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Multiple myeloma, young patient

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https://www.readbyqxmd.com/read/28402945/a-prospective-open-label-multicenter-observational-study-to-evaluate-the-efficacy-and-safety-of-bortezomib-melphalan-prednisone-as-initial-treatment-for-autologous-stem-cell-transplantation-ineligible-patients-with-multiple-myeloma
#1
Min Kyoung Kim, Kihyun Kim, Chang-Ki Min, Jae-Yong Kwak, Sang-Byung Bae, Sung-Soo Yoon, Je-Jung Lee, Ki Hwan Kim, Seung-Hyun Nam, Yeung-Chul Mun, Hyo Jung Kim, Sung Hwa Bae, Ho-Jin Shin, Jung-Hee Lee, Joon Seong Park, Seong Hyun Jeong, Mark Hong Lee, Yang-Soo Kim, Ho Sup Lee, Keon Woo Park, Won-Sik Lee, Sang Min Lee, Jeong-Ok Lee, Myung Soo Hyun, Deog Yeon Jo, Sung-Nam Lim, Jae Hoon Lee, Do-Yeun Cho, Young Rok Do, Jeong-A Kim, Seong Kyu Park, Jin Seok Kim, Soo-Jeong Kim, Hawk Kim, Hyeon Gyu Yi, Joon Ho Moon, Chul Won Choi, Sung-Hyun Kim, Young-Don Joo, Hoon-Gu Kim, Byung Soo Kim, Moo-Rim Park, Moo-Kon Song, Su-Youn Kim
Bortezomib-melphalan-prednisone (VMP) showed superior efficacy versus MP as first-line treatment for transplantation-ineligible multiple myeloma (MM). This study investigated the efficacy of VMP for Korean patients with MM.Overall, 177 MM patients received 9 cycles of VMP in this prospective, multicenter, observational study. The primary endpoint was 2-year progression-free survival (PFS).Thirty-nine (22%) patients were aged ≥ 75 years and 83 (47.4%) patients had International Staging System stage III. A median of 5 cycles were delivered...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28387460/marizomib-for-central-nervous-system-multiple-myeloma
#2
Ashraf Badros, Zeba Singh, Binod Dhakal, Young Kwok, Ann MacLaren, Paul Richardson, Mohit Trikha, Parameswaran Hari
Marizomib, a natural marine product, is an irreversible proteasome inhibitor currently under investigation in relapsed-refractory multiple myeloma (RRMM) and malignant glioma. Central nervous system-multiple myeloma (CNS-MM) is a rare manifestation of extra-medullary disease with few therapeutic options, highlighting the unmet clinical need in these patients. Marizomib demonstrated encouraging activity in RRMM and has emerging clinical activity in glioma, making it a potential CNS-MM therapeutic intervention...
April 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28352187/risk-of-subsequent-primary-malignancies-among-patients-with-prior-colorectal-cancer-a-population-based-cohort-study
#3
Jiao Yang, Shuting Li, Meng Lv, Yinying Wu, Zheling Chen, Yanwei Shen, Biyuan Wang, Ling Chen, Min Yi, Jin Yang
BACKGROUND: The site-distribution pattern and relative risk of subsequent primary malignancies (SPMs) in colorectal cancer (CRC) patients remains to be determined. MATERIALS AND METHODS: A population-based cohort of 288,390 CRC patients diagnosed between 1973 and 2012 from the Surveillance, Epidemiology, and End Results database was retrospectively reviewed. Standardized incidence ratios were calculated to estimate the relative risk for SPMs. RESULTS: The overall risk of SPMs increased in CRC patients (standardized incidence ratio 1...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28273121/polymer-micelle-formulation-for-the-proteasome-inhibitor-drug-carfilzomib-anticancer-efficacy-and-pharmacokinetic-studies-in-mice
#4
Ji Eun Park, Se-Eun Chun, Derek Reichel, Jee Sun Min, Su-Chan Lee, Songhee Han, Gongmi Ryoo, Yunseok Oh, Shin-Hyung Park, Heon-Min Ryu, Kyung Bo Kim, Ho-Young Lee, Soo Kyung Bae, Younsoo Bae, Wooin Lee
Carfilzomib (CFZ) is a peptide epoxyketone proteasome inhibitor approved for the treatment of multiple myeloma (MM). Despite the remarkable efficacy of CFZ against MM, the clinical trials in patients with solid cancers yielded rather disappointing results with minimal clinical benefits. Rapid degradation of CFZ in vivo and its poor penetration to tumor sites are considered to be major factors limiting its efficacy against solid cancers. We previously reported that polymer micelles (PMs) composed of biodegradable block copolymers poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL) can improve the metabolic stability of CFZ in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28159578/autologous-hematopoietic-cell-transplantation-in-patients-with-multiple-myeloma-effect-of-age
#5
Binod Dhakal, Ariel Nelson, Guru Subramanian Guru Murthy, Raphael Fraser, Daniel Eastwood, Mehdi Hamadani, Marcello Pasquini, Anita D'Souza, Parameswaran Hari
BACKGROUND: In the novel and pre-novel agent era, high-dose therapy, followed by autologous hematopoietic cell transplantation (AHCT), has been shown to prolong survival in patients with multiple myeloma (MM) in randomized trials. However, these trials only included patients aged ≤ 65 years. Given that the median age at diagnosis is 66 years, it is important to know the outcomes of AHCT in older patients. Similarly, definite outcomes of AHCT in very young patients (aged < 50 years) are also lacking because they represent a very small proportion of patients in clinical trials...
