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Sample records for human multiple myeloma

  1. Novel human multiple myeloma cell line UHKT-893

    Czech Academy of Sciences Publication Activity Database

    Uherková, L.; Vančurová, I.; Vyhlídalová, I.; Pleschnerová, M.; Špička, I.; Mihalová, R.; Březinová, J.; Hodný, Zdeněk; Čermáková, K.; Polanská, V.; Marinov, I.; Jedelský, P.L.; Kuželová, K.; Stöckbauer, P.

    2013-01-01

    Roč. 37, č. 3 (2013), s. 320-326 ISSN 0145-2126 Institutional support: RVO:68378050 Keywords : human myeloma cell line * human multiple myeloma * plasma cell * IL-6 dependence * immunoglobulin * free light chain Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.692, year: 2013

  2. Multiple myeloma.

    LENUS (Irish Health Repository)

    Collins, Conor D

    2012-02-01

    Advances in the imaging and treatment of multiple myeloma have occurred over the past decade. This article summarises the current status and highlights how an understanding of both is necessary for optimum management.

  3. Multiple myeloma

    International Nuclear Information System (INIS)

    Sohn, Jeong Ick; Ha, Choon Ho; Choi, Karp Shik

    1994-01-01

    Multiple myeloma is a malignant plasma cell tumor that is thought to originate proliferation of a single clone of abnormal plasma cell resulting production of a whole monoclonal paraprotein. The authors experienced a case of multiple myeloma with severe mandibular osteolytic lesions in 46-year-old female. As a result of careful analysis of clinical, radiological, histopathological features, and laboratory findings, we diagnosed it as multiple myeloma, and the following results were obtained. 1. Main clinical symptoms were intermittent dull pain on the mandibular body area, abnormal sensation of lip and pain due to the fracture on the right clavicle. 2. Laboratory findings revealed M-spike, reversed serum albumin-globulin ratio, markedly elevated ESR and hypercalcemia. 3. Radiographically, multiple osteolytic punched-out radiolucencies were evident on the skull, zygoma, jaw bones, ribs, clavicle and upper extremities. Enlarged liver and increased uptakes on the lesional sites in RN scan were also observed. 4. Histopathologically, markedly hypercellular marrow with sheets of plasmoblasts and megakaryocytes were also observed.

  4. Immunomodulation of multiple myeloma.

    Science.gov (United States)

    Tohnya, Tanyifor M; Figg, William D

    2004-11-01

    Multiple myeloma is a multi-process disease, and these different processes are responsible for the reduced sensitivity to chemotherapy and radiotherapy, hence the relapse and refractory nature of multiple myeloma. Emphasis is now placed on the hypothesis that myeloma cell growth, inhibition of apoptosis and drug resistance are dependent on immunomodulatory cytokines such as IL-6 and pro-angiogenic factors such as VEGF. In addition to its anti-angiogenic effects, the immunomodulatory properties of thalidomide make it a possible therapy for patients with advanced multiple myeloma. This has lead to the clinical development of a number of immunomodulatory thalidomide analogues (IMiDs) which are more potent and have less side effects than the parent drug, thalidomide. In the August 15(th) issue of Journal of Clinical Oncology, Schey SA et al. suggested that an IMiD (CC-4047) maybe efficacious due to T-cell co-stimulation, and safe in patients with relapsed or refractory multiple myeloma. This article demonstrates a supporting role for IMiDs as immunomodulatory adjuvant therapy.

  5. Cerebral metastases from multiple myeloma

    International Nuclear Information System (INIS)

    Norum, J.; Wist, E.; Dahl, I.M.; University Hospital, Tromsoe

    1991-01-01

    The authors report a patient with multiple intracerebral lesions from myeloma. The case also demonstrates that myeloma is a radiosensitive tumour and that radiotherapy is important to keep in mind when intracranial lesions are revealed. (orig.)

  6. NF-kappa B modulation is involved in celastrol induced human multiple myeloma cell apoptosis.

    Directory of Open Access Journals (Sweden)

    Haiwen Ni

    Full Text Available Celastrol is an active compound extracted from the root bark of the traditional Chinese medicine Tripterygium wilfordii Hook F. To investigate the effect of celastrol on human multiple myeloma cell cycle arrest and apoptosis and explore its molecular mechanism of action. The activity of celastrol on LP-1 cell proliferation was detected by WST-8 assay. The celastrol-induced cell cycle arrest was analyzed by flow cytometry after propidium iodide staining. Nuclear translocation of the nuclear factor kappa B (NF-κB was observed by fluorescence microscope. Celastrol inhibited cell proliferation of LP-1 myeloma cell in a dose-dependent manner with IC50 values of 0.8817 µM, which was mediated through G1 cell cycle arrest and p27 induction. Celastrol induced apoptosis in LP-1 and RPMI 8226 myeloma cells in a time and dose dependent manner, and it involved Caspase-3 activation and NF-κB pathway. Celastrol down-modulated antiapoptotic proteins including Bcl-2 and survivin expression. The expression of NF-κB and IKKa were decreased after celastrol treatment. Celastrol effectively blocked the nuclear translocation of the p65 subunit and induced human multiple myeloma cell cycle arrest and apoptosis by p27 upregulation and NF-kB modulation. It has been demonstrated that the effect of celastrol on NF-kB was HO-1-independent by using zinc protoporphyrin-9 (ZnPPIX, a selective heme oxygenase inhibitor. From the results, it could be inferred that celastrol may be used as a NF-kB inhibitor to inhibit myeloma cell proliferation.

  7. Curability of Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Raymond Alexanian

    2012-01-01

    Full Text Available Among 792 patients with multiple myeloma treated from 1987 to 2010 and assessed after 18 months, there were 167 patients with complete remission. For those 60 patients treated between 1987–1998 and with long followup, the latest relapse occurred after 11.8 years, so that 13 patients have remained in sustained complete remission for longer than 12 years (range 12–22 years. These results suggest that 3% of all patients treated during that period may be cured of multiple myeloma. In addition to immunofixation, more sensitive techniques for the detection of residual disease should be applied more consistently in patients with apparent complete remission in order to identify those with potential cure.

  8. Apoptotic effects of non-edible parts of Punica granatum on human multiple myeloma cells.

    Science.gov (United States)

    Kiraz, Yağmur; Neergheen-Bhujun, Vidushi S; Rummun, Nawraj; Baran, Yusuf

    2016-02-01

    Multiple myeloma is of great concern since existing therapies are unable to cure this clinical condition. Alternative therapeutic approaches are mandatory, and the use of plant extracts is considered interesting. Punica granatum and its derived products were suggested as potential anticancer agents due to the presence of bioactive compounds. Thus, polypenolic-rich extracts of the non-edible parts of P. granatum were investigated for their antiproliferative and apoptotic effects on U266 multiple myeloma cells. We demonstrated that there were dose-dependent decreases in the proliferation of U266 cells in response to P. granatum extracts. Also, exposure to the extracts triggered apoptosis with significant increases in loss of mitochondrial membrane potential in U266 cells exposed to the leaves and stem extracts, while the flower extract resulted in slight increases in loss of MMP. These results were confirmed by Annexin-V analysis. These results documented the cytotoxic and apoptotic effects of P. granatum extracts on human U266 multiple myeloma cells via disruption of mitochondrial membrane potential and increasing cell cycle arrest. The data suggest that the extracts can be envisaged in cancer chemoprevention and call for further exploration into the potential application of these plant parts.

  9. Multiple myeloma: 45 cases

    International Nuclear Information System (INIS)

    Yang, Hee Chul; Suh, Jin Suck; Park, Chang Yun

    1990-01-01

    We evaluated 45 cases of multiple myelomas retrospectively confirmed in Severance Hospital from the period of 1983-1989. In order to assess the radiologic features of the multiple myeloma and to assist in possible early diagnosis and treatment. The result were as follows: 1. IgG(41%) was the most common immunoglobulin type secreted followed by light chain(36%). IgA(19%) and IgD(2%). Two percent of the patients had non-secretory type. 89% of patients were in their stage III of the disease. 2. Among the 45 patients, 96% had abnormal plain radiographic findings with average number of 4.5 lesions. Common sites were the spine, rib, skull, pelvis, and humerus in descending orders. The findings were localized or diffuse osteolytic bone destruction(85%). osteoporosis(49%), pathologic fracture and endosteal scalloping(55%). Osteoporosis was more prominent in stage III than stage II. 3. Both plain X-ray and radioisotope study was available for comparison in 28 patients. Concordance between the two studies were 44%, lesions detected only on plain X-ray film were 51%, and lesions detected only on the radioisotope were 5%. The plain radiography was able to detect only 54% of bone lesions confirmed by bone marrow biopsy. With the above results, accurate evaluation of bone lesions in multiple myeloma may be difficult with radiologic studies only. But familiarity with these radiologic findings of the this disease entity is necessary for early suspicion of the disease, thus for early diagnosis and treatment

  10. Proton pump inhibitors induce a caspase-independent antitumor effect against human multiple myeloma.

    Science.gov (United States)

    Canitano, Andrea; Iessi, Elisabetta; Spugnini, Enrico Pierluigi; Federici, Cristina; Fais, Stefano

    2016-07-01

    Multiple Myeloma (MM) is the second most common hematological malignancy and is responsive to a limited number of drugs. Unfortunately, to date, despite the introduction of novel drugs, no relevant increase in survival rates has been obtained. Proton pump inhibitors (PPIs) have been shown to have significant antitumor action as single agents as well as in combination with chemotherapy. This study investigates the potential anti-tumor effectiveness of two PPIs, Lansoprazole and Omeprazole, against human MM cells. We found that Lansoprazole exerts straightforward efficacy against myeloma cells, even at suboptimal concentrations (50 µM), while Omeprazole has limited cytotoxic action. The Lansoprazole anti-MM effect was mostly mediated by a caspase-independent apoptotic-like cytotoxicity, with only a secondary anti-proliferative action. This study provides clear evidence supporting the use of Lansoprazole in the strive against MM with an efficacy proven much higher than current therapeutical approaches and without reported side effects. It is however conceivable that, consistent with the results obtained in other human tumors, Lansoprazole may well be combined with existing anti-myeloma therapies with the aim to improve the low level of efficacy of the current strategies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Introduction: multiple myeloma.

    Science.gov (United States)

    Cook, Richard

    2008-09-01

    Multiple myeloma (MM) is the most common type of primary bone tumor, affecting approximately 50,000 patients in the United States. Although it is currently not curable, recent advancements in treatment are bringing myeloma closer to becoming a chronic disease instead of a terminal illness. To better understand the prevalence of MM as well as provide an overview of the costs associated with treatment. The goals of treatment in MM include eradicating all evidence of disease, controlling disease to prevent damage to target organs, preserving normal function and quality of life, relieving pain, and managing myeloma that is in remission. To achieve these goals, treatment must be individually tailored for each patient based on the patient's age, overall health status, symptoms, and laboratory test results. Advancements in the understanding of the pathogenesis of myeloma and the role of genetic mutations are leading to a new standard of treatment. Advancements in diagnostic technology, such as cytogenetic testing, are also being used to tailor treatment for each individual to work toward achieving better response rates, longer periods of remission, and improved quality of life. Increased costs associated with the improved therapies being used to treat MM, and the comorbid conditions associated with the disease, present a challenge to managed care. Health plans and formulary decision makers need to better understand the complexity of therapy to best use resources. The economic burden to the patient must also be considered when developing treatment strategies. Better understanding of the pathophysiology of MM, including the role of cytogenetics, is leading to the development and use of novel agents and treatment options. Head-to-head studies comparing treatments must be performed to best balance the costs associated with treatment and the benefits of improved survival rates and maintaining quality of life.

  12. Multiple Myeloma: Patient Handbook

    Science.gov (United States)

    ... information about myeloma in a caring and compassionate man- ner. IMF InfoLine specialists can be reached at InfoLine@myeloma.org, or 800-452-CURE (2873) or 818-487-7455. Terms and definitions Albumin (ALB): Simple water-soluble protein that is ...

  13. Case report 383: Multiple myeloma

    International Nuclear Information System (INIS)

    Kouwenberg, J.J.; Simons, A.J.

    1986-01-01

    A unique and obviously extremely rare example of multiple myeloma has been presented, affecting the peripheral appendicular skeleton and not the hematopoietic system of the axial skeleton, radiologically and probably pathologically. Only one other similar case has been described. The radiological features were confirmed by the pathological studies: a biopsy specimen obtained from a large osteolytic lesion in a patella showed the typical stigma of multiple myeloma; a biopsy from the iliac creast showed no abnormality. (orig./SHA)

  14. Multiple myeloma: diagnosis and treatment.

    Science.gov (United States)

    Nau, Konrad C; Lewis, William D

    2008-10-01

    Multiple myeloma, the most common bone malignancy, is occurring with increasing frequency in older persons. Typical symptoms are bone pain, malaise, anemia, renal insufficiency, and hypercalcemia. Incidental discovery on comprehensive laboratory panels is common. The disease is diagnosed with serum or urine protein electrophoresis or immunofixation and bone marrow aspirate analysis. Skeletal radiographs are important in staging multiple myeloma and revealing lytic lesions, vertebral compression fractures, and osteoporosis. Magnetic resonance imaging and positron emission tomography or computed tomography are emerging as useful tools in the evaluation of patients with myeloma; magnetic resonance imaging is preferred for evaluating acute spinal compression. Nuclear bone scans and dual energy x-ray absorptiometry have no role in the diagnosis and staging of myeloma. The differential diagnosis of monoclonal gammopathies includes monoclonal gammopathy of uncertain significance, smoldering (asymptomatic) and symptomatic multiple myeloma, amyloidosis, B-cell non-Hodgkin lymphoma, Waldenström macroglobulinemia, and rare plasma cell leukemia and heavy chain diseases. Patients with monoclonal gammopathy of uncertain significance or smoldering multiple myeloma should be followed closely, but not treated. Symptomatic multiple myeloma is treated with chemotherapy followed by autologous stem cell transplantation, if possible. Melphalan, prednisolone, dexamethasone, vincristine, doxorubicin, bortezomib, and thalidomide and its analogue lenalidomide have been used successfully. It is important that family physicians recognize and appropriately treat multiple myeloma complications. Bone pain is treated with opiates, bisphosphonates, radiotherapy, vertebroplasty, or kyphoplasty; nephrotoxic nonsteroidal anti-inflammatory drugs should be avoided. Hypercalcemia is treated with isotonic saline infusions, steroids, furosemide, or bisphosphonates. Because of susceptibility to infections

  15. Therapeutic advancements in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Alessandro eGozzetti

    2014-09-01

    Full Text Available Multiple myeloma survival has significantly improved in latest years, due to a broad spectrum of novel agents available for treatment. The introduction of thalidomide, bortezomib and lenalidomide together with autologous stem cell transplantation has dramatically prolonged complete remissions rate, progression free survivals resulting ultimately in prolonged survivals in myeloma patients. Moreover, novel strategies of treatment such as consolidation and maintenance are being used to implement responses. A number of new drugs such as carfilzomib and pomalidomide are already in clinical practice, and new kids on the block are entering, making the future of myeloma patients brighter.

  16. Palliative radiotherapy for multiple myeloma

    International Nuclear Information System (INIS)

    Furusawa, Mitsuhiro; Baba, Yuji; Murakami, Ryuji; Yokoyama, Toshimi; Nishimura, Ryuichi; Uozumi, Hideaki; Takada, Chitose; Takahashi, Mutsumasa

    1995-01-01

    This study reviews the experience of palliative radiotherapy to patients with multiple myeloma to define the optimal dose for pain relief. The records of 31 patients (66 sites) with multiple myeloma irradiated for palliation at Kumamoto University hospital between 1985 and 1994 were reviewed. Total dose ranged from 8 to 50 Gy, with a mean of 32.2 Gy. Symptoms included pain (78.1%), neurological abnormalities (28.1%), and palpable masses (34.3%). Symptomatic remission was obtained in 45 of 46 evaluable sites (97.8%). Complete remission of symptoms were obtained in 28.3%, and partial remission in 69.6%. According to fraction size, there was no significant difference between 3-5 Gy and 1.8-2 Gy. The incidence of complete remission increased when a total dose of more than 20 Gy was given. When the quality of life is considered, hypofractionation was recommended for the palliative radiation therapy of multiple myeloma. (author)

  17. Stimulation of Toll-like receptor-1/2 combined with Velcade increases cytotoxicity to human multiple myeloma cells

    International Nuclear Information System (INIS)

    Abdi, J; Mutis, T; Garssen, J; Redegeld, F

    2013-01-01

    An increasing body of evidence supports the important role of adhesion to bone marrow microenvironment components for survival and drug resistance of multiple myeloma (MM) cells. Previous studies suggested that stimulation of Toll-like receptors by endogenous ligands released during inflammation and tissue damage may be pro-tumorigenic, but no studies have been performed in relation to modulation of cell adhesion and drug cytotoxicity. Here, we investigated the effect of TLR1/2 activation on adhesion of human myeloma cells to fibronectin, and their sensitivity to the proteasome inhibitor Velcade. It was found that TLR1/2 activation with Pam3CSK4 increased the cytotoxicity of Velcade in L363, OPM-2 and U266 human myeloma cells. This effect was not related to a decreased adhesion of the cells to fibronectin, but TLR1/2 activation stimulated the caspase-3 activity in Velcade-treated myeloma cells, which may be responsible for the enhanced cell death. Inhibitors of NF-κB and MAPK reduced the stimulatory effect. These findings indicate that TLR activation of MM cells could bypass protective effects of cell adhesion and suggest that TLR signaling may also have antitumorigenic potential

  18. Skeletal surveys in multiple myeloma

    International Nuclear Information System (INIS)

    Sebes, J.I.; Niell, H.B.; Palmieri, G.M.A.; Reidy, T.J.

    1986-01-01

    Thirty-three patients with multiple myeloma were studied with serial skeletal surveys, serum immunoglobulin levels, and postabsorptive urinary hydroxyproline (Spot-HYPRO) determinations. Twenty receiving chemotherapy were also followed with skeletal surveys in order to evaluate bone response to treatment. A close association was found between skeletal findings and changes in immunoglubulin levels with positive correlation in 71% of the patients. A similar association was found between skeletal disease and Spot-HYPRO level changes in 65%. Five of 12 patients (42%) with partial or complete clinical response to chemotherapy, demonstrated improvement in the appearance of skeletal lesions. Positive correlation between the roentgenographic changes and clinical markers of myeloma as well as therapeutic response, indicates that skeletal surveys are useful and effective in monitoring patients with multiple myeloma. (orig.)

  19. Multiple myeloma and plasmacytomas

    International Nuclear Information System (INIS)

    Mill, W.B.; Wasserman, T.H.

    1987-01-01

    Radiation therapy is the primary modality of treatment in the management of solitary plasmacytomas. The dose of radiation recommended is 5500 to 6000 cGy in 6 to 8 weeks. Disseminated myeloma is primarily treated with chemotherapy, which frequently includes melphalan and prednisone. Other drugs that are active in this disease are cyclophophamide, vincristine, procarbazine, BCNU, and doxorubicin. Adjuvant radiation therapy is indicated for painful bone lesions, for prevention and treatment of pathologic features of long bones, for spinal cord compression, and to relieve pressure from soft tissue masses. Myeloma is a relatively radiosensitive tumor requiring only 1000 to 2000 cGy in 1 to 2 weeks to relieve most painful lesions

  20. Daratumumab-mediated lysis of primary multiple myeloma cells is enhanced in combination with the human anti-KIR antibody IPH2102 and lenalidomide

    DEFF Research Database (Denmark)

    Nijhof, I. S.; Lammerts van Bueren, J. J.; van Kessel, B.

    2015-01-01

    Despite recent treatment improvements, multiple myeloma remains an incurable disease. Since antibody-dependent cell-mediated cytotoxicity is an important effector mechanism of daratumumab, we explored the possibility of improving daratumumab-mediated cell-mediated cytotoxicity by blocking natural...... killer cell inhibitory receptors with the human monoclonal anti-KIR antibody IPH2102, next to activation of natural killer cells with the immune modulatory drug lenalidomide. In 4-hour antibody-dependent cell-mediated cytotoxicity assays, IPH2102 did not induce lysis of multiple myeloma cell lines...... effective treatment strategies can be designed for multiple myeloma by combining daratumumab with agents that independently modulate natural killer cell function....

  1. Antitumoral Effect of Hibiscus sabdariffa on Human Squamous Cell Carcinoma and Multiple Myeloma Cells.

    Science.gov (United States)

    Malacrida, Alessio; Maggioni, Daniele; Cassetti, Arianna; Nicolini, Gabriella; Cavaletti, Guido; Miloso, Mariarosaria

    2016-10-01

    Cancer is a leading cause of death worldwide. Despite therapeutic improvements, some cancers are still untreatable. Recently there has been an increasing interest in the use of natural substances for cancer prevention and treatment. Hibiscus sabdariffa (HS) is a plant, belonging to Malvaceae family, widespread in South Asia and Central Africa. HS extract (HSE) used in folk medicine, gained researchers' interest thanks to its antioxidant, anti-inflammatory, and chemopreventive properties. In the present study, we initially assessed HSE effect on a panel of human tumor cell lines. Then we focused our study on the following that are most sensitive to HSE action cell lines: Multiple Myeloma (MM) cells (RPMI 8226) and Oral Squamous Cell Carcinoma (OSCC) cells (SCC-25). In both RPMI 8226 and SCC-25 cells, HSE impaired cell growth, exerted a reversible cytostatic effect, and reduced cell motility and invasiveness. We evaluated the involvement of MAPKs ERK1/2 and p38 in HSE effects by using specific inhibitors, U0126 and SB203580, respectively. For both SCC-25 and RPMI 8226, HSE cytostatic effect depends on p38 activation, whereas ERK1/2 modulation is crucial for cell motility and invasiveness. Our results suggest that HSE may be a potential therapeutic agent against MM and OSCC.

  2. Multiple myeloma with extramedullary disease.

    Science.gov (United States)

    Oriol, Albert

    2011-11-01

    Plasmacytoma is a tumor mass consisting of atypical plasma cells. Incidence of plasmacytomas associated with multiple myeloma range from 7% to 17% at diagnosis and from 6% to 20% during the course of the disease. In both situations, occurrence of extramedullary disease has been consistently associated with a poorer prognosis of myeloma. Extramedullary relapse or progression occurs in a variety of clinical circumstances and settings, and therefore requires individualization of treatment. Alkylating agents, bortezomib, and immunomodulatory drugs, along with corticoids, have been used to treat extramedullary relapse but, because of the relatively low frequency or detection rate of extramedullary relapse, no efficacy data are available from controlled studies in this setting.

  3. Drugs Approved for Multiple Myeloma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for multiple myeloma and other plasma cell neoplasms. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  4. Emerging therapies in multiple myeloma.

    Science.gov (United States)

    El-Amm, Joelle; Tabbara, Imad A

    2015-06-01

    The treatment of multiple myeloma has evolved significantly over the past 2 decades due to the use of high-dose chemotherapy and autologous stem cell transplantation, and the subsequent introduction of the immunomodulatory agents (thalidomide and lenalidomide) and the proteasome inhibitor (bortezomib). The median overall survival of multiple myeloma patients has increased significantly with patients younger than age 50 years experiencing a 10-year survival rate of around 40%. However, despite the increased effectiveness of the first-line agents, the majority of patients will eventually relapse and become drug resistant. Promising novel therapies have recently emerged and are being used to treat relapsed and refractory patients. This review will cover the clinical data regarding these emergent therapies that include new generation of proteasome inhibitors (carfilzomib, ixazomib, oprozomib, and marizomib), immunomodulatory drugs (pomalidomide), monoclonal antibodies (elotuzumab and daratumumab), signal transduction modulator (perifosine), and histone deacetylase inhibitors (vorinostat and panobinostat).

  5. Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma

    DEFF Research Database (Denmark)

    Lokhorst, Henk M; Plesner, Torben; Laubach, Jacob P

    2015-01-01

    BACKGROUND: Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy. METHODS: In part 1...... interval [CI], 4.2 to 8.1), and 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months. CONCLUSIONS: Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma. (Funded by Janssen...

  6. Genetic variants and multiple myeloma risk

    DEFF Research Database (Denmark)

    Martino, Alessandro; Campa, Daniele; Jurczyszyn, Artur

    2014-01-01

    BACKGROUND: Genetic background plays a role in multiple myeloma susceptibility. Several single-nucleotide polymorphisms (SNP) associated with genetic susceptibility to multiple myeloma were identified in the last years, but only a few of them were validated in independent studies. METHODS...... with multiple myeloma risk (P value range, 0.055-0.981), possibly with the exception of the SNP rs2227667 (SERPINE1) in women. CONCLUSIONS: We can exclude that the selected polymorphisms are major multiple myeloma risk factors. IMPACT: Independent validation studies are crucial to identify true genetic risk...

  7. Immunoparesis in newly diagnosed Multiple Myeloma patients

    DEFF Research Database (Denmark)

    Sorrig, Rasmus; Klausen, Tobias W.; Salomo, Morten

    2017-01-01

    Immunoparesis (hypogammaglobulinemia) is associated to an unfavorable prognosis in newly diagnosed Multiple myeloma (MM) patients. However, this finding has not been validated in an unselected population-based cohort. We analyzed 2558 newly diagnosed MM patients in the Danish Multiple Myeloma...

  8. [Association of Kaposi sarcoma--multiple myeloma. A new case].

    Science.gov (United States)

    Cohen, J D; Thomas, E; Garnier, N; Hellier, I; Durand, L; Guilhou, J J; Baldet, P; Blotman, F

    2000-11-01

    Kaposi's disease is an angiogenic multifocal cancer process that has several forms, namely Mediterranean, African, HIV-associated, and secondary to a preexisting immunodepressive state (hematological disorder, corticosteroid therapy, immunodepressive treatment). Whatever its form, Kaposi's sarcoma is probably associated with a chronic viral human herpes type 8 infection (HHV8). This virus has been implicated in the pathogenesis of multiple myeloma (17 cases recorded to date). In the present study, a further case of Kaposi's sarcoma associated with multiple myeloma has been reported. However, Epstein-Barr virus, cytomegalovirus, hepatitis B and C, HIV and HHV8 serologies were negative. Radiotherapy on the lower limbs was initiated. It is concluded that HHV8 does not appear to play a pathogenic role in cases of multiple myeloma, given the rarity of the association between Kaposi's sarcoma/multiple myeloma/HHV8.

  9. Small molecule CP-31398 induces reactive oxygen species-dependent apoptosis in human multiple myeloma.

    Science.gov (United States)

    Arihara, Yohei; Takada, Kohichi; Kamihara, Yusuke; Hayasaka, Naotaka; Nakamura, Hajime; Murase, Kazuyuki; Ikeda, Hiroshi; Iyama, Satoshi; Sato, Tsutomu; Miyanishi, Koji; Kobune, Masayoshi; Kato, Junji

    2017-09-12

    Reactive oxygen species (ROS) are normal byproducts of a wide variety of cellular processes. ROS have dual functional roles in cancer cell pathophysiology. At low to moderate levels, ROS act as signaling transducers to activate cell proliferation, migration, invasion, and angiogenesis. In contrast, high levels of ROS induce cell death. In multiple myeloma (MM), ROS overproduction is the trigger for apoptosis induced by several anticancer compounds, including proteasome inhibitors. However, no drugs for which oxidative stress is the main mechanism of action are currently used for treatment of MM in clinical situations. In this study, we demonstrate that the p53-activating small molecule CP-31398 (CP) effectively inhibits the growth of MM cell lines and primary MM isolates from patients. CP also suppresses the growth of MM xenografts in mice. Mechanistically, CP was found to induce intrinsic apoptosis in MM cells via increasing ROS production. Interestingly, CP-induced apoptosis occurs regardless of the p53 status, suggesting that CP has additional mechanisms of action. Our findings thus indicate that CP could be an attractive candidate for treatment of MM patients harboring p53 abnormalities; this satisfies an unmet clinical need, as such individuals currently have a poor prognosis.

  10. Isolation of Human CD138+ Microparticles from the Plasma of Patients with Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Sabna Rajeev Krishnan

    2016-01-01

    Full Text Available The confinement of multiple myeloma (MM to the bone marrow microenvironment requires an invasive bone marrow biopsy to monitor the malignant compartment. The existing clinical tools used to determine treatment response and tumor relapse are limited in sensitivity mainly because they indirectly measure tumor burden inside the bone marrow and fail to capture the patchy, multisite tumor infiltrates associated with MM. Microparticles (MPs are 0.1- to 1.0-μm membrane vesicles, which contain the cellular content of their originating cell. MPs are functional mediators and convey prothrombotic, promalignant, proresistance, and proinflammatory messages, establishing intercellular cross talk and bypassing the need for direct cell-cell contact in many pathologies. In this study, we analyzed plasma cell–derived MPs (CD138+ from deidentified MM patients (n = 64 and normal subjects (n = 18 using flow cytometry. The morphology and size of the MPs were further analyzed using scanning electron microscopy. Our study shows the proof of a systemic signature of MPs in MM patients. We observed that the levels of MPs were significantly elevated in MM corresponding to the tumor burden. We provide the first evidence for the presence of MPs in the peripheral blood of MM patients with potential applications in personalized MM clinical monitoring.

  11. Ex Vivo Maintenance of Primary Human Multiple Myeloma Cells through the Optimization of the Osteoblastic Niche.

    Science.gov (United States)

    Zhang, Wenting; Gu, Yexin; Sun, Qiaoling; Siegel, David S; Tolias, Peter; Yang, Zheng; Lee, Woo Y; Zilberberg, Jenny

    2015-01-01

    We previously reported a new approach for culturing difficult-to-preserve primary patient-derived multiple myeloma cells (MMC) using an osteoblast (OSB)-derived 3D tissue scaffold constructed in a perfused microfluidic environment and a culture medium supplemented with patient plasma. In the current study, we used this biomimetic model to show, for the first time, that the long-term survival of OSB is the most critical factor in maintaining the ex vivo viability and proliferative capacity of MMC. We found that the adhesion and retention of MMC to the tissue scaffold was meditated by osteoblastic N-cadherin, as one of potential mechanisms that regulate MMC-OSB interactions. However, in the presence of MMC and patient plasma, the viability and osteogenic activity of OSB became gradually compromised, and consequently MMC could not remain viable over 3 weeks. We demonstrated that the long-term survival of both OSB and MMC could be enhanced by: (1) optimizing perfusion flow rate and patient-derived plasma composition in the culture medium and (2) replenishing OSB during culture as a practical means of prolonging MMC's viability beyond several weeks. These findings were obtained using a high-throughput well plate-based perfusion device from the perspective of optimizing the ex vivo preservation of patient-derived MM biospecimens for downstream use in biological studies and chemosensitivity analyses.

  12. Ex Vivo Maintenance of Primary Human Multiple Myeloma Cells through the Optimization of the Osteoblastic Niche.

    Directory of Open Access Journals (Sweden)

    Wenting Zhang

    Full Text Available We previously reported a new approach for culturing difficult-to-preserve primary patient-derived multiple myeloma cells (MMC using an osteoblast (OSB-derived 3D tissue scaffold constructed in a perfused microfluidic environment and a culture medium supplemented with patient plasma. In the current study, we used this biomimetic model to show, for the first time, that the long-term survival of OSB is the most critical factor in maintaining the ex vivo viability and proliferative capacity of MMC. We found that the adhesion and retention of MMC to the tissue scaffold was meditated by osteoblastic N-cadherin, as one of potential mechanisms that regulate MMC-OSB interactions. However, in the presence of MMC and patient plasma, the viability and osteogenic activity of OSB became gradually compromised, and consequently MMC could not remain viable over 3 weeks. We demonstrated that the long-term survival of both OSB and MMC could be enhanced by: (1 optimizing perfusion flow rate and patient-derived plasma composition in the culture medium and (2 replenishing OSB during culture as a practical means of prolonging MMC's viability beyond several weeks. These findings were obtained using a high-throughput well plate-based perfusion device from the perspective of optimizing the ex vivo preservation of patient-derived MM biospecimens for downstream use in biological studies and chemosensitivity analyses.

  13. Pleural Effusion in Multiple Myeloma.

    Science.gov (United States)

    Wang, Zhuo; Xia, Guoguang; Lan, Ling; Liu, Fayong; Wang, Yanxun; Liu, Baoyue; Ding, Yi; Dai, Li; Zhang, Yunjian

    2016-01-01

    Pleural effusion is rarely observed in patients with multiple myeloma (MM). Myeloma cell infiltration or invasion to the pleura is very rare. This study aimed to investigate the clinical characteristics of pleural effusion in patients with MM. We retrospectively reviewed the medical records of patients diagnosed with pleural effusion, MM, and pleural effusion with MM between 2004 and 2014 at Beijing Jishuitan Hospital. The present study included patients with pleural effusion who underwent cytological, bacteriological, biochemical and other testing. The cytopathology of abnormal pleural effusion cells was not diagnostic, thus flow cytometry was performed. MM was defined using the diagnosis standard of NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) 2014 for MM. This study included 3,480 pleural effusion patients and 319 MM patients. There were 34 patients with both MM and pleural effusion (17 men and 17 women). The average age was 63 years (range, 48-84 years). Pleural effusion with MM was caused by congestive heart disease, chronic renal failure, hypoalbuminemia, pulmonary infarctions, cirrhosis, pulmonary arterial hypertension, parapneumonic effusion, tuberculous pleural effusion, and myelomatous pleural effusion (MPE). The diagnosis of MPE was confirmed by the detection of myeloma cells in the pleural fluid using flow cytometric analyses. There were only 2 MPE cases in our study. The first MPE case was a woman. The first clinical manifestation was pleural effusion, and the diagnosis was non-secretory MM, DSS stage IIIA (Durie-Salmon staging system); ISS stage I (the International Staging System). The second MPE case was a man who was diagnosed with MM IgA-κ, DSS stage IIIA; ISS stage II. The detection rate of MPE was very low. MPE tended to present with yellow exudates and the lack of physical and chemical characteristics. Furthermore, patients with MPE exhibited many yellow nodules on the pleura. These nodules were lobulated and had abundant

  14. Radiotherapy for solitary plasmacytoma and multiple myeloma

    International Nuclear Information System (INIS)

    Schmaus, M.C.; Neuhof, D.

    2014-01-01

    Solitary plasmacytoma and multiple myeloma require a differentiated radiotherapy. The irradiation for plasmacytoma with an adequate total dose (medullary 40-50 Gy or extramedullary 50-60 Gy) leads to a high degree of local control with a low rate of side effects. In cases of multiple myeloma radiotherapy will achieve effective palliation, both in terms of recalcification as well as reduction of neurological symptoms and analgesia. In terms of analgesia the rule is the higher the single dose fraction the faster the reduction of pain. As part of a conditioning treatment prior to stem cell transplantation radiotherapy contributes to the establishment of a graft versus myeloma effect (GVM). (orig.) [de

  15. NCI collaborates with Multiple Myeloma Research Foundation

    Science.gov (United States)

    The National Cancer Institute (NCI) announced a collaboration with the Multiple Myeloma Research Foundation (MMRF) to incorporate MMRF's wealth of genomic and clinical data on the disease into the NCI Genomic Data Commons (GDC), a publicly available datab

  16. Heterogeneity in the multiple myeloma tumor clone

    NARCIS (Netherlands)

    Guikema, Jeroen E. J.; Hovenga, Sjoerd; Vellenga, Edo; Bos, Nicolaas A.

    2004-01-01

    Multiple Myeloma (MM) is a plasma cell malignancy which is characterized by a very heterogeneous disease outcome. Heterogeneity in plasma cell characteristics, including morphology, maturation status, immunophenotype and genetic abnormalities partly account for the variable disease outcome. Although

  17. Heterogeneity in the multiple myeloma tumor clone

    NARCIS (Netherlands)

    Guikema, JEJ; Hovenga, S; Vellenga, E; Bos, NA

    Multiple Myeloma ( MM) is a plasma cell malignancy which is characterized by a very heterogeneous disease outcome. Heterogeneity in plasma cell characteristics, including morphology, maturation status, immunophenotype and genetic abnormalities partly account for the variable disease outcome.

  18. Hemibody irradiation in multiple myeloma

    International Nuclear Information System (INIS)

    Tobias, J.S.; Richards, J.D.M.; Blackman, G.M.; Joannides, T.; Trask, C.W.L.; Nathan, J.I.

    1985-01-01

    Eighteen patients with multiple myeloma were treated by hemibody irradiation using large single fractions, usually to a dose of 10 Gy (lower half) and 7.5 GY (upper half). All except one patient had previously been treated by multiple courses of conventional chemotherapy with melphalan and prednisone, and were considered to be resistant to further chemotherapy. In most cases, local field irradiation had also been given for symptomatic bone pain. Of the 13 patients who had symptoms at the start of hemibody irradiation, 11 improved sufficiently for their analgesia requirement to be reduced. In eight patients, there was a significant fall in circulating immunoglobulin but no patient with Bence-Jones proteinuria had complete resolution of this biochemical abnormality. Although thrombocytopenia and neutropenia were common, only two patients required platelet transfusion and the treatment was in general extremely well tolerated. Survival following hemibody irradiation was similar to the survival reported from the use of 'second-line' chemotherapy and we feel that hemibody irradiation is a more acceptable alternative for most patients. (orig.)

  19. Targeted therapy of multiple myeloma.

    Science.gov (United States)

    Dolloff, Nathan G; Talamo, Giampaolo

    2013-01-01

    Multiple myeloma (MM) is a plasma cell malignancy and the second most common hematologic cancer. MM is characterized by the accumulation of malignant plasma cells within the bone marrow, and presents clinically with a broad range of symptoms, including hypercalcemia, renal insufficiency, anemia, and lytic bone lesions. MM is a heterogeneous disease associated with genomic instability, where patients may express multiple genetic abnormalities that affect several oncogenic pathways. Commonly detected genetic aberrations are translocations involving immunoglobulin heavy chain (IgH) switch regions (chromosome 14q32) and oncogenes such as c-maf [t(14:16)], cyclin D1 [t(11:14)], and FGFR3/MMSET [t(4:14)]. Advances in the basic understanding of MM and the development of novel agents, such as the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide and the proteasome inhibitor bortezomib, have increased therapeutic response rates and prolonged patient survival. Despite these advances MM remains incurable in the majority of patients, and it is therefore critical to identify additional therapeutic strategies and targets for its treatment. In this chapter, we review the underlying genetic components of MM and discuss the results of recent clinical trials that demonstrate the effectiveness of targeted agents in the management of MM. In addition, we discuss experimental therapies that are currently in clinical development along with their molecular rationale in the treatment of MM.

  20. MULTIPLE MYELOMA-LIKE SPINAL MRI FINDINGS IN SKELETAL FLUOROSIS: AN UNUSUAL PRESENTATION OF FLUORIDE TOXICITY IN HUMAN

    Directory of Open Access Journals (Sweden)

    Javed Ahsan Quadri

    2016-11-01

    Full Text Available Endemic fluorosis is a worldwide environmental problem due to excessive fluoride, commonly due to increased drinking water fluoride levels but sometimes due to other sources such food with high fluoride content. In India, 21 of the 35 states are known to have health problems associated with fluoride toxicity. The present report is a case of a 50-year-old female who was seen with progressive spinal complications and a MRI of the spine suggestive of multiple myeloma. The MRI of the lumbo-sacral spine showed a diffuse and heterogeneous marrow signal of the lower dorsal and lumbo-sacral vertebrae. The MRI was also suggestive of coarse trabeculation and appeared predominantly hypointanse on the T1W image and had mixed signal intensity on the T2W image. These findings were suggestive of neoplastic bone marrow infiltration and the presence of a proliferative disorder, with multiple myeloma being the most likely. During the patient workup, it was found that other family members were also having similar complications and, after investigation of these family members, it was found that they are suffering from systemic fluorosis. The patient was then evaluated for skeletal fluorosis and this condition was found to be present. Multiple myeloma was ruled out by the finding of a negative serum protein electrophoresis. The spinal complications appeared to be mainly due to the compression of the spinal cord and nerve roots by protruding osteophytes, thickening of the posterior longitudinal ligament, and thickening of the ligamentum flavum resulting in a compressive myeloradiculopathy and compressive myelopathy. The finding of multiple myeloma- like findings on the spinal MRI in association with skeletal fluorosis was considered to be a very rare event. This case report underlines the need to consider the presence of spinal skeletal fluorosis when evaluating spinal complications with unusual pseudo-multiple myeloma-like changes on the spinal MRI.

  1. CARs in the Lead Against Multiple Myeloma

    DEFF Research Database (Denmark)

    Ormhøj, Maria; Bedoya, Felipe; Frigault, Matthew J.

