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t(4:14) multiple myeloma

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https://www.readbyqxmd.com/read/29105343/racial-disparity-in-utilization-of-therapeutic-modalities-among-multiple-myeloma-patients-a-seer-medicare-analysis
#1
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...
November 3, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29081188/-cytogenetic-abnormalities-and-prognosis-of-532-patients-with-multiple-myeloma
#2
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
#3
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-Rd. This pre-planned analysis assessed the efficacy and safety of IRd versus 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...
October 20, 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
#4
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...
October 18, 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
#5
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 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 I 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 upon progression during treatment...
October 10, 2017: Blood
https://www.readbyqxmd.com/read/28984511/interbody-distraction-and-vertebral-body-reconstruction-with-polymethylmethacrylate-for-the-treatment-of-pathological-fractures
#6
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...
October 6, 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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28869617/a-phase-1-trial-of-90-y-zevalin-radioimmunotherapy-with-autologous-stem-cell-transplant-for-multiple-myeloma
#10
A Dispenzieri, A D'Souza, M A Gertz, K Laumann, G Wiseman, M Q Lacy, B LaPlant, F Buadi, S R Hayman, S K Kumar, D Dingli, W J Hogan, S M Ansell, D A Gastineau, D J Inwards, I N Micallef, L F Porrata, P B Johnston, M R Litzow, T E Witzig
This phase 1 study (clinical trial NCT00477815) was conducted to determine the maximum tolerated dose (MTD) of yttrium-90 ibritumomab tiuxetan ((90)Y-Zevalin) with high dose melphalan (HDM) therapy in multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT). In a 3+3 trial design, 30 patients received rituximab 250 mg/m(2) with indium-111 ibritumomab tiuxetan ((111)In-Zevalin) for dosimetry (day -22); rituximab 250 mg/m(2) with escalating doses of (90)Y-Zevalin (day -14); melphalan 100 mg/m(2) (days -2,-1) followed by ASCT (day 0) and sargramostim (GM-CSF, day 0) until neutrophil engraftment...
October 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28867196/a-novel-phenylphthalimide-derivative-pegylated-tc11-improves-pharmacokinetic-properties-and-induces-apoptosis-of-high-risk-myeloma-cells-via-g2-m-cell-cycle-arrest
#11
Shuji Aida, Masashi Hozumi, Daiju Ichikawa, Kazuki Iida, Yuko Yonemura, Noriko Tabata, Taketo Yamada, Maiko Matsushita, Takeshi Sugai, Hiroshi Yanagawa, Yutaka Hattori
Despite the development of new drugs for multiple myeloma (MM), the prognosis of MM patients with high-risk cytogenetic abnormalities such as t (4; 14) and del17p remains poor. We reported that a novel phenylphthalimide derivative, TC11, induced apoptosis of MM cells in vitro and in vivo, and TC11 directly bound to α-tubulin and nucleophosmin-1 (NPM1). However, TC11 showed low water solubility and poor pharmacokinetic properties. Here we synthesized a water-soluble TC11-derivative, PEG(E)-TC11, in which HOEtO-TC11 is pegylated with PEG through an ester bond, and we examined its anti-myeloma activity...
November 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28862698/prognostic-implications-of-abnormalities-of-chromosome-13-and-the-presence-of-multiple-cytogenetic-high-risk-abnormalities-in-newly-diagnosed-multiple-myeloma
#12
M Binder, S V Rajkumar, R P Ketterling, P T Greipp, A Dispenzieri, M Q Lacy, M A Gertz, F K Buadi, S R Hayman, Y L Hwa, S R Zeldenrust, J A Lust, S J Russell, N Leung, P Kapoor, R S Go, W I Gonsalves, R A Kyle, S K Kumar
Fluorescence in situ hybridization evaluation is essential for initial risk stratification in multiple myeloma. While the presence of specific cytogenetic high-risk abnormalities (HRA) is known to confer a poor prognosis, less is known about the cumulative effect of multiple HRA. We studied 1181 patients with newly diagnosed multiple myeloma who received novel agents as first-line therapy. High-risk abnormalities were defined as t(4;14), t(14;16), t(14;20) and del(17p). There were 884 patients (75%) without any HRA and 297 patients (25%) with HRA, including 262 (22%) with one HRA and 35 (3%) with two HRA...