March 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28089441/prognostic-implications-of-monosomies-in-patients-with-multiple-myeloma
#6
Sang-Yong Shin, Hyeon-Seok Eom, Ji Yeon Sohn, Hyewon Lee, Boram Park, Jungnam Joo, Ja-Hyun Jang, Mi-Na Lee, Jung Kwon Kim, Sun-Young Kong
BACKGROUND: Cytogenetic analysis aides in risk stratification for patients with multiple myeloma (MM). Although several cytogenetic aberrations have been reported to be prognostic, less is known about the association between the presence of monosomies and prognosis. The present study evaluated the prevalence and prognostic implications of monosomies in patients with MM. MATERIALS AND METHODS: Karyotypes were determined using conventional cytogenetics and fluorescence in situ hybridization (FISH)...
March 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/27983708/the-hk2-dependent-warburg-effect-and-mitochondrial-oxidative-phosphorylation-in-cancer-targets-for-effective-therapy-with-3-bromopyruvate
#7
REVIEW
Paweł Lis, Mariusz Dyląg, Katarzyna Niedźwiecka, Young H Ko, Peter L Pedersen, Andre Goffeau, Stanisław Ułaszewski
This review summarizes the current state of knowledge about the metabolism of cancer cells, especially with respect to the "Warburg" and "Crabtree" effects. This work also summarizes two key discoveries, one of which relates to hexokinase-2 (HK2), a major player in both the "Warburg effect" and cancer cell immortalization. The second discovery relates to the finding that cancer cells, unlike normal cells, derive as much as 60% of their ATP from glycolysis via the "Warburg effect", and the remaining 40% is derived from mitochondrial oxidative phosphorylation...
December 15, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27957423/crystalline-podocytopathy-and-tubulopathy-without-overt-glomerular-proteinuria-in-a-patient-with-multiple-myeloma
#8
Eun Jeong Lee, Su Yeon Lee, So Young Park, Yonjin Kim, Jae Shin Choi, Mi Jeoung Kim, Ji Hyeon Park, Jung Eun Lee, Ghee Young Kwon, Yoon-Goo Kim
Crystalline nephropathy is a rare yet well-known condition associated with multiple myeloma and other light chain-secreting disorders. Paraproteins that are resistant to proteolysis crystallize within proximal tubular cells and cause light-chain proximal tubulopathy, which presents clinically as Fanconi syndrome. Podocytes are rarely affected, and the crystalline inclusions within podocytes are typically precipitated, yielding significant glomerular proteinuria. Here we report a case of extensive crystalline inclusions primarily within podocytes and proximal tubules that presented only with Fanconi syndrome and renal insufficiency...
December 2016: Kidney Research and Clinical Practice
https://www.readbyqxmd.com/read/27922862/improved-detection-of-minimal-residual-disease-by-11c-methionine-pet-ct-in-a-young-patient-with-unusual-extramedullary-presentation-of-recurrent-multiple-myeloma
#9
Carmelo Caldarella, Salvatore Annunziata, Livio Pagano, Valerio De Stefano, Vittoria Rufini
Extramedullary relapse of multiple myeloma (MM) is uncommon. A 40-year-old woman with history of MM underwent PET/CT using C-methionine (C-MET) after the detection of a vulvar lesion on MRI, biopsy proven to be extramedullary relapse of MM. The vulvar lesion was negative at the F-FDG PET/CT but showed high uptake of C-MET; focal uptake of both F-FDG and C-MET was shown within the muscles of the left leg, histologically confirmed as extramedullary relapse of MM. F-FDG PET/CT performed after chemotherapy showed no uptake in both sites, whereas posttreatment C-MET PET/CT showed persistence of residual uptake within the vulvar lesion...