    2017-01-01

    The recent clinical success of CD19-directed chimeric antigen receptor (CAR) T cell therapy in chronic and acute leukemia has led to increased interest in broadening this technology to other hematological malignancies and solid tumors. Now, advances are being made using CAR T cell technology...... to target myeloma antigens such as B cell maturation antigen (BCMA), CD138, and kappa-light chain as well as CD19 on putative myeloma stem cells. To date, only a limited number of multiple myeloma patients have received CAR T cell therapy but preliminary results have been encouraging. In this review, we...... summarize the recently reported results of clinical trials conducted utilizing CAR T cell therapy in multiple myeloma (MM)....

  2. Histone deacetylase inhibitors in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Sarah Deleu

    2009-06-01

    Full Text Available Novel drugs such as bortezomib and high dose chemotherapy combined with stem cell transplantation improved the outcome of multiple myeloma patients in the past decade. However, multiple myeloma often remains incurable due to the development of drug resistance governed by the bone marrow micro-environment. Therefore targeting new pathways to overcome this resistance is needed. Histone deacetylase (HDAC inhibitors represent a new class of anti-myeloma agents. Inhibiting HDACs results in histone hyperacetylation and alterations in chromatine structure, which, in turn, cause growth arrest differentiation and/or apoptosis in several tumor cells. Here we summarize the molecular actions of HDACi as a single agent or in combination with other drugs in different in vitro and in vivo myeloma models and in (preclinical trials.

  3. Sexual dysfunction in multiple myeloma: survivorship care plan of the International Myeloma Foundation Nurse Leadership Board.

    Science.gov (United States)

    Richards, Tiffany A; Bertolotti, Page A; Doss, Deborah; McCullagh, Emily J

    2011-08-01

    The World Health Organization describes sexuality as a "central aspect of being human throughout life and encompasses sex, gender identities and roles, sexual orientation, eroticism, pleasure, intimacy, and reproduction. Sexuality is influenced by the interaction of biological, psychological, social, economic, political, cultural, ethical, legal, historical, religious, and spiritual factors." Currently, no research has been conducted regarding sexual dysfunction in patients with multiple myeloma; therefore, information related to the assessment and evaluation of sexual dysfunction is gleaned from other malignancies and diseases. In this article, members of the International Myeloma Foundation's Nurse Leadership Board discuss the definition, presentation, and causes of sexual dysfunction; provide recommendations for sexual assessment practices; and promote discussion among patients with multiple myeloma, their healthcare providers, and their partners.

  4. Somatostatin and opioid receptors do not regulate proliferation or apoptosis of the human multiple myeloma U266 cells

    Directory of Open Access Journals (Sweden)

    Allouche Stéphane

    2009-06-01

    Full Text Available Abstract Background opioid and somatostatin receptors (SSTRs that can assemble as heterodimer were individually reported to modulate malignant cell proliferation and to favour apoptosis. Materials and methods: SSTRs and opioid receptors expression were examined by RT-PCR, western-blot and binding assays, cell proliferation was studied by XTT assay and propidium iodide (PI staining and apoptosis by annexin V-PI labelling. Results almost all human malignant haematological cell lines studied here expressed the five SSTRs. Further experiments were conducted on the human U266 multiple myeloma cells, which express also μ-opioid receptors (MOP-R. XTT assays and cell cycle studies provide no evidence for a significant effect upon opioid or somatostatin receptors stimulation. Furthermore, neither direct effect nor potentiation of the Fas-receptor pathway was detected on apoptosis after these treatments. Conclusion these data suggest that SSTRs or opioid receptors expression is not a guaranty for an anti-tumoral action in U266 cell line.

  5. Induction of Apoptosis in Human Multiple Myeloma Cell Lines by Ebselen via Enhancing the Endogenous Reactive Oxygen Species Production

    OpenAIRE

    Zhang, Liang; Zhou, Liwei; Du, Jia; Li, Mengxia; Qian, Chengyuan; Cheng, Yi; Peng, Yang; Xie, Jiayin; Wang, Dong

    2014-01-01

    Ebselen a selenoorganic compound showing glutathione peroxidase like activity is an anti-inflammatory and antioxidative agent. Its cytoprotective activity has been investigated in recent years. However, experimental evidence also shows that ebselen causes cell death in several cancer cell types whose mechanism has not yet been elucidated. In this study, we examined the effect of ebselen on multiple myeloma (MM) cell lines in vitro. The results showed that ebselen significantly enhanced the pr...

  6. Positive findings on bone scan in multiple myeloma

    International Nuclear Information System (INIS)

    Lin Lin

    2004-01-01

    We report a case of multiple myeloma in which the CT only shows osteolytic lesions and MRI only shows compressive fractrue, but the scan shows some interesting imaging that make us to think of multiple myeloma. (authors)

  7. Smoldering multiple myeloma risk factors for progression

    DEFF Research Database (Denmark)

    Sørrig, Rasmus; Klausen, Tobias W; Salomo, Morten

    2016-01-01

    Several risk scores for disease progression in Smoldering Multiple Myeloma (SMM) patients have been proposed, however, all have been developed using single center registries. To examine risk factors for time to progression (TTP) to Multiple Myeloma (MM) for SMM we analyzed a nationwide population......-based cohort of 321 newly diagnosed SMM patients registered within the Danish Multiple Myeloma Registry between 2005 and 2014. Significant univariable risk factors for TTP were selected for multivariable Cox regression analyses. We found that both an M-protein ≥ 30g/l and immunoparesis significantly influenced......-high risk of transformation to MM. Using only immunoparesis and M-protein ≥ 30g/l, we created a scoring system to identify low, intermediate and high risk SMM. This first population-based study of SMM patients confirms that an M-protein ≥ 30g/l and immunoparesis remain important risk factors for progression...

  8. Intratibial injection of human multiple myeloma cells in NOD/SCID IL-2Rγ(null mice mimics human myeloma and serves as a valuable tool for the development of anticancer strategies.

    Directory of Open Access Journals (Sweden)

    Julia Schueler

    Full Text Available BACKGROUND: We systematically analyzed multiple myeloma (MM cell lines and patient bone marrow cells for their engraftment capacity in immunodeficient mice and validated the response of the resulting xenografts to antimyeloma agents. DESIGN AND METHODS: Using flow cytometry and near infrared fluorescence in-vivo-imaging, growth kinetics of MM cell lines L363 and RPMI8226 and patient bone marrow cells were investigated with use of a murine subcutaneous bone implant, intratibial and intravenous approach in NOD/SCID, NOD/SCID treated with CD122 antibody and NOD/SCID IL-2Rγ(null mice (NSG. RESULTS: Myeloma growth was significantly increased in the absence of natural killer cell activity (NSG or αCD122-treated NOD/SCID. Comparison of NSG and αCD122-treated NOD/SCID revealed enhanced growth kinetics in the former, especially with respect to metastatic tumor sites which were exclusively observed therein. In NSG, MM cells were more tumorigenic when injected intratibially than intravenously. In NOD/SCID in contrast, the use of juvenile long bone implants was superior to intratibial or intravenous cancer cell injection. Using the intratibial NSG model, mice developed typical disease symptoms exclusively when implanted with human MM cell lines or patient-derived bone marrow cells, but not with healthy bone marrow cells nor in mock-injected animals. Bortezomib and dexamethasone delayed myeloma progression in L363- as well as patient-derived MM cell bearing NSG. Antitumor activity could be quantified via flow cytometry and in vivo imaging analyses. CONCLUSIONS: Our results suggest that the intratibial NSG MM model mimics the clinical situation of the disseminated disease and serves as a valuable tool in the development of novel anticancer strategies.

  9. Cyclic AMP induces apoptosis in multiple myeloma cells and inhibits tumor development in a mouse myeloma model

    International Nuclear Information System (INIS)

    Follin-Arbelet, Virginie; Hofgaard, Peter O; Hauglin, Harald; Naderi, Soheil; Sundan, Anders; Blomhoff, Rune; Bogen, Bjarne; Blomhoff, Heidi K

    2011-01-01

    Multiple myeloma is an incurable disease requiring the development of effective therapies which can be used clinically. We have elucidated the potential for manipulating the cAMP signaling pathway as a target for inhibiting the growth of multiple myeloma cells. As a model system, we primarily used the murine multiple myeloma cell line MOPC315 which can be grown both in vivo and in vitro. Human multiple myeloma cell lines U266, INA-6 and the B-cell precursor acute lymphoblastic leukemia cell line Reh were used only for in vitro studies. Cell death was assessed by flow cytometry and western blot analysis after treatment with cAMP elevating agents (forskolin, prostaglandin E2 and rolipram) and cAMP analogs. We followed tumor growth in vivo after forskolin treatment by imaging DsRed-labelled MOPC315 cells transplanted subcutaneously in BALB/c nude mice. In contrast to the effect on Reh cells, 50 μM forskolin more than tripled the death of MOPC315 cells after 24 h in vitro. Forskolin induced cell death to a similar extent in the human myeloma cell lines U266 and INA-6. cAMP-mediated cell death had all the typical hallmarks of apoptosis, including changes in the mitochondrial membrane potential and cleavage of caspase 3, caspase 9 and PARP. Forskolin also inhibited the growth of multiple myeloma cells in a mouse model in vivo. Elevation of intracellular levels of cAMP kills multiple myeloma cells in vitro and inhibits development of multiple myeloma in vivo. This strongly suggests that compounds activating the cAMP signaling pathway may be useful in the field of multiple myeloma

  10. Curcumin Enhances Cytotoxic Effects of Bortezomib in Human Multiple Myeloma H929 Cells: Potential Roles of NF-κB/JNK

    Directory of Open Access Journals (Sweden)

    Qing-Xian Bai

    2012-04-01

    Full Text Available Combined curcumin and PS-341 treatment has been reported to enhance cytotoxicity and minimize adverse effects through ERK and p38MAPK mechanisms in human multiple myeloma cells. However, whether JNK plays similar role in this process remains unclear. In the present study, we found combined treatment altered NF-κB p65 expressions and distributions in multiple myeloma H929 cells. Western blot analysis showed combined treatment inactivated NF-κB while activated JNK signaling. Pre-treatment with JNK inhibitor SP600125 could attenuate NF-κB inactivation and restored H929 cells’ survival. These results suggested that curcumin might enhance the cytotoxicity of PS-341 by interacting with NF-κB, at least in part, through JNK mechanism.

  11. Genetic variations in multiple myeloma I

    DEFF Research Database (Denmark)

    Vangsted, A.; Klausen, T.W.; Vogel, Ulla Birgitte

    2012-01-01

    Few risk factors have been established for the plasma cell disorder multiple myeloma, but some of these like African American ethnicity and a family history of B-cell lymphoproliferative diseases suggest a genetic component for the disease. Genetic variation represents the genetic basis of variab......Few risk factors have been established for the plasma cell disorder multiple myeloma, but some of these like African American ethnicity and a family history of B-cell lymphoproliferative diseases suggest a genetic component for the disease. Genetic variation represents the genetic basis...

  12. Immune resistance of Multiple Myeloma : the role of the microenvironment

    NARCIS (Netherlands)

    de Haart, SJ

    2017-01-01

    Immunotherapeutic strategies in Multiple Myeloma are under development. In this thesis we present a new perspective in optimizing immunotherapy in Multiple Myeloma patient. We propose that currently, immunotherapy is limited in efficacy through interactions of Multiple Myeloma cells with the bone

  13. The Danish National Multiple Myeloma Registry

    DEFF Research Database (Denmark)

    Gimsing, Peter; Holmström, Morten Orebo; Klausen, Tobias Wirenfelt

    2016-01-01

    AIM: The Danish National Multiple Myeloma Registry (DMMR) is a population-based clinical quality database established in January 2005. The primary aim of the database is to ensure that diagnosis and treatment of plasma cell dyscrasia are of uniform quality throughout the country. Another aim...... diagnosed patients with multiple myeloma (MM), smoldering MM, solitary plasmacytomas, and plasma cell leukemia in Denmark are registered annually; ~350 patients. Amyloid light-chain amyloidosis, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome......), monoclonal gammopathy of undetermined significance and monoclonal gammopathy of undetermined significance with polyneuropathy have been registered since 2014. MAIN VARIABLES: The main registered variables at diagnosis are patient demographics, baseline disease characteristics, myeloma-defining events...

  14. Technetium-99m Sestamibi in Multiple Myeloma

    International Nuclear Information System (INIS)

    Saber, R.A.

    2002-01-01

    Technetium-99m 2-methoxy - isobutyl - isonitrile (99mTc-MIBI) has been reported to be useful in evaluating patients with multiple myeloma. The aim of this study is to evaluate the role of technetium-99m sestamibi (99mTc-MIBI) scintigraphy in the diagnosis. staging and follow-up of patients with multiple myeloma. Methods and Materials: twenty-five consecutive patients with multiple myeloma were studied using 99mTc- MIBI. Of the 25 patients included in this study, 6 were in stage I, II in stage II and 8 in stage III. Anterior and posterior whole-body imaging were obtained 20 min after I.V. injection of 740 MBq of 99mTc-MIBI. Four different MIBI patterns could be described in our patients: physiological (P), diffuse (D), focal (F) and combined diffuse and focal (D+F). All patients in stages II and III as well as 3 patients in stage I were treated with chemotherapy (cyclophosphamide and prednisone) then 99mTc-MlBI scans were repeated after 6 courses. Results: in comparison to conventional X-ray skeletal survey, 99mTc-MIBI scans showed a higher number of myeloma bone disease at diagnosis. All patients with stage II and III multiple myeloma were positive with 99mTc-MlBl scans at diagnosis. The pattern of positive MIBI accumulation was diffuse in 13 (52%) patients, focal in 4 (16%) and combined focal and diffuse in 6 (24%) patients. The intensity of 99mTc-MIBI correlated with disease activity as determined by lactate dehydrogenase (LDH), number of plasma cells in bone marrow and serum electrophoresis. There was a direct correlation between 99mTc-MIBI scan result and clinical outcome of patients following 6 courses of chemotherapy. Sensitivity and specificity of 99mTc-MIBI scintigraphy in detecting myeloma bone lesions were 92% and 90% respectively. Conclusion: 99mTc-MIBI scintigraphy is a reliable method to evaluate bone marrow activity in patients with multiple myeloma and follow-up of myeloma bone lesions

  15. Plasmacytoma Infiltrating Leiomyoma in Multiple Myeloma

    Science.gov (United States)

    2018-01-19

    REPORT TYPE 3. DATES COVERED (From - To) 01/19/2018 Poster 01/19/2018-01/21/2018 4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Plasmacytoma...Infiltrating Leiomyoma in Multiple Myeloma Sb. GRANT NUMBER Sc. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Sd. PROJECT NUMBER Capt Eden, Rina Se. TASK NUMBER Sf

  16. musculoskeletal presentation of multiple myeloma at general

    African Journals Online (AJOL)

    2014-09-01

    Sep 1, 2014 ... Results: A total of 62 patients were diagnosed with multiple myeloma, 63% were female. ... Conclusion: Presence of bone pain and anaemia should alert the clinician to investigate along the ... not found to fall among the ten most common cancers ..... Dugan LO, Dugan DA, Dugan WM Jr. Back pain: the.

  17. The Role of Immunotherapy in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Mehmet Kocoglu

    2016-01-01

    Full Text Available Multiple myeloma is the second most common hematologic malignancy. The treatment of this disease has changed considerably over the last two decades with the introduction to the clinical practice of novel agents such as proteasome inhibitors and immunomodulatory drugs. Basic research efforts towards better understanding of normal and missing immune surveillence in myeloma have led to development of new strategies and therapies that require the engagement of the immune system. Many of these treatments are under clinical development and have already started providing encouraging results. We, for the second time in the last two decades, are about to witness another shift of the paradigm in the management of this ailment. This review will summarize the major approaches in myeloma immunotherapies.

  18. Implications of Heterogeneity in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Sanjay de Mel

    2014-01-01

    Full Text Available Multiple myeloma is the second most common hematologic malignancy in the world. Despite improvement in outcome, the disease is still incurable for most patients. However, not all myeloma are the same. With the same treatment, some patients can have very long survival whereas others can have very short survival. This suggests that there is underlying heterogeneity in myeloma. Studies over the years have revealed multiple layers of heterogeneity. First, clinical parameters such as age and tumor burden could significantly affect outcome. At the genetic level, there are also significant heterogeneity ranging for chromosome numbers, genetic translocations, and genetic mutations. At the clonal level, there appears to be significant clonal heterogeneity with multiple clones coexisting in the same patient. At the cell differentiation level, there appears to be a hierarchy of clonally related cells that have different clonogenic potential and sensitivity to therapies. These levels of complexities present challenges in terms of treatment and prognostication as well as monitoring of treatment. However, if we can clearly delineate and dissect this heterogeneity, we may also be presented with unique opportunities for precision and personalized treatment of myeloma. Some proof of concepts of such approaches has been demonstrated.

  19. Fundamentals in the management of multiple myeloma.

    Science.gov (United States)

    Fadilah, S A W

    2010-09-01

    Progress in our understanding of multiple myeloma and its treatment has resulted in a more tailored approach to patient management, with different therapeutics regimens for different patient populations. The decision to initiate therapy depends primarily on the presence of symptoms which has to balance the chance of tumor clearance and against the risks of treatment related mortality. Selection of appropriate initial treatment should be based primarily on patient's characteristics (biologic age, co-morbidities), the disease characteristics (tumor burden and genetic risk profile) and the expected toxicity profile of the different regimens. When treatment begins, in younger transplant eligible patients the goal is to achieve high quality responses with intensive therapies as the quality of response appears to be important surrogates for long-term outcome. In the majority of myeloma patients in whom intensive treatment is not an option due to advanced age and co-morbidities, treatment should emphasize on optimal disease control to obtain symptomatic relief and to maintain a satisfactory quality of life. The introduction of novel agents has substantially changed the treatment paradigm of this otherwise incurable disease. The utilization of these drugs has moved from relapse setting to the front line setting and has benefited all patient groups. Because of these rapid developments and many treatment options we need good quality clinical studies to guide clinical practice in the management of patients with multiple myeloma. This review presents an update on current concepts of diagnosis and treatment of patients with multiple myeloma and provides recommendations on tailored therapies with particular reference to the local practice. The information presented herein may be used by the health care providers caring for myeloma patients as a guideline to counsel patients to understand their disease and the treatment better.

  20. Natural killer cell lines preferentially kill clonogenic multiple myeloma cells and decrease myeloma engraftment in a bioluminescent xenograft mouse model.

    Science.gov (United States)

    Swift, Brenna E; Williams, Brent A; Kosaka, Yoko; Wang, Xing-Hua; Medin, Jeffrey A; Viswanathan, Sowmya; Martinez-Lopez, Joaquin; Keating, Armand

    2012-07-01

    Novel therapies capable of targeting drug resistant clonogenic MM cells are required for more effective treatment of multiple myeloma. This study investigates the cytotoxicity of natural killer cell lines against bulk and clonogenic multiple myeloma and evaluates the tumor burden after NK cell therapy in a bioluminescent xenograft mouse model. The cytotoxicity of natural killer cell lines was evaluated against bulk multiple myeloma cell lines using chromium release and flow cytometry cytotoxicity assays. Selected activating receptors on natural killer cells were blocked to determine their role in multiple myeloma recognition. Growth inhibition of clonogenic multiple myeloma cells was assessed in a methylcellulose clonogenic assay in combination with secondary replating to evaluate the self-renewal of residual progenitors after natural killer cell treatment. A bioluminescent mouse model was developed using the human U266 cell line transduced to express green fluorescent protein and luciferase (U266eGFPluc) to monitor disease progression in vivo and assess bone marrow engraftment after intravenous NK-92 cell therapy. Three multiple myeloma cell lines were sensitive to NK-92 and KHYG-1 cytotoxicity mediated by NKp30, NKp46, NKG2D and DNAM-1 activating receptors. NK-92 and KHYG-1 demonstrated 2- to 3-fold greater inhibition of clonogenic multiple myeloma growth, compared with killing of the bulk tumor population. In addition, the residual colonies after treatment formed significantly fewer colonies compared to the control in a secondary replating for a cumulative clonogenic inhibition of 89-99% at the 20:1 effector to target ratio. Multiple myeloma tumor burden was reduced by NK-92 in a xenograft mouse model as measured by bioluminescence imaging and reduction in bone marrow engraftment of U266eGFPluc cells by flow cytometry. This study demonstrates that NK-92 and KHYG-1 are capable of killing clonogenic and bulk multiple myeloma cells. In addition, multiple myeloma

  1. The impact of comorbidity on mortality in multiple myeloma

    DEFF Research Database (Denmark)

    Gregersen, Henrik; Vangsted, Annette Juul; Abildgaard, Niels

    2017-01-01

    To describe the prevalence of comorbidity and its impact on survival in newly diagnosed multiple myeloma patients compared with population controls. Cases of newly diagnosed symptomatic multiple myeloma during the 2005-2012 period were identified in the Danish National Multiple Myeloma Registry....... For each myeloma patient, 10 members of the general population matched by age and sex were chosen from the national Civil Registration System. Data on comorbidity in the myeloma patients and the general population comparison cohort were collected by linkage to the Danish National Patient Registry (DNPR......). Cox proportional hazards regression models were used to evaluate the prognostic significance of comorbidity. The study included 2190 cases of multiple myeloma and 21,900 population controls. The comorbidity was increased in multiple myeloma patients compared with population controls, odds ratio (OR) 1...

  2. Plasma cell morphology in multiple myeloma and related disorders.

    Science.gov (United States)

    Ribourtout, B; Zandecki, M

    2015-06-01

    Normal and reactive plasma cells (PC) are easy to ascertain on human bone marrow films, due to their small mature-appearing nucleus and large cytoplasm, the latter usually deep blue after Giemsa staining. Cytoplasm is filled with long strands of rough endoplasmic reticulum and one large Golgi apparatus (paranuclear hof), demonstrating that PC are dedicated mainly to protein synthesis and excretion (immunoglobulin). Deregulation of the genome may induce clonal expansion of one PC that will lead to immunoglobulin overproduction and eventually to one among the so-called PC neoplasms. In multiple myeloma (MM), the number of PC is over 10% in most patients studied. Changes in the morphology of myeloma PC may be inconspicuous as compared to normal PC (30-50% patients). In other instances PC show one or several morphological changes. One is related to low amount of cytoplasm, defining lymphoplasmacytoid myeloma (10-15% patients). In other cases (40-50% patients), named immature myeloma cases, nuclear-cytoplasmic asynchrony is observed: presence of one nucleolus, finely dispersed chromatin and/or irregular nuclear contour contrast with a still large and blue (mature) cytoplasm. A peculiar morphological change, corresponding to the presence of very immature PC named plasmablasts, is observed in 10-15% cases. Several prognostic morphological classifications have been published, as mature myeloma is related to favorable outcome and immature myeloma, peculiarly plasmablastic myeloma, is related to dismal prognosis. However, such classifications are no longer included in current prognostic schemes. Changes related to the nucleus are very rare in monoclonal gammopathy of unknown significance (MGUS). In contrast, anomalies related to the cytoplasm of PC, including color (flaming cells), round inclusions (Mott cells, Russell bodies), Auer rod-like or crystalline inclusions, are reported in myeloma cases as well as in MGUS and at times in reactive disorders. They do not correspond

  3. New Genetic Insights and Therapy in Multiple Myeloma

    NARCIS (Netherlands)

    K.L. Wu

    2007-01-01

    textabstractIn the last decade, several significant advances in myeloma therapy have occurred with the pace of change accelerated with the introduction of new anti-myeloma agents. The approach to the treatment of multiple myeloma has become more complex with an array of therapeutic options,

  4. Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma

    Science.gov (United States)

    Yang, Jing; He, Jin; Wang, Ji; Cao, Yabing; Ling, Jianhua; Qian, Jianfei; Lu, Yong; Li, Haiyan; Zheng, Yuhuan; Lan, Yongsheng; Hong, Sungyoul; Matthews, Jairo; Starbuck, Michael W; Navone, Nora M; Orlowski, Robert Z.; Lin, Pei; Kwak, Larry W.; Yi, Qing

    2012-01-01

    Bone destruction is a hallmark of multiple myeloma and affects more than 80% of patients. However, current therapy is unable to completely cure and/or prevent bone lesions. Although it is accepted that myeloma cells mediate bone destruction by inhibition of osteoblasts and activation of osteoclasts, the underlying mechanism is still poorly understood. This study demonstrates that constitutive activation of p38 mitogen-activated protein kinase in myeloma cells is responsible for myeloma-induced osteolysis. Our results show that p38 is constitutively activated in most myeloma cell lines and primary myeloma cells from patients. Myeloma cells with high/detectable p38 activity, but not those with low/undetectable p38 activity, injected into SCID or SCID-hu mice caused bone destruction. Inhibition or knockdown of p38 in human myeloma reduced or prevented myeloma-induced osteolytic bone lesions without affecting tumor growth, survival, or homing to bone. Mechanistic studies showed that myeloma cell p38 activity inhibited osteoblastogenesis and bone formation and activated osteoclastogenesis and bone resorption in myeloma-bearing SCID mice. This study elucidates a novel molecular mechanism—sactivation of p38 signaling in myeloma cells—by which myeloma cells induce osteolytic bone lesions and indicates that targeting myeloma cell p38 may be a viable approach to treating or preventing myeloma bone disease. PMID:22425892

  5. Radiotherapy in the treatment of multiple myeloma.

    Science.gov (United States)

    Bosch, A; Frias, Z

    1988-12-01

    Fifty-nine patients with multiple myeloma referred for treatment of painful bony lesions received irradiation to 95 local areas, and 16 of the 59 were irradiated using hemibody techniques. Pain relief was obtained in practically all of the irradiated regions. Most local areas were treated to doses of 3000 cGy in 10 to 15 fractions. Patients with generalized pain due to multiple site involvement were treated with single dose hemibody irradiation, to doses of 600 cGy to the upper hemibody, and of 800 cGy to the lower hemibody. This treatment was well tolerated and side effects minimal. Median survival from diagnosis was 30 months and the survival at 1, 3, and 5 years was 80%, 42%, and 12% respectively. Key articles on radiation therapy of multiple myeloma are reviewed and discussed. Since all patients eventually relapse after chemotherapy, the role of radiotherapy using present techniques should be fully evaluated and considered as an alternative in the primary treatment of multiple myeloma.

  6. Advancements in Nanomedicine for Multiple Myeloma.

    Science.gov (United States)

    Detappe, Alexandre; Bustoros, Mark; Mouhieddine, Tarek H; Ghoroghchian, P Peter

    2018-06-01

    In the past decades, considerable progress has been made in our understanding and treatment of multiple myeloma. Several challenges remain including our abilities to longitudinally image tumor responses to treatment, to combine various therapeutic agents with different mechanisms of action but with overlapping toxicities, and to efficiently harness the power of the immune system to augment remission and/or to induce permanent cures. Nanomedicine may help to address many of these outstanding issues, affording novel diagnostic capabilities and offering disruptive technologies that promise to revolutionize treatment. Here, we review recent developments and the future of nanomedicine for multiple myeloma, highlighting new considerations in nanoparticle designs that may help to augment active targeting, to facilitate longitudinal imaging, and to improve drug delivery. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Multiple myeloma associated with acquired cutis laxa.

    Science.gov (United States)

    Cho, S Y; Maguire, R F

    1980-08-01

    Acquired cutis laxa is a rare disorder characterized by diffuse laxity of the skin and loss of connective tissue support with involvement of the lungs, gastrointestinal tract, pelvic organs, and aorta. The case report presented herein describes a forty-six year old woman with multiple myeloma and cutis laxa. Her history included several severe allergic reactions and the gradual development of lax skin, loss of connective tissue support throughout the body, and emphysema. At autopsy, multiple myeloma, diffuse laxity of the skin, and panacinar emphysema were found. The amount of elastic fiber in the skin, lungs, and aorta was decreased and showed abnormal fragmentation. Results of direct immunofluorescence study demonstrated IgG bound to dermal elastic fibers. Speculation regarding an immunologic etiology of the elastic tissue abnormality is presented herein.

  8. Immunological Dysregulation in Multiple Myeloma Microenvironment

    OpenAIRE

    Romano, Alessandra; Conticello, Concetta; Cavalli, Maide; Vetro, Calogero; La Fauci, Alessia; Parrinello, Nunziatina Laura; Di Raimondo, Francesco

    2014-01-01

    Multiple Myeloma (MM) is a systemic hematologic disease due to uncontrolled proliferation of monoclonal plasma cells (PC) in bone marrow (BM). Emerging in other solid and liquid cancers, the host immune system and the microenvironment have a pivotal role for PC growth, proliferation, survival, migration, and resistance to drugs and are responsible for some clinical manifestations of MM. In MM, microenvironment is represented by the cellular component of a normal bone marrow together with extr...

  9. Multiple myeloma: radiology or bone scanning

    International Nuclear Information System (INIS)

    Leonard, R.C.F.; Owen, J.P.; Proctor, S.J.; Hamilton, P.J.

    1981-01-01

    A comparative study of radionuclide bone scanning and skeletal radiology in patients with multiple myeloma revealed four principal findings: (i) There were no cases of negative bone scans with positive skeletal radiographs. (ii) Lytic bone lesions were seriously underestimated by bone scans. (iii) Bone scans tended to pick up lesions in ribs missed on the skeletal surveys. (iv) Patients with bone pain were more likely to have positive bone scans and skeletal radiographs than asymptomatic patients. (author)

  10. Multiple myeloma presenting as mandibular pain

    LENUS (Irish Health Repository)

    Crowley, Miriam

    2016-10-01

    Introduction: Multiple myeloma (MM) is a systemic malignancy of plasma cells defined by monoclonal production of circulating immunoglobulins. Bone pain is a presenting feature in the majority of cases. Treatment may involve intravenous use of bisphosphonates, chemotherapy or haematopoietic stem cell transplantation. Here, we illustrate a first presentation of MM in a patient with mandibular pain and discuss radiographic, diagnostic and treatment challenges of orofacial issues in patients with MM.\\r\

  11. Clinicopathological features of plasmablastic multiple myeloma

    DEFF Research Database (Denmark)

    Møller, Hanne E H; Preiss, Birgitte S; Pedersen, Per

    2015-01-01

    Multiple myeloma (MM) is a common malignant hematological disease displaying considerable heterogeneity. Historical data indicate a prognostic significance of plasmablastic morphology, proliferation, and adverse cytogenetics, but there is little knowledge on the degree of interdependency......, which indicates that plasmablastic morphology reflects advanced and highly proliferative disease. However, plasmablastic morphology did not correlate with established adverse prognostic cytogenetics identified by FISH, for example, t(4;14), t(14;16) and del(17p)....

  12. Noninvasive imaging of multiple myeloma using near infrared fluorescent molecular probe

    Science.gov (United States)

    Hathi, Deep; Zhou, Haiying; Bollerman-Nowlis, Alex; Shokeen, Monica; Akers, Walter J.

    2016-03-01

    Multiple myeloma is a plasma cell malignancy characterized by monoclonal gammopathy and osteolytic bone lesions. Multiple myeloma is most commonly diagnosed in late disease stages, presenting with pathologic fracture. Early diagnosis and monitoring of disease status may improve quality of life and long-term survival for multiple myeloma patients from what is now a devastating and fatal disease. We have developed a near-infrared targeted fluorescent molecular probe with high affinity to the α4β1 integrin receptor (VLA-4)overexpressed by a majority of multiple myeloma cells as a non-radioactive analog to PET/CT tracer currently being developed for human diagnostics. A near-infrared dye that emits about 700 nm was conjugated to a high affinity peptidomimmetic. Binding affinity and specificity for multiple myeloma cells was investigated in vitro by tissue staining and flow cytometry. After demonstration of sensitivity and specificity, preclinical optical imaging studies were performed to evaluate tumor specificity in murine subcutaneous and metastatic multiple myeloma models. The VLA-4-targeted molecular probe showed high affinity for subcutaneous MM tumor xenografts. Importantly, tumor cells specific accumulation in the bone marrow of metastatic multiple myeloma correlated with GFP signal from transfected cells. Ex vivo flow cytometry of tumor tissue and bone marrow further corroborated in vivo imaging data, demonstrating the specificity of the novel agent and potential for quantitative imaging of multiple myeloma burden in these models.

  13. Palliative radiation therapy for multiple myeloma

    International Nuclear Information System (INIS)

    Minowa, Yasushi; Sasai, Keisuke; Ishigaki, Takashi; Nagata, Yasushi; Hiraoka, Masahiro

    1996-01-01

    Radiation therapy is a useful palliative modality for refractory lesions of multiple myeloma. It has been reported that total doses of 10 to 20 Gy are usually adequate to obtain some degree of pain relief. However, there are many patients who need additional doses to obtain sufficient pain relief. In this study. we retrospectively analyzed the records of patients with multiple myeloma irradiated at our department, in an attempt to develop an effective treatment policy for this disease. Twenty-nine patients with 53 lesions were treated between 1968 and 1993. Total irradiation doses were 4 to 60 Gy (median 40 Gy) with daily fractions of 2 Gy or less, and 16 to 51 Gy (median 30 Gy) with daily fractions greater than 2 Gy. Evaluated were 59 symptoms, including pain (68%), neurological abnormalities (15%), and masses (28%). Symptomatic remission was obtained in 33 of 36 (92%) lesions with pain, 6 of 8 (75%) with neurological abnormalities, and 13 of 15 (87%) mass lesions. Pain was partially relieved at a median TDF of 34, and completely at a median TDF of 66 (equivalent to 40-42 Gy with daily fractions of 2 Gy). Radiation therapy is an effective and palliative treatment method for symptomatic multiple myeloma. However, the treatment seems to require higher radiation doses than those reported to obtain adequate relief of symptoms. (author)

  14. Multiple myeloma-derived MMP-13 mediates osteoclast fusogenesis and osteolytic disease

    DEFF Research Database (Denmark)

    Fu, Jing; Li, Shirong; Feng, Rentian

    2016-01-01

    Multiple myeloma (MM) cells secrete osteoclastogenic factors that promote osteolytic lesions; however, the identity of these factors is largely unknown. Here, we performed a screen of human myeloma cells to identify pro-osteoclastogenic agents that could potentially serve as therapeutic targets...

  15. Antibody-Based Therapies in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Yu-Tzu Tai

    2011-01-01

    Full Text Available The unmet need for improved multiple myeloma (MM therapy has stimulated clinical development of monoclonal antibodies (mAbs targeting either MM cells or cells of the bone marrow (BM microenvironment. In contrast to small-molecule inhibitors, therapeutic mAbs present the potential to specifically target tumor cells and directly induce an immune response to lyse tumor cells. Unique immune-effector mechanisms are only triggered by therapeutic mAbs but not by small molecule targeting agents. Although therapeutic murine mAbs or chimeric mAbs can cause immunogenicity, the advancement of genetic recombination for humanizing rodent mAbs has allowed large-scale production and designation of mAbs with better affinities, efficient selection, decreasing immunogenicity, and improved effector functions. These advancements of antibody engineering technologies have largely overcome the critical obstacle of antibody immunogenicity and enabled the development and subsequent Food and Drug Administration (FDA approval of therapeutic Abs for cancer and other diseases.

  16. Abnormal radiological features in a multiple myeloma patient: a case report and radiological review of myelomas

    DEFF Research Database (Denmark)

    Ghosh, Sujoy; Wadhwa, P; A, Kumar

    2011-01-01

    and porotic changes. Primary sclerotic manifestations are rare and occur in only 3% of cases. Although exceptional, multiple myeloma must be borne in mind in the presence of bone sclerosis. This report presents a patient with multiple myeloma with a sunburst/hair-on-end pattern on the radiograph and sclerotic...

  17. Inhibition of fatty acid metabolism reduces human myeloma cells proliferation.

    Directory of Open Access Journals (Sweden)

    José Manuel Tirado-Vélez

    Full Text Available Multiple myeloma is a haematological malignancy characterized by the clonal proliferation of plasma cells. It has been proposed that targeting cancer cell metabolism would provide a new selective anticancer therapeutic strategy. In this work, we tested the hypothesis that inhibition of β-oxidation and de novo fatty acid synthesis would reduce cell proliferation in human myeloma cells. We evaluated the effect of etomoxir and orlistat on fatty acid metabolism, glucose metabolism, cell cycle distribution, proliferation, cell death and expression of G1/S phase regulatory proteins in myeloma cells. Etomoxir and orlistat inhibited β-oxidation and de novo fatty acid synthesis respectively in myeloma cells, without altering significantly glucose metabolism. These effects were associated with reduced cell viability and cell cycle arrest in G0/G1. Specifically, etomoxir and orlistat reduced by 40-70% myeloma cells proliferation. The combination of etomoxir and orlistat resulted in an additive inhibitory effect on cell proliferation. Orlistat induced apoptosis and sensitized RPMI-8226 cells to apoptosis induction by bortezomib, whereas apoptosis was not altered by etomoxir. Finally, the inhibitory effect of both drugs on cell proliferation was associated with reduced p21 protein levels and phosphorylation levels of retinoblastoma protein. In conclusion, inhibition of fatty acid metabolism represents a potential therapeutic approach to treat human multiple myeloma.

  18. Small interfering RNA-mediated silencing of nicotinamide phosphoribosyltransferase (NAMPT and lysosomal trafficking regulator (LYST induce growth inhibition and apoptosis in human multiple myeloma cells: A preliminary study

    Directory of Open Access Journals (Sweden)

    Ivyna Pau Ni Bong

    2016-11-01

    Full Text Available Multiple myeloma (MM is a malignancy of B lymphocytes or plasma cells. Our array-based comparative genomic hybridization findings revealed chromosomal gains at 7q22.3 and 1q42.3, where nicotinamide (NAM phosphoribosyltransferase (NAMPT and lysosomal trafficking regulator (LYST genes are localized, respectively. This led us to further study the functions of these genes in myeloma cells. NAMPT is a key enzyme involved in nicotinamide adenine dinucleotide salvage pathway, and it is frequently overexpressed in human cancers. In contrast, little is known about the function of LYST in cancer. The expression of LYST is shown to affect lysosomal size, granule size, and autophagy in human cells. In this study, the effects of small interfering RNA (siRNA-mediated silencing of NAMPT and LYST on cell proliferation and apoptosis were evaluated in RPMI 8226 myeloma cells. Transfection efficiencies were determined by quantitative real time reverse transcriptase PCR. Cell proliferation was determined using MTT assay, while apoptosis was analyzed with flow cytometry using Annexin V-fluorescein isothiocyanate/propidium iodide assay. The NAMPT protein expression in siRNA-treated cells was estimated by enzyme-linked immunosorbent assay. Our results showed that NAMPT and LYST were successfully knockdown by siRNA transfection (p < 0.05. NAMPT or LYST gene silencing significantly inhibited cell proliferation and induced apoptosis in RPMI 8226 cells (p < 0.05. Silencing of NAMPT gene also decreased NAMPT protein levels (p < 0.01. Our study demonstrated that NAMPT and LYST play pivotal roles in the molecular pathogenesis of MM. This is the first report describing the possible functions of LYST in myelomagenesis and its potential role as a therapeutic target in MM.