September 1, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28826616/updated-analysis-of-calgb-alliance-100104-assessing-lenalidomide-versus-placebo-maintenance-after-single-autologous-stem-cell-transplantation-for-multiple-myeloma-a-randomised-double-blind-phase-3-trial
#13
Sarah A Holstein, Sin-Ho Jung, Paul G Richardson, Craig C Hofmeister, David D Hurd, Hani Hassoun, Sergio Giralt, Edward A Stadtmauer, Daniel J Weisdorf, Ravi Vij, Jan S Moreb, Natalie S Callander, Koen van Besien, Teresa G Gentile, Luis Isola, Richard T Maziarz, Asad Bashey, Heather Landau, Thomas Martin, Muzaffar H Qazilbash, Cesar Rodriguez, Brian McClune, Robert L Schlossman, Scott E Smith, Vera Hars, Kouros Owzar, Chen Jiang, Molly Boyd, Chelsea Schultz, Marcia Wilson, Parameswaran Hari, Marcelo C Pasquini, Mary M Horowitz, Thomas C Shea, Steven M Devine, Charles Linker, Kenneth C Anderson, Philip L McCarthy
BACKGROUND: In the CALGB (Alliance) 100104 study, lenalidomide versus placebo after autologous stem-cell transplantation (ASCT) was investigated for patients with newly diagnosed myeloma. That study showed improved time to progression and overall survival and an increase in second primary malignancies for lenalidomide at a median follow-up of 34 months. Here we report an updated intention-to-treat analysis of CALGB (Alliance) 100104 at a median follow-up of 91 months. METHODS: Patients were eligible for this randomised, double-blind, placebo-controlled, phase 3 trial if they had symptomatic disease requiring treatment; had received, at most, two induction regimens; and had achieved stable disease or better in the first 100 days after ASCT...
September 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28766538/-prognostic-value-of-1q21-amplification-in-multiple-myeloma
#14
T V Abramova, T N Obukhova, L P Mendeleeva, O S Pokrovskaya, E O Gribanova, V V Ryzhko, L A Grebenyuk, M V Nareyko, M V Solovyev, O M Votyakova, S M Kulikov, M A Rusinov, V G Savchenko
AIM: To determine the prevalence of amp1q21 and its relationship to the clinical manifestations of multiple myeloma (MM). SUBJECTS AND METHODS: In December 2009 to March 2016, a total 134 patients aged 30 to 81 years (median 57 years) underwent a pretreatment FISH-study of bone marrow (BM) with centromeric and locus-specific DNA probes to identify amp1q21, t(11;14), t(4;14), t(14;16), t(14;20), t(6;14), trisomies of chromosomes 5, 9, 15, del13q14, del17p13/TP53, and t(8q24)/cMYC...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28760306/high-risk-multiple-myeloma-definition-and-management
#15
REVIEW
Nisha S Joseph, Silvia Gentili, Jonathan L Kaufman, Sagar Lonial, Ajay K Nooka
The prognosis of patients with multiple myeloma has significantly improved after the introduction of novel concepts of immunomodulation and proteasome inhibition in myeloma therapies. In conjunction with the use of high-dose therapy and autologous stem cell transplantation, these newer antimyeloma agents facilitated the augmentation of deeper responses and as a result, enhanced survival outcomes. Despite mounting clinical evidence that novel therapies may mitigate the poor prognostic impact of some predictors historically considered "harbingers of doom" in myeloma such as t(4;14), the benefit of these advances is less evident in patients who present with genetically defined high-risk features such as presence of chromosomal abnormalities del17p, t(14;16), or t(14;20), or among patients presenting with plasma cell leukemia...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28693058/-a-prospective-multi-center-trial-of-non-interventional-and-observational-study-of-lenalidomide-in-chinese-patients-with-multiple-myeloma
#16
MULTICENTER STUDY
G M Wang, G Z Yang, Z X Huang, Y P Zhong, F Y Jin, A J Liao, X M Wang, Z Z Fu, H Liu, X L Li, J F Zhou, X Zhang, Y Hu, F Y Meng, X J Huang, W M Chen, J Lu
Objective: To evaluate the efficacy and safety of lenalidomide in a real-world clinical practice in Chinese patients with multiple myeloma (MM). Methods: It was a prospective, multi-center, observational study. A total of 165 consecutive patients with MM treated with lenalidomide-based regimens were enrolled in 12 hospitals from June 2013 to November 2015. Relevant information was recorded, such as baseline clinical data, cytogenetic abnormalities, treatment regimens, and duration of treatment, safety, and survival...
