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Multiple myeloma, young patient

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...
October 13, 2016: Oncotarget
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
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
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
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
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
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
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
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
Narges Gholizadeh, Masoumeh Mehdipour, Bita Rohani, Vahid Esmaeili
Extramedullary plasmacytomas are rare solitary soft tissue tumors that arise from proliferations of malignant transformed monoclonal plasma cells and can be diagnosed through biopsy and histopathologic examination. These lesions are closely associated with multiple myelomas, which should be ruled out in all these cases by necessary laboratory and radiographic examinations. A 25-year-old man was referred to our clinic with a rapidly-growing painless lesion measuring about 2.5×3×3 cm in the palatal side of the left maxillary second and third molar teeth...
June 2016: Journal of Dentistry
Sadia Sultan, Syed Mohammed Irfan, Saira Parveen, Ufaq Taufiq
BACKGROUND: Symptomatic multiple myeloma (MM) is an acquired B-cell malignant proliferation of anti- body secreting plasma cells, characterized by end organ damage due to monoclonal immunoglobulin secretion. The aim of this study wa to determine the stage stratification according to an international scoring system in adult Pakistani MM patients at presentation. MATERIALS AND METHODS: This single centre retrospective study extendedfrom January 2012 to December 2015...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
Sadia Sultan, Syed Mohammed Irfan, Saira Parveen, Hamza Ali, Maria Basharat
BACKGROUND: Multiple myeloma (MM) is an acquired clonal B-cell malignancy which primarily affects elderly individuals with an annual incidence of approximately 1% of all malignancies. Our aim is to study demographic and clinicopathological features of adult Pakistani MM patients at presentation. MATERIALS AND METHODS: This single centre retrospective study extended from January 2010 to December 2014. Data were retrieved from the patients' maintained records on predetermined performa...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
Christopher J Borgman
Multiple myeloma is a neoplastic plasma-cell disorder resulting from malignant plasma cells in the bone marrow. It can cause a hyperviscosity syndrome secondary to the paraproteinaemia associated with the disease. The increased hyperviscosity can lead to retinal vein occlusions and other ocular problems that may challenge clinicians. In patients with multiple myeloma and hypertension and/or diabetes mellitus, retinal changes appear similar and changes due to one disease or the other may be difficult to determine...
July 2016: Clinical & Experimental Optometry: Journal of the Australian Optometrical Association
Ho Sup Lee, Chang-Ki Min, Je-Jung Lee, Kihyun Kim, Seok Jin Kim, Dok Hyun Yoon, Hyeon-Seok Eom, Hyewon Lee, Won Sik Lee, Ho-Jin Shin, Ji Hyun Lee, Yong Park, Jae-Cheol Jo, Young Rok Do, Yeung-Chul Mun, Mark Hong Lee
In real clinical settings (not clinical trials), thalidomide has been accepted as maintenance therapy to patients with multiple myeloma (MM) because of the cost of drugs, the limitations of medical insurance, etc., in our country (South Korea). The purpose of this study was to evaluate the utility of thalidomide maintenance for improving survival in transplantation-eligible patients with MM in the real clinical field. Differences in survival rates were estimated in patients treated with or without thalidomide maintenance...
May 2016: Annals of Hematology
Shin Young Hyun, Sang Hoon Han, Soo-Jeong Kim, Ji Eun Jang, Yundeok Kim, Hyunsoo Cho, Jung Yeon Lee, June-Won Cheong, Yoo Hong Min, Jae-Woo Song, Jin Seok Kim
The aim of this study was to identify the risk factors associated with severe bacterial infection (SBI) in multiple myeloma (MM) patients during treatment with bortezomib-based regimens. A total of 98 patients with MM were evaluated during 427 treatment courses. SBI occurred in 57.1% (56/98) of the patients and during 19.0% (81/427) of the treatment courses. In the multivariate analysis for the factors associated with the development of SBI in each treatment course, poor performance status (Eastern Cooperative Oncology Group ≥ 2, P < 0...