  19. Small interfering RNA-mediated silencing of nicotinamide phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) induce growth inhibition and apoptosis in human multiple myeloma cells: A preliminary study

    Science.gov (United States)

    Bong, Ivyna Pau Ni; Ng, Ching Ching; Fakiruddin, Shaik Kamal; Lim, Moon Nian; Zakaria, Zubaidah

    2016-01-01

    Multiple myeloma (MM) is a malignancy of B lymphocytes or plasma cells. Our array-based comparative genomic hybridization findings revealed chromosomal gains at 7q22.3 and 1q42.3, where nicotinamide (NAM) phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) genes are localized, respectively. This led us to further study the fprotein expression in unctions of these genes in myeloma cells. NAMPT is a key enzyme involved in nicotinamide adenine dinucleotide salvage pathway, and it is frequently overexpressed in human cancers. In contrast, little is known about the function of LYST in cancer. The expression of LYST is shown to affect lysosomal size, granule size, and autophagy in human cells. In this study, the effects of small interfering RNA (siRNA)-mediated silencing of NAMPT and LYST on cell proliferation and apoptosis were evaluated in RPMI 8226 myeloma cells. Transfection efficiencies were determined by quantitative real time reverse transcriptase PCR. Cell proliferation was determined using MTT assay, while apoptosis was analyzed with flow cytometry using Annexin V-fluorescein isothiocyanate/propidium iodide assay. The NAMPT protein expression in siRNA-treated cells was estimated by enzyme-linked immunosorbent assay. Our results showed that NAMPT and LYST were successfully knockdown by siRNA transfection (p < 0.05). NAMPT or LYST gene silencing significantly inhibited cell proliferation and induced apoptosis in RPMI 8226 cells (p < 0.05). Silencing of NAMPT gene also decreased NAMPT protein levels (p < 0.01). Our study demonstrated that NAMPT and LYST play pivotal roles in the molecular pathogenesis of MM. This is the first report describing the possible functions of LYST in myelomagenesis and its potential role as a therapeutic target in MM. PMID:27754828

  20. Report from the European myeloma network on interphase FISH in multiple myeloma and related disorders

    NARCIS (Netherlands)

    F. Ross (F.); H. Avet-Loiseau; G. Ameye (Geneviève); N. Gutierrez (Norma); G. Liebisch (Gerhard); S. O'Connor (Sheila); K. Dalva (Klara); F. Fabris (Federica Margherita); A.M. Testi (Adele); M. Jarosova (M.); C. Hodkinson (Clare); A. Collin (Anna); G. Kerndrup (Gitte); P. Kuglik (Petr); D. Ladon (Dariusz); P. Bernasconi (Paolo); B. Maes (Bart); Z. Zemanova (Zuzana); K. Michalova (Kyra); L. Michau (Lucienne); K. Neben (Kai); N.E.U. Hermansen (N. Emil); K. Rack (Katrina); A. Rocci (Alberto); R. Protheroe (Rebecca); L. Chiecchio (Laura); H.A. Poirel (Hélène A); P. Sonneveld (Pieter); M. Nyegaard (M.); H.E. Johnsen (Hans)

    2012-01-01

    textabstractThe European Myeloma Network has organized two workshops on fluorescence in situ hybridization in multiple myeloma. The first aimed to identify specific indications and consensus technical approaches of current practice. A second workshop followed a quality control exercise in which 21

  1. A novel selective small-molecule PI3K inhibitor is effective against human multiple myeloma in vitro and in vivo

    International Nuclear Information System (INIS)

    Glauer, J; Pletz, N; Schön, M; Schneider, P; Liu, N; Ziegelbauer, K; Emmert, S; Wulf, G G; Schön, M P

    2013-01-01

    Developing effective therapies against multiple myeloma (MM) is an unresolved challenge. Phosphatidylinositol-3-kinase (PI3K) activation may be associated with tumor progression and drug resistance, and inhibiting PI3K can induce apoptosis in MM cells. Thus, targeting of PI3K is predicted to increase the susceptibility of MM to anticancer therapy. The lead compound of a novel class of PI3K inhibitors, BAY80-6946 (IC 50 =0.5 nM against PI3K-α), was highly efficacious in four different MM cell lines, where it induced significant antitumoral effects in a dose-dependent manner. The compound inhibited cell cycle progression and increased apoptosis (P<0.001 compared with controls). Moreover, it abrogated the stimulation conferred by insulin-like growth-factor-1, a mechanism relevant for MM progression. These cellular effects were paralleled by decreased Akt phosphorylation, the main downstream target of PI3K. Likewise, profound antitumoral activity was observed ex vivo, as BAY80-6946 significantly inhibited proliferation of freshly isolated myeloma cells from three patients (P<0.001 compared with vehicle). In addition, BAY80-6946 showed convincing in vivo activity against the human AMO-1 and MOLP-8 myeloma cell lines in a preclinical murine xenograft model, where treatment with 6 mg/kg every other day for 2 weeks reduced the cell numbers by 87.0% and 69.3%, respectively (P<0.001 compared with vehicle), without overt toxicity in treated animals

  2. Agricultural Exposures, Multiple Myeloma Etiology: Profile of Jonathan Hofmann

    Science.gov (United States)

    Tenure-track investigator Jonathan Hofmann, Ph.D., M.P.H., has established a research program in the Occupational and Environmental Epidemiology Branch focused on the role of agricultural exposures in the etiology of multiple myeloma and other cancers, and on understanding the biological mechanisms that influence the development and progression of multiple myeloma.

  3. A case of multiple myeloma presenting as a bullous dermatosis

    Directory of Open Access Journals (Sweden)

    Gul Ulker

    2008-01-01

    Full Text Available Multiple myeloma is a malignant plasma cell proliferative disorder that produces a monoclonal immunoglobulin protein. The skin involvement and the development of bullous disease are rarely seen features in multiple myeloma. We present a 55-year-old man with a longstanding, large, tense bullous eruption and hypertrophic scars over his body accompanied recently with weight loss and fatique. He had no response to the previous treatments, which included oral glucocorticoids and dapsone. Histologic examination of the lesions revealed subepidermal bullae, while no immunoflourescence staining was observed. In a further detailed labarotory examination, multiple myeloma was detected. After the treatment of multiple myeloma with chemotherapy, the lesions regressed. Patients with longstanding, recurrent, unusual bullous eruption should be investigated for the development of multiple myeloma.

  4. Multiple myeloma of the jaw: A case report

    Directory of Open Access Journals (Sweden)

    Shubhasini A Raghavan

    2014-01-01

    Full Text Available Multiple myeloma is a systemic B-cell lymphoproliferative disease that causes osteolytic lesions in the vertebra, ribs, pelvic bone, skull and jaw. Rarely jaw lesions are seen as the first sign in multiple myeloma. This is a case report with follow up of a 57-year-old female patient, previously treated for osteoporosis, who presented with a swelling of the jaw. On radiographic examination, she was found to have osteolytic lesions in the mandible and skull bones. These conventional aids led to the diagnosis of multiple myeloma thereby proving that the osteoporotic lesions were a part of the spectrum of multiple myeloma. The patient underwent chemotherapy and is currently on follow-up. This case report emphasizes the importance of early diagnosis of multiple myeloma in the jaw using readily available technologies and illustrates the contribution that oral assessment can provide.

  5. Silica Nanoparticles Sensitize Human Multiple Myeloma Cells to Snake (Walterinnesia aegyptia Venom-Induced Apoptosis and Growth Arrest

    Directory of Open Access Journals (Sweden)

    Douaa Sayed

    2012-01-01

    Full Text Available Background. Multiple myeloma (MM, an almost incurable disease, is the second most common blood cancer. Initial chemotherapeutic treatment could be successful; however, resistance development urges the use of higher toxic doses accompanied by hematopoietic stem cell transplantation. The establishment of more effective treatments that can overcome or circumvent chemoresistance has become a priority. We recently demonstrated that venom extracted from Walterinnesia aegyptia (WEV either alone or in combination with silica nanoparticles (WEV+NPs mediated the growth arrest and apoptosis of prostate cancer cells. In the present study, we evaluated the impact of WEV alone and WEV+NP on proliferation and apoptosis of MM cells. Methods. The impacts of WEV alone and WEV+NP were monitored in MM cells from 70 diagnosed patients. The influences of WEV and WEV+NP were assessed with flow cytometry analysis. Results. WEV alone and WEV+NP decreased the viability of MM cells. Using a CFSE proliferation assay, we found that WEV+NP strongly inhibited MM cell proliferation. Furthermore, analysis of the cell cycle using the propidium iodide (PI staining method indicated that WEV+NP strongly altered the cell cycle of MM cells and enhanced the induction of apoptosis. Conclusions. Our data reveal the biological effects of WEV and WEV+NP on MM cells that enable these compounds to function as effective treatments for MM.

  6. Induction of Apoptosis in Human Multiple Myeloma Cell Lines by Ebselen via Enhancing the Endogenous Reactive Oxygen Species Production

    Directory of Open Access Journals (Sweden)

    Liang Zhang

    2014-01-01

    Full Text Available Ebselen a selenoorganic compound showing glutathione peroxidase like activity is an anti-inflammatory and antioxidative agent. Its cytoprotective activity has been investigated in recent years. However, experimental evidence also shows that ebselen causes cell death in several cancer cell types whose mechanism has not yet been elucidated. In this study, we examined the effect of ebselen on multiple myeloma (MM cell lines in vitro. The results showed that ebselen significantly enhanced the production of reactive oxygen species (ROS accompanied by cell viability decrease and apoptosis rate increase. Further studies revealed that ebselen can induce Bax redistribution from the cytosol to mitochondria leading to mitochondrial membrane potential ΔΨm changes and cytochrome C release from the mitochondria to cytosol. Furtherly, we found that exogenous addition of N-acetyl cysteine (NAC completely diminished the cell damage induced by ebselen. This result suggests that relatively high concentration of ebselen can induce MM cells apoptosis in culture by enhancing the production of endogenous ROS and triggering mitochondria mediated apoptotic pathway.

  7. Induction of apoptosis in human multiple myeloma cell lines by ebselen via enhancing the endogenous reactive oxygen species production.

    Science.gov (United States)

    Zhang, Liang; Zhou, Liwei; Du, Jia; Li, Mengxia; Qian, Chengyuan; Cheng, Yi; Peng, Yang; Xie, Jiayin; Wang, Dong

    2014-01-01

    Ebselen a selenoorganic compound showing glutathione peroxidase like activity is an anti-inflammatory and antioxidative agent. Its cytoprotective activity has been investigated in recent years. However, experimental evidence also shows that ebselen causes cell death in several cancer cell types whose mechanism has not yet been elucidated. In this study, we examined the effect of ebselen on multiple myeloma (MM) cell lines in vitro. The results showed that ebselen significantly enhanced the production of reactive oxygen species (ROS) accompanied by cell viability decrease and apoptosis rate increase. Further studies revealed that ebselen can induce Bax redistribution from the cytosol to mitochondria leading to mitochondrial membrane potential ΔΨm changes and cytochrome C release from the mitochondria to cytosol. Furtherly, we found that exogenous addition of N-acetyl cysteine (NAC) completely diminished the cell damage induced by ebselen. This result suggests that relatively high concentration of ebselen can induce MM cells apoptosis in culture by enhancing the production of endogenous ROS and triggering mitochondria mediated apoptotic pathway.

  8. Tracking human multiple myeloma xenografts in NOD-Rag-1/IL-2 receptor gamma chain-null mice with the novel biomarker AKAP-4

    International Nuclear Information System (INIS)

    Mirandola, Leonardo; Yu, Yuefei; Jenkins, Marjorie R; Chiaramonte, Raffaella; Cobos, Everardo; John, Constance M; Chiriva-Internati, Maurizio

    2011-01-01

    Multiple myeloma (MM) is a fatal malignancy ranking second in prevalence among hematological tumors. Continuous efforts are being made to develop innovative and more effective treatments. The preclinical evaluation of new therapies relies on the use of murine models of the disease. Here we describe a new MM animal model in NOD-Rag1null IL2rgnull (NRG) mice that supports the engraftment of cell lines and primary MM cells that can be tracked with the tumor antigen, AKAP-4. Human MM cell lines, U266 and H929, and primary MM cells were successfully engrafted in NRG mice after intravenous administration, and were found in the bone marrow, blood and spleen of tumor-challenged animals. The AKAP-4 expression pattern was similar to that of known MM markers, such as paraproteins, CD38 and CD45. We developed for the first time a murine model allowing for the growth of both MM cell lines and primary cells in multifocal sites, thus mimicking the disease seen in patients. Additionally, we validated the use of AKAP-4 antigen to track tumor growth in vivo and to specifically identify MM cells in mouse tissues. We expect that our model will significantly improve the pre-clinical evaluation of new anti-myeloma therapies

  9. Bortezomib in the management of multiple myeloma

    Directory of Open Access Journals (Sweden)

    Jacob P Laubach

    2009-09-01

    Full Text Available Jacob P Laubach, Constantine S Mitsiades, Teru Hideshima, Robert Schlossman, Dharminder Chauhan, Nikhil Munshi, Irene Ghobrial, Nicole Carreau, Kenneth C Anderson, Paul G RichardsonDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USAAbstract: Multiple myeloma (MM is a B-cell malignancy characterized by clonal expansion of plasma cells within the bone marrow, the presence of a serum and/or urine monoclonal protein, lytic bone lesions, and anemia. On a cellular level, the disease is characterized by complex interactions between tumor cells and the surrounding bone marrow microenvironment. Understanding of the relationship between malignant plasma cells and the microenvironment has sparked ongoing efforts to develop targeted therapeutic agents for treatment of this disease. The successful development of the first-in-class small-molecule proteasome inhibitor bortezomib occurred as a result of these efforts. This review focuses on the rationale for bortezomib therapy in the treatment of patients with newly diagnosed and relapsed MM, important treatment-related side effects, and future directions for use of bortezomib and other, emerging proteasome inhibitors.Keywords: multiple myeloma, bortezomib, stem cell transplantation, peripheral neuropathy

  10. Identify multiple myeloma stem cells: Utopia?

    Science.gov (United States)

    Saltarella, Ilaria; Lamanuzzi, Aurelia; Reale, Antonia; Vacca, Angelo; Ria, Roberto

    2015-01-26

    Multiple myeloma (MM) is a hematologic malignancy of monoclonal plasma cells which remains incurable despite recent advances in therapies. The presence of cancer stem cells (CSCs) has been demonstrated in many solid and hematologic tumors, so the idea of CSCs has been proposed for MM, even if MM CSCs have not been define yet. The existence of myeloma CSCs with clonotypic B and clonotypic non B cells was postulated by many groups. This review aims to focus on these distinct clonotypic subpopulations and on their ability to develop and sustain MM. The bone marrow microenvironment provides to MM CSCs self-renewal, survival and drug resistance thanks to the presence of normal and cancer stem cell niches. The niches and CSCs interact each other through adhesion molecules and the interplay between ligands and receptors activates stemness signaling (Hedgehog, Wnt and Notch pathways). MM CSCs are also supposed to be responsible for drug resistance that happens in three steps from the initial cancer cell homing microenvironment-mediated to development of microenvironment-independent drug resistance. In this review, we will underline all these aspects of MM CSCs.

  11. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma

    DEFF Research Database (Denmark)

    Mellqvist, Ulf-Henrik; Gimsing, Peter; Hjertner, Oyvind

    2013-01-01

    The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370...

  12. Interleukin-6, a new target for therapy in multiple myeloma?

    NARCIS (Netherlands)

    van Oers, M. H.; van Zaanen, H. C.; Lokhorst, H. M.

    1993-01-01

    During the past few years much insight has been gained into the immunobiology of multiple myeloma. It has become evident that the growth of myeloma cells is regulated by cytokines, notably interleukin-6. In this paper a brief review is given of the evidence derived from in vitro as well as in vivo

  13. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

    NARCIS (Netherlands)

    P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth)

    2005-01-01

    textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

  14. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma.

    Science.gov (United States)

    Dimopoulos, Meletios A; Oriol, Albert; Nahi, Hareth; San-Miguel, Jesus; Bahlis, Nizar J; Usmani, Saad Z; Rabin, Neil; Orlowski, Robert Z; Komarnicki, Mieczyslaw; Suzuki, Kenshi; Plesner, Torben; Yoon, Sung-Soo; Ben Yehuda, Dina; Richardson, Paul G; Goldschmidt, Hartmut; Reece, Donna; Lisby, Steen; Khokhar, Nushmia Z; O'Rourke, Lisa; Chiu, Christopher; Qin, Xiang; Guckert, Mary; Ahmadi, Tahamtan; Moreau, Philippe

    2016-10-06

    Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1-2 study involving patients with relapsed or refractory multiple myeloma. In this phase 3 trial, we randomly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone (control group) or in combination with daratumumab (daratumumab group). The primary end point was progression-free survival. At a median follow-up of 13.5 months in a protocol-specified interim analysis, 169 events of disease progression or death were observed (in 53 of 286 patients [18.5%] in the daratumumab group vs. 116 of 283 [41.0%] in the control group; hazard ratio, 0.37; 95% confidence interval [CI], 0.27 to 0.52; P<0.001 by stratified log-rank test). The Kaplan-Meier rate of progression-free survival at 12 months was 83.2% (95% CI, 78.3 to 87.2) in the daratumumab group, as compared with 60.1% (95% CI, 54.0 to 65.7) in the control group. A significantly higher rate of overall response was observed in the daratumumab group than in the control group (92.9% vs. 76.4%, P<0.001), as was a higher rate of complete response or better (43.1% vs. 19.2%, P<0.001). In the daratumumab group, 22.4% of the patients had results below the threshold for minimal residual disease (1 tumor cell per 10 5 white cells), as compared with 4.6% of those in the control group (P<0.001); results below the threshold for minimal residual disease were associated with improved outcomes. The most common adverse events of grade 3 or 4 during treatment were neutropenia (in 51.9% of the patients in the daratumumab group vs. 37.0% of those in the control group), thrombocytopenia (in 12.7% vs. 13.5%), and anemia (in 12.4% vs. 19.6%). Daratumumab-associated infusion-related reactions occurred in 47.7% of the patients and were mostly of grade 1 or 2. The addition of daratumumab to lenalidomide and dexamethasone significantly lengthened

  15. Immunological dysregulation in multiple myeloma microenvironment.

    Science.gov (United States)

    Romano, Alessandra; Conticello, Concetta; Cavalli, Maide; Vetro, Calogero; La Fauci, Alessia; Parrinello, Nunziatina Laura; Di Raimondo, Francesco

    2014-01-01

    Multiple Myeloma (MM) is a systemic hematologic disease due to uncontrolled proliferation of monoclonal plasma cells (PC) in bone marrow (BM). Emerging in other solid and liquid cancers, the host immune system and the microenvironment have a pivotal role for PC growth, proliferation, survival, migration, and resistance to drugs and are responsible for some clinical manifestations of MM. In MM, microenvironment is represented by the cellular component of a normal bone marrow together with extracellular matrix proteins, adhesion molecules, cytokines, and growth factors produced by both stromal cells and PC themselves. All these components are able to protect PC from cytotoxic effect of chemo- and radiotherapy. This review is focused on the role of immunome to sustain MM progression, the emerging role of myeloid derived suppressor cells, and their potential clinical implications as novel therapeutic target.

  16. Immunological Dysregulation in Multiple Myeloma Microenvironment

    Directory of Open Access Journals (Sweden)

    Alessandra Romano

    2014-01-01

    Full Text Available Multiple Myeloma (MM is a systemic hematologic disease due to uncontrolled proliferation of monoclonal plasma cells (PC in bone marrow (BM. Emerging in other solid and liquid cancers, the host immune system and the microenvironment have a pivotal role for PC growth, proliferation, survival, migration, and resistance to drugs and are responsible for some clinical manifestations of MM. In MM, microenvironment is represented by the cellular component of a normal bone marrow together with extracellular matrix proteins, adhesion molecules, cytokines, and growth factors produced by both stromal cells and PC themselves. All these components are able to protect PC from cytotoxic effect of chemo- and radiotherapy. This review is focused on the role of immunome to sustain MM progression, the emerging role of myeloid derived suppressor cells, and their potential clinical implications as novel therapeutic target.

  17. Therapy assessment in multiple myeloma with PET

    Energy Technology Data Exchange (ETDEWEB)

    Nanni, Cristina [Medicina Nucleare Metropolitana di Bologna, Bologna (Italy); Zamagni, Elena [Bologna University School of Medicine, Seragnoli Institute of Hematology, Bologna (Italy)

    2017-08-15

    Multiple myeloma is a plasma cell dyscrasia producing bone lytic lesions. In recent years, a wide spectrum of therapeutic approaches are available to treat the disease: an accurate therapy assessment has, therefore, become of utmost importance. In this field, imaging is becoming a cornerstone, especially in association with clinical parameters. Among imaging procedures, FDG PET/CT is recognized to provide reliable information, achieved in a very safe and fast procedure. The literature has produced very concordant results from different groups assessing the value of FDG PET/CT as a prognostic factor in general and in therapy assessment, but some issues remain regarding a standardization of image interpretation especially in borderline cases. So far, no data regarding nor other imaging compounds and the use of hybrid tomographs PET/MR are available to define therapy assessment in PET. (orig.)

  18. Development of Novel Immunotherapies for Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Ensaf M. Al-Hujaily

    2016-09-01

    Full Text Available Multiple myeloma (MM is a disorder of terminally differentiated plasma cells characterized by clonal expansion in the bone marrow (BM. It is the second-most common hematologic malignancy. Despite significant advances in therapeutic strategies, MM remains a predominantly incurable disease emphasizing the need for the development of new treatment regimens. Immunotherapy is a promising treatment modality to circumvent challenges in the management of MM. Many novel immunotherapy strategies, such as adoptive cell therapy and monoclonal antibodies, are currently under investigation in clinical trials, with some already demonstrating a positive impact on patient survival. In this review, we will summarize the current standards of care and discuss major new approaches in immunotherapy for MM.

  19. Central nervous system involvement by multiple myeloma

    DEFF Research Database (Denmark)

    Jurczyszyn, Artur; Grzasko, Norbert; Gozzetti, Alessandro

    2016-01-01

    The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate......, 97% patients received initial therapy for CNS disease, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. After a median follow-up of 3.5 years, the median overall survival (OS) from the onset of CNS involvement for the entire group was 7 months. Untreated...... untreated patients and patients with favorable cytogenetic profile might be prolonged due to systemic treatment and/or radiotherapy. This article is protected by copyright. All rights reserved....

  20. Immunogenic Targets for Specific Immunotherapy in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Lu Zhang

    2012-01-01

    Full Text Available Multiple myeloma remains an incurable disease although the prognosis has been improved by novel therapeutics and agents recently. Relapse occurs in the majority of patients and becomes fatal finally. Immunotherapy might be a powerful intervention to maintain a long-lasting control of minimal residual disease or to even eradicate disseminated tumor cells. Several tumor-associated antigens have been identified in patients with multiple myeloma. These antigens are expressed in a tumor-specific or tumor-restricted pattern, are able to elicit immune response, and thus could serve as targets for immunotherapy. This review discusses immunogenic antigens with therapeutic potential for multiple myeloma.

  1. A concise revised myeloma comorbidity index as a valid prognostic instrument in a large cohort of 801 multiple myeloma patients

    NARCIS (Netherlands)

    M. Engelhardt (Monika); Domm, A.-S. (Anne-Saskia); Dold, S.M. (Sandra Maria); G. Ihorst (Gabriele); Reinhardt, H. (Heike); Zober, A. (Alexander); Hieke, S. (Stefanie); Baayen, C. (Corine); Müller, S.J. (Stefan Jürgen); H. Einsele (Hermann); P. Sonneveld (Pieter); O. Landgren; M. Schumacher (M.); R. Wäsch (Ralph)

    2017-01-01

    textabstractWith growing numbers of elderly multiple myeloma patients, reliable tools to assess their vulnerability are required. The objective of the analysis herein was to develop and validate an easy to use myeloma risk score (revised Myeloma Comorbidity Index) that allows for risk prediction of

  2. Continuous lenalidomide treatment for newly diagnosed multiple myeloma

    DEFF Research Database (Denmark)

    Palumbo, Antonio; Hajek, Roman; Delforge, Michel

    2012-01-01

    Lenalidomide has tumoricidal and immunomodulatory activity against multiple myeloma. This double-blind, multicenter, randomized study compared melphalan-prednisone-lenalidomide induction followed by lenalidomide maintenance (MPR-R) with melphalan-prednisone-lenalidomide (MPR) or melphalan-prednis...

  3. Concomitant HIV infection in newly diagnosed multiple myeloma ...

    African Journals Online (AJOL)

    RESEARCH ... To compare the presenting features of HIV-positive patients diagnosed with MM ..... Especially since recent publications are showing trends of .... 18. Agrawal S, Deshpande A. A unique presentation of multiple myeloma in an ...

  4. Recombinant alpha-interferon as salvage therapy in multiple myeloma

    African Journals Online (AJOL)

    1989-08-05

    Aug 5, 1989 ... Ten patients with end-stage multiple myeloma refractory to conventional chemotherapy and ... malities and relief of pain using local radiotherapy. However, .... therapy programmes. However, the role of this agent remains.

  5. Maxillary Swelling as the First Evidence of Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Atsushi Kasamatsu

    2015-01-01

    Full Text Available Multiple myeloma is a malignant neoplasm of plasma cells characterized by proliferation of a single clone of abnormal immunoglobulin-secreting plasma cells. Since the amount of hemopoietic bone marrow is decreased in the maxilla, oral manifestations of multiple myeloma are less common in the maxilla than in the mandible. We report the case of 33-year-old Japanese man who presented with a mass in the right maxillary alveolar region. Computed tomography and magnetic resonance images showed a soft tissue mass in the right maxilla eroding the anterior and lateral walls of the maxillary sinus and extending into the buccal space. The biopsy results, imaging, and laboratory investigations led to the diagnosis of multiple myeloma. This case report suggests that oral surgeons and dentists should properly address oral manifestations as first indications of multiple myeloma.

  6. Maxillary Swelling as the First Evidence of Multiple Myeloma

    Science.gov (United States)

    Kasamatsu, Atsushi; Kimura, Yasushi; Tsujimura, Hideki; Kanazawa, Harusachi; Koide, Nao; Miyamoto, Isao; Endo-Sakamoto, Yosuke; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

    2015-01-01

    Multiple myeloma is a malignant neoplasm of plasma cells characterized by proliferation of a single clone of abnormal immunoglobulin-secreting plasma cells. Since the amount of hemopoietic bone marrow is decreased in the maxilla, oral manifestations of multiple myeloma are less common in the maxilla than in the mandible. We report the case of 33-year-old Japanese man who presented with a mass in the right maxillary alveolar region. Computed tomography and magnetic resonance images showed a soft tissue mass in the right maxilla eroding the anterior and lateral walls of the maxillary sinus and extending into the buccal space. The biopsy results, imaging, and laboratory investigations led to the diagnosis of multiple myeloma. This case report suggests that oral surgeons and dentists should properly address oral manifestations as first indications of multiple myeloma. PMID:26640721

  7. Stages of Plasma Cell Neoplasms (Including Multiple Myeloma)

    Science.gov (United States)

    ... cancer treatment is also called biotherapy or immunotherapy. Immunomodulators are a type of biologic therapy. Thalidomide , lenalidomide , and pomalidomide are immunomodulators used to treat multiple myeloma and other plasma ...

  8. Treatment Options for Plasma Cell Neoplasms (Including Multiple Myeloma)

    Science.gov (United States)

    ... cancer treatment is also called biotherapy or immunotherapy. Immunomodulators are a type of biologic therapy. Thalidomide , lenalidomide , and pomalidomide are immunomodulators used to treat multiple myeloma and other plasma ...

  9. The case of a multiple myeloma with hyperlipoproteinaemia

    International Nuclear Information System (INIS)

    Paluszewska, M.; Bobilewicz, D.; Gigier, A.; Zwolinski, J.; Kuratowska, Z.

    1994-01-01

    The case of a 52-year-old women with hyperlipoproteinaemia, xantomathosis and multiple myeloma was discussed. The lipid disorder was one of the first symptoms and the base for diagnosis. Hyperlipoproteinaemia was probably due to the monoclonal immunoglobulin and lipoprotein interaction or their impaired catabolism. Lipoprotein lipase activity was normal. Cytostatic therapy led to partial remission of multiple myeloma and lipoproteins concentration became normal. (author)

  10. Pulmonary Embolism as the First Manifestation of Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    N. Vallianou

    2013-01-01

    Full Text Available Multiple myeloma is considered a hypercoagulable state due to several mechanisms such as the increased IL-6 and immunoglobulins production, the defective fibrinolytic mechanism, and the acquired resistance to activated protein C that are involved in the pathogenesis and clinical futures of the disease. We describe a case of a female patient who presented to the hospital with pulmonary embolism as the first manifestation of the hypercoagulability of multiple myeloma.

  11. Primary laryngeal localization of multiple myeloma: A case report

    OpenAIRE

    Allegra, Eugenia; Marino, Nicol?; Modica, Domenico; Emmanuele, Carmela; Saita, Vincenzo

    2017-01-01

    Multiple myeloma is a lymphoproliferative disease that may involve the bone marrow as well as extramedullary soft tissues. However, laryngeal localization of multiple myeloma is extremely rare. We herein present the case of a 68-year-old male patient with a history of dyspnea, dysphonia and dysphagia. Laryngoscopic examination revealed a lesion involving the right glottis and right vestibular (false) vocal fold, with absence of ipsilateral laryngeal motility and constriction of the airway. Co...

  12. Can dentists detect multiple myeloma through oral manifestations?

    Directory of Open Access Journals (Sweden)

    Thaís Miranda Xavier de Almeida

    2018-01-01

    Full Text Available Objective: To review published data on oral manifestations of multiple myeloma. Methods: An electronic database search was performed of articles published from 1971 to November 2016 in order to identify studies that reported oral manifestations of patients with multiple myeloma. Case reports and case series with oral manifestations of multiple myeloma in English were included in the study. An additional search was performed of the references of the selected articles. Results: Thirty-seven articles that reported 81 patients with oral manifestations of multiple myeloma were selected: 30 case reports (82% and seven case series (18%. The most common clinical features in the dental cavity were swelling (65.4%, bone pain (33.3%, paresthesia (27.1% and amyloidosis lesions (11.1%. Osteolytic lesions detected on imaging exams were reported in the majority of the patients (90.1% as plasmacytomas or ‘punched-out’ lesions. Conclusions: Swelling and osteolytic lesions represent the most common clinical and radiographic signs of the jaws relating to multiple myeloma, respectively. Keywords: Multiple Myeloma, Oral Manifestations, Mouth, Jaws

  13. A Pictorial Review on Extraosseous Manifestations of Multiple Myelomas

    International Nuclear Information System (INIS)

    Seo, Jung Min; Lee, Kyung Soo; Yi, Chin A; Kim, Seong Hyun; Park, Byung Kwan; Han, Boo Kyung; Kim, Hyung Jin

    2011-01-01

    Extraosseous involvement of multiple myelomas can be seen clinically or radiologically in approximately 10-20% of patients at the time of initial diagnosis and may develop in an additional 15% of patients over the course of the disease. The condition can arise in any tissue of the body and its presence has been associated with more aggressive disease, a guarded prognosis, or high-dose chemotherapy. Imaging findings of extraosseous multiple myelomas are diverse. They usually show high enhancement on contrast-medium enhanced CT scans, exhibit iso-signal intensity on both T1- and T2- weighted images, and variable 18F-fluorine deoxyglucose (FDG) uptake at PET. The disease may simulate an infectious condition since it may be concurrent with underlying multiple myelomas per se or it may occur during myeloma treatment including stem cell transplantation.

  14. A murine model of human myeloma bone disease

    NARCIS (Netherlands)

    Garrett, I.R.; Dallas, S.; Radl, J.; Mundy, G.R.

    1997-01-01

    Myeloma causes a devastating and unique form of osteolytic bone disease. Although osteoclast activation is responsible for bone destruction, the precise mechanisms by which myeloma cells increase osteoclast activity have not been defined. An animal model of human myeloma bone disease mould help in

  15. Monitoring multiple myeloma patients treated with daratumumab

    DEFF Research Database (Denmark)

    McCudden, Christopher; Axel, Amy E; Slaets, Dominique

    2016-01-01

    BACKGROUND: Monoclonal antibodies are promising anti-myeloma treatments. As immunoglobulins, monoclonal antibodies have the potential to be identified by serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE). Therapeutic antibody interference with standard clinical SPE and ...

  16. The pituitary tumor transforming gene 1 (PTTG-1: An immunological target for multiple myeloma

    Directory of Open Access Journals (Sweden)

    Gagliano Nicoletta

    2008-04-01

    Full Text Available Abstract Background Multiple Myeloma is a cancer of B plasma cells, which produce non-specific antibodies and proliferate uncontrolled. Due to the potential relapse and non-specificity of current treatments, immunotherapy promises to be more specific and may induce long-term immunity in patients. The pituitary tumor transforming gene 1 (PTTG-1 has been shown to be a novel oncogene, expressed in the testis, thymus, colon, lung and placenta (undetectable in most other tissues. Furthermore, it is over expressed in many tumors such as the pituitary adenoma, breast, gastrointestinal cancers, leukemia, lymphoma, and lung cancer and it seems to be associated with tumorigenesis, angiogenesis and cancer progression. The purpose was to investigate the presence/rate of expression of PTTG-1 in multiple myeloma patients. Methods We analyzed the PTTG-1 expression at the transcriptional and the protein level, by PCR, immunocytochemical methods, Dot-blot and ELISA performed on patient's sera in 19 multiple myeloma patients, 6 different multiple myeloma cell lines and in normal human tissue. Results We did not find PTTG-1 presence in the normal human tissue panel, but PTTG-1 mRNA was detectable in 12 of the 19 patients, giving evidence of a 63% rate of expression (data confirmed by ELISA. Four of the 6 investigated cell lines (66.6% were positive for PTTG-1. Investigations of protein expression gave evidence of 26.3% cytoplasmic expression and 16% surface expression in the plasma cells of multiple myeloma patients. Protein presence was also confirmed by Dot-blot in both cell lines and patients. Conclusion We established PTTG-1's presence at both the transcriptional and protein levels. These data suggest that PTTG-1 is aberrantly expressed in multiple myeloma plasma cells, is highly immunogenic and is a suitable target for immunotherapy of multiple myeloma.

  17. Radiography and bone scintigraphy in multiple myeloma: a comparative analysis

    International Nuclear Information System (INIS)

    Ludwig, H.; Kumpan, W.; Sinzinger, H.

    1982-01-01

    The sensitivity of radionuclide imaging for detecting skeletal lesions was compared with that of radiography by evaluating 573 different anatomical sites in 41 patients with multiple myeloma. Radiography revealed a significantly greater number of myeloma-related bone lesions than did radionuclide imaging. Of the 179 myeloma-related bone lesions detected when both techniques were applied, 163 were seen by radiography and 82 by radionuclide imaging. Ninety-seven lesions were detected by radiography alone and 16 lesions seen by scintiscanning only, yielding a sensitivity of 91% for the former and of 46% for the latter technique. Radionuclide imaging proved superior to radiography only occasionally in the rib cage, and rarely in other anatomical sites. These findings suggest that radiography is the method of first choice in obtaining a skeletal survey in patients with multiple myeloma. In cases with continued pain, unexplained by standard radiography, the skeletal survey should be supplemented by tomography and radionuclide imaging. (author)

  18. Renal failure in patients with multiple myeloma.

    Science.gov (United States)

    Almueilo, Samir H

    2015-01-01

    Renal dysfunction is encountered in 20-25% of patients with multiple myeloma (MM) at the time of diagnosis. There is often a precipitating event. Several biochemical and clinical correlations with renal failure in MM have been reported. Renal failure in MM is associated with worse outcome of the disease. We retrospectively analyzed the medical records of 64 patients with MM admitted to our institution during the period January 1992 to December 2012. Abnormal renal function was observed in 24 (37.5%) patients and 17 (26.6%) of them had renal failure; 14 of the 17 (82.4%) of patients with renal failure had Stage III MM. Urine Bence- Jones protein was positive in ten (58.8%) patients with renal failure versus ten (21.3%) patients without renal failure (P = 0.004). Potential precipitating factors of renal failure were determined in nine patients. Renal function normalized in 11 patients with simple measures, while six patients required hemodialysis; one remained dialysis dependent till time of death. Early mortality occurred in five (29.4%) patients with renal failure as compared with two (4.3%) patients in the group without renal failure (P = 0.005). In conclusion, renal failure is associated with a higher tumor burden and Bence-Jones proteinuria in patients with MM. It is reversible in the majority of patients; however, early mortality tends to be higher in patients with persistent renal failure.

  19. Targeting the Pim kinases in multiple myeloma.

    LENUS (Irish Health Repository)

    Keane, N A

    2015-07-17

    Multiple myeloma (MM) is a plasma cell malignancy that remains incurable. Novel treatment strategies to improve survival are urgently required. The Pims are a small family of serine\\/threonine kinases with increased expression across the hematological malignancies. Pim-2 shows highest expression in MM and constitutes a promising therapeutic target. It is upregulated by the bone marrow microenvironment to mediate proliferation and promote MM survival. Pim-2 also has a key role in the bone destruction typically seen in MM. Additional putative roles of the Pim kinases in MM include trafficking of malignant cells, promoting oncogenic signaling in the hypoxic bone marrow microenvironment and mediating resistance to therapy. A number of Pim inhibitors are now under development with lead compounds entering the clinic. The ATP-competitive Pim inhibitor LGH447 has recently been reported to have single agent activity in MM. It is anticipated that Pim inhibition will be of clinical benefit in combination with standard treatments and\\/or with novel drugs targeting other survival pathways in MM.

  20. Multiple Myeloma in a Patient with Acromegaly

    Directory of Open Access Journals (Sweden)

    Yu Mi Kang

    2015-03-01

    Full Text Available Acromegaly is a slowly progressing condition resulting from excess growth hormone (GH, generally caused by a GH-secreting pituitary adenoma. Cancer is the third most common cause of mortality in patients with acromegaly, and insulin-like growth factor 1 (IGF-1 is known to influence tumor formation by increasing cell proliferation and inhibiting apoptosis. Multiple myeloma (MM is a plasma cell neoplasm, and previous studies have suggested the possible role of IGF-1 in its development of MM. However, no cases of acromegaly accompanied with MM have been reported in Asia to date. We here report the case of a 58-year-old woman with acromegaly accompanied with MM who presented with longstanding acromegalic manifestations resulting from a GH-secreting pituitary adenoma and also exhibited anemia, a reversed albumin/globulin ratio, and plasmacytosis on bone marrow examination. Because IGF-1 has been suggested to play an important role in the development and progression of MM, the patient promptly underwent surgical removal of the pituitary adenoma via a transsphenoidal approach. Since there is currently no consensus on therapeutic guidelines and suggested prognosis for MM with acromegaly, long-term follow-up of such cases is needed.

  1. Leukemia, multiple myeloma, and malignant lymphoma

    International Nuclear Information System (INIS)

    Ichimaru, M.; Ishimaru, T.; Ohkita, T.

    1986-01-01

    Excess risk of leukemia among atomic bomb (A-bomb) survivors increased with radiation dose in Hiroshima and Nagasaki. The incidence of all types of leukemia, except chronic lymphocytic leukemia, has increased among A-bomb survivors. However, chronic myelogenous leukemia (CML) is thought to be the most characteristic type of the A-bomb induced leukemias. The highest risk of leukemia among A-bomb survivors was recognized in 1951 and has not yet disappeared in survivors in Hiroshima. Excess risk of leukemia in the younger age at time of bomb (ATB) groups appeared early; however, in older age ATB groups it appeared much later especially among Hiroshima survivors. In both cities the effect of radiation exposure on the occurrence of CML was more clearly observable in the younger age ATB groups and occurred more frequently in Hiroshima. Leukemia among individuals exposed in utero and children of A-bomb survivors has not increased significantly. The relationship between radiation induced leukemia and chromosome abnormalities is discussed. Twenty years after the A-bomb, the risk of multiple myeloma (MM) increased among survivors aged 20-59 years ATB. Non-Hodgkin's malignant lymphoma also increased among A-bomb survivors and showed roughly the same tendency as MM

  2. Leukemia, multiple myeloma, and malignant lymphoma

    International Nuclear Information System (INIS)

    Ichimaru, Michito; Ohkita, Takeshi; Ishimaru, Toranosuke.