February 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/27863287/bone-health-in-the-elderly-cancer-patient-a-siog-position-paper
#10
REVIEW
J J Body, E Terpos, B Tombal, P Hadji, A Arif, A Young, M Aapro, R Coleman
More than a third of cancers are diagnosed in people over the age of 75. Androgen deprivation for prostate cancer and aromatase inhibitors in breast cancer accelerate age-related bone loss and increase fracture rates. BMD should be checked by dual energy X-ray absorptiometry at baseline and, dependent on risk, every 12-24months. Sufficient calcium, vitamin D and exercise are part of primary fracture prevention. Resistance exercise in particular may improve functional activity and bone density. In men at increased fracture risk and women with postmenopausal early breast cancer, antiresorptive treatment is warranted to reduce fracture rate and to increase overall survival in breast cancer...
December 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27795516/treatment-strategy-in-untreated-transplant-eligible-multiple-myeloma-patients
#11
REVIEW
Kazutaka Sunami
Autologous stem cell transplantation (ASCT) is known to be superior to conventional chemotherapies and has been established as a standard of care for young patients with multiple myeloma. In the first decade of this century, novel agents such as thalidomide, bortezomib, and lenalidomide became clinically available, and several clinical trials using these drugs as induction therapies, conditioning regimens, and post-transplant consolidation and maintenance therapies have been reported, leading to increasing improvement in treatment results as compared to conventional therapies...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27764795/a-novel-3d-mesenchymal-stem-cell-model-of-the-multiple-myeloma-bone-marrow-niche-biologic-and-clinical-applications
#12
Jana Jakubikova, Danka Cholujova, Teru Hideshima, Paulina Gronesova, Andrea Soltysova, Takeshi Harada, Jungnam Joo, Sun-Young Kong, Raphael E Szalat, Paul G Richardson, Nikhil C Munshi, David M Dorfman, Kenneth C Anderson
Specific niches within the tumor bone marrow (BM) microenvironment afford a sanctuary for multiple myeloma (MM) clones due to stromal cell-tumor cell interactions, which confer survival advantage and drug resistance. Defining the sequelae of tumor cell interactions within the MM niches on an individualized basis may provide the rationale for personalized therapies. To mimic the MM niche, we here describe a new 3D co-culture ex-vivo model in which primary MM patient BM cells are co-cultured with mesenchymal stem cells (MSC) in a hydrogel 3D system...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27641727/vemurafenib-in-combination-with-cobimetinib-in-relapsed-and-refractory-extramedullary-multiple-myeloma-harboring-the-braf-v600e-mutation
#13
Ulrich J M Mey, Christoph Renner, Roger von Moos
BRAF mutations are present in a variety of cancers and cause constitutive activation of the Ras-Raf-MEK-ERK signaling pathway. In cutaneous malignant melanoma, combined treatment with BRAF and MEK inhibitors is associated with high response rates and has been shown to improve progression free as well as overall survival compared to BRAF inhibition alone. In multiple myeloma, BRAF mutations are detectable only in a minority of patients. Only few data are available regarding the clinical activity of BRAF inhibitors in BRAF-positive multiple myeloma patients, including some anecdotal reports on remarkable responses in individuals being resistant to all other available anti-myeloma treatment approaches...
September 19, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27548407/impact-of-marital-status-insurance-status-income-and-race-ethnicity-on-the-survival-of-younger-patients-diagnosed-with-multiple-myeloma-in-the-united-states
#14
Luciano J Costa, Ilene K Brill, Elizabeth E Brown
BACKGROUND: Recent advances in the treatment of multiple myeloma (MM) have been associated with improved survival, predominantly among young and white patients. The authors hypothesized that sociodemographic factors, adjusted for race/ethnicity, influence the survival of younger patients with MM. METHODS: Overall survival (OS) data were obtained for individuals included in the Surveillance, Epidemiology, and End Results (SEER-18) program who were diagnosed with MM before the age of 65 years between 2007 and 2012...
October 15, 2016: Cancer
https://www.readbyqxmd.com/read/27536655/amyloid-arthropathy-of-the-hip-joint-associated-with-multiple-myeloma-a-case-report
#15
Yoon Je Cho, Young Soo Chun, Kee Hyung Rhyu, Yong Koo Park, Kyung Nam Ryu, Ji Seon Park, Huo Liang, Gwang Young Jung, Won Ju Shin
Amyloidosis is a disease characterized by the deposition of non-soluble fibrous protein in multiple tissues with a number of possible causes. This protein deposition can occur in any tissue, yet is most commonly seen in kidneys, heart, and gastrointestinal tracts. However, invasion to bone tissues is not often reported. The deposition of amyloid proteins in bone tissues may result in joint pain and pathological fractures; it is important to elucidate the causes and detect early to determine prognosis and treat optimally...