July 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28680482/combination-of-t-4-14-del-17p13-del-1p32-and-1q21-gain-fish-probes-identifies-clonal-heterogeneity-and-enhances-the-detection-of-adverse-cytogenetic-profiles-in-233-newly-diagnosed-multiple-myeloma
#17
Thomas Smol, Annika Dufour, Sabine Tricot, Mathieu Wemeau, Laure Stalnikiewicz, Franck Bernardi, Christine Terré, Benoît Ducourneau, Hervé Bisiau, Agnès Daudignon
BACKGROUND: Our aim was to set the FISH combination of del(17p13), t(4;14), 1q21 gain and del(1p32), four adverse cytogenetic factors rarely evaluated together, and compare our technical thresholds with those defined in the literature. METHODS: Two hundred thirty-three patients with MM at diagnosis were studied using FISH to target 4 unfavorable cytogenetic abnormalities: 17p13 deletion, t(4;14) translocation, 1p32 deletion and 1q21 gain. Technical thresholds were determined for each probe using isolated CD138-expressing PC from patients without MM...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/28655925/natural-history-of-t-11-14-multiple-myeloma
#18
A Lakshman, M A Moustafa, S V Rajkumar, A Dispenzieri, M A Gertz, F K Buadi, M Q Lacy, D Dingli, A L Fonder, S R Hayman, M A Hobbs, W I Gonsalves, Y L Hwa, P Kapoor, N Leung, R S Go, Y Lin, T V Kourelis, J A Lust, S J Russell, S R Zeldenrust, R A Kyle, S K Kumar
Translocation (11;14) on interphase fluorescent in situ hybridization in plasma cells is regarded as a standard risk prognostic marker in multiple myeloma based on studies conducted before introduction of current therapies. We identified 365 patients with t(11;14), and 730 matched controls:132 patients with non-(11;14) translocations and 598 patients with no chromosomal translocation. The median progression-free survival for the three groups were 23.0 (95% confidence interval (CI), 20.8-27.6), 19.0 (95% CI, 15...
June 27, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28655599/final-results-of-a-phase-1-study-of-vorinostat-pegylated-liposomal-doxorubicin-and-bortezomib-in-relapsed-or-refractory-multiple-myeloma
#19
Peter M Voorhees, Cristina Gasparetto, Dominic T Moore, Diane Winans, Robert Z Orlowski, David D Hurd
INTRODUCTION/BACKGROUND: Deacetylase inhibitors have synergistic activity in combination with proteasome inhibitors and anthracyclines in preclinical models of multiple myeloma (MM). We therefore evaluated the safety and efficacy of the deacetylase inhibitor vorinostat in combination with pegylated liposomal doxorubicin (PLD) and bortezomib in relapsed/refractory MM. PATIENTS AND METHODS: Thirty-two patients were treated with PLD and bortezomib in combination with escalating doses of vorinostat on days 4 to 11 or 1 to 14...
May 10, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28655091/-outcomes-of-lenalidomide-based-treatment-for-57-patients-of-relapsed-or-refractory-multiple-myeloma
#20
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
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