    1986-01-01

    Excess risk of leukemia among atomic bomb (A-bomb) survivors increased with radiation dose in Hiroshima and Nagasaki. The incidence of all types of leukemia, except chronic lymphocytic leukemia, has increased among A-bomb survivors. However, chronic myelogenous leukemia (CML) is thought to be the most characteristic type of the A-bomb induced leukemias. The highest risk of leukemia among A-bomb survivors was recognized in 1951 and has not yet disappeared in survivors in Hiroshima. Excess risk of leukemia in the younger age at time of bomb (ATB) groups appeared early; however, in the older age ATB groups it appeared much later especially among Hiroshima survivors. In both cities the effect of radiation exposure on the occurrence of CML was more clearly observable in the younger age ATB groups and occurred more frequently in Hiroshima. Leukemia among individuals exposed in utero and children of A-bomb survivors has not increased significantly. The relationship between radiation induced leukemia and chromosome abnormalities is discussed. Twenty years after the A-bomb, the risk of multiple myeloma (MM) increased among survivors aged 20 - 59 years ATB. Non-Hodgkin's malignant lymphoma also increased among A-bomb survivors and showed roughly the same tendency as MM. (author)

  3. Association between intracranial plasmacytoma and multiple myeloma: clinicopathological outcome study.

    Science.gov (United States)

    Schwartz, T H; Rhiew, R; Isaacson, S R; Orazi, A; Bruce, J N

    2001-11-01

    Intracranial plasmacytomas are rare lesions that can arise from the calvarium, dura, or cranial base and exhibit a benign course unless associated with myeloma. Attention has recently been focused on the role of the cell adhesion molecules CD56 and CD31 in the pathogenesis of myeloma. No such information is available for intracranial plasmacytomas and myeloma-associated lesions. We investigated the relationship between CD56 and CD31 expression, intracranial location, and progression to myeloma for a series of nine intracranial plasmacytomas (three dural, one calvarial, and five cranial base lesions). These parameters were also correlated with proliferation indices, as assessed by MIB-1 immunostaining of the histological sections. A single pathologist (AO) performed immunohistochemical analyses and reviewed all slides. Intracranial plasmacytomas presented more commonly in female patients (89%). The three dural lesions were CD56- and CD31-negative and exhibited MIB-1 staining of less than 10%; no patient developed myeloma or recurrence. Of the five cranial base lesions, three were CD56-positive, none was CD31-positive, and two exhibited MIB-1 labeling of more than 45%, with plasmablastic morphological features. Compared with other intracranial plasmacytomas, five of five patients with cranial base lesions developed bone marrow biopsy-proven myeloma (P myeloma soon after diagnosis. Both of the two highly proliferative plasmablastic lesions recurred, one after gross total resection without radiotherapy and the other after a biopsy and 2000-cGy radiotherapy. Among intracranial plasmacytomas, cranial base location was the strongest predictor of the development of multiple myeloma. Expression of the cell adhesion molecules CD31 and CD56 was not predictive of outcome. Extramedullary dural-based lesions were CD56-negative and were not associated with myeloma. A high proliferation index and plasmablastic morphological features were predictive of a short time to recurrence

  4. Interferon-alpha in the treatment of multiple myeloma

    DEFF Research Database (Denmark)

    Khoo, T.L.; Joshua, D.; Gibson, J.

    2011-01-01

    Interferons are soluble proteins produced naturally by cells in response to viruses. It has both anti-proliferative and immunomodulating properties and is one of the first examples of a biological response modifier use to treat the hematological malignancy multiple myeloma. Interferon has been used......-induction agent with other chemotherapy regimens, and as maintenance therapy after conventional chemotherapy or complete remission after autologous or allogeneic transplantation. Interferon as a single induction agent or co-induction agent with other chemotherapy agents appears only to have minimal benefit...... in myeloma. Its role as maintenance therapy in the plateau phase of myeloma also remains uncertain. More recently, the use of interferon must now compete with the "new drugs" - thalidomide, lenalidomide and bortezomib in myeloma treatment. Will there be a future role of interferon in the treatment...

  5. Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells

    DEFF Research Database (Denmark)

    Standal, Therese; Seidel, Carina; Hjertner, Øyvind

    2002-01-01

    Multiple myeloma (MM) is a hematologic malignancy characterized by accumulation of plasma cells in the bone marrow (BM). Bone destruction is a complication of the disease and is usually associated with severe morbidity. The balance between receptor activator of nuclear factor-kappaB (NF-kappaB......) ligand and osteoprotegerin (OPG) is of major importance in bone homeostasis. We have recently shown that serum OPG levels are lower in patients with myeloma than in healthy individuals. Here we show that myeloma cells can bind, internalize, and degrade OPG, thereby providing a possible explanation...... for the lower levels of OPG in the BM of patients with MM. This process is dependent on interaction of OPG with heparan sulfates on the myeloma cells. The results suggest a novel biologic mechanism for the bone disease associated with MM and that treatment of the bone disease with OPG lacking the heparin...

  6. The 5T mouse multiple myeloma model: Absence of c-myc oncogene rearrangement in early transplant generations

    NARCIS (Netherlands)

    Radl, J.; Punt, Y.A.; Enden-Vieveen, M.H.M. van den; Bentvelzen, P.A.J.; Bakkus, M.H.C.; Akker T., W. van den; Benner, R.

    1990-01-01

    Consistent chromosomal translocations involving the c-myc cellular oncogene and one of the three immunoglobulin loci are typical for human Burkitt's lymphoma, induced mouse plasmacytoma (MPC) and spontaneously arising rat immunocytoma (RIC). Another plasma cell malignancy, multiple myeloma (MM),

  7. Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy

    DEFF Research Database (Denmark)

    Toftmann Hansen, Charlotte; Pedersen, Per T.; Jensen, Bo Amdi

    Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy.......Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy....

  8. Guidelines for supportive care in multiple myeloma 2011.

    Science.gov (United States)

    Snowden, John A; Ahmedzai, Sam H; Ashcroft, John; D'Sa, Shirley; Littlewood, Timothy; Low, Eric; Lucraft, Helen; Maclean, Rhona; Feyler, Sylvia; Pratt, Guy; Bird, Jennifer M

    2011-07-01

    Supportive care plays an increasingly important role in the modern management of multiple myeloma. While modern treatments have significantly prolonged overall and progression free survival through improved disease control, the vast majority of patients remain incurable, and live with the burden of the disease itself and the cumulative side effects of treatments. Maintenance of quality of life presents challenges at all stages of the disease from diagnosis through the multiple phases of active treatment to the end of life. Written on behalf of the British Committee for Standards in Haematology (BCSH) and the UK Myeloma Forum (UKMF), these evidence based guidelines summarize the current national consensus for supportive and symptomatic care in multiple myeloma in the following areas; pain management, peripheral neuropathy, skeletal complications, infection, anaemia, haemostasis and thrombosis, sedation, fatigue, nausea, vomiting, anorexia, constipation, diarrhoea, mucositis, bisphosphonate-induced osteonecrosis of the jaw, complementary therapies, holistic needs assessment and end of life care. Although most aspects of supportive care can be supervised by haematology teams primarily responsible for patients with multiple myeloma, multidisciplinary collaboration involving specialists in palliative medicine, pain management, radiotherapy and surgical specialities is essential, and guidance is provided for appropriate interdisciplinary referral. These guidelines should be read in conjunction with the BCSH/UKMF Guidelines for the Diagnosis and Management of Multiple Myeloma 2011. © 2011 Blackwell Publishing Ltd.

  9. Late diagnosis of multiple myeloma: a case report

    Science.gov (United States)

    Syahreza, A.; Gatot, D.; Mardia, A. I.

    2018-03-01

    Multiple myeloma is a challenging hematologic case to handle. Sometimes the disease is diagnosed too late for the patient and doctor. Therefore, careful approaches are needed to manage the patient. A 66-year-old mansuffersfrom low back pain since one year before he came to the hospital. He was diagnosed multiple compression fractures by orthopedic and had undergone two surgeries in one year. Punched out lesions werein skull radiology and lumbar compression in lumbar MRI. After further investigation, plasmacytoma and M protein in urine electrophoresis were founded. Significant improvement found after bortezomib and dexamethasone were given.Diagnosis and management of multiple myeloma is a challenge for a doctor. Systematically approach is needed for a patient with a recurrent fracture. Even a novel therapies are not widely available in our country.We reported a late diagnosis of multiple myeloma and had a significant improvement after bortezomib and dexamethasone therapy.

  10. Free light chains of immunoglobulins in the diagnosis and prognosis of multiple myeloma

    Directory of Open Access Journals (Sweden)

    N. V. Lyubimova

    2017-01-01

    Full Text Available Background: Analysis of free light chains of immunoglobulins (FLC in the serum is an effective method in the diagnosis of multiple myeloma. Plasma cells produce two types of FLC: κand λ-FLC. FLC, which are not incorporated into monoclonal intact immunoglobulins, are released into circulation, and then are filtered and reabsorbed in kidneys depending on their molecular weight. Circulating FLC commonly form homodimers, known as Bence-Jones protein, which is a biomarker of Bence-Jones multiple myeloma. According to the international guidelines, the ratio κ/λ FLC is an important diagnostic criterion of multiple myeloma. Aim: To evaluate the diagnostic and prognostic value of serum FLC in multiple myeloma patients. Materials and methods: We examined 118 patients with multiple myeloma, admitted to the Department of Hemoblastosis Chemotherapy of N.N. Blokhin Russian Cancer Research Center from 2010 to 2016, and 68 healthy men and women. Serum concentrations of FLC were measured with an immunoturbidimetric method using the test-system Freelite Human Lambda and Freelite Human Kappa (Binding Site Inc.. Results: The levels of monoclonal κor λ-FLC in patients with G-, A-myeloma and Bence-Jones multiple myeloma were significantly higher than those in the control group (p < 0.005. The diagnostic sensitivity of quantification of FLC and their ratio was 87.3% and 89.8%, and in combination with the use of immune electrophoresis it was close to 100%. Analysis of progression free survival and overall survival showed significant differences (p < 0.04 between the groups of patients according their κ/λ FLC ratio. The basal value of κ/λ FLC ratio of less than 0.04 and more than 140 was a  predictor of unfavorable outcome. Conclusion: The inclusion of the determination of serum FLC into the assessment plan of patients with suspected monoclonal gammapathy makes it possible to increase diagnostic sensitivity of the available methods for paraprotein

  11. Report from the European Myeloma Network on interphase FISH in multiple myeloma and related disorders

    DEFF Research Database (Denmark)

    Ross, Fiona M; Avet-Loiseau, Hervé; Ameye, Geneviève

    2012-01-01

    The European Myeloma Network has organized two workshops on fluorescence in situ hybridization in multiple myeloma. The first aimed to identify specific indications and consensus technical approaches of current practice. A second workshop followed a quality control exercise in which 21 laboratories...... analyzed diagnostic cases of purified plasma cells for recurrent abnormalities. The summary report was discussed at the EHA Myeloma Scientific Working Group Meeting 2010. During the quality control exercise, there was acceptable agreement on more than 1,000 tests. The conclusions from the exercise were...... that the primary clinical applications for FISH analysis were for newly diagnosed cases of MM or frank relapse cases. A range of technical recommendations included: 1) material should be part of the first draw of the aspirate; 2) samples should be sent at suitable times to allow for the lengthy processing...

  12. A compound chimeric antigen receptor strategy for targeting multiple myeloma.

    Science.gov (United States)

    Chen, K H; Wada, M; Pinz, K G; Liu, H; Shuai, X; Chen, X; Yan, L E; Petrov, J C; Salman, H; Senzel, L; Leung, E L H; Jiang, X; Ma, Y

    2018-02-01

    Current clinical outcomes using chimeric-antigen receptors (CARs) against multiple myeloma show promise in the eradication of bulk disease. However, these anti-BCMA (CD269) CARs observe relapse as a common phenomenon after treatment due to the reemergence of either antigen-positive or -negative cells. Hence, the development of improvements in CAR design to target antigen loss and increase effector cell persistency represents a critical need. Here, we report on the anti-tumor activity of a CAR T-cell possessing two complete and independent CAR receptors against the multiple myeloma antigens BCMA and CS1. We determined that the resulting compound CAR (cCAR) T-cell possesses consistent, potent and directed cytotoxicity against each target antigen population. Using multiple mouse models of myeloma and mixed cell populations, we are further able to show superior in vivo survival by directed cytotoxicity against multiple populations compared to a single-expressing CAR T-cell. These findings indicate that compound targeting of BCMA and CS1 on myeloma cells can potentially be an effective strategy for augmenting the response against myeloma bulk disease and for initiation of broader coverage CAR therapy.

  13. Multiple myeloma in a captive lion (Panthera leo

    Directory of Open Access Journals (Sweden)

    Adrian S.W. Tordiffe

    2013-09-01

    Full Text Available Multiple myeloma is a rare, systemic proliferation of neoplastic plasma cells. A case was reported in an 11-year-old male captive lion (Panthera leo at the National Zoological Gardens of South Africa, Pretoria. The classic features of symptomatic multiple myeloma were all evident in this case; namely osteolytic lesions, monoclonal gammopathy in the serum with excretion of monoclonal proteins in the urine, neoplastic plasma cells in the bone marrow and associated renal failure and anaemia. In addition, similar to the common pattern of this disease in domestic felids, at least three extramedullary tumours were found and several organs were infiltrated by neoplastic plasma cells. The cytoplasm of approximately 50%of the neoplastic round cells, including a few giant myeloma cells, stained weakly to strongly using immunohistochemical stains for B-lymphocytes (CD79a. The normal haematological parameters and lack of any osteolytic lesions in the lion at the time of the first evaluation suggest that the primary neoplastic cells could have originated from one of the extramedullary tumour sites. Only two cases of multiple myeloma have previously been reported in captive wild felids. To the authors’ knowledge, there are no case reports of multiple myeloma in lions.

  14. New experimental model of multiple myeloma.

    Science.gov (United States)

    Telegin, G B; Kalinina, A R; Ponomarenko, N A; Ovsepyan, A A; Smirnov, S V; Tsybenko, V V; Homeriki, S G

    2001-06-01

    NSO/1 (P3x63Ay 8Ut) and SP20 myeloma cells were inoculated to BALB/c OlaHsd mice. NSO/1 cells allowed adequate stage-by-stage monitoring of tumor development. The adequacy of this model was confirmed in experiments with conventional cytostatics: prospidium and cytarabine caused necrosis of tumor cells and reduced animal mortality.

  15. Localized cutaneous mucinosis associated with multiple myeloma: A rare presentation

    Directory of Open Access Journals (Sweden)

    Parvaiz Anwar Rather

    2014-01-01

    Full Text Available Lichen myxoedematosus (LM, a form of primary cutaneous mucinosis, may present either as localized less severe form called papular mucinosis or diffuse more severe form called scleromyxoedema. The diffuse form is almost always associated with monoclonal gammopathy, whereas localized form is not. We report an atypical case of localized form of LM associated with multiple myeloma in a 66-year-old male, who presented with asymptomatic waxy papular eruption on extremities, which on histopathological examination confirmed the diagnosis of cutaneous mucinosis. After initially being put on steroids and hydroxychloroquine with minimal improvement, patient subsequently presented with encephalopathy and on evaluation revealed hypernatremia, hypercalcemia, hypergammaglobulinemia, reversal of albumin-globulin (A/G ratio, azotemia, and lytic lesions in skull X-ray. Bone marrow aspiration and biopsy confirmed multiple myeloma. Patient was successfully treated with standard treatment regimen for multiple myeloma with bortezumib and dexamethasone and his skin lesions subsided completely.

  16. Plasma Cell Neoplasms (Including Multiple Myeloma)—Patient Version

    Science.gov (United States)

    Plasma cell neoplasms occur when abnormal plasma cells form cancerous tumors. When there is only one tumor, the disease is called a plasmacytoma. When there are multiple tumors, it is called multiple myeloma. Start here to find information on plasma cell neoplasms treatment, research, and statistics.

  17. Whole body MR in patients with multiple myeloma

    International Nuclear Information System (INIS)

    Piekarek, A.; Sosnowski, P.; Nowicki, A.; Komarnicki, M.

    2009-01-01

    Background: Multiple myeloma is a cancer of plasma cells which leads to bone marrow infiltration. Aim: Whole-body MR is the most sensitive imaging method available to detect multiple myeloma lesions. Ma terial and methods: MR scans were performed in 100 patients with multiple myeloma who were receiving treatment in the Haematology Clinic in Poznan in the years 2005 - 2006. Whole-body MR scans were performed with general coil 1.0 T in STIR sequences and T1 sequences, in coronal and sagittal planes with scanning area covering the head, neck, trunk and the limbs (FOV for specific regions was 36 -48 cm). The bone lesions were classified as focal (monofocal/multifocal lesions), infiltrative, mixed and 'salt and pepper' type. Depending on the size of the lesions the patients were included in one of three groups according to Salmon-Durie Plus classification. Results: Four main types of multiple myeloma were distinguished based on MR scans: focal (48 patients; monofocal in 10 patients), infiltrative (17 patients), mixed type (19 patients) and 'salt and pepper' type (4 patients). The remaining 12 patients had no multiple myeloma lesions in the bone marrow. Additionally, in 18% of patients a soft tissue mass could be observed. According to Salmon-Durie Plus categorisation 27 subjects were classified as having stage I, 16 patients stage and 57 patients stage III disease. In 12% of patients MR data changed the disease staging. Conclusions: WB MR is a sensitive and effective diagnostic method with an important impact on staging and further treatment of multiple myeloma. (authors)

  18. A Case of Mediastinal Extramedullary Plasmacytoma Associated with Multiple Myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Min, Ji Hye; Kim, Tae Sung; Ko, Young Hyeh; Kim, Ki Hyun [Samsung Medical Center, Sungkyunkwan University, Seoul (Korea, Republic of)

    2010-08-15

    Extramedullary plasmacytoma is a rare manifestation of multiple myeloma, and involvement of the mediastinum by extramedullary plasmacytoma is very rare. We report here on a rare case of a large mediastinal extramedullary plasmacytoma and several pleural nodules with pleural effusions in a 45-year-old male patient with multiple myeloma that involved the thoracic spine and the calvarium. The mediastinal extramedullary plasmacytoma manifested on CT as an 11 x 4.5 cm-sized, relatively homogeneous, mildly enhancing, anterior mediastinal mass with several pleural nodules, and this simulated malignant lymphoma or malignant thymic epithelial tumor.

  19. The Imipridone ONC201 Induces Apoptosis and Overcomes Chemotherapy Resistance by Up-Regulation of Bim in Multiple Myeloma.

    Science.gov (United States)

    Tu, Yong-Sheng; He, Jin; Liu, Huan; Lee, Hans C; Wang, Hua; Ishizawa, Jo; Allen, Joshua E; Andreeff, Michael; Orlowski, Robert Z; Davis, Richard E; Yang, Jing

    2017-10-01

    In multiple myeloma, despite recent improvements offered by new therapies, disease relapse and drug resistance still occur in the majority of patients. Therefore, there is an urgent need for new drugs that can overcome drug resistance and prolong patient survival after failure of standard therapies. The imipridone ONC201 causes downstream inactivation of ERK1/2 signaling and has tumoricidal activity against a variety of tumor types, while its efficacy in preclinical models of myeloma remains unclear. In this study, we treated human myeloma cell lines and patient-derived tumor cells with ONC201. Treatment decreased cellular viability and induced apoptosis in myeloma cell lines, with IC50 values of 1 to 1.5 μM, even in those with high risk features or TP53 loss. ONC201 increased levels of the pro-apoptotic protein Bim in myeloma cells, resulting from decreased phosphorylation of degradation-promoting Bim Ser69 by ERK1/2. In addition, myeloma cell lines made resistant to several standard-of-care agents (by chronic exposure) were equally sensitive to ONC201 as their drug-naïve counterparts, and combinations of ONC201 with proteasome inhibitors had synergistic anti-myeloma activity. Overall, these findings demonstrate that ONC201 kills myeloma cells regardless of resistance to standard-of-care therapies, making it promising for clinical testing in relapsed/refractory myeloma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. The Imipridone ONC201 Induces Apoptosis and Overcomes Chemotherapy Resistance by Up-Regulation of Bim in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Yong-sheng Tu

    2017-10-01

    Full Text Available In multiple myeloma, despite recent improvements offered by new therapies, disease relapse and drug resistance still occur in the majority of patients. Therefore, there is an urgent need for new drugs that can overcome drug resistance and prolong patient survival after failure of standard therapies. The imipridone ONC201 causes downstream inactivation of ERK1/2 signaling and has tumoricidal activity against a variety of tumor types, while its efficacy in preclinical models of myeloma remains unclear. In this study, we treated human myeloma cell lines and patient-derived tumor cells with ONC201. Treatment decreased cellular viability and induced apoptosis in myeloma cell lines, with IC50 values of 1 to 1.5 μM, even in those with high risk features or TP53 loss. ONC201 increased levels of the pro-apoptotic protein Bim in myeloma cells, resulting from decreased phosphorylation of degradation-promoting Bim Ser69 by ERK1/2. In addition, myeloma cell lines made resistant to several standard-of-care agents (by chronic exposure were equally sensitive to ONC201 as their drug-naïve counterparts, and combinations of ONC201 with proteasome inhibitors had synergistic anti-myeloma activity. Overall, these findings demonstrate that ONC201 kills myeloma cells regardless of resistance to standard-of-care therapies, making it promising for clinical testing in relapsed/refractory myeloma.

  1. Clinical Application of {sup 18}F-FDG PET in Multiple Myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Su Jin; Choi, Joon Young [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2009-12-15

    This review focuses on the clinical use of {sup 18}F-FDG PET to evaluate multiple myeloma. {sup 18}F-FDG PET is useful for diagnosis, staging of multiple myeloma and differential diagnosis of myeloma related disease such as monoclonal gammopathy of undetermined significance or plasmacytoma. For therapy response, {sup 18}F-FDG PET may be effective after chemotherapy for multiple myeloma and radiotherapy for plasmacytoma.

  2. Clinical Application of 18F-FDG PET in Multiple Myeloma

    International Nuclear Information System (INIS)

    Lee, Su Jin; Choi, Joon Young

    2009-01-01

    This review focuses on the clinical use of 18 F-FDG PET to evaluate multiple myeloma. 18 F-FDG PET is useful for diagnosis, staging of multiple myeloma and differential diagnosis of myeloma related disease such as monoclonal gammopathy of undetermined significance or plasmacytoma. For therapy response, 18 F-FDG PET may be effective after chemotherapy for multiple myeloma and radiotherapy for plasmacytoma

  3. Sarcoidosis and multiple myeloma: Concurrent presentation of an unusual association

    Directory of Open Access Journals (Sweden)

    Vidya Nair

    2016-01-01

    Full Text Available Literature on concurrent association of sarcoidosis with lymphoproliferative malignancies other than lymphoma e.g. multiple myeloma is meager. The rarity of the situation prompted us to report this patient who was a 51-year-old woman with a 2-years history of breathlessness, cough with expectoration, chest pain and backache. Initial evaluation revealed mild anemia, increased alkaline phosphatase with chest skiagram showing both lower zone non homogenous opacities with calcified hilar lymph nodes. CECT chest showed mediastinal with bilateral hilar lymphadenopathy, parenchymal fibrosis, traction bronchiectasis, ground glass opacities, septal and peribronchovascular thickening affecting mid and lower lung zones bilaterally. MRI Dorsolumbar spine was suggestive of marrow infiltrative disorder. EBUS FNA of intrathoracic nodes, EBB and TBLB confirmed sarcoidosis. PET CT revealed hyper metabolic activity in lung, multiple lymph nodes and lytic bone lesions. Serum protein electrophoresis and immunofixation revealed a monoclonal paraprotein, immunoglobulin IgG kappa type. Bone marrow biopsy revealed an increase in plasma cells (15%, but no granulomas. Diagnosis of Indolent or multiple myeloma with sarcoidosis was established. 12 cases of sarcoidosis and multiple myeloma have been reported in literature, and mostly preceding the onset of multiple myeloma by many years, in our case both were diagnosed concurrently.

  4. Alpha-particles induce autophagy in multiple myeloma cells

    Directory of Open Access Journals (Sweden)

    Joelle Marcelle Gaschet

    2015-10-01

    Full Text Available Objectives: Radiations emitted by the radionuclides in radioimmunotherapy (RIT approaches induce direct killing of the targeted cells as well as indirect killing through bystander effect. Our research group is dedicated to the development of α-RIT, i.e RIT using α-particles especially for the treatment of multiple myeloma (MM. γ-irradiation and β-irradiation have been shown to trigger apoptosis in tumor cells. Cell death mode induced by 213Bi α-irradiation appears more controversial. We therefore decided to investigate the effects of 213Bi on MM cell radiobiology, notably cell death mechanisms as well as tumor cell immunogenicity after irradiation.Methods: Murine 5T33 and human LP-1 multiple myeloma (MM cell lines were used to study the effects of such α-particles. We first examined the effects of 213Bi on proliferation rate, double strand DNA breaks, cell cycle and cell death. Then, we investigated autophagy after 213Bi irradiation. Finally, a co-culture of dendritic cells (DC with irradiated tumour cells or their culture media was performed to test whether it would induce DC activation.Results: We showed that 213Bi induces DNA double strand breaks, cell cycle arrest and autophagy in both cell lines but we detected only slight levels of early apoptosis within the 120 hours following irradiation in 5T33 and LP-1. Inhibition of autophagy prevented 213Bi induced inhibition of proliferation in LP-1 suggesting that this mechanism is involved in cell death after irradiation. We then assessed the immunogenicity of irradiated cells and found that irradiated LP-1 can activate DC through the secretion of soluble factor(s, however no increase in membrane or extracellular expression of danger associated molecular patterns (DAMPs was observed after irradiation.Conclusion: This study demonstrates that 213Bi induces mainly necrosis in MM cells, low levels of apoptosis and also autophagy that might be involved in tumor cell death.

  5. MR imaging studies of multiple myeloma in the vertebral column

    International Nuclear Information System (INIS)

    Albert, S.; Leeds, N.E.

    1990-01-01

    This paper studies the sensitivity and characteristics of MR imaging in the diagnosis of myeloma in the vertebral column. The cervical, thoracic, and lumbar spines of 12 patients with known multiple myeloma were imaged with small flip angle, fast gradient-echo, proton-density (FPD) as well as spin-echo T1-weighted, T2-weighted, and intermediate (SE 2,000/20-30) imaging. The FPD images were acquired with pulse sequence gradient recalled acquisition in a steady state at a magnetic field strength of 1.5T with use of a license-plate and a circular surface coil

  6. Sequential hemi-body radiotherapy in advanced multiple myeloma

    International Nuclear Information System (INIS)

    Jaffe, J.P.; Bosch, A.; Raich, P.C.

    1979-01-01

    Eleven patients with advanced multiple myeloma refractory to standard chemotherapy were treated with a regimen of sequential hemi-body radiotherapy consisting of 800 rad midplane in a single dose to each half. 9/10 patients experienced significant relief of skeletal pain and there were 5/11 objective tumor responses with one complete remission. Treatment-related morbidity was significant and consisted primarily of nausea and emesis, bone marrow suppression, and pneumonitis. This therapy is helpful in the management of advanced myeloma, and should be studied earlier in the course of the disease

  7. European perspective on multiple myeloma treatment stratgies in 2014

    DEFF Research Database (Denmark)

    Ludwig, Heinz; Sonneveld, Pieter; Davies, Faith

    2014-01-01

    The treatment of multiple myeloma has undergone significant changes and has resulted in the achievement of molecular remissions, the prolongation of remission duration, and extended survival becoming realistic goals, with a cure being possible in a small but growing number of patients. In addition...... recommendations for the management of patients with myeloma. Treatment approaches depend on "fitness," with chronological age still being an important discriminator for selecting therapy. In younger, fit patients, a short three drug-based induction treatment followed by autologous stem cell transplantation (ASCT...

  8. Nephrogenic Diabetes Insipidus: A Rare Presentation in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Mehdi Dehghani

    2012-04-01

    Full Text Available We report a case of multiple myeloma that presented with anorexia, fatigue, high erythrocyte sedimentation rate, bone marrow plasmacytosis of more than 30%, polyuria,and low urine specific gravity. This unusual presentation was diagnosed as nephrogenic diabetes insipidus secondary to a proximal tubular dysfunction. The tubular functional disturbance appeared to be related to thepresence of lambda-type light chains. The patient was treated withdesmopressine without response. After one month of treatment with thalidomide and dexamethasone for myeloma there was a dramatic response with decreased urine output.

  9. Multiple myeloma on polycythemia vera following radioactive phosphorus therapy

    International Nuclear Information System (INIS)

    West, W.O.

    1976-01-01

    A 74-year-old white man with established polycythemia vera was treated with radioactive phosphorus after phlebotomies alone failed to control his disease. About 2 3 / 4 years later he died of multiple myeloma. The mutagenic effect of radioactive phosphorus may have caused or possibly accelerated preexisting myeloma. Basic nonmalignant disease deserves careful consideration before radiation or radiomimetic agents are used. One might consider a probably less mutagenic drug such as hydroxyurea in patients with polycythemia vera when phlebotomy alone does not give good control of red cell mass and thrombocytosis

  10. Iodine-based contrast media, multiple myeloma and monoclonal gammopathies

    DEFF Research Database (Denmark)

    Stacul, Fulvio; Bertolotto, Michele; Thomsen, Henrik S

    2018-01-01

    OBJECTIVES: Many radiologists and clinicians still consider multiple myeloma (MM) and monoclonal gammopathies (MG) a contraindication for using iodine-based contrast media. The ESUR Contrast Media Safety Committee performed a systematic review of the incidence of post-contrast acute kidney injury...

  11. Multiple myeloma presenting as CEA-producing rectal cancer.

    Science.gov (United States)

    Talamo, Giampaolo; Barochia, Amitkumar; Zangari, Maurizio; Loughran, Thomas P

    2010-03-31

    We report the case of a 57-year-old patient with multiple myeloma, characterized by extramedullary involvement of the rectum at presentation. Malignant plasma cells were found to produce carcinoembryonic antigen (CEA), a tumor antigen more commonly associated with rectal adenocarcinomas.

  12. Multiple myeloma presenting as CEA-producing rectal cancer

    Directory of Open Access Journals (Sweden)

    Giampaolo Talamo

    2010-03-01

    Full Text Available We report the case of a 57-year old patient with multiple myeloma, characterized by extramedullary involvement of the rectum at presentation. Malignant plasma cells were found to produce carcinoembryonic antigen (CEA, a tumor antigen more commonly associated with rectal adenocarcinomas.

  13. Serum galectin-1 in patients with multiple myeloma

    DEFF Research Database (Denmark)

    Andersen, Morten Nørgaard; Ludvigsen, Maja; Abildgaard, Niels

    2017-01-01

    with worse disease state or poor outcome. Gal-1 can be secreted from cells by an unknown mechanism, and levels in blood samples were associated with high tumor burden and worse disease state in cHL and CLL patients. However, serum levels of Gal-1 have never been investigated in patients with multiple myeloma...

  14. Chest wall tumor at relapse of multiple myeloma | Tazi | African ...

    African Journals Online (AJOL)

    We report the case of a 70-year-old Moroccan man who was diagnosed with stage IIIA IgA kappa multiple myeloma according to Durie and Salmon classification. He was an alcohol abuser and heavy smoker (2 packs per day). He was admitted to our department for thoracic pain, persistent and increasing. He also ...

  15. Aberrant microRNA expression in multiple myeloma

    DEFF Research Database (Denmark)

    Dimopoulos, Konstantinos; Gimsing, Peter; Grønbæk, Kirsten

    2013-01-01

    Multiple myeloma (MM) is a devastating disease with a complex biology, and in spite of improved survivability by novel treatment strategies over the last decade, MM is still incurable by current therapy. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression at a post...

  16. Multiple myeloma in Nigeria: An insight to the clinical, laboratory ...

    African Journals Online (AJOL)

    ... the clinician to investigate along the lines of MM. Majority of patients have osteolytic lesions on X‑ray and pathological fractures, and benefit from melphalan based combinations in situations where facilities for transplant are not available. Key words: Clinical features, chemotherapy, laboratory features, multiple myeloma, ...

  17. Expression of Mucin-1 in multiple myeloma and its precursors

    DEFF Research Database (Denmark)

    Andrulis, Mindaugas; Ellert, Elena; Mandel, Ulla

    2014-01-01

    AIMS: Recent reports suggest a possible role for extracellular (MUC1N) and transmembrane (MUC1C) subunits of Mucin 1 (MUC1) in the pathogenesis of multiple myeloma (MM). Nuclear translocation of MUC1C is involved in activation of various oncogenic signalling pathways and both MUC1 subunits...

  18. Measuring the frailty index of multiple myeloma cancer patients

    DEFF Research Database (Denmark)

    Corradini, Andrea; Bøgelund Hansen, Martin; Savic, Toma

    2016-01-01

    We report on a responsive web-based application that we have been developing for the cancer hospital in Vejle, Denmark. The application administers and handles systematic frailty scoring of patients with multiple myeloma and helps doctors make a more efficient and effective treatment choice. The ...

  19. Cytogenetic findings in mouse multiple myeloma and Waldenstrom's macroglobulinemia

    NARCIS (Netherlands)

    vandenAkker, TW; Radl, J; FrankenPostma, E; Hagemeijer, A

    Multiple myeloma (MM) and Waldenstrom's macroglobulinemia-like lymphoma (MW) appear spontaneously in C57BL/KaLwRij mice at a frequency of 0.5% and 0.2%, respectively, They can readily be propagated by intravenous transfer of mainly bone marrow or spleen cells into syngeneic recipients. Previous

  20. Magnetic resonance imaging of the spine in multiple myeloma

    International Nuclear Information System (INIS)

    Tanaka, Masato; Nakahara, Shinnosuke; Koura, Hiroshi; Kai, Nobuo; Asaumi, Koji; Tanaka, Shunsuke; Sezaki, Tatsuo; Fukuda, Shunichi; Sunami, Kazutaka

    2000-01-01

    The characteristics of diagnostic imaging of the spine in multiple myeloma were examined. Twenty-one patients with stage II-III multiple myeloma (male=12, female=9, mean age=64) underwent MRI of the spine. Other diagnostic imaging modalities used in these patients included, CT bone scintigraphy, and radiography. All images of the spine were assessed and compared with the MRI images. The type of progression was evaluated based on the tumor distribution classification established by Sezaki. T1-weighted images of all 21 patients showed low signals in vertebral bodies, including 14 cases with a focal low signal intensity and 7 cases with diffuse low signal intensity. On the T2-weighted images, 15 of the 21 cases (71%) showed equivalent signals, while T2*-weighted images obtained by the field-echo method yielded high signals in 10 out of 11 cases. It was difficult to differentiate between senile osteoporosis and multiple myeloma by MRI, but CT images clearly distinguished between them. The results suggested that fat-suppressive T1-contrast images and T2*-weighted images are useful in detecting lesions, especially focal low signal intensity lesions. Patients with the multiple-lesion-tumor type of disease were more likely to develop paralysis more than those with the diffuse myeloproliferative type. Thus, the tumor distribution classification established by Sezaki was useful in considering radiotherapy for the treatment of patients at risk of paralysis. Bone scintigraphy revealed accumulation only in spinal lesions caused by compression fractures, while CT appeared to be useful in localizing the diffuse myeloproliferative type of lesions. The problems associated with diagnosis by MRI are differentiation of multiple myeloma from senile osteoporosis and metastatic bone tumors of the spine. There are few specific findings in multiple myeloma. (K.H.)

  1. Daratumumab: a first-in-class CD38 monoclonal antibody for the treatment of multiple myeloma

    Directory of Open Access Journals (Sweden)

    Larysa Sanchez

    2016-06-01

    Full Text Available Abstract Daratumumab is a human monoclonal antibody that targets CD38, a cell surface protein that is overexpressed on multiple myeloma (MM cells. Preclinical studies have shown that daratumumab induces MM cell death through several mechanisms, including complement-dependent cytotoxicity (CDC, antibody-dependent cell-mediated cytotoxicity (ADCC, antibody-dependent cellular phagocytosis (ADCP, and apoptosis. Given the encouraging efficacy and acceptable safety profile of daratumumab demonstrated in clinical trials, daratumumab has emerged as a novel treatment option for myeloma and became the first monoclonal antibody approved by the FDA for the treatment of MM.

  2. Young Adult and Usual Adult Body Mass Index and Multiple Myeloma Risk: A Pooled Analysis in the International Multiple Myeloma Consortium (IMMC).

    Science.gov (United States)

    Birmann, Brenda M; Andreotti, Gabriella; De Roos, Anneclaire J; Camp, Nicola J; Chiu, Brian C H; Spinelli, John J; Becker, Nikolaus; Benhaim-Luzon, Véronique; Bhatti, Parveen; Boffetta, Paolo; Brennan, Paul; Brown, Elizabeth E; Cocco, Pierluigi; Costas, Laura; Cozen, Wendy; de Sanjosé, Silvia; Foretová, Lenka; Giles, Graham G; Maynadié, Marc; Moysich, Kirsten; Nieters, Alexandra; Staines, Anthony; Tricot, Guido; Weisenburger, Dennis; Zhang, Yawei; Baris, Dalsu; Purdue, Mark P

    2017-06-01

    Background: Multiple myeloma risk increases with higher adult body mass index (BMI). Emerging evidence also supports an association of young adult BMI with multiple myeloma. We undertook a pooled analysis of eight case-control studies to further evaluate anthropometric multiple myeloma risk factors, including young adult BMI. Methods: We conducted multivariable logistic regression analysis of usual adult anthropometric measures of 2,318 multiple myeloma cases and 9,609 controls, and of young adult BMI (age 25 or 30 years) for 1,164 cases and 3,629 controls. Results: In the pooled sample, multiple myeloma risk was positively associated with usual adult BMI; risk increased 9% per 5-kg/m 2 increase in BMI [OR, 1.09; 95% confidence interval (CI), 1.04-1.14; P = 0.007]. We observed significant heterogeneity by study design ( P = 0.04), noting the BMI-multiple myeloma association only for population-based studies ( P trend = 0.0003). Young adult BMI was also positively associated with multiple myeloma (per 5-kg/m 2 ; OR, 1.2; 95% CI, 1.1-1.3; P = 0.0002). Furthermore, we observed strong evidence of interaction between younger and usual adult BMI ( P interaction adult BMI may increase multiple myeloma risk and suggest that healthy BMI maintenance throughout life may confer an added benefit of multiple myeloma prevention. Cancer Epidemiol Biomarkers Prev; 26(6); 876-85. ©2017 AACR . ©2017 American Association for Cancer Research.

  3. Holistic needs assessment in advanced, intensively treated multiple myeloma patients.

    Science.gov (United States)

    Boland, E G; Boland, J W; Ezaydi, Y; Greenfield, D M; Ahmedzai, S H; Snowden, J A

    2014-10-01

    It is recommended that patients with multiple myeloma should be assessed for unmet holistic needs at key times in their disease trajectory. The aim of this exploratory study was to characterise the holistic needs of advanced, intensively treated multiple myeloma using a structured assessment tool. Patients with multiple myeloma who had undergone a haematopoietic stem cell transplantation and subsequent treatment for at least one episode of progressive disease but were in stable plateau phase were included in the study. Patients' holistic needs were assessed using the self-reporting tool, Sheffield Profile for Assessment and Referral for Care (SPARC). Thirty-two patients with a median age of 60 years at assessment and a median of 5.5 years from diagnosis were recruited. Using the SPARC, half of the patients reported tiredness as 'quite a bit/very much,' while one third complained that daytime somnolence and insomnia were 'quite a bit/very much.' Forty-four percent of patients reported pain. One third of patients were bothered and distressed by the side effects from their treatment and were worried about long-term effects of their treatment. Thirty-one percent of patients felt that the effect of their condition had an impact on their sexual life, and 40 % were worried about the effect that their illness was having on their family or other people. This is the first study to use a self-reported holistic needs assessment tool in multiple myeloma. A multidimensional structured questionnaire like the SPARC could provide a useful first step in the effective delivery of supportive and palliative care for patients with multiple myeloma.

  4. Hypophosphatemic osteomalacia: an unusual clinical presentation of multiple myeloma.

    Science.gov (United States)

    Reyskens, M; Sleurs, K; Verresen, L; Janssen, M; van den Bergh, J; van den Berg, J; Geusens, P

    2015-07-01

    An unusual case of a 75-year-old man is presented who had multiple stress fractures due to adult onset hypophosphatemic osteomalacia, which was the result of Fanconi syndrome, with light chain cast proximal tubulopathy due to multiple myeloma. A 75-year-old man presented with diffuse pain and muscle weakness. He had multiple stress fractures, low serum phosphate, decreased renal tubular reabsorption of phosphate, and normal PTH and FGF23, indicating adult onset hypophosphatemic osteomalacia. Phosphate supplements with calcitriol resulted in clinical recovery and healing of stress fractures. Because of proteinuria, a renal biopsy was performed that revealed Fanconi syndrome with light chain cast proximal tubulopathy and light kappa chains were found in serum and urine. A bone biopsy confirmed the diagnosis of multiple myeloma, and treatment with chemotherapy resulted in cytological and clinical recovery.

