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t(4:14) multiple myeloma

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https://www.readbyqxmd.com/read/28915594/identification-of-precision-treatment-strategies-for-relapsed-refractory-multiple-myeloma-by-functional-drug-sensitivity-testing
#1
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
#2
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
#3
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...
September 4, 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
#4
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...
September 1, 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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 FISH in plasma cells is regarded as a standard risk prognostic marker in multiple myeloma (MM) 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 with no chromosomal translocation. The median progression-free survival (PFS) for the three groups were 23.0 (95% CI, 20.8-27.6), 19.0 (95% CI, 15.8-22.7) and 28.3 (95% CI, 25.7-30.6) months respectively [P<0...
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
#12
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
#13
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/28624792/mb4-2-mb4-3-transcripts-of-igh-mmset-fusion-gene-in-t-4-14-pos-multiple-myeloma-indicate-poor-prognosis
#14
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...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28595472/correction-to-grzasko-r-et%C3%A2-al-chromosome-1-amplification-has-similar-prognostic-value-to-del-17p13-and-t-4-14-p16-q32-in-multiple-myeloma-patients-analysis-of-real-life-data-from-the-polish-myeloma-study-group
#15
https://www.readbyqxmd.com/read/28584253/prediction-of-outcome-in-newly-diagnosed-myeloma-a-meta-analysis-of-the-molecular-profiles-of-1905-trial-patients
#16
V Shah, A L Sherborne, B A Walker, D C Johnson, E M Boyle, S Ellis, D B Begum, P Z Proszek, J R Jones, C Pawlyn, S Savola, M W Jenner, M T Drayson, R G Owen, R S Houlston, D A Cairns, W M Gregory, G Cook, F E Davies, G H Jackson, G J Morgan, M F Kaiser
Robust establishment of survival in multiple myeloma (MM) and its relationship to recurrent genetic aberrations is required as outcomes are variable despite apparent similar staging. We assayed copy number alterations (CNA) and translocations in 1036 patients from the NCRI Myeloma XI trial and linked these to overall survival (OS) and progression-free survival. Through a meta-anlysis of these data with data from MRC Myeloma IX trial, totalling 1905 newly diagnosed MM patients (NDMM), we confirm the association of t(4;14), t(14;16), t(14;20), del(17p) and gain(1q21) with poor prognosis with hazard ratios (HRs) for OS of 1...
June 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28550183/somatic-mutation-spectrum-in-monoclonal-gammopathy-of-undetermined-significance-indicates-a-less-complex-genomic-landscape-compared-to-multiple-myeloma
#17
Aneta Mikulasova, Christopher P Wardell, Alexander Murison, Eileen M Boyle, Graham H Jackson, Jan Smetana, Zuzana Kufova, Ludek Pour, Viera Sandecka, Martina Almasi, Pavla Vsianska, Evzen Gregora, Petr Kuglik, Roman Hajek, Faith E Davies, Gareth J Morgan, Brian A Walker
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant precursor of multiple myeloma with a 1% risk of progression per year. Although targeted analyses have shown the presence of specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS genes mutations, little is known about the molecular mechanism of malignant transformation. We have performed whole exome sequencing together with CGH+SNP array analysis in 33 flow-cytometry separated abnormal plasma cell samples from MGUS patients to describe somatic gene mutations and chromosome changes at the genome-wide level...
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28525891/identification-of-precision-treatment-strategies-for-relapsed-refractory-multiple-myeloma-by-functional-drug-sensitivity-testing
#18
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...
May 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28498418/identification-and-expression-of-mmsa-8-and-its-clinical-significance-in-multiple-myeloma
#19
Rui He, Nan Yang, Pengyu Zhang, Jie Liu, Junhui Li, Fulin Zhou, Wanggang Zhang
In our previous studies, we identified 12 multiple myeloma (MM)-associated antigens by serological analysis of tumor-associated antigens with a recombinant cDNA expression library (SEREX) on MM. MM-associated antigen-8 (MMSA-8) was one of the new antigens identified. We determined the 3'- and 5'-ends of MMSA-8 using SMART-rapid amplification of cDNA ends (RACE) and then cloned its full-length cDNA in the U266 cell line. The full cDNA sequence revealed that MMSA-8 is RPS27A-related transcript variant 1 that is specifically associated with MM...
June 2017: Oncology Reports
https://www.readbyqxmd.com/read/28461396/pembrolizumab-pomalidomide-and-low-dose-dexamethasone-for-relapsed-refractory-multiple-myeloma
#20
Ashraf Badros, Elizabeth Hyjek, Ning Ma, Alexander Lesokhin, Ahmet Dogan, Aaron P Rapoport, Mehmet Kocoglu, Emily Lederer, Sunita Philip, Todd Milliron, Cameron Dell, Olga Goloubeva, Zeba Singh
Programmed death 1 (PD-1) receptor and its ligand (PD-L1) facilitate immune evasion in multiple myeloma (MM). We hypothesized that pembrolizumab, PD-1-antibody, can enhance anti-myeloma cellular immunity generated by pomalidomide leading to improved clinical responses. In this single-center, phase II study, 48 patients with relapsed/refractory MM (RRMM) received 28-days cycles of pembrolizumab, 200 mg intravenously every 2 weeks, pomalidomide 4 mg daily for 21 days and dexamethasone 40 mg weekly. Patients had a median of 3 (range: 2-5) lines of therapy, median age 64 (range: 35-83) years and had received both immune modulatory agent and proteasome inhibitor; (35 [73%] of 48) were refractory to both; (31 [70%]) had received an autologous transplant and (30 [62%]) had high-risk cytogenetics...
May 1, 2017: Blood
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