June 2016: Hip & Pelvis
https://www.readbyqxmd.com/read/27421913/diagnostic-performances-of-m-protein-tests-according-to-the-clinical-presentations-of-kidney-disease
#16
Eun Hee Koo, Jung-Ho Shin, Hye Ryoun Jang, Hyung-Doo Park, Gee-Young Kwon, Wooseong Huh, Dae Joong Kim, Yoon-Goo Kim, Ha Young Oh, Jung Eun Lee
BACKGROUND: Screening for monoclonal immunoglobulin (MIg) is critical in patients with kidney disease. METHODS: We identified 943 subjects who underwent kidney biopsy and at least one of monoclonal (M)-protein tests (serum and urine electrophoresis [EP], serum and urine immunofixation [IF], and serum free light chain [FLC] ratio). The sensitivities of several combinations of the 5 tests were examined by clinical presentations of kidney disease. RESULTS: The sensitivities of serum EP, urine EP, and the serum FLC ratio were 65%, 68%, and 71%, respectively, which were lower than those of serum IF (79%) and urine IF (87%) to detect MIg...
September 2016: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/27365142/thalidomide-based-induction-regimens-are-as-effective-as-bortezomib-based-regimens-in-elderly-patients-with-multiple-myeloma-with-cereblon-expression
#17
Sung-Hoon Jung, Hyun-Jung Choi, Myung-Geun Shin, Seung-Shin Lee, Eu Chang Hwang, Tae-Young Jung, Min-Seok Cho, Deok-Hwan Yang, Jae-Sook Ahn, Yeo-Kyeoung Kim, Hyeoung-Joon Kim, Je-Jung Lee
Cereblon (CRBN) has been identified as a primary target of immunomodulatory drugs and is considered a biomarker for the prediction of outcomes after thalidomide- or lenalidomide-based treatments. In this study, we evaluated CRBN expression in bone marrow (BM) tissue at diagnosis and investigated the relationship between CRBN expression and treatment outcomes after thalidomide- or bortezomib-based front-line therapies in 89 elderly patients with multiple myeloma (MM). CRBN expression at the time of diagnosis was evaluated with immunohistochemical (IHC) staining for myeloma cells in paraffin wax-embedded BM tissue...
October 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27358777/first-line-vs-delayed-transplantation-in-myeloma-certainties-and-controversies
#18
REVIEW
Annamaria Brioli
Since the middle of 1990s autologous stem cell transplantation has been the cornerstone for the treatment of young patients with multiple myeloma (MM). In the last decade the introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors (PI), has dramatically changed the therapeutic scenario of this yet incurable disease. Due to the impressive results achieved with IMiDs and PI both in terms of response rates and in terms of progression free and overall survival, and to the toxicity linked to high dose therapy and autologous stem cell transplantation (ASCT), a burning question nowadays is whether all young patients should be offered autotransplantation up front or if this should be reserved for the time of relapse...
June 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/27349765/cyclophosphamide-and-bortezomib-with-prednisone-or-dexamethasone-for-the-treatment-of-relapsed-and-refractory-multiple-myeloma
#19
Donna E Reece, Young Trieu, Esther Masih-Khan, Eshetu G Atenafu, Christine Chen, Anca Prica, Rodger Tiedemann, Suzanne Trudel, Vishal Kukreti
INTRODUCTION: Cyclophosphamide, bortezomib, and prednisone (CyBorP) is a highly effective, well-tolerated regimen in relapsed/refractory multiple myeloma. CyBorP, originally developed at our center to include weekly bortezomib (Bor) and alternate-day prednisone (P), was recently modified so that weekly dexamethasone (D) replaced prednisone. PATIENTS AND METHODS: To assess the effectiveness and tolerability of CyBorP/D in real-world practice, we identified 96 relapsed/refractory patients who received ≥ 1 28-day cycle of CyBorP/D, consisting of cyclophosphamide 300 mg/m(2) (days 1, 8, 15, and 22), Bor 1...
July 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/27342591/circulating-immune-cell-phenotype-can-predict-the-outcome-of-lenalidomide-plus-low-dose-dexamethasone-treatment-in-patients-with-refractory-relapsed-multiple-myeloma
#20
Sung-Eun Lee, Ji-Young Lim, Da-Bin Ryu, Tae Woo Kim, Jae-Ho Yoon, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Seok Lee, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min, Myungshin Kim, Chang-Ki Min
Although the antimyeloma effect of lenalidomide is associated with activation of the immune system, the exact in vivo immunomodulatory mechanisms of lenalidomide combined with low-dose dexamethasone (Len-dex) in refractory/relapsed multiple myeloma (RRMM) patients remain unclear. In this study, we analyzed the association between immune cell populations and clinical outcomes in patients receiving Len-dex for the treatment of RRMM. Peripheral blood samples from 90 RRMM patients were taken on day 1 of cycles 1 (baseline), 2, 3, and 4 of Len-dex therapy...
August 2016: Cancer Immunology, Immunotherapy: CII
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