  5. Apigenin inhibits proliferation and induces apoptosis in human multiple myeloma cells through targeting the trinity of CK2, Cdc37 and Hsp90

    Directory of Open Access Journals (Sweden)

    Xu Yuan-Ji

    2011-08-01

    Full Text Available Abstract Background Multiple myeloma (MM is a B-cell malignancy that is largely incurable and is characterized by the accumulation of malignant plasma cells in the bone marrow. Apigenin, a common flavonoid, has been reported to suppress proliferation in a wide variety of solid tumors and hematological cancers; however its mechanism is not well understood and its effect on MM cells has not been determined. Results In this study, we investigated the effects of apigenin on MM cell lines and on primary MM cells. Cell viability assays demonstrated that apigenin exhibited cytotoxicity against both MM cell lines and primary MM cells but not against normal peripheral blood mononuclear cells. Together, kinase assays, immunoprecipitation and western blot analysis showed that apigenin inhibited CK2 kinase activity, decreased phosphorylation of Cdc37, disassociated the Hsp90/Cdc37/client complex and induced the degradation of multiple kinase clients, including RIP1, Src, Raf-1, Cdk4 and AKT. By depleting these kinases, apigenin suppressed both constitutive and inducible activation of STAT3, ERK, AKT and NF-κB. The treatment also downregulated the expression of the antiapoptotic proteins Mcl-1, Bcl-2, Bcl-xL, XIAP and Survivin, which ultimately induced apoptosis in MM cells. In addition, apigenin had a greater effects in depleting Hsp90 clients when used in combination with the Hsp90 inhibitor geldanamycin and the histone deacetylase inhibitor vorinostat. Conclusions Our results suggest that the primary mechanisms by which apigenin kill MM cells is by targeting the trinity of CK2-Cdc37-Hsp90, and this observation reveals the therapeutic potential of apigenin in treating multiple myeloma.

  6. Evolutionary Dynamics of Tumor-Stroma Interactions in Multiple Myeloma.

    Directory of Open Access Journals (Sweden)

    Javad Salimi Sartakhti

    Full Text Available Cancer cells and stromal cells cooperate by exchanging diffusible factors that sustain tumor growth, a form of frequency-dependent selection that can be studied in the framework of evolutionary game theory. In the case of multiple myeloma, three types of cells (malignant plasma cells, osteoblasts and osteoclasts exchange growth factors with different effects, and tumor-stroma interactions have been analysed using a model of cooperation with pairwise interactions. Here we show that a model in which growth factors have autocrine and paracrine effects on multiple cells, a more realistic assumption for tumor-stroma interactions, leads to different results, with implications for disease progression and treatment. In particular, the model reveals that reducing the number of malignant plasma cells below a critical threshold can lead to their extinction and thus to restore a healthy balance between osteoclast and osteoblast, a result in line with current therapies against multiple myeloma.

  7. Metastatic Breast Cancer or Multiple Myeloma? Camouflage by Lytic Lesions

    Directory of Open Access Journals (Sweden)

    Bruce Hough

    2010-01-01

    Full Text Available We report a case of a female with stage I infiltrating ductal carcinoma who received adjuvant therapy including trastuzumab. One year later she developed lytic lesions and was retreated with trastuzumab that was held after she developed symptomatic heart failure. Lytic lesions were attributed to relapse of breast cancer, and cardiac failure attributed to prior trastuzumab therapy. After complications necessitated multiple hospitalizations, a further workup revealed that the lytic lesions were not metastatic breast cancer but multiple myeloma. Her advanced multiple myeloma was associated with systemic amyloidosis involving gut and heart, which ultimately led to her demise. This report addresses the pitfalls of overlapping symptoms and the question of which patients with suspected metastatic disease should undergo a biopsy.

  8. Modern imaging techniques in patients with multiple myeloma

    International Nuclear Information System (INIS)

    Bannas, Peter; Adam, G.; Derlin, T.; Kroeger, N.

    2013-01-01

    Imaging studies are essential for both diagnosis and initial staging of multiple myeloma, as well as for differentiation from other monoclonal plasma cell diseases. Apart from conventional radiography, a variety of newer imaging modalities including whole-body low-dose-CT, whole-body MRI and 18F-FDG PET/CT may be used for detection of osseous and extraosseous myeloma manifestations. Despite of known limitations such as limited sensitivity and specificity and the inability to detect extraosseous lesions, conventional radiography still remains the gold standard for staging newly diagnosed myeloma, partly due to its wide availability and low costs. Whole-body low-dose CT is increasingly used due to its higher sensitivity for the detection of osseous lesions and its ability to diagnose extraosseous lesions, and is replacing conventional radiography at selected centres. The highest sensitivity for both detection of bone marrow disease and extraosseous lesions can be achieved with whole-body MRI or 18F-FDG PET/CT. Diffuse bone marrow infiltration may be visualized by whole-body MRI with high sensitivity. Whole-body MRI is at least recommended in all patients with normal conventional radiography and in all patients with an apparently solitary plasmacytoma of bone. To obtain the most precise readings, optimized examination protocols and dedicated radiologists and nuclear medicine physicians familiar with the complex and variable morphologies of myeloma lesions are required. (orig.)

  9. Effects of short-hairpin RNA-inhibited {beta}-catenin expression on the growth of human multiple myeloma cells in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Wenqing, E-mail: liangwenqing_1234@126.com [Department of Orthopaedics, Shaoxing People' s Hospital, 568 Zhongxing North Road, Shaoxing 312000 (China); Yang, Chengwei [Department of Spinal Surgery, Lanzhou General Hospital, Lanzhou Military Area Command, 333 Nanbinhe Road, Lanzhou 730050 (China); Qian, Yu [Department of Orthopaedics, Shaoxing People' s Hospital, 568 Zhongxing North Road, Shaoxing 312000 (China); Fu, Qiang, E-mail: chyygklwq@hotmail.com [Department of Orthopaedics, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433 (China)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer {beta}-Catenin expression were markedly down-regulated by CTNNB1 shRNA. Black-Right-Pointing-Pointer CTNNB1 shRNA could inhibit the proliferation of RPMI8226 cells. Black-Right-Pointing-Pointer Significantly profound apoptotic cell death in CTNNB1 shRNA cells. Black-Right-Pointing-Pointer In vivo, CTNNB1 silence led to a growth inhibition of myeloma growth. Black-Right-Pointing-Pointer c-myc and {beta}-catenin in the expression cells of cleaved caspase-3 were increased. -- Abstract: Multiple myeloma (MM) is thrombogenic as a consequence of multiple hemostatic effects. Overexpression of {beta}-catenin has been observed in several types of malignant tumors, including MM. However, the relationship between {beta}-catenin expression and MM remains unclear. In the present study, RNA interference was used to inhibit {beta}-catenin expression in RPMI8226 cells. RT-PCR and Western blotting analyses showed that {beta}-catenin mRNA and protein expression were markedly down-regulated by CTNNB1 shRNA. Western blotting showed that the protein levels of cyclin D1 and glutamine synthetase were downregulated and supported the transcriptional regulatory function of {beta}-catenin. The MTT assay showed that CTNNB1 shRNA could have significant inhibitory effects on the proliferation of RPMI8226 cells. The TOPflash reporter assay demonstrated significant downregulation after CTNNB1 shRNA transfection in RPMI8226 cells. Flow cytometric analyses also showed significantly profound apoptosis in CTNNB1 shRNA cells. We found CTNNB1 silence led to growth inhibition of MM growth in vivo. Immunohistochemical analyses showed that c-myc and {beta}-catenin were reduced in CTNNB1 shRNA tumor tissues, but that expression of cleaved caspase-3 was increased. These results show that {beta}-catenin could be a new therapeutic agent that targets the biology of MM cells.

  10. Association between diffuse idiopathic skeletal hyperostosis and multiple myeloma

    International Nuclear Information System (INIS)

    Scutellari, P.N.; Orzincolo, C.D.; Castaldi, G.

    1995-01-01

    Radiologic studies were performed over a 26-month period in a series of 97 consecutive patients with multiple myeloma (56 male and 41 female, aged 42-91 years). Both myelomatous bone lesions and hyperostosis similar to DISH were found in these patients. The prevalence of DISH in association with multiple myeloma (21 male and 8 females patients) was higher (29.8%) than in our control group (973 patients, 449 male and 524 female) or in the general population (15-20%). The involved segments of the column were thoracic in 11 males and 7 females, cervical in 8 males and 2 females, and lumbar in 5 males and 4 females. Ossifying enthesopathy in the pelvis (''whiskering'') was observed in 7 males and 1 female. (orig./MG)

  11. Association between diffuse idiopathic skeletal hyperostosis and multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Scutellari, P.N. [Inst. of Radiology, Ferrara Univ. School of Medicine (Italy); Orzincolo, C.D. [Dept. of Radiology, St. Anna Hospital, Ferrara (Italy); Castaldi, G. [Dept. of Medicine, St. Maria delle Croci Hospital, Ravenna (Italy)

    1995-10-01

    Radiologic studies were performed over a 26-month period in a series of 97 consecutive patients with multiple myeloma (56 male and 41 female, aged 42-91 years). Both myelomatous bone lesions and hyperostosis similar to DISH were found in these patients. The prevalence of DISH in association with multiple myeloma (21 male and 8 females patients) was higher (29.8%) than in our control group (973 patients, 449 male and 524 female) or in the general population (15-20%). The involved segments of the column were thoracic in 11 males and 7 females, cervical in 8 males and 2 females, and lumbar in 5 males and 4 females. Ossifying enthesopathy in the pelvis (``whiskering``) was observed in 7 males and 1 female. (orig./MG)

  12. Whole bone marrow irradiation for the treatment of multiple myeloma

    International Nuclear Information System (INIS)

    Coleman, M.; Saletan, S.; Wolf, D.; Nisce, L.; Wasser, J.; McIntyre, O.R.; Tulloh, M.

    1982-01-01

    Nine patients with multiple myeloma were treated with whole bone marrow irradiation. Six had heavily pretreated disease refractory to chemotherapy. Three had stable disease lightly pretreated by chemotherapy. A modification of the ''three and two'' total nodal radiation technique was employed. Although varying and often severe treatment related cytopenia occurred, infectious complications, clinical bleeding, and nonhematalogic complications were minimal. Five of nine patients showed a decrease in monoclonal protein components, and one showed an increase during treatment. These preliminary results indicate that a reduction of tumor cell burden may occur in patients following whole bone marrow irradiation and that the technique is feasible. Whole bone marrow irradiation combined with chemotherapy represents a new conceptual therapeutic approach for multiple myeloma

  13. Extraosseous Multiple Myeloma with Retroperitoneal Manifestation: A Case Report

    International Nuclear Information System (INIS)

    Berdugo, Juan Oswaldo; Nieto, Sonia Janeth; Garzon, Julian Gonzalo

    2008-01-01

    This paper presents a case of a 57 years old man (patient of Hospital Militar Central of Bogota, Colombia) with weight loss and a mass in the right clavicle. Plain film radiography shows a lytic lesion in the sternum side of the clavicle. biopsy reports a plasmacytomas, radiotherapy was performed. Three years later lesions of similar characteristics within ribs and a focal lesion in left testicle were detected. The diagnosis was multiple myeloma, Chemotherapy and orquidectomy were performed. One year after, patient complained of diffuse abdominal pain and loss weight, contrast abdominal CT was performed. Computed tomography showed a left heterogeneous mass with irregular contours that involved the retroperitoneal space occupying its three compartments. Biopsy was performed and reported pleomorphicplasmocytic proliferation with nuclear enlargement and hyperchromic nuclei consistent with multiple myeloma with abdominal involvement.

  14. Multiple myeloma: Results of radiotherapy in skeletal lesions

    International Nuclear Information System (INIS)

    Budach, V.; Hueltenschmidt, B.; Stuschke, M.; Stueben, G.; Sack, H.; Bamberg, M.

    1991-01-01

    In this retrospective study the records of 157 patients with the diagnosis of multiple myeloma were evaluated with regard to subjective pain relief after a series of radiation therapy at 389 local sites. The most frequently treated region was the spine (50.2%), followed by the thoracic wall (17.9%) and the upper and lower extremities (17.8%). The median survival after diagnosis of all patients was 36 months. 88.4% of all treated sites showed good to moderate response in terms of pain remission after irradiation. It is shown that pain relief is significantly dependent on the total dose but independent of the dose per fraction. A total dose of 30 Gy in two weeks (5x3 Gy/week) is recommended as a well tolerated and reasonable treatment option to achieve maximum palliation and minimum hospitalization time for patients in whom multiple myeloma is diagnosed. (orig.) [de

  15. Pathological study of multiple myeloma in atomic bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Takaki, Y.; Kishikawa, M.; Bundo, K. (Nagasaki Univ. (Japan). School of Medicine)

    1980-11-01

    Pathological records of autopsies carried out in Nagasaki from '46 to '77 were reviewed. Of 9331 autopsies, 5787 were unexposed cases and were used as a control. 9.2% of the deaths were due to hematologic disorders. There was no evidence that the incidence of multiple myeloma among a-bomb survivors increased compared with the control. The incidences of leukemia, lymphoma and aplastic anemia were also listed.

  16. Spontaneous acute subdural hematoma in a patient with multiple myeloma

    Directory of Open Access Journals (Sweden)

    Abrar Ahad Wani

    2012-01-01

    Full Text Available Acute spontaneous subdural hematoma in a patient of multiple myeloma receiving chemotherapy is an unknown event, needing an urgent neurosurgical management. We report this patient who presented with progressive neurological deterioration and a low platelet count. She was successfully managed by craniotomy and evacuation of subdural hematoma with intraoperative transfusion of platelets. The acute spontaneous subdural hematoma in her was probably related to the bleeding diathesis due to thrombocytopenia associated with chemotherapy.

  17. Risk of vertebral compression fractures in multiple myeloma patients

    OpenAIRE

    Anitha, D.; Thomas, Baum; Jan, Kirschke S.; Subburaj, Karupppasamy

    2017-01-01

    Abstract The purpose of this study was to develop and validate a finite element (FE) model to predict vertebral bone strength in vitro using multidetector computed tomography (MDCT) images in multiple myeloma (MM) patients, to serve as a complementing tool to assess fracture risk. In addition, it also aims to differentiate MM patients with and without vertebral compression fractures (VCFs) by performing FE analysis on vertebra segments (T1?L5) obtained from in vivo routine MDCT imaging scans....

  18. Rheumatic polymyalgia like presentation of multiple myeloma and amyloidosis

    International Nuclear Information System (INIS)

    Medina, Yimy F; Martinez, Jose Bernardo; Restrepo, Jose Felix; Rondon, Federico; Iglesias Gamarra, Antonio

    2005-01-01

    Polymyalgia rheumatica is a disorder with defined clinical characteristics and may be the initial expression or to be associated to other diseases. Although it is not associated to neoplastic diseases, may be their initial manifestation. We report a patient who presented the initial complaining of polymyalgia rheumatica as a manifestation of another illness, amyloidosis associated to multiple myeloma. We also discuss the clinical characteristics of these entities and revised the available literature with regard to this association

  19. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma.

    Science.gov (United States)

    Stewart, A Keith; Rajkumar, S Vincent; Dimopoulos, Meletios A; Masszi, Tamás; Špička, Ivan; Oriol, Albert; Hájek, Roman; Rosiñol, Laura; Siegel, David S; Mihaylov, Georgi G; Goranova-Marinova, Vesselina; Rajnics, Péter; Suvorov, Aleksandr; Niesvizky, Ruben; Jakubowiak, Andrzej J; San-Miguel, Jesus F; Ludwig, Heinz; Wang, Michael; Maisnar, Vladimír; Minarik, Jiri; Bensinger, William I; Mateos, Maria-Victoria; Ben-Yehuda, Dina; Kukreti, Vishal; Zojwalla, Naseem; Tonda, Margaret E; Yang, Xinqun; Xing, Biao; Moreau, Philippe; Palumbo, Antonio

    2015-01-08

    Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P=0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P=0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life. In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.).

  20. Recent advances in multiple myeloma: a Korean perspective

    OpenAIRE

    Hong, Junshik; Lee, Jae Hoon

    2016-01-01

    Epidemiologically, multiple myeloma (MM) is a malignant disorder of plasma cells with a higher incidence among Western populations than among Asians. However, there is growing evidence of a recent increase in the age-standardized incidence rate (ASR) of MM in Asian countries, particularly Korea. Application of novel agents has resulted in significant improvement of treatment outcomes, and the advances are ongoing with the recent introduction and U.S. Food and Drug Administration?s approval of...

  1. Renal complications in multiple myeloma and related disorders: survivorship care plan of the International Myeloma Foundation Nurse Leadership Board.

    Science.gov (United States)

    Faiman, Beth M; Mangan, Patricia; Spong, Jacy; Tariman, Joseph D

    2011-08-01

    Kidney dysfunction is a common clinical feature of symptomatic multiple myeloma. Some degree of renal insufficiency or renal failure is present at diagnosis or will occur during the course of the disease and, if not reversed, will adversely affect overall survival and quality of life. Chronic insults to the kidneys from other illnesses, treatment, or multiple myeloma itself can further damage renal function and increase the risk for additional complications, such as anemia. Patients with multiple myeloma who have light chain (Bence Jones protein) proteinuria may experience renal failure or progress to end-stage renal disease (ESRD) and require dialysis because of light chain cast nephropathy. Kidney failure in patients with presumed multiple myeloma also may result from amyloidosis, light chain deposition disease, or acute tubular necrosis caused by nephrotoxic agents; therefore, identification of patients at risk for kidney damage is essential. The International Myeloma Foundation's Nurse Leadership Board has developed practice recommendations for screening renal function, identifying positive and negative contributing risk and environmental factors, selecting appropriate therapies and supportive care measures to decrease progression to ESRD, and enacting dialysis to reduce and manage renal complications in patients with multiple myeloma.

  2. Smoldering multiple myeloma: prevalence and current evidence guiding treatment decisions

    Directory of Open Access Journals (Sweden)

    Blum A

    2018-04-01

    Full Text Available Agnieszka Blum, Despina Bazou, Peter O’Gorman Department of Hematology, Mater Misericordiae University Hospital, Dublin, UK Abstract: Smoldering multiple myeloma (SMM is an asymptomatic plasma cell proliferative disorder associated with risk of progression to symptomatic multiple myeloma (MM or amyloidosis. In comparison to monoclonal gammopathy of undetermined significance (MGUS, SMM has a much higher risk of progression to MM. Thanks to advances in our understanding of the risk factors, the subset of patients with ultra-high risk of progression to MM (80%–90% at 2 years has been identified. The revision of the diagnostic criteria resulted in changes in the management of this cohort of patients. In contrast to the management guidelines for MGUS patients, SMM patients need to be studied more intensively in order to identify biomarkers necessary for accurate risk stratification. In this review, we focus on the risk of progression from SMM to MM, as well as the influence of early treatment on overall survival, time to progression and quality of life. Keywords: smoldering multiple myeloma, risk factor, biomarker, genomic aberrations, glycan analysis

  3. Case Report: Multiple Myeloma with Gangrene of Extremities

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    N Gharahi

    2009-07-01

    Full Text Available Introduction: Multiple myeloma represents a malignant proliferation of plasma cells derived from a single clone and it results in bone pain or fracture, renal failure, susceptibility to infections, anemia and hypercalcemia. The hyper viscosity syndrome is rare. Cryoglobulins are immunoglubulins that precipitate at temperatures less than 37degrees Celsius. Monoclonal cryoglobulins are usually present along with a specific hematologic disorder and are often asymptomatic. We report a second case of multiple myeloma with gangrene of all four extremities. Case: The Patient was a 77 year–old farmer with a 2 weeks history of coldness, pain and discoloration of the fingers of both the extremities which had extended to the mid forearm and shin regions. It was accompanied by skin erosions of the lower extremities, dark spots on the ear auricles and discoloration of the tip of the nose. On physical examination, quadrigangrene associated with ischemia of the auricles and tip of nose was seen. Serum proteins electrophoresis demonstrated monoclonal gammopathy and serum was positive for cryoglobulin, Bone marrow study showed neoplastic plasma cells infiltration. The patient was diagnosed as cryoglobulinemia based on multiple myeloma and treated accordingly.

  4. Sacroplasty for Local or Massive Localization of Multiple Myeloma

    International Nuclear Information System (INIS)

    Basile, Antonio; Tsetis, Dimitrios; Cavalli, Maide; Fiumara, Paolo; Raimondo, Francesco Di; Coppolino, Francesco; Coppolino, Carmelo; Mundo, Elena; Desiderio, Carla; Granata, Antonio; Patti, Maria Teresa

    2010-01-01

    The purpose of this study was to assess the efficacy of cementoplasty in the treatment of sacral multiple myelomas. We retrospectively reviewed the records of eight patients (four women and four men; age range 47-68 years; mean age 57.8) who underwent cementoplasty for painful osteolytic localization of multiple myeloma between April 2007 and May 2009. The patients had difficulty walking because of increasing pain. Six patients had persistent pain despite other cementoplasties for vertebral and femoral localization, whereas two patients referred at the time of diagnosis had only sacral lesions. The clinical indication for treatment was (1) a pain intensity score ≥5 on visual analogue scale (VAS) and (2) pain totally or partially refractory to analgesic treatment in patients with a life expectancy >3 months. Technical planning was based on computed tomography and/or magnetic resonance imaging. Six patients had previously undergone radiotherapy or chemotherapy and were receiving varying doses of analgesics, whereas sacroplasty represented the first treatment for two patients. Five patients had monolateral local involvement, and the other patients had massive involvement of the sacrum; Technical success was achieved in all cases. We had only one small and asymptomatic foraminal leak. All patients experienced improvement in symptoms after the procedure, as demonstrated by improved VAS scores and performance status (PS) and decreased analgesic dose constant during follow-up. In our experience, percutaneous stabilization can be used effectively and safely in patients with focal or extensive involvement of the sacrum by multiple myeloma.

  5. Computed Tomography diagnosis of skeletal involvement in multiple myeloma

    International Nuclear Information System (INIS)

    Scutellari, Pier Nuccio; Galeotti, Roberto; Leprotti, Stefano; Piva, Nadia; Spanedda, Romedio

    1997-01-01

    The authors assess the role of Computed Topography in the diagnosis and management of multiple myeloma (MM) and investigate if Computed Tomography findings can influence the clinical approach, prognosis and treatment. 273 multiple myeloma patients submitted to Computed Tomography June 1994, to December, 1996. The patients were 143 men and 130 women (mean age: 65 years): 143 were stage I, 38 stage II and 92 stage III according to Durie and Salomon's clinical classification. All patients were submitted to blood tests, spinal radiography and Computed Tomography, the latter with serial 5-mm scans on several vertebral bodies. Computed Tomography despicted vertebral arch and process involvement in 3 cases with the vertebral pedicle sign. Moreover, Computed Tomography proved superior to radiography in showing the spread of myelomatous masses into the soft tissues in a case with solitary permeative lesion in the left public bone, which facilitated subsequent biopsy. As for extraosseous localizations, Computed Tomography demonstrated thoracic soft tissue (1 woman) and pelvic (1 man) involvement by myelomtous masses penetrating into surrounding tissues. In our series, only a case of osteosclerotic bone myeloma was observed in the pelvis, associated with lytic abnormalities. Computed Tomography findings do not seem to improve the clinical approach and therapeutic management of the disease. Nevertheless, the authors reccommend Computed Tomography for some myelomatous conditions, namely: a) in the patients with focal bone pain but normal skeletal radiographs; b) in the patients with M protein, bone marrow plasmocytosis and back pain, but with an incoclusive multiple myeloma diagnosis; c) to asses bone spread in the regions which are anatomically complex or difficult to study with radiography and to depict soft tissue involvement; d) for bone biopsy

  6. Circumvention of Mcl-1-dependent drug resistance by simultaneous Chk1 and MEK1/2 inhibition in human multiple myeloma cells.

    Science.gov (United States)

    Pei, Xin-Yan; Dai, Yun; Felthousen, Jessica; Chen, Shuang; Takabatake, Yukie; Zhou, Liang; Youssefian, Leena E; Sanderson, Michael W; Bodie, Wesley W; Kramer, Lora B; Orlowski, Robert Z; Grant, Steven

    2014-01-01

    The anti-apoptotic protein Mcl-1 plays a major role in multiple myeloma (MM) cell survival as well as bortezomib- and microenvironmental forms of drug resistance in this disease. Consequently, there is a critical need for strategies capable of targeting Mcl-1-dependent drug resistance in MM. The present results indicate that a regimen combining Chk1 with MEK1/2 inhibitors effectively kills cells displaying multiple forms of drug resistance stemming from Mcl-1 up-regulation in association with direct transcriptional Mcl-1 down-regulation and indirect disabling of Mcl-1 anti-apoptotic function through Bim up-regulation and increased Bim/Mcl-1 binding. These actions release Bak from Mcl-1, accompanied by Bak/Bax activation. Analogous events were observed in both drug-naïve and acquired bortezomib-resistant MM cells displaying increased Mcl-1 but diminished Bim expression, or cells ectopically expressing Mcl-1. Moreover, concomitant Chk1 and MEK1/2 inhibition blocked Mcl-1 up-regulation induced by IL-6/IGF-1 or co-culture with stromal cells, effectively overcoming microenvironment-related drug resistance. Finally, this regimen down-regulated Mcl-1 and robustly killed primary CD138+ MM cells, but not normal hematopoietic cells. Together, these findings provide novel evidence that this targeted combination strategy could be effective in the setting of multiple forms of Mcl-1-related drug resistance in MM.

  7. Circumvention of Mcl-1-dependent drug resistance by simultaneous Chk1 and MEK1/2 inhibition in human multiple myeloma cells.

    Directory of Open Access Journals (Sweden)

    Xin-Yan Pei

    Full Text Available The anti-apoptotic protein Mcl-1 plays a major role in multiple myeloma (MM cell survival as well as bortezomib- and microenvironmental forms of drug resistance in this disease. Consequently, there is a critical need for strategies capable of targeting Mcl-1-dependent drug resistance in MM. The present results indicate that a regimen combining Chk1 with MEK1/2 inhibitors effectively kills cells displaying multiple forms of drug resistance stemming from Mcl-1 up-regulation in association with direct transcriptional Mcl-1 down-regulation and indirect disabling of Mcl-1 anti-apoptotic function through Bim up-regulation and increased Bim/Mcl-1 binding. These actions release Bak from Mcl-1, accompanied by Bak/Bax activation. Analogous events were observed in both drug-naïve and acquired bortezomib-resistant MM cells displaying increased Mcl-1 but diminished Bim expression, or cells ectopically expressing Mcl-1. Moreover, concomitant Chk1 and MEK1/2 inhibition blocked Mcl-1 up-regulation induced by IL-6/IGF-1 or co-culture with stromal cells, effectively overcoming microenvironment-related drug resistance. Finally, this regimen down-regulated Mcl-1 and robustly killed primary CD138+ MM cells, but not normal hematopoietic cells. Together, these findings provide novel evidence that this targeted combination strategy could be effective in the setting of multiple forms of Mcl-1-related drug resistance in MM.

  8. Radiological diagnostics of multiple myeloma; Radiologische Diagnostik des multiplen Myeloms

    Energy Technology Data Exchange (ETDEWEB)

    D' Anastasi, M.; Grandl, S.; Reiser, M.F.; Baur-Melnyk, A. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany)

    2014-06-15

    Robust and reliable imaging methods are required to estimate the skeletal tumor load in multiple myeloma, as well as for the diagnosis of extraskeletal manifestations. Imaging also plays an essential role in the assessment of fracture risk and of vertebral fractures. The conventional skeletal survey has been the gold standard in the imaging of multiple myeloma for many years. Other modalities which have been investigated and are in use are whole-body computed tomography (WBCT), 18F-fluorodeoxyglucose positron emission tomography computed tomography (FDG PET-CT) and whole-body magnetic resonance imaging (WBMRI). These techniques are able to depict both mineralized bone and the bone marrow with a high sensitivity for myeloma lesions. Several studies have shown that cross-sectional imaging is superior to the skeletal survey in the detection of myeloma lesions and WBMRI has been shown to be significantly more sensitive than WBCT for the detection of focal myeloma lesions as well as for diffuse infiltration. The FDG PET-CT technique has a sensitivity comparable to WBMRI. Due to the higher sensitivity in the detection of myeloma lesions WBCT and WBMRI should replace the skeletal survey. A WBCT should be performed if there is suspicion of multiple myeloma. If no focal lesions are found WBMRI or at least MRI of the spine and pelvis should be additionally performed if available. If WBMRI has been initially performed and focal lesions are present, an additional WBCT may be performed to assess the extent of bone destruction and fracture risk. In cases of monoclonal gammopathy of undetermined significance (MGUS), solitary and smoldering myeloma, a WBMRI, if available, should be performed in addition to WBCT. (orig.) [German] Die Aufgabe der bildgebenden Diagnostik beim multiplen Myelom (MM) ist die zuverlaessige Erfassung der Tumorlast im Skelett sowie auch der extraskelettalen Manifestationen und der assoziierten Komplikationen (z. B. Wirbelkoerperfrakturen, Frakturgefahr

  9. CUTANEOUS INVOLVEMENT IN MULTIPLE MYELOMA AT AN UNUSUAL SITE: A RARE CASE REPORT

    Directory of Open Access Journals (Sweden)

    Lohit Kumar

    2015-05-01

    Full Text Available Multiple myeloma is a rare cancer. According to the most recent data from the Surveillance, Epidemiology, and End Results (SEER program, multiple myeloma is the second most common haematological malignancy in the U.S. (after non - Hodgkin lymphoma, constitutes 1% of all cancers and constitutes 2% of all cancer deaths. Cutaneous involvement of multiple myeloma during treatment period is uncommon with fewer described in literature. Moreover, metastatic cutaneous involvement at the sole of the foot during treatment period of a IgA kappa type multiple myeloma patient followed by death has not encountered in literature. We have reported such a case

  10. Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration

    OpenAIRE

    Nabissi, Massimo; Morelli, Maria Beatrice; Offidani, Massimo; Amantini, Consuelo; Gentili, Silvia; Soriani, Alessandra; Cardinali, Claudio; Leoni, Pietro; Santoni, Giorgio

    2016-01-01

    Several studies showed a potential anti-tumor role for cannabinoids, by modulating cell signaling pathways involved in cancer cell proliferation, chemo-resistance and migration. Cannabidiol (CBD) was previously noted in multiple myeloma (MM), both alone and in synergy with the proteasome inhibitor bortezomib, to induce cell death. In other type of human cancers, the combination of CBD with ?9-tetrahydrocannabinol (THC) was found to act synergistically with other chemotherapeutic drugs suggest...

  11. Phase 2 study of tabalumab, a human anti-B-cell activating factor antibody, with bortezomib and dexamethasone in patients with previously treated multiple myeloma.

    Science.gov (United States)

    Raje, Noopur S; Moreau, Philippe; Terpos, Evangelos; Benboubker, Lotfi; Grząśko, Norbert; Holstein, Sarah A; Oriol, Albert; Huang, Shang-Yi; Beksac, Meral; Kuliczkowski, Kazimierz; Tai, Datchen F; Wooldridge, James E; Conti, Ilaria; Kaiser, Christopher J; Nguyen, Tuan S; Cronier, Damien M; Palumbo, Antonio

    2017-03-01

    In this double-blind, Phase 2 study, 220 patients with relapsed/refractory multiple myeloma were randomly assigned 1:1:1 to receive placebo (N = 72), tabalumab 100 mg (N = 74), or tabalumab 300 mg (N = 74), each in combination with dexamethasone 20 mg and subcutaneous bortezomib 1·3 mg/m 2 on a 21-day cycle. No significant intergroup differences were observed among primary (median progression-free survival [mPFS]) or secondary efficacy outcomes. The mPFS was 6·6, 7·5 and 7·6 months for the tabalumab 100, 300 mg and placebo groups, respectively (tabalumab 100 mg vs. placebo Hazard ratio (HR) [95% confidence interval (CI)] = 1·13 [0·80-1·59], P = 0·480; tabalumab 300 mg vs. placebo HR [95% CI] = 1·03 [0·72-1·45], P = 0·884). The most commonly-reported treatment-emergent adverse events were thrombocytopenia (37%), fatigue (37%), diarrhoea (35%) and constipation (32%). Across treatments, patients with low baseline BAFF (also termed TNFSF13B) expression (n = 162) had significantly longer mPFS than those with high BAFF expression (n = 55), using the 75th percentile cut-off point (mPFS [95% CI] = 8·3 [7·0-9·3] months vs. 5·8 [3·7-6·6] months; HR [95% CI] = 1·59 [1·11-2·29], P = 0·015). Although generally well tolerated, PFS was not improved during treatment with tabalumab compared to placebo. A higher dose of 300 mg tabalumab did not improve efficacy compared to the 100 mg dose. Nonetheless, BAFF appears to have some prognostic value in patients with multiple myeloma. © 2016 John Wiley & Sons Ltd.

  12. Neovascular niche for human myeloma cells in immunodeficient mouse bone.

    Directory of Open Access Journals (Sweden)

    Hirono Iriuchishima

    Full Text Available The interaction with bone marrow (BM plays a crucial role in pathophysiological features of multiple myeloma (MM, including cell proliferation, chemoresistance, and bone lesion progression. To characterize the MM-BM interactions, we utilized an in vivo experimental model for human MM in which a GFP-expressing human MM cell line is transplanted into NOG mice (the NOG-hMM model. Transplanted MM cells preferentially engrafted at the metaphyseal region of the BM endosteum and formed a complex with osteoblasts and osteoclasts. A subpopulation of MM cells expressed VE-cadherin after transplantation and formed endothelial-like structures in the BM. CD138(+ myeloma cells in the BM were reduced by p53-dependent apoptosis following administration of the nitrogen mustard derivative bendamustine to mice in the NOG-hMM model. Bendamustine maintained the osteoblast lining on the bone surface and protected extracellular matrix structures. Furthermore, bendamustine suppressed the growth of osteoclasts and mesenchymal cells in the NOG-hMM model. Since VE-cadherin(+ MM cells were chemoresistant, hypoxic, and HIF-2α-positive compared to the VE-cadherin(- population, VE-cadherin induction might depend on the oxygenation status. The NOG-hMM model described here is a useful system to analyze the dynamics of MM pathophysiology, interactions of MM cells with other cellular compartments, and the utility of novel anti-MM therapies.

  13. Myelomatous ascites as an initial manifestation of extramedullary involvement of multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seo Youn; Lee, Hae Kyung; Yi, Boem Ha; Lee, Min Hee; Kim, Hee Kyung; Park, Seong Kyu [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of)

    2017-03-15

    Multiple myeloma is a common hematological malignancy. Aggressive myeloma invades the organs outside the bone marrow, lymph, or reticuloendothelial systems. Among the extramedullary involvements of multiple myeloma, myelomatous ascites are extremely rare and are associated with a poor prognosis. We describe a case of myelomatous ascites as an initial manifestation of extramedullary involvement of multiple myeloma in 39-year-old patient. The patient was treated with high-dose chemotherapy, but extensive extramedullary involvement progressed, and the patient expired approximately five months after the initial detection of ascites.

  14. Management of relapsed multiple myeloma: recommendations of the International Myeloma Working Group.

    Science.gov (United States)

    Laubach, J; Garderet, L; Mahindra, A; Gahrton, G; Caers, J; Sezer, O; Voorhees, P; Leleu, X; Johnsen, H E; Streetly, M; Jurczyszyn, A; Ludwig, H; Mellqvist, U-H; Chng, W-J; Pilarski, L; Einsele, H; Hou, J; Turesson, I; Zamagni, E; Chim, C S; Mazumder, A; Westin, J; Lu, J; Reiman, T; Kristinsson, S; Joshua, D; Roussel, M; O'Gorman, P; Terpos, E; McCarthy, P; Dimopoulos, M; Moreau, P; Orlowski, R Z; Miguel, J S; Anderson, K C; Palumbo, A; Kumar, S; Rajkumar, V; Durie, B; Richardson, P G

    2016-05-01

    The prognosis for patients multiple myeloma (MM) has improved substantially over the past decade with the development of new, more effective chemotherapeutic agents and regimens that possess a high level of anti-tumor activity. In spite of this important progress, however, nearly all MM patients ultimately relapse, even those who experience a complete response to initial therapy. Management of relapsed MM thus represents a vital aspect of the overall care for patients with MM and a critical area of ongoing scientific and clinical research. This comprehensive manuscript from the International Myeloma Working Group provides detailed recommendations on management of relapsed disease, with sections dedicated to diagnostic evaluation, determinants of therapy, and general approach to patients with specific disease characteristics. In addition, the manuscript provides a summary of evidence from clinical trials that have significantly impacted the field, including those evaluating conventional dose therapies, as well as both autologous and allogeneic stem cell transplantation. Specific recommendations are offered for management of first and second relapse, relapsed and refractory disease, and both autologous and allogeneic transplant. Finally, perspective is provided regarding new agents and promising directions in management of relapsed MM.

  15. In vitro sensitization of human lymphocytes to a myeloma cell-related antigen

    International Nuclear Information System (INIS)

    Whitson, M.E.; Griffin, G.D.; Novelli, G.D.; Solomon, A.

    1981-01-01

    Peripheral blood lymphocytes from normal human donors were cocultivated with cells from two established human multiple myeloma cell lines, RPMI 8226 and K-737, and with lymphoblastoid cells from a third B cell line, RAMM. After a comparison of three methods of lymphocyte sensitization, a 6-day incubation protocol with equal numbers of normal lymphocytes and mitomycin C-treated tumor cells was selected. Cells fom the RPMI 8226 myeloma line stimulated the differentiation of lymphocytes into cytotoxic effector cells as measured by 51 Cr release from labeled target cells. The RPMI 8226-sensitized lymphocytes were cytotoxic for myeloma cells (RPMI 8226 and K-737) and for lymphoblastoid cells (RAMM) but not for cells from human lung tumor lines (A549, A427, MB9812), a breast carcinoma line (ALAB), a normal diploid fibroblast line (HSBP), or normal lymphocytes

  16. In vitro sensitization of human lymphocytes to a myeloma cell-related antigen

    Energy Technology Data Exchange (ETDEWEB)

    Whitson, M.E. (Univ. of South Carolina, Columbia); Griffin, G.D.; Novelli, G.D.; Solomon, A.

    1981-01-01

    Peripheral blood lymphocytes from normal human donors were cocultivated with cells from two established human multiple myeloma cell lines, RPMI 8226 and K-737, and with lymphoblastoid cells from a third B cell line, RAMM. After a comparison of three methods of lymphocyte sensitization, a 6-day incubation protocol with equal numbers of normal lymphocytes and mitomycin C-treated tumor cells was selected. Cells fom the RPMI 8226 myeloma line stimulated the differentiation of lymphocytes into cytotoxic effector cells as measured by /sup 51/Cr release from labeled target cells. The RPMI 8226-sensitized lymphocytes were cytotoxic for myeloma cells (RPMI 8226 and K-737) and for lymphoblastoid cells (RAMM) but not for cells from human lung tumor lines (A549, A427, MB9812), a breast carcinoma line (ALAB), a normal diploid fibroblast line (HSBP), or normal lymphocytes.

  17. Radiation therapy for the palliation of multiple myeloma

    International Nuclear Information System (INIS)

    Leigh, B.R.; Kurtts, T.A.; Mack, C.F.; Matzner, M.B.; Shimm, D.S.

    1993-01-01

    This study reviews the experience at the University of Arizona in an effort to define the minimum effective radiation dose for durable pain relief in the majority of patients with symptomatic multiple myeloma. The records of 101 patients with multiple myeloma irradiated for palliation at the University of Arizona between 1975 and 1990 were reviewed. Three hundred sixteen sites were treated. Ten sites were asymptomatic, including six hemibody fields with advanced disease unresponsive to chemotherapy and four local fields with impending pathological fractures. Three hundred six evaluable symptomatic sites remained. The most common symptom was bone pain. Other symptoms included neurological impairment with a palpable mass. Total tumor dose ranged from 3.0 to 60 Gy, with a mean of 25 Gy. Symptom relief was obtained in 297 of 306 evaluable symptomatic sites (97%). Complete relief of symptoms was obtained in 26% and partial relief in 71%. Symptom relief was obtained in 92% of sites receiving a total dose less than 10 Gy (n = 13) and 98% of sites receiving 10 Gy or more (n = 293). No dose-response could be demonstrated. The likelihood of symptom relief was not influenced by the location of the lesion or the use of concurrent chemotherapy. Of the 297 responding sites, 6% (n = 19) relapsed after a median symptom-free interval of 16 months. Neither the probability of relapse nor the time to relapse was related to the radiation dose. Retreatment of relapsing sites provided effective palliation in all cases. Radiation therapy is effective in palliating local symptoms in multiple myeloma. A total dose of 10 Gy should provide durable symptom relief in the majority of patients. 16 refs., 3 figs., 4 tabs

  18. Intracranial involvement in plasmacytomas and multiple myeloma: a pictorial essay

    Energy Technology Data Exchange (ETDEWEB)

    Cerase, Alfonso; Gennari, Paola; Monti, Lucia; Venturi, Carlo [Azienda Ospedaliera Universitaria Senese, Unit of Diagnostic and Therapeutic Neuroradiology, and InterDepartmental Center of Nuclear Magnetic Resonance, Policlinico ' Santa Maria alle Scotte' , Siena (Italy); Tarantino, Annachiara; Muccio, Carmine Franco [Azienda Ospedaliera ' G. Rummo' , Unit of Neuroradiology, Department of Neurosciences, Benevento (Italy); Gozzetti, Alessandro [University of Siena, Unit of Hematology and Transplants, Policlinico ' Santa Maria alle Scotte' , Siena (Italy); Di Blasi, Arturo [Azienda Ospedaliera ' G. Rummo' , Unit of Pathology, Department of Oncology, Benevento (Italy)

    2008-08-15

    The purpose of this pictorial essay is to increase awareness of the clinical presentation, neuroradiological findings, treatment options, and neuroradiological follow-up of plasmacytomas and multiple myeloma with intracranial growth. This pictorial essay reviews the clinical features and neuroradiological findings in seven patients (four women, three men; age range at diagnosis 62-82 years) followed in two institutions. Six patients, one with IgG-{kappa} plasmacytoma, and five with IgG-{kappa}(n=3), IgG-{lambda}(n=1), and nonsecretory (n=1) multiple myeloma, had been seen over a period of 9 years in one institution, and the other patient with IgG-{kappa} plasmacytoma had been seen over a period of 3.5 years in the other. Intracranial involvement is rare, most frequently resulting from osseous lesions in the cranial vault, skull base, nose, or paranasal sinuses. Primary dural or leptomeningeal involvement is rarer. Some typical findings of a dural and/or osseous plasmacytoma include iso- to hyperdensity on CT scan, T1 equal to high signal intensity and T2 markedly hypointense signal on MRI, and high vascularity possibly documented on intraarterial digital subtraction angiography. However, the neuroradiological findings generally lack specificity, since they are generally no different from those of meningioma, metastasis, lymphoma, dural sarcoma, plasma cell granuloma, infectious meningitis, and leptomeningeal carcinomatosis. The spectrum of clinical and neuroradiological evaluation shows that intracranial involvement from plasmacytoma and multiple myeloma must be taken into account in the differential diagnosis of cranial osseous and meningeal disease. (orig.)