April 2016: Journal of Korean Medical Science
Seon Young Kim, Kyongok Im, Si Nae Park, Jung-Ah Kim, Sung-Soo Yoon, Dong Soon Lee
We performed cytoplasmic fluorescence in situ hybridization assays of light chain amyloidosis (AL). In total, 234 patients were enrolled: 28 patients with AL, 24 with monoclonal gammopathy of undetermined significance (MGUS), and 182 with multiple myeloma (MM). Chromosomal abnormalities were detected in 13 of 22 (59%) AL patients without MM. All 13 patients demonstrated IGH rearrangement, and t(11;14)/IGH-CCND1 was most frequent (32%). Chromosome gain was not observed in AL patients without MM. These findings were dissimilar to findings in MGUS patients, in whom trisomy 9 was the most frequent abnormality...
May 2016: Leukemia Research
Jonghoon Park, Eok Park, Cheol-Kyu Jung, Seung-Wan Kang, Byung Gyu Kim, Youngjoo Jung, Tae Hun Kim, Ji-Young Lim, Sung-Eun Lee, Chang-Ki Min, Kwang-Ai Won
BACKGROUND: The proteasome is a validated anti-cancer target and various small-molecule inhibitors are currently in clinical development or on the market. However, adverse events and resistance associated with those proteasome inhibitors indicate the need for a new generation of drugs. Therefore, we focused on developing an oral proteasome inhibitor with improved efficacy and safety profiles. METHOD: The in vitro inhibition of the 20S proteasome catalytic activities was determined in human multiple myeloma (MM) cellular lysates with fluorogenic peptide substrates specific for each catalytic subunit...
2016: BMC Cancer
Neha Korde, Yong Zhang, Kelsey Loeliger, Andrea Poon, Olga Simakova, Adriana Zingone, Rene Costello, Richard Childs, Pierre Noel, Samuel Silver, Mary Kwok, Clifton Mo, Neal Young, Ola Landgren, Elaine Sloand, Irina Maric
Pure red cell aplasia (PRCA) is a rare disorder characterized by inhibition of erythroid precursors in the bone marrow and normochromic, normocytic anaemia with reticulocytopenia. Among 51 PRCA patients, we identified 12 (24%) patients having monoclonal gammopathy, monoclonal gammopathy of undetermined significance or smouldering multiple myeloma, with presence of monoclonal protein or abnormal serum free light chains and atypical bone marrow features of clonal plasmacytosis, hypercellularity and fibrosis. Thus far, three patients treated with anti-myeloma based therapeutics have responded with reticulocyte recovery and clinical transfusion independence, suggesting plasma cells play a key role in the pathogenesis of this specific monoclonal gammopathy-associated PRCA...
June 2016: British Journal of Haematology
Elizabeth A Punnoose, Joel D Leverson, Franklin Peale, Erwin R Boghaert, Lisa D Belmont, Nguyen Tan, Amy Young, Michael Mitten, Ellen Ingalla, Walter C Darbonne, Anatol Oleksijew, Paul Tapang, Peng Yue, Jason Oeh, Leslie Lee, Sophie Maiga, Wayne J Fairbrother, Martine Amiot, Andrew J Souers, Deepak Sampath
BCL-2 family proteins dictate survival of human multiple myeloma cells, making them attractive drug targets. Indeed, multiple myeloma cells are sensitive to antagonists that selectively target prosurvival proteins such as BCL-2/BCL-XL (ABT-737 and ABT-263/navitoclax) or BCL-2 only (ABT-199/GDC-0199/venetoclax). Resistance to these three drugs is mediated by expression of MCL-1. However, given the selectivity profile of venetoclax it is unclear whether coexpression of BCL-XL also affects antitumor responses to venetoclax in multiple myeloma...
May 2016: Molecular Cancer Therapeutics
Young Mi Park
Breast plasmacytoma is an extremely rare tumor. It can occur as a primary isolated tumor or as an extramedullary manifestation in multiple myeloma. This report describes the unusual case of a primary extramedullary plasmacytoma that progressed to multiple myeloma within 15 months in a 35-year-old woman. The patient had been initially diagnosed with a primary extramedullary plasmacytoma of the epidural soft tissue at the cervical 6-thoracic 1 spine level and the stomach. The patient had received chemotherapy and the disease had been in remission...
2016: Case Reports in Medicine
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