14;16); additionally, patients were assessed for 1q21 amplification...
December 14, 2017: Blood
https://www.readbyqxmd.com/read/29040969/comparison-of-igh-profile-signals-using-t-4-14-and-igh-break-apart-probes-by-fish-in-multiple-myeloma
#15
Thomas Smol, Agnès Daudignon
We compared immunoglobulin heavy chain gene (IGH) signal patterns in multiple myeloma (MM) using the FGFR3-IGH and the IGH break-apart probes to facilitate their understanding and analysis. Forty-nine patients with MM were studied. FISH was performed on samples sorted with an FGFR3-IGH dual-color, dual-fusion translocation probe and an IGH dual-color break-apart rearrangement probe. The IGH deletions were found in 7 MM analyzed with the FGFR3-IGH probe and all confirmed by the IGH break-apart probe. The additional IGH signals were associated with different patterns using the IGH break-apart probe: a normal pattern in 9 cases, trisomy 14 in 3 cases, and splits of IGH in 7 cases...
2017: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/29018077/efficacy-of-venetoclax-as-targeted-therapy-for-relapsed-refractory-t-11-14-multiple-myeloma
#16
Shaji Kumar, Jonathan L Kaufman, Cristina Gasparetto, Joseph Mikhael, Ravi Vij, Brigitte Pegourie, Lofti Benboubker, Thierry Facon, Martine Amiot, Philippe Moreau, Elizabeth A Punnoose, Stefanie Alzate, Martin Dunbar, Tu Xu, Suresh K Agarwal, Sari Heitner Enschede, Joel D Leverson, Jeremy A Ross, Paulo C Maciag, Maria Verdugo, Cyrille Touzeau
Venetoclax is a selective, orally bioavailable BCL-2 inhibitor that induces cell death in multiple myeloma (MM) cells, particularly in those harboring t(11;14), which express high levels of BCL-2 relative to BCL-XL and MCL-1. In this phase 1 study, patients with relapsed/refractory MM received venetoclax monotherapy. After a 2-week lead-in with weekly dose escalation, daily venetoclax was given at 300, 600, 900, or 1200 mg in dose-escalation cohorts and 1200 mg in the safety expansion. Dexamethasone could be added on progression during treatment...
November 30, 2017: Blood
https://www.readbyqxmd.com/read/28984511/interbody-distraction-and-vertebral-body-reconstruction-with-polymethylmethacrylate-for-the-treatment-of-pathological-fractures
#17
Scott L Zuckerman, Ganesh Rao, Laurence D Rhines, Ian E McCutcheon, Richard G Everson, Claudio E Tatsui
OBJECTIVE Treatment of epidural spinal cord compression (ESCC) caused by tumor includes surgical decompression and stabilization followed by postoperative radiation. In the case of severe axial loading impairment, anterior column reconstruction is indicated. The authors describe the use of interbody distraction to restore vertebral body height and correct kyphotic angulation prior to reconstruction with polymethylmethacrylate (PMMA), and report the long-term durability of such reconstruction. METHODS A single institution, prospective series of patients with ESCC undergoing single-stage decompression, anterior column reconstruction, and posterior instrumentation from 2013 to 2016 was retrospectively analyzed...
December 2017: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/28978130/body-fat-composition-as-predictive-factor-for-treatment-response-in-patients-with-newly-diagnosed-multiple-myeloma-subgroup-analysis-of-the-prospective-gmmg-mm5-trial
#18
Jonathan P GroΔ, Johanna Nattenmüller, Stefan Hemmer, Diana Tichy, Julia Krzykalla, Hartmut Goldschmidt, Uta Bertsch, Stefan Delorme, Hans-Ulrich Kauczor, Jens Hillengass, Maximilian Merz
INTRODUCTION/BACKGROUND: Obesity is a well-known risk factor for malignant tumors and increased body mass index (BMI) is correlated to the risk of developing multiple myeloma (MM). The correlation of body fat composition with disease activity, adverse events and treatment response of MM patients has not been investigated yet. PATIENTS AND METHODS: A subgroup of 108 patients from a single institution enrolled in the prospective GMMG-MM5 trial, who received a whole-body low-dose computed tomography (WBLDCT) before induction therapy, were included in this study...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915594/identification-of-precision-treatment-strategies-for-relapsed-refractory-multiple-myeloma-by-functional-drug-sensitivity-testing
#19
Muntasir Mamun Majumder, Raija Silvennoinen, Pekka Anttila, David Tamborero, Samuli Eldfors, Bhagwan Yadav, Riikka Karjalainen, Heikki Kuusanmäki, Juha Lievonen, Alun Parsons, Minna Suvela, Esa Jantunen, Kimmo Porkka, Caroline A Heckman
Novel agents have increased survival of multiple myeloma (MM) patients, however high-risk and relapsed/refractory patients remain challenging to treat and their outcome is poor. To identify novel therapies and aid treatment selection for MM, we assessed the ex vivo sensitivity of 50 MM patient samples to 308 approved and investigational drugs. With the results we i) classified patients based on their ex vivo drug response profile; ii) identified and matched potential drug candidates to recurrent cytogenetic alterations; and iii) correlated ex vivo drug sensitivity to patient outcome...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881672/mb4-2-mb4-3-transcripts-of-igh-mmset-fusion-gene-in-t-4-14-pos-multiple-myeloma-indicate-poor-prognosis
#20
Feng Li, Yong-Ping Zhai, Ting Lai, Qian Zhao, Hui Zhang, Yu-Mei Tang, Jian Hou
Multiple myeloma (MM) patients with t(4;14) is a heterogeneous group. Prognostic tools capable of predicting the outcome of patients are currently lacking. The MM SET domain (MMSET) protein is universally overexpressed and has been suggested to have an important tumorigenic role. This study analyzed whether the overexpression of full-length (MB4-1) or truncated forms (MB4-2 and MB4-3) of MMSET influence the prognosis of t(4;14)(pos) MM patients. A total of 53 symptomatic t(4;14)(pos) MM patients were retrospectively analyzed...
August 1, 2017: Oncotarget
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