  19. Economic and clinical impact of multiple myeloma to managed care.

    Science.gov (United States)

    Cook, Richard

    2008-09-01

    Because of the development of novel agents such as immunomodulators, proteasome inhibitors, and bisphosphonates, the standards of care for the multiple myeloma (MM) patient have changed. The costs associated with current and emerging therapies, as well as supportive care, are significant and pose a tremendous financial burden to both patients and managed care. To review the economic impact of MM and to weigh the advantages and disadvantages of current treatments in bringing value for prolonged life versus the cost of treatment. This chapter will also discuss the need for thorough data review and pharmacoeconomic analyses to determine the most cost-effective therapies. Although MM accounts for only a small percentage of all cancer types, the costs associated with treating and managing it are among the highest. Recent developments in diagnosing, treating, and managing myeloma have led to novel treatment strategies. Immunomodulators, proteasome inhibitors, and bisphosphonates are improving response rates and preserving quality of life. However, these agents are not replacing older treatment modalities, but being used in addition to them. Intensive chemotherapy, stem cell transplantation, and supportive care are all important components in achieving treatment goals. Costs associated with stem cell transplants and complications of the disease add to the economic burden of myeloma. Additional costs for routine diagnostics to measure the progression of the disease or response to treatment need to be considered. Complications (e.g., lytic bone disease, infection, anemia, and renal failure) also add to morbidity and mortality, thus increasing the burden to the patient and the health care system as a whole. Financial and time constraints of caregivers must also be considered, as well as the added administrative burdens to health care providers. New standards of care in the treatment and management of myeloma are likely to lead to significant increases in costs. Although

  20. Effects of radiotherapy in the treatment of multiple myeloma

    International Nuclear Information System (INIS)

    Ochtrop, Thomas Alexander

    2015-01-01

    Palliative irradiation of osteolytic lesions is a considerable component in the treatment for patients with multiple myeloma. In this study, we analyzed the efficacy of irradiation in these patients. Patients and methods: We retrospectively analyzed 153 patients with multiple myeloma who were admitted to our department between 1989 and 2013. According to the staging system of Durie and Salmon 116 patients were classified as stage III. 107/153 patients were treated with radiotherapy of at least one and up to 6 bony lesions at different times. In order to evaluate the effect of local radiotherapy on pain relief and bone recalcification a uni- and multivariate analysis was performed using a binary logistic regression model to correct for multiple measurements. Complete information on dose, fractionation and volume of radiotherapy was available from 81 patients treated in 136 target volumes for pain relief, and from 69 patients treated in 108 target volumes for recalcification. Total radiation doses varied between 8 Gy to 50 Gy (median dose 25 Gy in 2.5 Gy fractions, 5 times a week). Results: Radiotherapy resulted in complete local pain relief in 31% and partial local pain relief in 54% of the patients. In the univariate analysis, higher total radiation doses (p = 0.023) and higher age (p = 0.014) at the time of radiotherapy were significantly associated with a higher likelihood of pain relief, whereas no significant association was detected for concurrent systemic treatment, type and stage of myeloma and location of bone lesions. The same variables were independent predictors for pain relief in the multivariate analysis. Recalcification was observed in 48% of irradiated bone lesions. In the uni- and multivariate analysis higher radiation doses were significantly associated (p = 0.048) with an increased likelihood of recalcification. Side effects of radiotherapy were generally mild. Conclusions: Higher total biological radiation doses were associated with better pain

  1. External radiation in spinal cord compression in multiple myeloma

    International Nuclear Information System (INIS)

    Rao, G.H.; Ayyagiri, S.; Dutta, T.K.; Gupta, B.D.; Gulati, D.R.

    1978-01-01

    The place of radiotherapy in 14 cases of spinal cord compression in multiple myeloma is outlined. The modalities of treatment and the role of surgery and radiation as decompression methods are emphasised. Complete recovery is seen in 50 percent of the patients in this small group with judicious combination of surgical and/or radiation decompression. Chemotherapy as systematic treatment must be given in all the cases after decompression procedures. It is suggested that reactive oedema after irradiation is only speculative and radiation alone as primary treatment may be recommended in selected cases. (author)

  2. Central neurotoxicity of immunomodulatory drugs in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Urmeel H. Patel

    2015-03-01

    Full Text Available Immunomodulatory drugs (IMiDs currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient, lenalidomide (4 patients, and pomalidomide (1 patient was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy.

  3. Central neurotoxicity of immunomodulatory drugs in multiple myeloma.

    Science.gov (United States)

    Patel, Urmeel H; Mir, Muhammad A; Sivik, Jeffrey K; Raheja, Divisha; Pandey, Manoj K; Talamo, Giampaolo

    2015-02-24

    Immunomodulatory drugs (IMiDs) currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient), lenalidomide (4 patients), and pomalidomide (1 patient) was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy.

  4. Cancer Associated Fibroblasts and Tumor Growth: Focus on Multiple Myeloma

    International Nuclear Information System (INIS)

    De Veirman, Kim; Rao, Luigia; De Bruyne, Elke; Menu, Eline; Van Valckenborgh, Els; Van Riet, Ivan; Frassanito, Maria Antonia; Di Marzo, Lucia; Vacca, Angelo; Vanderkerken, Karin

    2014-01-01

    Cancer associated fibroblasts (CAFs) comprise a heterogeneous population that resides within the tumor microenvironment. They actively participate in tumor growth and metastasis by production of cytokines and chemokines, and the release of pro-inflammatory and pro-angiogenic factors, creating a more supportive microenvironment. The aim of the current review is to summarize the origin and characteristics of CAFs, and to describe the role of CAFs in tumor progression and metastasis. Furthermore, we focus on the presence of CAFs in hypoxic conditions in relation to multiple myeloma disease

  5. A Very Rare Presentation of Multiple Myeloma: Unilateral Raccoon Eye

    Directory of Open Access Journals (Sweden)

    Ceyhun Varım

    2015-08-01

    Two thirds of patients complain of bone pain, especially lower back pain. MM could be diagnosed after a pathologic fracture occurs in one third of patients. Presentation with symptoms related to hyperviscosity, hypercalcemia and bleeding tendency could also be observed. A rare presentation of MM is peri-orbital ecchymotic lesion (raccoon eye. Here, we report a 64 years old, male patient presented with unilateral raccoon eye and high erythrocyte sedimentation rate (ESR to internal medicine outpatient. The patient was referred to hematology outpatient and was diagnosed with multiple myeloma.

  6. Cancer Associated Fibroblasts and Tumor Growth: Focus on Multiple Myeloma

    Energy Technology Data Exchange (ETDEWEB)

    De Veirman, Kim, E-mail: kdeveirm@vub.ac.be [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Rao, Luigia [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine, University of Bari Medical School, Bari I-70124 (Italy); De Bruyne, Elke; Menu, Eline; Van Valckenborgh, Els [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Van Riet, Ivan [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Stem Cell Laboratory, Division of Clinical Hematology, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels 1090 (Belgium); Frassanito, Maria Antonia [Department of Biomedical Sciences and Human Oncology, Section of General Pathology, University of Bari Medical School, Bari I-70124 (Italy); Di Marzo, Lucia; Vacca, Angelo [Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine, University of Bari Medical School, Bari I-70124 (Italy); Vanderkerken, Karin, E-mail: kdeveirm@vub.ac.be [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium)

    2014-06-27

    Cancer associated fibroblasts (CAFs) comprise a heterogeneous population that resides within the tumor microenvironment. They actively participate in tumor growth and metastasis by production of cytokines and chemokines, and the release of pro-inflammatory and pro-angiogenic factors, creating a more supportive microenvironment. The aim of the current review is to summarize the origin and characteristics of CAFs, and to describe the role of CAFs in tumor progression and metastasis. Furthermore, we focus on the presence of CAFs in hypoxic conditions in relation to multiple myeloma disease.

  7. Extramedullary plasmacytomas in the context of multiple myeloma.

    Science.gov (United States)

    Aguado, Beatriz; Iñigo, Belen; Sastre, Jose L; Oriol, Albert

    2011-11-01

    Plasmacytoma is a frequent complication of multiple myeloma, either at diagnosis or within disease progression. The extramedullary disease confers a poorer prognosis and is biologically distinct with high-risk molecular and histological features, being resistant to conventional treatments. Radiation therapy remains the most effective treatment for extramedullary lesions to achieve local control. There are very limited data from randomized trials regarding the most appropriate systemic treatment. Case reports such as those presented here, as well as retrospective analysis of series, suggest that lenalidomide is an effective agent, in combination with dexamethasone, in this setting. Additional studies are needed to define the proper management of this condition.

  8. [New drugs in the treatment of multiple myeloma].

    Science.gov (United States)

    Oriol, Albert; Motlló, Cristina

    2014-09-15

    Progress in the treatment of multiple myeloma in the last decade has been able to delay, but ultimately not to prevent, the development of resistances and most patients still die of the disease or its related complications. New drugs have been developed including new alkylating agents, proteasome inhibitors and immunomodulators but also monoclonal antibodies and drugs with new mechanisms of action. Hopefully, this new generation of targeted agents will improve the results of the initial therapy, avoid relapses and development of resistances and provide better and less toxic options for the relapsed and refractory patient. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  9. Morganella morganii Pericarditis in a Patient with Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Takafumi Nakao

    2013-01-01

    Full Text Available Purulent pericarditis caused by Morganella morganii is extremely rare. We report herein a case of a 61-year-old man who presented with chest pain and dyspnea fourteen days after chemotherapy for multiple myeloma. Echocardiogram and computed tomography revealed a massive pericardial effusion and associated cardiac tamponade. Pericardiocentesis was performed. Pericardial fluid was found to be purulent, and Morganella morganii was isolated from the fluid. The patient was successfully treated with antibiotic therapy and surgical drainage of the fluid. Morganella morganii should be considered a possible pathogen when immunocompromised patients develop purulent pericarditis.

  10. External radiation in spinal cord compression in multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Rao, G H; Ayyagiri, S; Dutta, T K; Gupta, B D; Gulati, D R [Post-Graduate Inst. of Medical Education and Research, Chandigarh (India). Dept. of Radiotherapy

    1978-02-01

    The place of radiotherapy in 14 cases of spinal cord compression in multiple myeloma is outlined. The modalities of treatment and the role of surgery and radiation as decompression methods are emphasised. Complete recovery is seen in 50 percent of the patients in this small group with judicious combination of surgical and/or radiation decompression. Chemotherapy as systematic treatment must be given in all the cases after decompression procedures. It is suggested that reactive oedema after irradiation is only speculative and radiation alone as primary treatment may be recommended in selected cases.

  11. Alpha Particles Induce Autophagy in Multiple Myeloma Cells.

    Science.gov (United States)

    Gorin, Jean-Baptiste; Gouard, Sébastien; Ménager, Jérémie; Morgenstern, Alfred; Bruchertseifer, Frank; Faivre-Chauvet, Alain; Guilloux, Yannick; Chérel, Michel; Davodeau, François; Gaschet, Joëlle

    2015-01-01

    Radiation emitted by the radionuclides in radioimmunotherapy (RIT) approaches induce direct killing of the targeted cells as well as indirect killing through the bystander effect. Our research group is dedicated to the development of α-RIT, i.e., RIT using α-particles especially for the treatment of multiple myeloma (MM). γ-irradiation and β-irradiation have been shown to trigger apoptosis in tumor cells. Cell death mode induced by (213)Bi α-irradiation appears more controversial. We therefore decided to investigate the effects of (213)Bi on MM cell radiobiology, notably cell death mechanisms as well as tumor cell immunogenicity after irradiation. Murine 5T33 and human LP-1 MM cell lines were used to study the effects of such α-particles. We first examined the effects of (213)Bi on proliferation rate, double-strand DNA breaks, cell cycle, and cell death. Then, we investigated autophagy after (213)Bi irradiation. Finally, a coculture of dendritic cells (DCs) with irradiated tumor cells or their culture media was performed to test whether it would induce DC activation. We showed that (213)Bi induces DNA double-strand breaks, cell cycle arrest, and autophagy in both cell lines, but we detected only slight levels of early apoptosis within the 120 h following irradiation in 5T33 and LP-1. Inhibition of autophagy prevented (213)Bi-induced inhibition of proliferation in LP-1 suggesting that this mechanism is involved in cell death after irradiation. We then assessed the immunogenicity of irradiated cells and found that irradiated LP-1 can activate DC through the secretion of soluble factor(s); however, no increase in membrane or extracellular expression of danger-associated molecular patterns was observed after irradiation. This study demonstrates that (213)Bi induces mainly necrosis in MM cells, low levels of apoptosis, and autophagy that might be involved in tumor cell death.

  12. Correlation of proliferative and clonogenic tumor cells in multiple myeloma

    International Nuclear Information System (INIS)

    Karp, J.E.; Burke, P.J.; Saylor, P.L.; Humphrey, R.L.

    1984-01-01

    To expand on the findings from previous clinical trials that the growth of residual tumor is increased at a predictable time following initial drug administration, malignant plasma cells from bone marrows of patients with multiple myeloma (MM) were examined for changes in proliferation and clonogenicity induced in vivo by cyclophosphamide and in vitro by drug-induced humoral stimulatory activity. Peak plasma cell [ 3 H]thymidine labeling index (LI) occurred predictably following drug and paralleled changes in agar colony formation by marrow cells obtained during therapy. Colony-forming capacity of pretreatment MM marrow populations was enhanced when those cells were cultured with humoral stimulatory activity, similar to the increased colony formation detected in Day 9 postcyclophosphamide marrows at the time of peak plasma cell LI. To further define a relationship between proliferative plasma cells and colony-forming tumor cells, MM marrows were fractionated by sedimentation on an isokinetic gradient. Enrichment of a proliferative tumor cell cohort was achieved, evidenced by [ 3 H]thymidine LI. Colony-forming cells were also enriched by isokinetic gradient sedimentation, and agar colony formation by MM marrow cell fractions correlated with the kinetic characteristics of the isolated subpopulations. These studies of whole and fractionated human MM marrow cell populations suggest that the kinetically active cells which are induced to proliferate in vivo and in vitro are closely related to the clonogenic tumor cells which produce colonies in agar and which, like those cells measured by [ 3 H]thymidine LI, respond to growth stimulation by drug-induced humoral stimulatory activity

  13. Interleukin-6 counteracts therapy-induced cellular oxidative stress in multiple myeloma by up-regulating manganese superoxide dismutase

    OpenAIRE

    Brown, Charles O.; Salem, Kelley; Wagner, Brett A.; Bera, Soumen; Singh, Neeraj; Tiwari, Ajit; Choudhury, Amit; Buettner, Garry R.; Goel, Apollina

    2012-01-01

    IL (interleukin)-6, an established growth factor for multiple myeloma cells, induces myeloma therapy resistance, but the resistance mechanisms remain unclear. The present study determines the role of IL-6 in re-establishing intracellular redox homoeostasis in the context of myeloma therapy. IL-6 treatment increased myeloma cell resistance to agents that induce oxidative stress, including IR (ionizing radiation) and Dex (dexamethasone). Relative to IR alone, myeloma cells treated with IL-6 plu...

  14. Transcatheter shunt embolotherapy in multiple myeloma with high output heart failure

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Ho [Wonkwang University School of Medicine, Iksan (Korea, Republic of); Ko, Gi Young; Yoon, Hyun Ki; Sung, Kyu Bo [Ulsan University College of Medicine, Seoul (Korea, Republic of)

    2002-12-01

    High-output heart failure may be fairly common in patients with multiple myeloma and is associated with severe bone involvement. In this report, we describe the case of a 67-year-old man with multiple myeloma who presented with high output heart failure subsequently treated by transcatheter arterial embolization.

  15. Transcatheter shunt embolotherapy in multiple myeloma with high output heart failure

    International Nuclear Information System (INIS)

    Kim, Jeong Ho; Ko, Gi Young; Yoon, Hyun Ki; Sung, Kyu Bo

    2002-01-01

    High-output heart failure may be fairly common in patients with multiple myeloma and is associated with severe bone involvement. In this report, we describe the case of a 67-year-old man with multiple myeloma who presented with high output heart failure subsequently treated by transcatheter arterial embolization

  16. Cytokinetically quiescent (G0/G1) human multiple myeloma cells are susceptible to simultaneous inhibition of Chk1 and MEK1/2.

    Science.gov (United States)

    Pei, Xin-Yan; Dai, Yun; Youssefian, Leena E; Chen, Shuang; Bodie, Wesley W; Takabatake, Yukie; Felthousen, Jessica; Almenara, Jorge A; Kramer, Lora B; Dent, Paul; Grant, Steven

    2011-11-10

    Effects of Chk1 and MEK1/2 inhibition were investigated in cytokinetically quiescent multiple myeloma (MM) and primary CD138(+) cells. Coexposure to the Chk1 and MEK1/2 inhibitors AZD7762 and selumetinib (AZD6244) robustly induced apoptosis in various MM cells and CD138(+) primary samples, but spared normal CD138(-) and CD34(+) cells. Furthermore, Chk1/MEK1/2 inhibitor treatment of asynchronized cells induced G(0)/G(1) arrest and increased apoptosis in all cell-cycle phases, including G(0)/G(1). To determine whether this regimen is active against quiescent G(0)/G(1) MM cells, cells were cultured in low-serum medium to enrich the G(0)/G(1) population. G(0)/G(1)-enriched cells exhibited diminished sensitivity to conventional agents (eg, Taxol and VP-16) but significantly increased susceptibility to Chk1 ± MEK1/2 inhibitors or Chk1 shRNA knock-down. These events were associated with increased γH2A.X expression/foci formation and Bim up-regulation, whereas Bim shRNA knock-down markedly attenuated lethality. Immunofluorescent analysis of G(0)/G(1)-enriched or primary MM cells demonstrated colocalization of activated caspase-3 and the quiescent (G(0)) marker statin, a nuclear envelope protein. Finally, Chk1/MEK1/2 inhibition increased cell death in the Hoechst-positive (Hst(+)), low pyronin Y (PY)-staining (2N Hst(+)/PY(-)) G(0) population and in sorted small side-population (SSP) MM cells. These findings provide evidence that cytokinetically quiescent MM cells are highly susceptible to simultaneous Chk1 and MEK1/2 inhibition.

  17. Hypercoagulable states in patients with multiple myeloma can affect the thalidomide-associated venous thromboembolism.

    Science.gov (United States)

    Talamo, Giampaolo P; Ibrahim, Sulfi; Claxton, David; Tricot, Guido J; Fink, Louis M; Zangari, Maurizio

    2009-07-01

    The therapeutic use of thalidomide in patients with multiple myeloma is often complicated by the development of venous thromboembolism. The objective of the present study was to identify hypercoagulable states associated with development of venous thromboembolism in thalidomide-treated multiple myeloma patients. We screened 49 consecutive multiple myeloma patients treated with thalidomide at baseline for hypercoagulability. With a median follow-up of 11 months, 10 of 49 multiple myeloma patients developed a thrombotic episode. Laboratory assays revealed an underlying abnormality in nine of the 10 patients; hypercoagulable screenings were normal in 36 of the 39 patients who did not develop venous thromboembolism (P < 0.0001). Our retrospective study results suggest that the multiple myeloma patients with thromboembolic complications during treatment with thalidomide have a frequent concomitant underlying thrombophilic state.

  18. [Multiple myeloma : What has been confirmed in therapy?

    Science.gov (United States)

    Baertsch, M-A; Goldschmidt, H

    2017-12-01

    Multiple myeloma (MM) is a malignancy of terminally differentiated B cells/plasma cells and is primarily located in the bone marrow. Symptomatic multiple myeloma typically presents with osteolyses, anemia, reduced renal function, and/or hypercalcemia. In the case of such MM-related end organ damage, urgent systemic treatment is indicated. In order to prevent end organ damage, current guidelines now recommend treatment initiation already when certain biomarkers are met. Current first-line treatment is based on proteasome inhibition and immunomodulation. Eligible patients still benefit from the addition of high-dose chemotherapy and autologous stem cell transplantation. Radiotherapy and orthopedic interventions play an important role in the treatment of localized skeletal complications. For relapsed MM, five novel agents have been approved in Europe during the last two years. These are second-generation proteasome inhibitors (carfilzomib, ixazomib) as well as first-in-class monoclonal antibodies (daratumumab, elotuzumab) and a histone deacetylase inhibitor (panobinostat). Triple combinations based on the established regimens lenalidomide/dexamethasone and bortezomib/dexamethasone plus one of the novel agents have been shown to significantly prolong progression-free survival. Median overall survival of patients with MM has doubled since the turn of the millennium.

  19. Fatal case of Herbaspirillum seropedicae bacteremia secondary to pneumonia in an end-stage renal disease patient with multiple myeloma.

    Science.gov (United States)

    Suwantarat, Nuntra; Adams, La'Tonzia L; Romagnoli, Mark; Carroll, Karen C

    2015-08-01

    Herbaspirillum spp. are rare causes of human infections associated primarily with bacteremia in cancer patients. We report the first fatal case of bacteremia secondary to pneumonia caused by Herbaspirillum seropedicae in a 65-year-old man with end-stage renal disease and multiple myeloma. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Autologous Graft versus Host Disease: An Emerging Complication in Patients with Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Anu Batra

    2014-01-01

    Full Text Available Autologous graft versus host disease (autoGVHD is a rare transplant complication with significant morbidity and mortality. It has been hypothesized that patients with multiple myeloma might be predisposed to autoGVHD through dysregulation of the immune response resulting from either their disease, the immunomodulatory agents (IMiDs used to treat it, or transplant conditioning regimen. Hematopoietic progenitor cell (HPC products were available from 8 multiple myeloma patients with biopsy-proven autoGVHD, 16 matched multiple myeloma patients who did not develop autoGVHD, and 7 healthy research donors. The data on number of transplants prior to developing autoGVHD, mobilization regimens, exposure to proteasome inhibitors, use of IMiDs, and class I human leukocyte antigen types (HLA A and B were collected. The HPC products were analyzed by flow cytometry for expression of CD3, CD4, CD8, CD25, CD56, and FoxP3. CD3+ cell number was significantly lower in autoGVHD patients compared to unaffected controls (P=0.047. On subset analysis of CD3+ cells, CD8+ cells (but not CD4+ cells were found to be significantly lower in patients with autoGVHD (P=0.038. HLA-B55 expression was significantly associated with development of autoGVHD (P=0.032. Lower percentages of CD3+ and CD8+ T-cells and HLA-B55 expression may be predisposing factors for developing autoGVHD in myeloma.

  1. Systemic irradiation in multiple myeloma: a report on nineteen cases

    International Nuclear Information System (INIS)

    Rostom, A.Y.; O'Cathail, S.M.; Folkes, A.

    1984-01-01

    Nineteen patients with relapsed or resistant multiple myeloma were treated with sequential half-body irradiation (12) and half-body irradiation only (seven). Haematological toxicity was acceptable and recovery was complete in all but two of the 19 patients following half-body irradiation. However, only six of the 12 patients who subsequently had the remaining half irradiated completely recovered. Blood transfusions were required to correct anaemia in six patients, a platelet transfusion was given to one and one patient required both platelet and blood transfusions. No serious haematological complications were observed. Six of the 13 patients who received upper half-body irradiation of probable chest infection, while one patient of the six who received lower half-body irradiation died of this complication. Some of the seven deaths may have been due to radiation pneumonitis. Two patients developed brain secondaries, possibly indicating a change in the natural history of myeloma produced by this new treatment. Subjective improvement was observed in 17 patients and relief of pain usually occurred within the first 24 h. Objective responses were noted in six patients. The median survival for all patients was 6 months with five patients alive 11-28 months at the time of writing. (author)

  2. Recent advances in multiple myeloma: a Korean perspective.

    Science.gov (United States)

    Hong, Junshik; Lee, Jae Hoon

    2016-09-01

    Epidemiologically, multiple myeloma (MM) is a malignant disorder of plasma cells with a higher incidence among Western populations than among Asians. However, there is growing evidence of a recent increase in the age-standardized incidence rate (ASR) of MM in Asian countries, particularly Korea. Application of novel agents has resulted in significant improvement of treatment outcomes, and the advances are ongoing with the recent introduction and U.S. Food and Drug Administration's approval of newer agents, including carfilzomib, ixazomib, elotuzumab, and daratumumab. In concert with the technical advances in the cytogenetic and molecular diagnostics of MM, modifications of its diagnosis and staging system have been attempted for better risk stratification. The modified diagnostic criteria from the International Myeloma Working Group in 2014 enabled a strategy of more active treatment for some patients with smoldering MM, with an ultra-high risk of progression, and fine-tuned the definition of end-organ damage, known as CRAB (hypercalcemia, renal insufficiency, anemia, and bone lesions). Considering Korea's trend of aging at an unprecedented rate, we can expect that the ASR of MM will maintain a gradual increase for many years to come; therefore, MM will be a cancer of critical importance from both medical and socioeconomic perspectives in Korea.

  3. Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

    DEFF Research Database (Denmark)

    Mitchell, Jonathan S; Li, Ni; Weinhold, Niels

    2016-01-01

    Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a ...

  4. Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Plasma cell neoplasms occur when abnormal plasma cells or myeloma cells form tumors in the bones or soft tissues of the body. Multiple myeloma, plasmacytoma, lymphoplasmacytic lymphoma, and monoclonal gammopathy of undetermined significance (MGUS) are different types of plasma cell neoplasms. Find out about risk factors, symptoms, diagnostic tests, prognosis, and treatment for these diseases.

  5. New treatment strategies for multiple myeloma by targeting Bcl-2 and the mevalonate pathway

    NARCIS (Netherlands)

    Donk, N.W.C.J. van de

    2003-01-01

    Multiple myeloma is a B-lineage neoplasia. Enhanced proliferation and defects in the regulation of programmed cell death account for the expansion of the malignant clone. Emergence of drug resistance is the primary cause of treatment failure in myeloma. Various studies have indicated that inhibition

  6. Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients

    NARCIS (Netherlands)

    Broyl, Annemiek; Hose, Dirk; Lokhorst, Henk; de Knegt, Yvonne; Peeters, Justine; Jauch, Anna; Bertsch, Uta; Buijs, Arjan; Stevens-Kroef, Marian; Beverloo, H. Berna; Vellenga, Edo; Zweegman, Sonja; Kersten, Marie-Josée; van der Holt, Bronno; el Jarari, Laila; Mulligan, George; Goldschmidt, Hartmut; van Duin, Mark; Sonneveld, Pieter

    2010-01-01

    To identify molecularly defined subgroups in multiple myeloma, gene expression profiling was performed on purified CD138(+) plasma cells of 320 newly diagnosed myeloma patients included in the Dutch-Belgian/German HOVON-65/GMMG-HD4 trial. Hierarchical clustering identified 10 subgroups; 6

  7. Biochemical markers of bone metabolism reflect osteoclastic and osteoblastic activity in multiple myeloma

    DEFF Research Database (Denmark)

    Abildgaard, N; Glerup, H; Rungby, Jørgen

    2000-01-01

    In order to evaluate the use of recently developed assays of bone metabolism in multiple myeloma we performed a histomorphometric study of bone biopsies in 16 myeloma patients. Furthermore, we measured the levels of interleukin-6 (IL-6), soluble IL-6 receptor (IL-6sR), IL-1beta, tumour necrosis f...

  8. Preclinical Evidence for the Therapeutic Potential of CD38-Targeted Immuno-Chemotherapy in Multiple Myeloma Patients Refractory to Lenalidomide and Bortezomib

    DEFF Research Database (Denmark)

    Nijhof, I. S.; Groen, R. W. J.; Noort, W. A.

    2015-01-01

    lenalidomide- and/or bortezomib-refractory patients. In these assays, lenalidomide but not bortezomib, synergistically enhanced daratumumab-mediated multiple myeloma lysis through activation of natural killer cells. Finally, in an in vivo xenograft model, only the combination of daratumumab with lenalidomide......Purpose: Novel therapeutic agents have significantly improved the survival of patients with multiple myeloma. Nonetheless, the prognosis of patients with multiple myeloma who become refractory to the novel agents lenalidomide and bortezomib is very poor, indicating the urgent need for new...... therapeutic options for these patients. The human CD38 monoclonal antibody daratumumab is being evaluated as a novel therapy for multiple myeloma. Prompted with the encouraging results of ongoing clinical phase I/II trials, we now addressed the potential value of daratumumab alone or in combination...

  9. Effects of daratumumab on natural killer cells and impact on clinical outcomes in relapsed or refractory multiple myeloma

    DEFF Research Database (Denmark)

    Casneuf, Tineke; Xu, Xu Steven; Adams, Homer C

    2017-01-01

    Daratumumab, a human CD38 imunoglobulin G 1κ monoclonal antibody, has demonstrated clinical activity and a manageable safety profile in monotherapy and combination therapy clinical trials in relapsed and/or refractory multiple myeloma. CD38 is expressed at high levels on myeloma cells and......, to a lesser extent, on immune effector cells, including natural killer (NK) cells, which are important for daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Here, the pharmacodynamic effects of daratumumab monotherapy on NK cells, and the effect of NK cell dynamics on daratumumab efficacy...

  10. Magnetic resonance appearance of monoclonal gammopathies of unknown significance and multiple myeloma. The GRI Study Group.

    Science.gov (United States)

    Bellaïche, L; Laredo, J D; Lioté, F; Koeger, A C; Hamze, B; Ziza, J M; Pertuiset, E; Bardin, T; Tubiana, J M

    1997-11-01

    A prospective multicenter study. To evaluate the use of magnetic resonance imaging, in the differentiation between monoclonal gammopathies of unknown significance and multiple myeloma. Although multiple myeloma has been studied extensively with magnetic resonance imaging, to the authors' knowledge, no study has evaluated the clinical interest of magnetic resonance imaging in the differentiation between monoclonal gammopathies of unknown significance and multiple myeloma. The magnetic resonance examinations of the thoracolumbar spine in 24 patients with newly diagnosed monoclonal gammopathies of unknown significance were compared with those performed in 44 patients with newly diagnosed nontreated multiple myeloma. All findings on magnetic resonance examination performed in patients with monoclonal gammopathies of unknown significance were normal, whereas findings on 38 (86%) of the 44 magnetic resonance examinations performed in patients with multiple myeloma were abnormal. Magnetic resonance imaging can be considered as an additional diagnostic tool in differentiating between monoclonal gammopathies of unknown significance and multiple myeloma, which may be helpful when routine criteria are not sufficient. An abnormal finding on magnetic resonance examination in a patient with monoclonal gammopathies of unknown significance should suggest the diagnosis of multiple myeloma after other causes of marrow signal abnormalities are excluded. Magnetic resonance imaging also may be proposed in the long-term follow-up of monoclonal gammopathies of unknown significance when a new biologic or clinical event suggests the diagnosis of malignant monoclonal gammopathy.

  11. Endothelial progenitor cells display clonal restriction in multiple myeloma

    International Nuclear Information System (INIS)

    Braunstein, Marc; Özçelik, Tayfun; Bağişlar, Sevgi; Vakil, Varsha; Smith, Eric LP; Dai, Kezhi; Akyerli, Cemaliye B; Batuman, Olcay A

    2006-01-01

    In multiple myeloma (MM), increased neoangiogenesis contributes to tumor growth and disease progression. Increased levels of endothelial progenitor cells (EPCs) contribute to neoangiogenesis in MM, and, importantly, covary with disease activity and response to treatment. In order to understand the mechanisms responsible for increased EPC levels and neoangiogenic function in MM, we investigated whether these cells were clonal by determining X-chromosome inactivation (XCI) patterns in female patients by a human androgen receptor assay (HUMARA). In addition, EPCs and bone marrow cells were studied for the presence of clonotypic immunoglobulin heavy-chain (IGH) gene rearrangement, which indicates clonality in B cells; thus, its presence in EPCs would indicate a close genetic link between tumor cells in MM and endothelial cells that provide tumor neovascularization. A total of twenty-three consecutive patients who had not received chemotherapy were studied. Screening in 18 patients found that 11 displayed allelic AR in peripheral blood mononuclear cells, and these patients were further studied for XCI patterns in EPCs and hair root cells by HUMARA. In 2 patients whose EPCs were clonal by HUMARA, and in an additional 5 new patients, EPCs were studied for IGH gene rearrangement using PCR with family-specific primers for IGH variable genes (V H ). In 11 patients, analysis of EPCs by HUMARA revealed significant skewing (≥ 77% expression of a single allele) in 64% (n = 7). In 4 of these patients, XCI skewing was extreme (≥ 90% expression of a single allele). In contrast, XCI in hair root cells was random. Furthermore, PCR amplification with V H primers resulted in amplification of the same product in EPCs and bone marrow cells in 71% (n = 5) of 7 patients, while no IGH rearrangement was found in EPCs from healthy controls. In addition, in patients with XCI skewing in EPCs, advanced age was associated with poorer clinical status, unlike patients whose EPCs had random XCI

  12. Ibrutinib targets microRNA-21 in multiple myeloma cells by inhibiting NF-κB and STAT3.

    Science.gov (United States)

    Ma, Jing; Gong, Wei; Liu, Su; Li, Qian; Guo, Mengzheng; Wang, Jinhan; Wang, Suying; Chen, Naiyao; Wang, Yafei; Liu, Qiang; Zhao, Hui

    2018-01-01

    The oncogenic microRNA-21 contributes to the pathogenesis of multiple myeloma. Ibrutinib (also referred to as PCI-32765), an inhibitor of Bruton's tyrosine kinase, while its effects on multiple myeloma have not been well described. Here, we show that microRNA-21 is an oncogenic marker closely linked with progression of multiple myeloma. Moreover, ibrutinib attenuates microRNA-21 expression in multiple myeloma cells by inhibiting nuclear factor-κB and signal transducer and activator of transcription 3 signaling pathways. Taken together, our results suggest that ibrutinib is a promising potential treatment for multiple myeloma. Further investigation of mechanisms of ibrutinib function in multiple myeloma will be necessary to evaluate its use as a novel multiple myeloma treatment.

  13. Preclinical studies in support of defibrotide for the treatment of multiple myeloma and other neoplasias.

    Science.gov (United States)

    Mitsiades, Constantine S; Rouleau, Cecile; Echart, Cinara; Menon, Krishna; Teicher, Beverly; Distaso, Maria; Palumbo, Antonio; Boccadoro, Mario; Anderson, Kenneth C; Iacobelli, Massimo; Richardson, Paul G

    2009-02-15

    Defibrotide, an orally bioavailable polydisperse oligonucleotide, has promising activity in hepatic veno-occlusive disease, a stem cell transplantation-related toxicity characterized by microangiopathy. The antithrombotic properties of defibrotide and its minimal hemorrhagic risk could serve for treatment of cancer-associated thrombotic complications. Given its cytoprotective effect on endothelium, we investigated whether defibrotide protects tumor cells from cytotoxic antitumor agents. Further, given its antiadhesive properties, we evaluated whether defibrotide modulates the protection conferred to multiple myeloma cells by bone marrow stromal cells. Defibrotide lacks significant single-agent in vitro cytotoxicity on multiple myeloma or solid tumor cells and does not attenuate their in vitro response to dexamethasone, bortezomib, immunomodulatory thalidomide derivatives, and conventional chemotherapeutics, including melphalan and cyclophosphamide. Importantly, defibrotide enhances in vivo chemosensitivity of multiple myeloma and mammary carcinoma xenografts in animal models. In cocultures of multiple myeloma cells with bone marrow stromal cells in vitro, defibrotide enhances the multiple myeloma cell sensitivity to melphalan and dexamethasone, and decreases multiple myeloma-bone marrow stromal cell adhesion and its sequelae, including nuclear factor-kappaB activation in multiple myeloma and bone marrow stromal cells, and associated cytokine production. Moreover, defibrotide inhibits expression and/or function of key mediators of multiple myeloma interaction with bone marrow stromal cell and endothelium, including heparanase, angiogenic cytokines, and adhesion molecules. Defibrotide's in vivo chemosensitizing properties and lack of direct in vitro activity against tumor cells suggest that it favorably modulates antitumor interactions between bone marrow stromal cells and endothelia in the tumor microenvironment. These data support clinical studies of defibrotide in

  14. Salvage Therapy of Multiple Myeloma: The New Generation Drugs

    Directory of Open Access Journals (Sweden)

    Alessandra Romano

    2014-01-01

    Full Text Available During the past decade, overall results of treatment of multiple myeloma (MM have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs. However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways.

  15. Salvage Therapy of Multiple Myeloma: The New Generation Drugs

    Science.gov (United States)

    Romano, Alessandra; Conticello, Concetta; Di Raimondo, Cosimo; Schinocca, Elena; La Fauci, Alessia; Parrinello, Nunziatina Laura; Chiarenza, Annalisa

    2014-01-01

    During the past decade, overall results of treatment of multiple myeloma (MM) have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs). However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways. PMID:24967371

  16. Herpes zoster in multiple myeloma patients during bortezomib treatment

    Directory of Open Access Journals (Sweden)

    I. N. Nazarova

    2011-01-01

    Full Text Available Recent advances in multiple myeloma (MM treatment associated with new drug use including bortezomib. Experiences in wide ambul atory drug use confirm therapy success for this serious disease, but at the same time reveals the most common side effects. One of th e most significant is the reactivation of Herpes zoster , which leads to decrease MM therapy results because of inability to perform standard therapy in these patients. Literature data and own experiences about reactivation of Herpes zoster during bortezomib therapy as monothe rapy and in combination, which varies from 7 to 34% according to different authors and 25% of own experiences, is presented. Treatment and preventive schedule of this complication are shown.

  17. New insights into the pathophysiology of multiple myeloma

    International Nuclear Information System (INIS)

    Tothova, E.; Kafkova, A.

    2013-01-01

    The last decade has seen significant advances in our understanding of the biology of multiple myeloma (MM) and our approaches to its treatment. As a result of these advances, the median survival of patients has increased and we can now achieve a cure in at least some patients. This improved knowledge about MM biology needs to be rapidly translated and transformed into diagnostic and therapeutic applications to finally achieve cure in a larger proportion of patients. Genetic mutations leading to chromosomal translocations and deletions play a key role in the progression to active, malignant MM. As a part of these translation efforts, novel drugs that inhibit oncogenic proteins over expressed in defined molecular subgroups of the disease, are currently being developed. Identification of potential therapeutic targets in the bone marrow microenvironment is leading to the development of therapies that are changing the standard of care for MM patients. (author)

  18. Multiple myeloma in an Amur tiger (Panthera tigris altaica

    Directory of Open Access Journals (Sweden)

    Alison M. Lee

    2017-10-01

    Full Text Available The Amur tiger (Panthera tigris altaica is an endangered tiger subspecies. An adult zoo-bred female was found collapsed, and died despite supportive treatment. Hematology and biochemistry showed pancytopenia and hyperglobulinemia, and serum protein electrophoresis revealed a monoclonal band in the β-globulin region. Necropsy demonstrated hemoabdomen, multifocal lytic bone marrow lesions, splenomegaly, and hemorrhagic hepatic nodules, with left medial lobe rupture. There were mutifocal hemorrhages in the subcutis, lung, epicardium, and intestinal mucosa. Histopathology demonstrated plasmacytoid cells infiltrating the bone marrow, liver and spleen, and circulating within blood vessels. On immunohistochemistry, cell infiltrates of the three tissues were positive for λ light chains, bone marrow infiltrates were positive for MUM-1 and bone marrow and spleen infiltrates were positive for CD20. These findings indicate that this animal died of hemoabdomen subsequent to multiple myeloma. This is the first time this disease has been reported in a tiger.

  19. The Mutational Landscape of Circulating Tumor Cells in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Yuji Mishima

    2017-04-01

    Full Text Available The development of sensitive and non-invasive “liquid biopsies” presents new opportunities for longitudinal monitoring of tumor dissemination and clonal evolution. The number of circulating tumor cells (CTCs is prognostic in multiple myeloma (MM, but there is little information on their genetic features. Here, we have analyzed the genomic landscape of CTCs from 29 MM patients, including eight cases with matched/paired bone marrow (BM tumor cells. Our results show that 100% of clonal mutations in patient BM were detected in CTCs and that 99% of clonal mutations in CTCs were present in BM MM. These include typical driver mutations in MM such as in KRAS, NRAS, or BRAF. These data suggest that BM and CTC samples have similar clonal structures, as discordances between the two were restricted to subclonal mutations. Accordingly, our results pave the way for potentially less invasive mutation screening of MM patients through characterization of CTCs.

  20. The role of epigenetics in the biology of multiple myeloma

    DEFF Research Database (Denmark)

    Dimopoulos, K; Gimsing, P; Grønbæk, K

    2014-01-01

    Several recent studies have highlighted the biological complexity of multiple myeloma (MM) that arises as a result of several disrupted cancer pathways. Apart from the central role of genetic abnormalities, epigenetic aberrations have also been shown to be important players in the development of MM......, and a lot of research during the past decades has focused on the ways DNA methylation, histone modifications and noncoding RNAs contribute to the pathobiology of MM. This has led to, apart from better understanding of the disease biology, the development of epigenetic drugs, such as histone deacetylase...... inhibitors that are already used in clinical trials in MM with promising results. This review will present the role of epigenetic abnormalities in MM and how these can affect specific pathways, and focus on the potential of novel 'epidrugs' as future treatment modalities for MM....

  1. The novel immunotoxin HM1.24-ETA′ induces apoptosis in multiple myeloma cells

    International Nuclear Information System (INIS)

    Staudinger, M; Glorius, P; Burger, R; Kellner, C; Klausz, K; Günther, A; Repp, R; Klapper, W; Gramatzki, M; Peipp, M

    2014-01-01

    Despite new treatment modalities, the clinical outcome in a substantial number of patients with multiple myeloma (MM) has yet to be improved. Antibody-based targeted therapies for myeloma patients could make use of the HM1.24 antigen (CD317), a surface molecule overexpressed on malignant plasma cells and efficiently internalized. Here, a novel immunotoxin, HM1.24-ETA′, is described. HM1.24-ETA′ was generated by genetic fusion of a CD317-specific single-chain Fv (scFv) antibody and a truncated variant of Pseudomonas aeruginosa exotoxin A (ETA′). HM1.24-ETA′ inhibited growth of interleukin 6 (IL-6)-dependent and -independent myeloma cell lines. Half-maximal growth inhibition was observed at concentrations as low as 0.3 nM. Target cell killing occurred via induction of apoptosis and was unaffected in co-culture experiments with bone marrow stromal cells. HM1.24-ETA′ efficiently triggered apoptosis of freshly isolated/cryopreserved cells of patients with plasma cell leukemia and MM and was active in a preclinical severe combined immunodeficiency (SCID) mouse xenograft model. Importantly, HM1.24-ETA′ was not cytotoxic against CD317-positive cells from healthy tissue (monocytes, human umbilical vein endothelial cells). These results indicate that CD317 may represent a promising target structure for specific and efficient immunotoxin therapy for patients with plasma cell tumors

  2. Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders

    DEFF Research Database (Denmark)

    Rawstron, Andy C; Orfao, Alberto; Beksac, Meral

    2008-01-01

    The European Myeloma Network (EMN) organized two flow cytometry workshops. The first aimed to identify specific indications for flow cytometry in patients with monoclonal gammopathies, and consensus technical approaches through a questionnaire-based review of current practice in participating...

  3. Light chain deposition disease in multiple myeloma: MR imaging features correlated with histopathological findings

    International Nuclear Information System (INIS)

    Baur, A.; Staebler, A.; Reiser, M.; Lamerz, R.; Bartl, R.

    1998-01-01

    The clinical, histopathological, and imaging findings on MRI of a 56-year-old woman with light chain deposition disease occurring in multiple myeloma are presented. Light chain deposition disease is a variant of multiple myeloma with distinct clinical and histological characteristics. MRI of this patient also revealed an infiltration pattern in the bone marrow distinct from that of typical multiple myeloma. Multiple small foci of low signal intensity were present on T1- and T2-weighted spin echo and STIR images, corresponding to conglomerates of light chains in bone marrow biopsy. Contrast-enhanced T1-weighted spin echo images show diffuse enhancement of 51% over all vertebral bodies, with a minor enhancement of the focal conglomerates of light chains. Light chain deposition disease in multiple myeloma should be added to the list of those few entities with normal radiographs and discrete low-signal marrow lesions on T1- and T2-weighted spin echo pulse sequences. (orig.)

  4. Drug response prediction in high-risk multiple myeloma

    DEFF Research Database (Denmark)

    Vangsted, A J; Helm-Petersen, S; Cowland, J B

    2018-01-01

    from high-risk patients by GEP70 at diagnosis from Total Therapy 2 and 3A to predict the response by the DRP score of drugs used in the treatment of myeloma patients. The DRP score stratified patients further. High-risk myeloma with a predicted sensitivity to melphalan by the DRP score had a prolonged...

  5. Evaluation of serial bone X-ray examination in multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Wahlin, A.; Holm, J.; Osterman, G.; Norberg, B. (University Hospital, Umeaa (Sweden). Dept. of Internal Medicine and Diagnostic Radiology I)

    1982-01-01

    Fifteen patients with multiple myeloma stage III were treated with a combination of cytostatics and plasmapheresis in a sequential trial running for 60 weeks. Thirteen patients showed clinical improvement and ten a reduction of thieir myeloma protein by at least 50%. Bone X-ray examination was performed every 15 weeks. Progression of bone lesions was seen in one patient, whereas the radiographic picture was unchanged in the others. It is concluded that bone X-ray, although essential in the diagnosis and staging of multiple myeloma, is not suitable for the monitoring of patients during treatment.

  6. Whole-Body MRI versus PET in assessment of multiple myeloma disease activity.

    LENUS (Irish Health Repository)

    Shortt, Conor P

    2009-04-01

    The purpose of this study was to compare FDG PET; whole-body MRI; and the reference standard, bone marrow aspiration and biopsy, to determine the best imaging technique for assessment of disease activity in multiple myeloma.

  7. Plasma Cell Neoplasms (Including Multiple Myeloma)—Health Professional Version

    Science.gov (United States)

    There are several types of plasma cell neoplasms, including monoclonal gammopathy of undetermined significance (MGUS), isolated plasmacytoma of the bone, extramedullary plasmacytoma, and multiple myeloma. Find evidence-based information on plasma cell neoplasms treatment, research, and statistics.

  8. Maintaining bone health in patients with multiple myeloma: survivorship care plan of the International Myeloma Foundation Nurse Leadership Board.

    Science.gov (United States)

    Miceli, Teresa S; Colson, Kathleen; Faiman, Beth M; Miller, Kena; Tariman, Joseph D

    2011-08-01

    About 90% of individuals with multiple myeloma will develop osteolytic bone lesions from increased osteoclastic and decreased osteoblastic activity. Severe morbidities from pathologic fractures and other skeletal events can lead to poor circulation, blood clots, muscle wasting, compromised performance status, and overall poor survival. Supportive care targeting bone disease is an essential adjunct to antimyeloma therapy. In addition, the maintenance of bone health in patients with multiple myeloma can significantly improve quality of life. Oncology nurses and other healthcare providers play a central role in the management of bone disease and maintenance throughout the course of treatment. Safe administration of bisphosphonates, promotion of exercise, maintenance of adequate nutrition, vitamin and mineral supplementation, scheduled radiographic examinations, and monitoring of bone complications are among the important functions that oncology nurses and healthcare providers perform in clinical practice.

  9. Detection of Extramedullary Multiple Myeloma in Liver by FDG-PET/CT

    International Nuclear Information System (INIS)

    Kim, Daeweung; Kim, Woo Hyoung; Kim, Myoung Hyoun; Choi, Keum Ha; Kim, Chang Guhn

    2014-01-01

    We present the case of a 42-year-old man with a painful mass lesion in the right shoulder that was detected by contrast-enhanced computed tomography (CT) and 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) positron emission tomography (PET)/CT. Excisional biopsy revealed infiltration of plasma cells with anaplastic features, consistent with solitary plasmacytoma (PC). Serum analysis showed elevation of serum free lambda light chain levels (27.78 mg/l), with an abnormally high kappa:lambda ratio (2.33) and high total proteins (10.4 g/dl). Serum protein electrophoresis revealed an M spike in the gamma-globulin region (56.1 %=5.8 g/dl). Subsequently, 18 F-FDG PET/CT revealed another hypermetabolic mass in the right lobe of the liver. CT-guided biopsy of the liver lesion revealed plasma cell myeloma, consistent with multiple myeloma. Multiple myeloma presenting as nodular liver masses is very rare in clinical practice. In a retrospective review of more than 2,000 patients, Talamo et al. reported only nine cases where there was nodular involvement of the liver by multiple myeloma. The organ most commonly involved was the liver, followed by pancreas, stomach, peritoneum with malignant ascites, colon, rectum, duodenum and ileum. Therefore, the literature published thus far has been limited to a few reports and case series. Among these reports, some had demonstrated the PET or PET/CT findings of nodular liver involvement of multiple myeloma. About 10 % of the solitary myelomas appeared as extramedullary PC or solitary PC of bone. In spite of the advances in therapy, the treatment of multiple myeloma is still palliative. However, solitary PC could be cured by resection or radiation therapy. Thus, differentiation between PC and multiple myeloma is essential in making a decision for the appropriate therapeutic regimen. 18 F-FDG PET/CT has the unique ability to detect and characterize malignant lesions in one single examination. Schirrmeister et al. reported that 18 F-FDG PET revealed

  10. Detection of Extramedullary Multiple Myeloma in Liver by FDG-PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Daeweung; Kim, Woo Hyoung; Kim, Myoung Hyoun; Choi, Keum Ha; Kim, Chang Guhn [Wonkwang Univ. School of Medicine, Iksan (Korea, Republic of)

    2014-06-15

    We present the case of a 42-year-old man with a painful mass lesion in the right shoulder that was detected by contrast-enhanced computed tomography (CT) and {sup 18}F-fluoro-2-deoxyglucose ({sup 18}F-FDG) positron emission tomography (PET)/CT. Excisional biopsy revealed infiltration of plasma cells with anaplastic features, consistent with solitary plasmacytoma (PC). Serum analysis showed elevation of serum free lambda light chain levels (27.78 mg/l), with an abnormally high kappa:lambda ratio (2.33) and high total proteins (10.4 g/dl). Serum protein electrophoresis revealed an M spike in the gamma-globulin region (56.1 %=5.8 g/dl). Subsequently, {sup 18}F-FDG PET/CT revealed another hypermetabolic mass in the right lobe of the liver. CT-guided biopsy of the liver lesion revealed plasma cell myeloma, consistent with multiple myeloma. Multiple myeloma presenting as nodular liver masses is very rare in clinical practice. In a retrospective review of more than 2,000 patients, Talamo et al. reported only nine cases where there was nodular involvement of the liver by multiple myeloma. The organ most commonly involved was the liver, followed by pancreas, stomach, peritoneum with malignant ascites, colon, rectum, duodenum and ileum. Therefore, the literature published thus far has been limited to a few reports and case series. Among these reports, some had demonstrated the PET or PET/CT findings of nodular liver involvement of multiple myeloma. About 10 % of the solitary myelomas appeared as extramedullary PC or solitary PC of bone. In spite of the advances in therapy, the treatment of multiple myeloma is still palliative. However, solitary PC could be cured by resection or radiation therapy. Thus, differentiation between PC and multiple myeloma is essential in making a decision for the appropriate therapeutic regimen. {sup 18}F-FDG PET/CT has the unique ability to detect and characterize malignant lesions in one single examination. Schirrmeister et al. reported that

  11. [Role of radiotherapy in the treatment of multiple myeloma].

    Science.gov (United States)

    Mose, S; Pfitzner, D; Rahn, A; Nierhoff, C; Schiemann, M; Böttcher, H D

    2000-11-01

    Chemotherapy is the treatment of choice in multiple myeloma; but there are no curative options. Therefore, the treatment rationale is characterized by reduction of symptoms and inhibition of complications. Regarding reduction of pain, treatment of (impending) fractures, and spinal cord compression radiation is an important part of palliative treatment. In our retrospective study we report the effect of radiotherapy on reduction of pain, recalcification and the reduction of neurological symptoms and evaluate factors which have an impact on therapeutic outcome. From 1, Jan 1988 to 31, Dec 1998, 42 patients (19 women, 23 men; range of ages 46 to 85 years, median age 64.9 years) with 71 target volumes were irradiated (median dose 36 Gy, 2 to 3 Gy 5 times/week) because of symptomatic disease (67/71: osseous pain, 45/71: fractures/impending fractures, 13/71: spinal cord compression) (Tables 1 and 2). The median time from diagnosis to the first course of radiotherapy was 11.9 months (0.3 to 90 months). At the time of first irradiation, 5 and 37 patients were in tumor Stage II and III (Salmon/Durie), respectively. The median value of the Karnofsky performance was 70% (40 to 90%). During follow-up (at least 6 months) in 85% of target volumes complete and partial pain relief (measured by patients' perception and the use of analgetic medication) was achieved; recurrences were seen in 8.8%. In 26/56 (46.4%) lesions evaluable a recalcification was seen whereas 17.9% showed progressive disease (comparison of radiographs before and after radiation). In 22.3% of all lesions initially with impending fracture (4/18) radiotherapy failed because of fracture after treatment (Tables 3 and 4). Simultaneous chemotherapy and a Karnofsky performance > or = 70 had a significant impact on a positive response to treatment, respectively. Spinal cord compression symptoms were reduced in 7/13 (53.8%) of patients (scaled due to the classification by Findlay 1987). The median survival from

  12. Imaging of multiple myeloma and related monoclonal plasma cell diseases. An update

    International Nuclear Information System (INIS)

    Weber, Marc-Andre; Delorme, Stefan; Hillengass, Jens

    2014-01-01

    Multiple myeloma is a hematologic disorder characterized by the infiltration and proliferation of monoclonal plasma cells mainly in the bone marrow. The main symptoms are hypercalcemia, renal impairment, cytopenia/anemia and bone disease - summarized as CRAB-criteria. Symptomatic multiple myeloma is consistently preceded by asymptomatic premalignant stages called monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Staging of multiple myeloma is based on the measurement of the monoclonal protein in serum and urine as well as the assessment of impairment of hematopoiesis, renal function and mineralized bone. In the last decade the development of novel therapeutic agents has led to an increase in response rates and survival time of patients with multiple myeloma, which further stresses the value of response assessment by imaging. Cross sectional imaging like MRI and CT is currently replacing conventional radiological surveys in the initial work-up and follow-up of patients with monoclonal plasma cell diseases. The added value of MRI is to improve initial staging by unraveling a diffuse infiltration of bone marrow by plasma cells, a focal pattern or a combination of both. Furthermore, a complete remission of myeloma confirmed by MRI and CT goes along with a better prognosis compared to a complete response based only on serological parameters.

  13. Long-term survival of patients with multiple myeloma and acute renal failure at presentation.

    Science.gov (United States)

    Lazarus, H M; Adelstein, D J; Herzig, R H; Smith, M C

    1983-03-01

    Eight patients presented with simultaneous multiple myeloma and acute renal failure requiring hemodialysis. Patients had no known pre-existing renal disease nor exposure to nephrotoxic agents or x-ray contrast dye. Renal failure was attributed to light chain nephropathy in all cases. In 4 of these patients the diagnosis of myeloma was initially unsuspected. Renal biopsies in 3 of these patients, and post-mortem material in a fourth revealed the changes of "myeloma kidney." No patient regained renal function and all required chronic hemodialysis. Among these eight patients, three survived for periods greater than 21 months.

  14. Phosphoinositide protein kinase PDPK1 is a crucial cell signaling mediator in multiple myeloma.

    Science.gov (United States)

    Chinen, Yoshiaki; Kuroda, Junya; Shimura, Yuji; Nagoshi, Hisao; Kiyota, Miki; Yamamoto-Sugitani, Mio; Mizutani, Shinsuke; Sakamoto, Natsumi; Ri, Masaki; Kawata, Eri; Kobayashi, Tsutomu; Matsumoto, Yosuke; Horiike, Shigeo; Iida, Shinsuke; Taniwaki, Masafumi

    2014-12-15

    Multiple myeloma is a cytogenetically/molecularly heterogeneous hematologic malignancy that remains mostly incurable, and the identification of a universal and relevant therapeutic target molecule is essential for the further development of therapeutic strategy. Herein, we identified that 3-phosphoinositide-dependent protein kinase 1 (PDPK1), a serine threonine kinase, is expressed and active in all eleven multiple myeloma-derived cell lines examined regardless of the type of cytogenetic abnormality, the mutation state of RAS and FGFR3 genes, or the activation state of ERK and AKT. Our results revealed that PDPK1 is a pivotal regulator of molecules that are essential for myelomagenesis, such as RSK2, AKT, c-MYC, IRF4, or cyclin Ds, and that PDPK1 inhibition caused the growth inhibition and the induction of apoptosis with the activation of BIM and BAD, and augmented the in vitro cytotoxic effects of antimyeloma agents in myeloma cells. In the clinical setting, PDPK1 was active in myeloma cells of approximately 90% of symptomatic patients at diagnosis, and the smaller population of patients with multiple myeloma exhibiting myeloma cells without active PDPK1 showed a significantly less frequent proportion of the disease stage III by the International Staging System and a significantly more favorable prognosis, including the longer overall survival period and the longer progression-free survival period by bortezomib treatment, than patients with active PDPK1, suggesting that PDPK1 activation accelerates the disease progression and the resistance to treatment in multiple myeloma. Our study demonstrates that PDPK1 is a potent and a universally targetable signaling mediator in multiple myeloma regardless of the types of cytogenetic/molecular profiles. ©2014 American Association for Cancer Research.

  15. Molecular purging of multiple myeloma cells by ex-vivo culture and retroviral transduction of mobilized-blood CD34+ cells

    Directory of Open Access Journals (Sweden)

    Corneo Gianmarco

    2007-07-01

    Full Text Available Abstract Background Tumor cell contamination of the apheresis in multiple myeloma is likely to affect disease-free and overall survival after autografting. Objective To purge myeloma aphereses from tumor contaminants with a novel culture-based purging method. Methods We cultured myeloma-positive CD34+ PB samples in conditions that retained multipotency of hematopoietic stem cells, but were unfavourable to survival of plasma cells. Moreover, we exploited the resistance of myeloma plasma cells to retroviral transduction by targeting the hematopoietic CD34+ cell population with a retroviral vector carrying a selectable marker (the truncated form of the human receptor for nerve growth factor, ΔNGFR. We performed therefore a further myeloma purging step by selecting the transduced cells at the end of the culture. Results Overall recovery of CD34+ cells after culture was 128.5%; ΔNGFR transduction rate was 28.8% for CD34+ cells and 0% for CD138-selected primary myeloma cells, respectively. Recovery of CD34+ cells after ΔNGFR selection was 22.3%. By patient-specific Ig-gene rearrangements, we assessed a decrease of 0.7–1.4 logs in tumor load after the CD34+ cell selection, and up to 2.3 logs after culture and ΔNGFR selection. Conclusion We conclude that ex-vivo culture and retroviral-mediated transduction of myeloma leukaphereses provide an efficient tumor cell purging.

  16. Detection and Characterization of Circulating Tumour Cells in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Liangxuan Zhang

    2016-06-01

    Full Text Available Multiple myeloma (MM remains an incurable disease despite recent therapeutic improvements. The ability to detect and characterize MM circulating tumour cells (CTCs in peripheral blood provides an alternative to replace or augment invasive bone marrow (BM biopsies with a simple blood draw, providing real-time, clinically relevant information leading to improved disease manage‐ ment and therapy selection. Here we have developed and qualified an enrichment-free, cell-based immunofluores‐ cence MM CTC assay that utilizes an automated digital pathology algorithm to distinguish MM CTCs from white blood cells (WBCs on the basis of CD138 and CD45 expression levels, as well as a number of morphological parameters. These MM CTCs were further characterized for expression of phospho-ribosomal protein S6 (pS6 as a readout for PI3K/AKT pathway activation. Clinical feasi‐ bility of the assay was established by testing blood samples from a small cohort of patients, where we detected popu‐ lations of both CD138pos and CD138neg MM CTCs. In this study, we developed an immunofluorescent cell-based assay to detect and characterize CTCs in MM.

  17. Detection and Characterization of Circulating Tumour Cells in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Liangxuan Zhang

    2016-01-01

    Full Text Available Multiple myeloma (MM remains an incurable disease despite recent therapeutic improvements. The ability to detect and characterize MM circulating tumour cells (CTCs in peripheral blood provides an alternative to replace or augment invasive bone marrow (BM biopsies with a simple blood draw, providing real-time, clinically relevant information leading to improved disease management and therapy selection. Here we have developed and qualified an enrichment-free, cell-based immunofluorescence MM CTC assay that utilizes an automated digital pathology algorithm to distinguish MM CTCs from white blood cells (WBCs on the basis of CD138 and CD45 expression levels, as well as a number of morphological parameters. These MM CTCs were further characterized for expression of phospho-ribosomal protein S6 (pS6 as a readout for PI3K/AKT pathway activation. Clinical feasibility of the assay was established by testing blood samples from a small cohort of patients, where we detected populations of both CD138 pos and CD138 neg MM CTCs. In this study, we developed an immunofluorescent cell-based assay to detect and characterize CTCs in MM.

  18. Early response to therapy and survival in multiple myeloma.

    Science.gov (United States)

    Schaar, C G; Kluin-Nelemans, J C; le Cessie, S; Franck, P F H; te Marvelde, M C; Wijermans, P W

    2004-04-01

    Whether the response to chemotherapy is a prognosticator in multiple myeloma (MM) is still not known. Therefore, the relationship between survival and the rate of monoclonal protein (M-protein) decrement during the first cycles of therapy was prospectively assessed in 262 patients with newly diagnosed MM that were included in a phase III trial (HOVON-16). M-proteins were collected monthly during melphalan-prednisone therapy (MP: melphalan 0.25 mg/kg, prednisone 1.0 mg/kg orally for 5 d every 4 weeks). Patients with light chain disease (n = 18), immunoglobulin M (IgM)-MM (n = 1) and no immunotyping (n = 1) were excluded. Of the 242 patients studied, 75% had IgG M-protein and 25% IgA; MM stages: I: 1%, II: 35% and III: 64%. The median M-protein decrease after the first cycle of MP was 21% for IgG and 27% for IgA, and declined to < 5% after four cycles. An obvious survival advantage was seen for patients who had an M-protein decrease of at least 30% after the first MP cycle, which became significant when an M-protein decrease of 40% or more was reached. As established prognostic parameters (Salmon & Durie stage, serum creatinine, and haemoglobin) also remained prognostically significant, we concluded that early response to MP predicts for survival in MM.

  19. Bortezomib: a novel therapy approved for multiple myeloma.

    Science.gov (United States)

    Richardson, Paul G; Anderson, Kenneth C

    2003-10-01

    Cellular homeostasis requires routine degradation of key regulatory proteins, including tumor suppressor gene products, transcription factors, cell-cycle proteins and their inhibitors, as well as damaged and misfolded proteins. A critical part of this process is mediated by the 26S proteasome, a multi-subunit enzyme found in the nucleus and cytoplasm of all eukaryotic cells. Because of its essential role in many cellular processes controlling growth and survival, the proteasome has been identified as a potential target for cancer therapy. Drugs known to inhibit proteasome activity have been shown to induce cell-cycle arrest and programmed cell death (apoptosis). The impact of this finding is heightened by research showing that cancer cells are more sensitive to the proapoptotic effects of proteasome inhibition than normal cells. Preclinical evidence using bortezomib, the only proteasome inhibitor to enter clinical trials, suggests that proteasome inhibition may be effective in the treatment of hematologic and solid malignancies by promoting apoptosis, retarding angiogenesis, and inhibiting tumor cell adhesion and production of growth factors by acting on molecules such as nuclear factor-kappaB. Further preclinical evidence suggests that the antitumor effects of cytotoxic chemotherapy or radiotherapy may be enhanced by the addition of a proteasome inhibitor. Bortezomib was recently approved for the treatment of multiple myeloma. It is currently being investigated, both as a single agent and in combination, in phase I and II trials in a variety of tumor types.

  20. Spotlight on ixazomib: potential in the treatment of multiple myeloma

    Directory of Open Access Journals (Sweden)

    Muz B

    2016-01-01

    Full Text Available Barbara Muz,1 Rachel Nicole Ghazarian,1,2 Monica Ou,1,3 Micah John Luderer,1 Hubert Daniel Kusdono,1,2 Abdel Kareem Azab1 1Department of Radiation Oncology, Cancer Biology Division, Washington University in St Louis School of Medicine, 2Department of Pharmaceutical and Administrative Sciences, St Louis College of Pharmacy, 3Department of Biology, St Louis University, St Louis, MO, USA Abstract: Despite the significant therapeutic advances achieved with proteasome inhibitors (PIs such as bortezomib and carfilzomib in prolonging the survival of patients with multiple myeloma, the development of drug resistance, peripheral neuropathy, and pharmacokinetic limitations continue to pose major challenges when using these compounds. Ixazomib is a second-generation PI with improved activity over other PIs. Unlike bortezomib and carfilzomib, which are administered by injection, ixazomib is the first oral PI approved by US Food and Drug Administration. This review discusses the biochemical properties, mechanisms of action, preclinical efficacy, and clinical trial results leading to the US Food and Drug Administration approval of ixazomib. Keywords: proteasome inhibitor, oral administration, biological mechanism, clinical trials

  1. Illegitimate WNT signaling promotes proliferation of multiple myeloma cells

    Science.gov (United States)

    Derksen, Patrick W. B.; Tjin, Esther; Meijer, Helen P.; Klok, Melanie D.; Mac Gillavry, Harold D.; van Oers, Marinus H. J.; Lokhorst, Henk M.; Bloem, Andries C.; Clevers, Hans; Nusse, Roel; van der Neut, Ronald; Spaargaren, Marcel; Pals, Steven T.

    2004-01-01

    The unrestrained growth of tumor cells is generally attributed to mutations in essential growth control genes, but tumor cells are also influenced by signals from the environment. In multiple myeloma (MM), the factors and signals coming from the bone marrow microenvironment are possibly even essential for the growth of the tumor cells. As targets for intervention, these signals may be equally important as mutated oncogenes. Given their oncogenic potential, WNT signals form a class of paracrine growth factors that could act to influence MM cell growth. In this paper, we report that MM cells have hallmarks of active WNT signaling, whereas the cells have not undergone detectable mutations in WNT signaling genes such as adenomatous polyposis coli and β-catenin (CTNNB1). We show that the malignant MM plasma cells overexpress β-catenin, including its N-terminally unphosphorylated form, suggesting active β-catenin/T cell factor-mediated transcription. Further accumulation and nuclear localization of β-catenin, and/or increased cell proliferation, was achieved by stimulation of WNT signaling with either Wnt3a, LiCl, or the constitutively active S33Y mutant of β-catenin. In contrast, by blocking WNT signaling by dominant-negative T cell factor, we can interfere with the growth of MM cells. We therefore suggest that MM cells are dependent on an active WNT signal, which may have important implications for the management of this incurable form of cancer. PMID:15067127

  2. Prognostic Value of Serum Free Light Chain in Multiple Myeloma.

    Science.gov (United States)

    El Naggar, Amel A; El-Naggar, Mostafa; Mokhamer, El-Hassan; Avad, Mona W

    2015-01-01

    The measurement of serum free light chain (sFLC) has been shown to be valuable in screening for the presence of plasma cell dyscrasia as well as for baseline prognosis in newly diagnosed patients. The aim of the present work was to study the prognostic value of sFLC in multiple myeloma in relation to other serum biomarkers, response to therapy and survival. Forty five newly diagnosed patients with MM were included in the study. Patients were divided into responders and non-responders groups according to response to therapy. sFLC and serum Amyloid A (SAA) were measured by immunonephelometry. The non-responders group showed a statistically significant higher kappa/lambda or lambda/kappa ratio and higher β2 microglobulin level, but lower albumin level at presentation, as compared to the responders group (P < 0.001). However, no statistically significant difference was detected between the two groups regarding SA A or calcium levels. Comparison between sFLC ratio obtained before and after therapy revealed significant decrease after treatment in the responders group (P = 0.05). Survival was significantly inferior in patients with an FLC ratio of ≥ 2.6 or ≤ 0.56 compared with those with an FLC ratio that was between 0.56 and 2.6 (P = 0.002).

  3. Multiple Myeloma in the Very Old: An IASIA Conference Report

    Science.gov (United States)

    Shapiro, Gary R.; Ershler, William B.; Badros, Ashraf; Cohen, Harvey J.; Dispenzieri, Angela; Flores, Irene Q.; Kanapuru, Bindu; Jurivich, Donald; Longo, Dan L.; Nourbakhsh, Ali; Palumbo, Antonio; Walston, Jeremy; Yates, Jerome W.

    2014-01-01

    Multiple myeloma (MM) in patients aged greater than 80 years poses an increasingly common challenge for oncology providers. A multidisciplinary workshop was held in which MM-focused hematologists/oncologists, geriatricians, and associated health-care team members discussed the state of research for MM therapy, as well as themes from geriatric medicine that pertain directly to this patient population. A summary statement of our discussions is presented here, in which we highlight several topics. MM disproportionately affects senior adults, and demographic trends indicate that this trend will accelerate. Complex issues impact cancer in seniors, and although factors such as social environment, comorbidities, and frailty have been well characterized in nononcological geriatric medicine, these themes have been inadequately explored in cancers such as MM, despite their clear relevance to this field. Therapeutically, novel agents have improved survival for MM patients of all ages, but less so for seniors than younger patients for a variety of reasons. Lastly, both MM- and treatment-related symptoms and toxicities require special attention in senior adults. Existing research provides limited insight into how best to manage these often complex patients, who are often not reflected in typical clinical trial populations. We hence offer suggestions for clinical trials that address knowledge gaps in how to manage very old and/or frail patients with MM, given the complicated issues that often surround this patient population. PMID:24700806

  4. Multiple Myeloma Macrophages: Pivotal Players in the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Simona Berardi

    2013-01-01

    Full Text Available Tumor microenvironment is essential for multiple myeloma (MM growth, progression, and drug resistance through provision of survival signals and secretion of growth and proangiogenic factors. This paper examines the importance of macrophages within MM bone marrow (BM microenvironment, referred to as MM-associated macrophages, as a potential niche component that supports tumor plasma cells. These macrophages are derived from peripheral blood monocytes recruited into the tumor. Upon activation by MM plasma cells and mesenchymal stromal cells, macrophages can release growth factors, proteolytic enzymes, cytokines, and inflammatory mediators that promote plasma cell growth and survival. Macrophages promote tumor progression through several mechanisms including angiogenesis, growth, and drug resistance. Indeed, these macrophages are essential for the induction of an angiogenic response through vasculogenic mimicry, and this ability proceeds in step with progression of the plasma cell tumors. Data suggest that macrophages play an important role in the biology and survival of patients with MM, and they may be a target for the MM antivascular management.

  5. Second auto-SCT for treatment of relapsed multiple myeloma.

    Science.gov (United States)

    Gonsalves, W I; Gertz, M A; Lacy, M Q; Dispenzieri, A; Hayman, S R; Buadi, F K; Dingli, D; Hogan, W J; Kumar, S K

    2013-04-01

    High-dose therapy and auto-SCT remain integral in the initial treatment of multiple myeloma (MM), and are increasingly being applied for management of relapsed disease. We examined the outcomes in 98 patients undergoing salvage auto-SCT (auto-SCT2) for relapsed MM after receiving an initial transplant (auto-SCT1) between 1994 and 2009. The median age at auto-SCT2 was 60 years (range: 35-74). The median time between auto-SCT1 and auto-SCT2 was 46 months (range: 10-130). Treatment-related mortality was seen in 4%. The median PFS from auto-SCT2 was 10.3 (95% confidence interval (CI): 7-14) months and the median OS from auto-SCT2 was 33 months (95% CI: 28-51). In a multivariable analysis, shorter time to progression (TTP) after auto-SCT1, not achieving a CR after auto-SCT2, higher number of treatment regimens before auto-SCT2 and a higher plasma cell labeling index at auto-SCT2 predicted for shorter PFS. However, only a shorter TTP after auto-SCT1 predicted for a shorter OS post auto-SCT2. Hence, auto-SCT2 is an effective and feasible therapeutic option for MM patients relapsing after other treatments, especially in patients who had a TTP of at least 12 months after their auto-SCT1.

  6. Tetraspanin 7 (TSPAN7) expression is upregulated in multiple myeloma patients and inhibits myeloma tumour development in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Cheong, Chee Man [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); Chow, Annie W.S. [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); Department of Haematology, SA Pathology, Adelaide 5000, SA (Australia); Fitter, Stephen [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); Hewett, Duncan R. [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); School of Medicine, University of Adelaide, Adelaide 5005, SA (Australia); Martin, Sally K. [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); Department of Haematology, SA Pathology, Adelaide 5000, SA (Australia); School of Medicine, University of Adelaide, Adelaide 5005, SA (Australia); Williams, Sharon A. [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); To, L. Bik [Department of Haematology, SA Pathology, Adelaide 5000, SA (Australia); and others

    2015-03-01

    Background: Increased expression of the tetraspanin TSPAN7 has been observed in a number of cancers; however, it is unclear how TSPAN7 plays a role in cancer progression. Methods: We investigated the expression of TSPAN7 in the haematological malignancy multiple myleoma (MM) and assessed the consequences of TSPAN7 expression in the adhesion, migration and growth of MM plasma cells (PC) in vitro and in bone marrow (BM) homing and tumour growth in vivo. Finally, we characterised the association of TSPAN7 with cell surface partner molecules in vitro. Results: TSPAN7 was found to be highly expressed at the RNA and protein level in CD138{sup +} MM PC from approximately 50% of MM patients. TSPAN7 overexpression in the murine myeloma cell line 5TGM1 significantly reduced tumour burden in 5TGM1/KaLwRij mice 4 weeks after intravenous adminstration of 5TGM1 cells. While TSPAN7 overexpression did not affect cell proliferation in vitro, TSPAN7 increased 5TGM1 cell adhesion to BM stromal cells and transendothelial migration. In addition, TSPAN7 was found to associate with the molecular chaperone calnexin on the cell surface. Conclusion: These results suggest that elevated TSPAN7 may be associated with better outcomes for up to 50% of MM patients. - Highlights: • TSPAN7 expression is upregulated in newly-diagnosed patients with active multiple myeloma. • Overexpression of TSPAN7 inhibits myeloma tumour development in vivo. • TSPAN7 interacts with calnexin at the plasma membrane in a myeloma cell line.

  7. The selective Aurora B kinase inhibitor AZD1152 is a potential new treatment for multiple myeloma.

    Science.gov (United States)

    Evans, Robert P; Naber, Claudia; Steffler, Tara; Checkland, Tamara; Maxwell, Christopher A; Keats, Jonathan J; Belch, Andrew R; Pilarski, Linda M; Lai, Raymond; Reiman, Tony

    2008-02-01

    Aurora kinases are potential targets for cancer therapy. Previous studies have validated Aurora kinase A as a therapeutic target in multiple myeloma (MM), and have demonstrated in vitro anti-myeloma effects of small molecule Aurora kinase inhibitors that inhibit both Aurora A and B. This study demonstrated that Aurora B kinase was strongly expressed in myeloma cell lines and primary plasma cells. The selective Aurora B inhibitor AZD1152-induced apoptotic death in myeloma cell lines at nanomolar concentrations, with a cell cycle phenotype consistent with that reported previously for Aurora B inhibition. In some cases, AZD1152 in combination with dexamethasone showed increased anti-myeloma activity compared with the use of either agent alone. AZD1152 was active against sorted CD138(+) BM plasma cells from myeloma patients but also, as expected, was toxic to CD138(-) marrow cells from the same patients. In a murine myeloma xenograft model, AZD1152-inhibited tumour growth at well-tolerated doses and induced cell death in established tumours, with associated mild, transient leucopenia. AZD1152 shows promise in these preclinical studies as a novel treatment for MM.

  8. Hypothalamic digoxin, hemispheric chemical dominance, and oncogenesis: evidence from multiple myeloma.

    Science.gov (United States)

    Kurup, Ravi Kumar; Kurup, Paramesware Achutha

    2003-12-01

    This study assessed the changes in the isoprenoid pathway and its metabolites digoxin, dolichol, and ubiquinone in multiple myeloma. The isoprenoid pathway and digoxin status were also studied for comparison in individuals of differing hemispheric dominance to find out the rote of cerebral dominance in the genesis of multiple myeloma and neoplasms. The following parameters were assessed: isoprenoid pathway metabolites, tyrosine and tryptophan catabolites, glycoconjugate metabolism, RBC membrane composition, and free radical metabolism--in multiple myeloma, as well as in individuals of differing hemispheric dominance. There was elevation in plasma HMG CoA reductase activity, serum digoxin, and dolichol, and a reduction in RBC membrane Na(+)-K+ ATPase activity, serum ubiquinone, and magnesium levels. Serum tryptophan, serotonin, nicotine, strychnine, and quinolinic acid were elevated, while tyrosine, dopamine, noradrenaline, and morphine were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions, the activity of GAG degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins, and serum glycolipids were elevated. The RBC membrane glycosaminoglycans, hexose, and fucose residues of glycoproteins, cholesterol, and phospholipids were reduced. The activity of all free-radical scavenging enzymes, concentration of glutathione, iron binding capacity, and ceruloplasmin decreased significantly, while the concentration of lipid peroxidation products and nitric oxide increased. Hyperdigoxinemia-related altered intracellular Ca++/Mg++ ratios mediated oncogene activation, dolichol-induced altered glycoconjugate metabolism, and ubiquinone deficiency-related mitochondrial dysfunction can contribute to the pathogenesis of multiple myeloma. The biochemical patterns obtained in multiple myeloma are similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. But all the patients with

  9. PET-CT for nuclear medicine diagnostics of multiple myeloma

    International Nuclear Information System (INIS)

    Dimitrakopoulou-Strauss, A.

    2014-01-01

    Functional or morphofunctional imaging modalities are used in myeloma patients for the diagnosis and therapy management within research protocols. Despite new staging criteria, which take into account the viability of a myeloma lesion, positron emission tomography (PET) is not used routinely. The impact of PET is therefore open. The role of PET and PET computed tomography (PET-CT) for the diagnosis and therapy management is discussed. The use of PET with 18F-fluorodeoxyglucose (FDG) allows the measurement of viable myeloma lesions and correlates with the stage of disease. A negative FDG examination correlates with a better prognosis. Furthermore, the number of focal lesions as well as the whole functional volume of myeloma lesions in FDG have a prognostic impact. Several studies have demonstrated the impact of FDG for the assessment of therapy monitoring and show that FDG is an earlier indicator for therapy response as compared to magnetic resonance imaging (MRI). The CT component of the new hybrid systems allows the assessment of osteolytic lesions in CT and their viability in FDG. The combination of PET with an MRT scanner allows the simultaneous measurement of bone marrow infiltration, focal lesions and their viability. The use of modern hybrid scanners, such as PET-CT and PET-MRT facilitates the simultaneous measurement of viable myeloma lesions, osteolytic lesions and bone marrow infiltration in the whole body; therefore, it is expected that these imaging modalities will play a greater role both in diagnosis and therapy management. (orig.) [de

  10. MULTIPLE MYELOMA PRESENTED AS AN ANTERIOR CHEST WALL MASS DIAGNOSED BY CYTOLOGICAL EXAMINATION : A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Parvathi

    2015-02-01

    Full Text Available Myeloma is a malignancy of terminally differentiated B cells (plasma cells that produce a complete and / or partial monoclonal immunoglobulin protein. Myeloma accounts for approximately 1% of all malignancies and 10% of haematological tumors. It becomes difficult to arrive at early diagnosis because myeloma manifests itself in different forms. The disease usually presents as bone pains, pathological fractures and anemia but can also present as swelling in jaw, orbit, rib, sternoclavicular area, scalp, paraspinal region and tonsil. We present a case of multiple myeloma in 63 year old male which presented as a soft tissue mass on anterior chest wall and diagnosed by FNAC . This case is presented because diagnosis was made on cytology and not many cases have been reported in literature where FNAC helped in making the diagnosis. This increases the hope of early diagnosis so that treatment can be advocated

  11. EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

    International Nuclear Information System (INIS)

    Huang, Er-Wen; Xue, Sheng-Jiang; Li, Xiao-Yan; Xu, Suo-Wen; Cheng, Jian-Ding; Zheng, Jin-Xiang; Shi, He; Lv, Guo-Li; Li, Zhi-Gang; Li, Yue; Liu, Chang-Hui; Chen, Xiao-Hui; Liu, Hong; Li, Jie; Liu, Chao

    2014-01-01

    Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma

  12. EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Er-Wen [Guangzhou Institute of Forensic Science, Guangzhou (China); Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Xue, Sheng-Jiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Li, Xiao-Yan [Department of Pharmacy, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Xu, Suo-Wen [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Cheng, Jian-Ding; Zheng, Jin-Xiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Shi, He; Lv, Guo-Li; Li, Zhi-Gang; Li, Yue; Liu, Chang-Hui; Chen, Xiao-Hui; Liu, Hong [Guangzhou Institute of Forensic Science, Guangzhou (China); Li, Jie, E-mail: mdlijie@sina.com [Department of Anaesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Liu, Chao, E-mail: liuchaogaj@21cn.com [Guangzhou Institute of Forensic Science, Guangzhou (China)

    2014-05-02

    Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma.

  13. Occupation and multiple myeloma: an occupation and industry analysis.

    Science.gov (United States)

    Gold, Laura S; Milliken, Kevin; Stewart, Patricia; Purdue, Mark; Severson, Richard; Seixas, Noah; Blair, Aaron; Davis, Scott; Hartge, Patricia; De Roos, Anneclaire J

    2010-08-01

    Multiple myeloma (MM) is an incurable plasma cell malignancy with a poorly understood etiology. The purpose of our research was to examine the relationships between lifetime occupations and MM in a relatively large case-control study. MM cases (n = 180) were identified through cancer registries in the Seattle-Puget Sound area and Detroit. Population-based controls (n = 481) were identified using random digit dialing and Medicare and Medicaid Services files. In-person interviews were conducted to ascertain occupational histories. Standard occupational classification (SOC) and standard industrial classification (SIC) codes were assigned to each job held by each participant. Unconditional logistic regression was used to generate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between MM and having ever worked in each occupation/industry and according to duration of employment in an occupation/industry. The risk of MM was associated with several manufacturing occupations and industries, including machine operators and tenders, not elsewhere classified (SOC 76) (OR = 1.8, CI = 1.0-3.3); textile, apparel, and furnishing machine operators and tenders (SOC 765) (OR = 6.0, CI = 1.7-21); and machinery manufacturing, except electrical (SIC 35) (OR = 3.3, CI = 1.7-6.7). Several service occupations and industries, such as food and beverage preparation (SOC 521) (OR = 2.0, CI = 1.1-3.8), were also associated with MM. One occupation that has been associated with MM in several previous studies, painters, paperhangers, and plasterers (SOC 644) was associated with a non-significantly elevated risk (OR = 3.6, CI = 0.7-19). We found associations between the risk of MM and employment in several manufacturing and service-related occupations and industries. Copyright 2010 Wiley-Liss, Inc.

  14. Current role of radiation therapy for multiple myeloma.

    Science.gov (United States)

    Talamo, Giampaolo; Dimaio, Christopher; Abbi, Kamal K S; Pandey, Manoj K; Malysz, Jozef; Creer, Michael H; Zhu, Junjia; Mir, Muhammad A; Varlotto, John M

    2015-01-01

    Radiation therapy (RT) is a treatment modality traditionally used in patients with multiple myeloma (MM), but little is known regarding the role and effectiveness of RT in the era of novel agents, i.e., immunomodulatory drugs and proteasome inhibitors. We retrospectively reviewed data from 449 consecutive MM patients seen at our institute in 2010-2012 to assess indications for RT as well as its effectiveness. Pain response was scored similarly to RTOG 0631 and used the Numerical Rating Pain Scale. Among 442 evaluable patients, 149 (34%) patients and 262 sites received RT. The most common indication for RT was palliation of bone pain (n = 109, 42%), followed by prevention/treatment of pathological fractures (n = 73, 28%), spinal cord compression (n = 26, 10%), and involvement of vital organs/extramedullary disease (n = 25, 10%). Of the 55 patients evaluable for pain relief, complete and partial responses were obtained in 76.4 and 7.2%, respectively. Prior RT did not significantly decrease the median number of peripheral blood stem cells collected for autologous transplant, even when prior RT was given to both the spine and pelvis. Inadequacy of stem cell collection for autologous stem cell transplant (ASCT) was not significantly different and it occurred in 9 and 15% of patients receiving no RT and spine/pelvic RT, respectively. None of the three cases of therapy-induced acute myelogenous leukemia/MDS occurred in the RT group. Despite the introduction of novel effective agents in the treatment of MM, RT remains a major therapeutic component for the management in 34% of patients, and it effectively provides pain relief while not interfering with successful peripheral blood stem cell collection for ASCT.

  15. Multiple Myeloma and lifetime occupation: results from the EPILYMPH study

    Directory of Open Access Journals (Sweden)

    Perrotta Carla

    2012-12-01

    Full Text Available Abstract Background The EPILYMPH study applied a detailed occupational exposure assessment approach to a large multi-centre case–control study conducted in six European countries. This paper analysed multiple myeloma (MM risk associated with level of education, and lifetime occupational history and occupational exposures, based on the EPILYMPH data set. Methods 277 MM cases and four matched controls per each case were included. Controls were randomly selected, matching for age (+/− 5 years, centre and gender. Lifetime occupations and lifetime exposure to specific workplace agents was obtained through a detailed questionnaire. Local industrial hygienists assessed likelihood and intensity for specific exposures. The odds ratio and 95% confidence intervals (OR, 95% CI were calculated for level of education, individual occupations and specific exposures. Unconditional logistic regression models were run for individual occupations and exposures. Results A low level of education was associated with MM OR=1.68 (95% CI 1.02-2.76. An increased risk was observed for general farmers (OR=1.77; 95% CI 1.05-2.99 and cleaning workers (OR=1.69; 95% CI 1.04-2.72 adjusting for level of education. Risk was also elevated, although not significant, for printers (OR=2.06; 95% CI 0.97-4.34. Pesticide exposure over a period of ten years or more increased MM risk (OR=1.62; 95% CI 1.01-2.58. Conclusion These results confirm an association of MM with farm work, and indicate its association with printing and cleaning. While prolonged exposure to pesticides seems to be a risk factor for MM, an excess risk associated with exposure to organic solvents could not be confirmed.

  16. Percutaneous vertebroplasty for multiple myeloma of the cervical spine

    International Nuclear Information System (INIS)

    Mont'Alverne, Francisco; Vallee, Jean-Noel; Guillevin, Remy; Cormier, Evelyne; Jean, Betty; Rose, Michelle; Chiras, Jacques; Caldas, Jose Guilherme

    2009-01-01

    Spinal involvement is a common presentation of multiple myeloma (MM); however, the cervical spine is the least common site of myelomatous involvement. Few studies evaluate the results of percutaneous vertebroplasty (PV) in the treatment of MM of the spine. The purpose of this series is to report on the use of PV in the treatment of MM of the cervical spine and to review the literature. From January 1994 to October 2007, four patients (three men and one woman; mean age, 45 years) who underwent five PV for painful MM in the cervical spine were retrospectively reviewed. The pain was estimated by the patient on a verbal analogic scale. Clinical follow-up was available for all patients (mean, 27.5 months; range, 1-96 months). The mean volume of cement injected per vertebral body was 2.3 ± 0.8 mL (range, 1.0-4.0 mL) with a mean vertebral filling of 55.0 ± 12.0% (range, 40.0-75.0%). Analgesic efficacy was achieved in all patients. One patient had a spinal instability due to a progression of spinal deformity noted on follow-up radiographs, without clinical symptoms. Cement leakage was detected in three (60%) of the five treated vertebrae. There was no clinical complication. The present series suggests that PV for MM of the cervical spine is safe and effective for pain control; nonetheless, the detrimental impact of the disease on bone quality should prompt close radiological follow-up after PV owing to the risk of spinal instability. (orig.)

  17. [Lentivirus-mediated shRNA silencing of LAMP2A inhibits the proliferation of multiple myeloma cells].

    Science.gov (United States)

    Li, Lixuan; Li, Jia

    2015-05-01

    To study the effects of lentivirus-mediated short hairpin RNA (shRNA) silencing of lysosome-associated membrane protein type 2A (LAMP2A) expression on the proliferation of multiple myeloma cells. The constructed shRNA lentiviral vector was applied to infect human multiple myeloma cell line MM.1S, and stable expression cell line was obtained by puromycin screening. Western blotting was used to verify the inhibitory effect on LAMP2A protein expression. MTT assay was conducted to detect the effect of knocked-down LAMP2A on MM.1S cell proliferation, and the anti-tumor potency of suberoylanilide hydroxamic acid (SAHA) against the obtained MM.1S LAMP2A(shRNA) stable cell line. Lactate assay was performed to observe the impact of low LAMP2A expression on cell glycolysis. The stable cell line with low LAMP2A expression were obtained with the constructed human LAMP2A-shRNA lentiviral vector. Down-regulation of LAMP2A expression significantly inhibited MM.1S cell proliferation and enhanced the anti-tumor activity of SAHA. Interestingly, decreased LAMP2A expression also inhibited MM.1S cell lactic acid secretion. Down-regulation of LAMP2A expression could inhibit cell proliferation in multiple myeloma cells.

  18. The orally available multikinase inhibitor regorafenib (BAY 73-4506) in multiple myeloma.

    Science.gov (United States)

    Breitkreutz, Iris; Podar, Klaus; Figueroa-Vazquez, Vianihuini; Wilhelm, Scott; Hayden, Patrick J; Anderson, Kenneth C; Raab, Marc S

    2018-05-01

    A promising approach to the treatment of multiple myeloma (MM) involves agents that target not only the myeloma cells directly, but also the tumor microenvironment which promotes tumor cell growth, angiogenesis, and MM bone disease. Here we investigate the orally available multikinase inhibitor, regorafenib (BAY 73-4506), for its therapeutic efficacy in MM. Regorafenib is a potent inhibitor of angiogenic (VEGFR 1-3, PDGFR-b) as well as oncogenic (c-KIT, RET, FGFR, Raf) kinases. We show that regorafenib induces apoptosis in all MM cell lines at below clinically achievable concentrations. Regorafenib overcomes the growth advantage conferred by a stroma cell MM and an endothelial cell MM, co-culture systems, and abrogates growth factor-stimulated MEK, ERK, and AKT phosphorylation at nanomolar to micromolar concentrations. Moreover, it inhibits endothelial cell growth and tubule formation, abrogates both VEGF secretion and VEGF-induced MM cell migration, inhibits osteoclastogenesis, and shows synergistic cytotoxicity with dexamethasone, the immunomodulatory drug pomalidomide, and the p110δ inhibitor idelalisib. Most importantly, regorafenib significantly delays tumor growth in a xenograft mouse model of human MM. These results provide the rationale for further clinical evaluation of regorafenib, alone and in combination, in the treatment of MM.

  19. JS-K, a GST-activated nitric oxide generator, induces DNA double-strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cells.

    Science.gov (United States)

    Kiziltepe, Tanyel; Hideshima, Teru; Ishitsuka, Kenji; Ocio, Enrique M; Raje, Noopur; Catley, Laurence; Li, Chun-Qi; Trudel, Laura J; Yasui, Hiroshi; Vallet, Sonia; Kutok, Jeffery L; Chauhan, Dharminder; Mitsiades, Constantine S; Saavedra, Joseph E; Wogan, Gerald N; Keefer, Larry K; Shami, Paul J; Anderson, Kenneth C

    2007-07-15

    Here we investigated the cytotoxicity of JS-K, a prodrug designed to release nitric oxide (NO(*)) following reaction with glutathione S-transferases, in multiple myeloma (MM). JS-K showed significant cytotoxicity in both conventional therapy-sensitive and -resistant MM cell lines, as well as patient-derived MM cells. JS-K induced apoptosis in MM cells, which was associated with PARP, caspase-8, and caspase-9 cleavage; increased Fas/CD95 expression; Mcl-1 cleavage; and Bcl-2 phosphorylation, as well as cytochrome c, apoptosis-inducing factor (AIF), and endonuclease G (EndoG) release. Moreover, JS-K overcame the survival advantages conferred by interleukin-6 (IL-6) and insulin-like growth factor 1 (IGF-1), or by adherence of MM cells to bone marrow stromal cells. Mechanistic studies revealed that JS-K-induced cytotoxicity was mediated via NO(*) in MM cells. Furthermore, JS-K induced DNA double-strand breaks (DSBs) and activated DNA damage responses, as evidenced by neutral comet assay, as well as H2AX, Chk2 and p53 phosphorylation. JS-K also activated c-Jun NH(2)-terminal kinase (JNK) in MM cells; conversely, inhibition of JNK markedly decreased JS-K-induced cytotoxicity. Importantly, bortezomib significantly enhanced JS-K-induced cytotoxicity. Finally, JS-K is well tolerated, inhibits tumor growth, and prolongs survival in a human MM xenograft mouse model. Taken together, these data provide the preclinical rationale for the clinical evaluation of JS-K to improve patient outcome in MM.

  20. Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN)

    DEFF Research Database (Denmark)

    Palumbo, Antonio; Bringhen, Sara; Ludwig, Heinz

    2011-01-01

    Most patients with newly diagnosed multiple myeloma (MM) are aged > 65 years with 30% aged > 75 years. Many elderly patients are also vulnerable because of comorbidities that complicate the management of MM. The prevalence of MM is expected to rise over time because of an aging population. Most...... elderly patients with MM are ineligible for autologous transplantation, and the standard treatment has, until recently, been melphalan plus prednisone. The introduction of novel agents, such as thalidomide, bortezomib, and lenalidomide, has improved outcomes; however, elderly patients with MM are more......, occurrence of serious nonhematologic adverse events during treatment should be carefully taken into account to adjust doses and optimize outcomes....

  1. Multiple myeloma in Nigeria: An insight to the clinical, laboratory ...

    African Journals Online (AJOL)

    The average percentage of bone marrow plasmacytosis at diagnosis ... of autologous stem cell transplantation (ASCT) for white, black, and ... Hospital Cancer Registry and Data Collation Institute. .... Figure 1: (a) Kaplan‑Meier survival curve for all myeloma patients, (b) Kaplan‑Meier survival curve for the different sexes b a ...

  2. Spontaneous tumour lysis syndrome in a case of multiple myeloma – A rare occurrence

    Directory of Open Access Journals (Sweden)

    Kavitha Saravu

    2013-03-01

    Full Text Available We describe a case of a 40-year-old male patient who was found to have multiple myeloma with spontaneous tumour lysis syndrome (TLS, following a compression fracture of the L–2 vertebrae. Multiple myeloma was confirmed by bone marrow analysis and the M–band on serum protein electrophoresis. Hyperuricaemia (26.2 mg/dL, hyperkalaemia (> 7.0 mEq/L, hyperphosphatemia (16.2 mg of phosphorus/dL, normocalcemia and acute kidney injury, prior to anticancer treatment suggested spontaneous TLS. Inciting events for tumour lysis, such as chemotherapy, dehydration and exposure to steroids were absent. Patient received hydration, hypourecemic drugs and haemodialysis. This case report highlights the rare presentation of multiple myeloma with spontaneous TLS.

  3. Monocyte/macrophage-derived soluble CD163: A novel biomarker in multiple myeloma

    DEFF Research Database (Denmark)

    Andersen, Morten Nørgaard; Abildgaard, Niels; Maniecki, Maciej B

    2014-01-01

    fluids (soluble CD163, sCD163). In this study, we examined serum sCD163 as a biomarker in patients with newly diagnosed multiple myeloma. METHODS: Peripheral blood (n = 104) and bone marrow (n = 17) levels of sCD163 were measured using an enzyme-linked immunosorbent assay. RESULTS: At diagnosis, high s......CD163 was associated with higher stage according to the International Staging System (ISS) and with other known prognostic factors in multiple myeloma (creatinine, C-reactive protein, and beta-2 microglobulin). Soluble CD163 decreased upon high-dose treatment, and in a multivariate survival analysis...... in bone marrow samples than in the matched blood samples, which indicate a localized production of sCD163 within the bone marrow microenvironment. CONCLUSIONS: Soluble CD163 was found to be a prognostic marker in patients with multiple myeloma. This may indicate that macrophages and/or monocytes have...

  4. A temporal study on #betta#2-microglobulin as marker for diagnosis and monitoring of multiple myeloma

    International Nuclear Information System (INIS)

    Neri, B.

    1982-01-01

    The most important objective carried on, in the field of oncology has been the finding of new means to improve diagnosis and monitoring of neoplastic diseases. So we have chronobiologically studied the behaviour of #betta# 2 -microglobulin, in three groups of patients: Group A: 11 healthy subjects; Group B: 11 untreated patients with multiple myeloma and Group C: 11 multiple myeloma patients, after treatment with polychemoterapy. #betta# 2 -microglobulin, was assayed in serum obtained at six consecutive 4-hourly intervals, by radioimmunoassay, the levels and the various rhythm parameters were analyzed by ''Group mean cosinor'' test. The data suggest, that a circadian rhythm for #betta# 2 -microglobulin in the three groups is not detectable; but ''mesor test'' establishes significant differences (p 2 -microglobulin, in diagnosis and monitoring of multiple myeloma, is suggested

  5. Multiple myeloma and central nervous system involvement: experience of a Brazilian center

    Directory of Open Access Journals (Sweden)

    Ana Luiza Miranda Silva Dias

    2018-01-01

    Full Text Available Introduction: The estimated involvement of the central nervous system in patients with multiple myeloma is rare at about 1%. The infiltration can be identified at the time multiple myeloma is diagnosed or during its progression. However, it is more common in refractory disease or during relapse. Methods: This retrospective cohort study reviewed data from medical records of patients followed up at the Gammopathy Outpatient Clinic of Santa Casa de Misericórdia de São Paulo from January 2008 to December 2016. Results: Twenty patients were included, with a median follow-up of 33.5 months after central nervous system infiltration. The prevalence was 7%. The median age at diagnosis of multiple myeloma was 56.1 years, with 70% of participants being female. Sixteen patients had central nervous system infiltration at diagnosis of multiple myeloma. Seventeen patients had exclusive osteodural lesions and three had infiltrations of the leptomeninge, of which one had exclusive involvement and two had associated osteodural lesions. The median overall survival was 40.3 months after central nervous system involvement. The median overall survival in the group with central nervous system infiltration at relapse was 7.4 months. The patients with leptomeningeal involvement had a median overall survival of 5.8 months. Conclusion: Central nervous system infiltration is a rare condition, but it should be considered as a possibility in patients with multiple myeloma and neurological symptoms. The best treatment regimen for this condition remains unknown and, in most cases, the prognosis is unfavorable. Keywords: Central nervous system, Multiple myeloma, Radiotherapy, Chemotherapy, Prognosis

  6. Recent advances in understanding multiple myeloma [version 1; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    Binod Dhakal

    2016-08-01

    Full Text Available There have been major recent advancements in the understanding and management of multiple myeloma. Diagnostic criteria have been revised and former ultra-high-risk smoldering multiple myeloma is now considered multiple myeloma in need of treatment. Understanding clonal progression, evolution, and tides not only has helped elucidate the disease behavior but might help expand therapeutic choices in order to select appropriate treatment for patients. Unprecedented response rates with modern triplet induction therapies containing proteasome inhibitor and immunomodulators have made this approach standard for initial treatment. The US Food and Drug Administration approved four new drugs (two targeted antibodies and two oral agents in 2015 in relapsed/refractory multiple myeloma and these drugs along with the other already-available drugs have now increased the choices of regimens. Even drugs without single-agent activity, such as panobinostat and elotuzumab, have an important role, especially in the proteasome inhibitor refractory setting. Recent studies done in the context of novel agent induction suggest that high-dose therapy followed by autologous transplant continues to improve response rates and progression-free survival, thus underscoring their role in transplant-eligible patients. Evolving paradigms in the treatment of multiple myeloma include newer promising immune approaches, such as adoptive cellular therapies, vaccines, or antibody-based immune manipulations. Though multiple myeloma is still considered incurable, it is clear that with the improved understanding of disease biology and clonal architecture of relapse combined with the availability of multi-targeted approaches, we are ever closer to a lasting cure or transformation into indolent and long-lasting disease courses or both.

  7. Novel tumor suppressor function of glucocorticoid-induced TNF receptor GITR in multiple myeloma.

    Directory of Open Access Journals (Sweden)

    Yang Liu

    Full Text Available Glucocorticoid-induced TNF receptor (GITR plays a crucial role in modulating immune response and inflammation, however the role of GITR in human cancers is poorly understood. In this study, we demonstrated that GITR is inactivated during tumor progression in Multiple Myeloma (MM through promoter CpG island methylation, mediating gene silencing in primary MM plasma cells and MM cell lines. Restoration of GITR expression in GITR deficient MM cells led to inhibition of MM proliferation in vitro and in vivo and induction of apoptosis. These findings were supported by the presence of induction of p21 and PUMA, two direct downstream targets of p53, together with modulation of NF-κB in GITR-overexpressing MM cells. Moreover, the unbalanced expression of GITR in clonal plasma cells correlated with MM disease progression, poor prognosis and survival. These findings provide novel insights into the pivotal role of GITR in MM pathogenesis and disease progression.

  8. Double filtration plasmapheresis in a dog with multiple myeloma and hyperviscosity syndrome

    Directory of Open Access Journals (Sweden)

    I. Lippi

    2015-08-01

    Full Text Available A 12 year old, 38 kg, mix-breed, intact male dog presented with a 20 day history of clinical signs consistent with hyperviscosity syndrome secondary to multiple myeloma. The dog received three double filtration plasmapheresis treatments on day 0, 7 and 22 after presentation. A significant (p<0.05 reduction in serum total protein, alpha-2 and gamma globulins was found following each treatment. These reductions were accompanied by a complete resolution, although temporary, of the clinical signs of hyperviscosity syndrome. The present study reported for the first time the use of double filtration plasmapheresis to reduce clinical signs of hyperviscosity syndrome in a dog with multiple myeloma.

  9. Role of radiotherapy in the treatment of multiple myeloma

    International Nuclear Information System (INIS)

    Mose, S.; Pfitzner, D.; Rahn, A.; Nierhoff, C.; Schiemann, M.; Boettcher, H.D.

    2000-01-01

    suppose that in multiple myeloma the local response to radiation is supported by a favorable performance status and simultaneous chemotherapy. Irradiation treatment does not change prognosis regarding overall survival. (orig.) [de

  10. Association of IgA multiple myeloma with pre-existing disease

    Energy Technology Data Exchange (ETDEWEB)

    Schafer, A.I.; Miller, J.B.

    1979-01-01

    A retrospective analysis of 153 patients with multiple myeloma was performed for evaluation of the possible significance of pre-existing disease. 37% of the group had no significant antecedent disorder. The most common prior illnesses were peptic ulcer disease and gallbladder disease. Of 12 patients in the group who had prior biliary tract disease and for whom immunoelectrophoretic studies were available, eight (66.7%) had IgA paraproteins. This figure is statistically higher than the 14.1% of prevalence of IgA paraproteins in those myeloma patients without biliary disease. We conclude that prior inflammatory gastrointestinal, pulmonary, and, particularly, biliary disease may be implicated in the pathogenesis of the IgA subset of multiple myeloma.

  11. Multivertebral and epidural involvement of the multiple myeloma, as confirmed by magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Okuda, Yasuhiro; Tamaki, Norihiko; Hosoda, Koukichi; Ehara, Kazumasa; Matsumoto, Satoshi

    1987-08-01

    A case is reported of a multiple myeloma exhibiting symptoms of paraparesis as an initial manifestation following tetraparesis, but with no particular common symptoms of multiple myeloma. Laboratory findings, however, strongly suggested multiple myeloma, and this was confirmed by a biopsy. Radiological investigations could not show all the features of this tumor invasion, but revealed only the osteosclerotic and destructive changes in the cervical and thoracic spine, plus a complete block at the C2 level. Magnetic resonance imaging, however, disclosed entire lesions. There existed multiple vertebral involvements and an epidural invasion of the tumor, continuing to an extraspinal mass. Multiple myeloma is a disorder with varied manifestations; it is rarely present as a primary neuropathological entity. Among these manifestations, initial neurological manifestations in the form of peripheral neuropathy have been reported most commonly. Unusual clinical presentations such as in our case may result in an erroneous and delayed diagnosis unless an early and correct identification of the lesion is made. Magnetic resonance imaging is thought to be the most useful technique to detect such a multiple lesion in the spinal canal with no invasive manipulation.

  12. Spinal focal lesion detection in multiple myeloma using multimodal image features

    Science.gov (United States)

    Fränzle, Andrea; Hillengass, Jens; Bendl, Rolf

    2015-03-01

    Multiple myeloma is a tumor disease in the bone marrow that affects the skeleton systemically, i.e. multiple lesions can occur in different sites in the skeleton. To quantify overall tumor mass for determining degree of disease and for analysis of therapy response, volumetry of all lesions is needed. Since the large amount of lesions in one patient impedes manual segmentation of all lesions, quantification of overall tumor volume is not possible until now. Therefore development of automatic lesion detection and segmentation methods is necessary. Since focal tumors in multiple myeloma show different characteristics in different modalities (changes in bone structure in CT images, hypointensity in T1 weighted MR images and hyperintensity in T2 weighted MR images), multimodal image analysis is necessary for the detection of focal tumors. In this paper a pattern recognition approach is presented that identifies focal lesions in lumbar vertebrae based on features from T1 and T2 weighted MR images. Image voxels within bone are classified using random forests based on plain intensities and intensity value derived features (maximum, minimum, mean, median) in a 5 x 5 neighborhood around a voxel from both T1 and T2 weighted MR images. A test data sample of lesions in 8 lumbar vertebrae from 4 multiple myeloma patients can be classified at an accuracy of 95% (using a leave-one-patient-out test). The approach provides a reasonable delineation of the example lesions. This is an important step towards automatic tumor volume quantification in multiple myeloma.

  13. Antiproliferative and Antiangiogenic Effects of Punica granatum Juice (PGJ) in Multiple Myeloma (MM).

    Science.gov (United States)

    Tibullo, Daniele; Caporarello, Nunzia; Giallongo, Cesarina; Anfuso, Carmelina Daniela; Genovese, Claudia; Arlotta, Carmen; Puglisi, Fabrizio; Parrinello, Nunziatina L; Bramanti, Vincenzo; Romano, Alessandra; Lupo, Gabriella; Toscano, Valeria; Avola, Roberto; Brundo, Maria Violetta; Di Raimondo, Francesco; Raccuia, Salvatore Antonio

    2016-10-01

    Multiple myeloma (MM) is a clonal B-cell malignancy characterized by an accumulation of clonal plasma cells (PC) in the bone marrow (BM) leading to bone destruction and BM failure. Despite recent advances in pharmacological therapy, MM remains a largely incurable pathology. Therefore, novel effective and less toxic agents are urgently necessary. In the last few years, pomegranate has been studied for its potential therapeutic properties including treatment and prevention of cancer. Pomegranate juice (PGJ) contains a number of potential active compounds including organic acids, vitamins, sugars, and phenolic components that are all responsible of the pro-apoptotic effects observed in tumor cell line. The aim of present investigation is to assess the antiproliferative and antiangiogenic potential of the PGJ in human multiple myeloma cell lines. Our data demonstrate the anti-proliferative potential of PGJ in MM cells; its ability to induce G0/G1 cell cycle block and its anti-angiogenic effects. Interestingly, sequential combination of bortezomib/PGJ improved the cytotoxic effect of the proteosome inhibitor. We investigated the effect of PGJ on angiogenesis and cell migration/invasion. Interestingly, we observed an inhibitory effect on the tube formation, microvessel outgrowth aorting ring and decreased cell migration and invasion as showed by wound-healing and transwell assays, respectively. Analysis of angiogenic genes expression in endothelial cells confirmed the anti-angiogenic properties of pomegranate. Therefore, PGJ administration could represent a good tool in order to identify novel therapeutic strategies for MM treatment, exploiting its anti-proliferative and anti-angiogenic effects. Finally, the present research supports the evidence that PGJ could play a key role of a future therapeutic approach for treatment of MM in order to optimize the pharmacological effect of bortezomib, especially as adjuvant after treatment.

  14. Antiproliferative and Antiangiogenic Effects of Punica granatum Juice (PGJ in Multiple Myeloma (MM

    Directory of Open Access Journals (Sweden)

    Daniele Tibullo

    2016-10-01

    Full Text Available Multiple myeloma (MM is a clonal B-cell malignancy characterized by an accumulation of clonal plasma cells (PC in the bone marrow (BM leading to bone destruction and BM failure. Despite recent advances in pharmacological therapy, MM remains a largely incurable pathology. Therefore, novel effective and less toxic agents are urgently necessary. In the last few years, pomegranate has been studied for its potential therapeutic properties including treatment and prevention of cancer. Pomegranate juice (PGJ contains a number of potential active compounds including organic acids, vitamins, sugars, and phenolic components that are all responsible of the pro-apoptotic effects observed in tumor cell line. The aim of present investigation is to assess the antiproliferative and antiangiogenic potential of the PGJ in human multiple myeloma cell lines. Our data demonstrate the anti-proliferative potential of PGJ in MM cells; its ability to induce G0/G1 cell cycle block and its anti-angiogenic effects. Interestingly, sequential combination of bortezomib/PGJ improved the cytotoxic effect of the proteosome inhibitor. We investigated the effect of PGJ on angiogenesis and cell migration/invasion. Interestingly, we observed an inhibitory effect on the tube formation, microvessel outgrowth aorting ring and decreased cell migration and invasion as showed by wound-healing and transwell assays, respectively. Analysis of angiogenic genes expression in endothelial cells confirmed the anti-angiogenic properties of pomegranate. Therefore, PGJ administration could represent a good tool in order to identify novel therapeutic strategies for MM treatment, exploiting its anti-proliferative and anti-angiogenic effects. Finally, the present research supports the evidence that PGJ could play a key role of a future therapeutic approach for treatment of MM in order to optimize the pharmacological effect of bortezomib, especially as adjuvant after treatment.

  15. Occupation, exposure to chemicals, sensitizing agents, and risk of multiple myeloma in Sweden.

    Science.gov (United States)

    Lope, Virginia; Pérez-Gómez, Beatriz; Aragonés, Nuria; López-Abente, Gonzalo; Gustavsson, Per; Plato, Nils; Zock, Jan-Paul; Pollán, Marina

    2008-11-01

    This study sought to identify occupations with high incidence of multiple myeloma and to investigate possible excess risk associated with occupational exposure to chemicals and sensitizing agents in Sweden. A historical cohort of 2,992,166 workers was followed up (1971--1989) through record linkage with the National Cancer and Death Registries. For each job category, age and period standardized incidence ratios and age and period adjusted relative risks of multiple myeloma were calculated using Poisson models. Exposure to chemicals and to sensitizing agents was also assessed using two job-exposure matrices. Men and women were analyzed separately. During follow-up, 3,127 and 1,282 myelomas were diagnosed in men and women, respectively. In men, excess risk was detected among working proprietors, agricultural, horticultural and forestry enterprisers, bakers and pastry cooks, dental technicians, stone cutters/carvers, and prison/reformatory officials. In women, this excess was observed among attendants in psychiatric care, metal workers, bakers and pastry cooks, and paper/paperboard product workers. Workers, particularly bakers and pastry cooks, exposed to high molecular weight sensitizing agents registered an excess risk of over 40% across the sexes. Occasional, although intense, exposure to pesticides was also associated with risk of myeloma in our cohort. Our study supports a possible etiologic role for farming and use of pesticides in myeloma risk. The high incidence found in both female and male bakers and pastry cooks has not been described previously. Further research is required to assess the influence of high molecular weight sensitizing agents on risk of multiple myeloma.

  16. A Phase I Dose-Escalation Study of Antibody BI-505 in Relapsed/Refractory Multiple Myeloma

    DEFF Research Database (Denmark)

    Hansson, Markus; Gimsing, Peter; Badros, Ashraf

    2015-01-01

    PURPOSE: This multicenter, first-in-human study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of BI-505, a human anti-ICAM-1 monoclonal antibody, in advanced relapsed/refractory multiple myeloma patients. EXPERIMENTAL DESIGN: BI-505 was given intravenously, every 2 weeks...... generally mild to moderate, and those attributed to study medication were mostly limited to the first dose and manageable with premedication and slower infusion. No maximum tolerated dose was identified. BI-505's half-life increased with dose while clearance decreased, suggesting target-mediated clearance...

  17. Cold atmospheric plasma as a potential tool for multiple myeloma treatment

    Science.gov (United States)

    Cui, Qingjie; Liu, Dingxin; Liu, Zhijie; Wang, Xiaohua; Yang, Yanjie; Feng, Miaojuan; Liang, Rong; Chen, Hailan; Ye, Kai; Kong, Michael G.

    2018-01-01

    Multiple myeloma (MM) is a fatal and incurable hematological malignancy thus new therapy need to be developed. Cold atmospheric plasma, a new technology that could generate various active species, could efficiently induce various tumor cells apoptosis. More details about the interaction of plasma and tumor cells need to be addressed before the application of gas plasma in clinical cancer treatment. In this study, we demonstrate that He+O2 plasma could efficiently induce myeloma cell apoptosis through the activation of CD95 and downstream caspase cascades. Extracellular and intracellular reactive oxygen species (ROS) accumulation is essential for CD95-mediated cell apoptosis in response to plasma treatment. Furthermore, p53 is shown to be a key transcription factor in activating CD95 and caspase cascades. More importantly, we demonstrate that CD95 expression is higher in tumor cells than in normal cells in both MM cell lines and MM clinical samples, which suggests that CD95 could be a favorable target for plasma treatment as it could selectively inactivate myeloma tumor cells. Our results illustrate the molecular details of plasma induced myeloma cell apoptosis and it shows that gas plasma could be a potential tool for myeloma therapy in the future. PMID:29719586

  18. An exploration of the lived experiences of individuals with relapsed multiple myeloma.

    LENUS (Irish Health Repository)

    Maher, K

    2012-02-01

    The experience of living with relapsed Multiple Myeloma (myeloma) for eight patients accessing treatment within a haematology unit in a large London hospital is explored in this study. Myeloma is recognised as incurable and is sometimes described as an \\'incurable chronic disease\\' with a main treatment option of chemotherapy. Hermeneutic phenomenology was the methodology used in conducting the study and data were collected through open-ended, unstructured interviews. Findings suggest that living with relapsed myeloma in the context of a chronic illness causes an ever-shifting perspective between illness and wellness consequently maintaining a state of uncertainty. The patients in this study placed importance on the emotional aspect of their experience. Hope, intuitive knowing and a fighting spirit were expressed as required positive elements that enabled living with relapsed myeloma. These assisted in maintaining normality, coping with bad news and adjusting to the illness. Pervading through the themes was the need to control uncertainty. Having strong support from significant others provided something to live for and the necessary social support required to promote a new orientation to life.

  19. Hemibody irradiation in stage III multiple myeloma: results of 20 patients

    International Nuclear Information System (INIS)

    Troussard, X.; Reman, O.; Macro, M.; Leporrier, M.; Roussel, A.

    1988-01-01

    The advanced forms of multiple myeloma of bone, stage III, or those with a large tumoral mass, characterized by a considerable number of myelomacells, pose difficult problems in treatment. Little progress has been made since the introduction of the alkylating agents, and combined chemotherapy does not seem to be any more effective in terms of survival. It is these severe forms that culminate in painful symptoms which are often difficult to eliminate. The radiosensitivity of myeloma led us to treat 20 patients affected by severe forms of the disease by total body irradiation in two stages, and we analyze here the effects of treatment and the tolerance for this technique

  20. Biased Iglambda expression in hypermutated IgD multiple myelomas does not result from receptor revision

    NARCIS (Netherlands)

    van der Burg, M.; Bende, R. J.; Aarts, W. M.; Langerak, A. W.; van Dongen, J. J. M.; van Noesel, C. J. M.

    2002-01-01

    Normal IgM(-)IgD(+) CD38(+) B cells and IgM(-)IgD(+) multiple myelomas (MM) are characterized by Cmu deletion, biased Iglambda expression and hypermutated IgV regions. The predominant Iglambda usage has been proposed as resulting from secondary Ig gene rearrangements during extensive clonal

  1. Breast amyloidosis in a female patient with multiple myeloma: Ultrasonographic and mammographic findings

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Ah Rhm; Kim, Joon Mee; Nam, Se Jin [Inha University Hospital, Incheon (Korea, Republic of)

    2017-05-15

    Amyloidosis is a rare disease characterized by pathological protein deposits in organs or tissues. Breast involvement by amyloidosis is rare. We report a female patient with amyloidosis in the breast, with underlying multiple myeloma, which presents as a focal asymmetry on a screening mammogram and a low suspicious mass lesion by ultrasonography.

  2. Metastatic calcification in a patient with multiple myeloma diagnosed as SDRA

    International Nuclear Information System (INIS)

    Munive, Abraham Ali; Ojeda Leon, Paulina; Caicedo, Monica

    2001-01-01

    We present the case of a 44 year-old man with multiple myeloma who presented with a fever that is managed initially as pneumonia multilobar and later because of the persistence of alveolar infiltrates and severe; hypoxaemia as SDRA. The patient in the end passed away and was diagnosed with a metastatic calcification through open lung biopsy

  3. Pathogenesis of Renal Failure in Multiple Myeloma: Any Role of Contrast Media?

    Directory of Open Access Journals (Sweden)

    Michele Mussap

    2014-01-01

    Full Text Available The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function.

  4. Pathogenesis of Renal Failure in Multiple Myeloma: Any Role of Contrast Media?

    Science.gov (United States)

    Mussap, Michele; Merlini, Giampaolo

    2014-01-01

    The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function. PMID:24877060

  5. N-cadherin-mediated interaction with multiple myeloma cells inhibits osteoblast differentiation

    NARCIS (Netherlands)

    Groen, Richard W. J.; de Rooij, Martin F. M.; Kocemba, Kinga A.; Reijmers, Rogier M.; de Haan-Kramer, Anneke; Overdijk, Marije B.; Aalders, Linda; Rozemuller, Henk; Martens, Anton C. M.; Bergsagel, P. Leif; Kersten, Marie José; Pals, Steven T.; Spaargaren, Marcel

    2011-01-01

    Multiple myeloma is a hematologic malignancy characterized by a clonal expansion of malignant plasma cells in the bone marrow, which is accompanied by the development of osteolytic lesions and/or diffuse osteopenia. The intricate bi-directional interaction with the bone marrow microenvironment plays

  6. N-cadherin-mediated interaction with multiple myeloma cells inhibits osteoblast differentiation

    NARCIS (Netherlands)

    Groen, R.W.J.; de Rooij, M.F.M.; Kocemba, K.A.; Reijmers, R.M.; de Haan-Kramer, A.; Overdijk, M.B.; Aalders, L.; Rozemuller, H.; Martens, A.C.M.; Bergsagel, P.L.; Kersten, M.J.; Pals, S.T.; Spaargaren, M.

    2011-01-01

    Background Multiple myeloma is a hematologic malignancy characterized by a clonal expansion of malignant plasma cells in the bone marrow, which is accompanied by the development of osteolytic lesions and/or diffuse osteopenia. The intricate bi-directional interaction with the bone marrow

  7. Paradoxical resistance of multiple myeloma to proteasome inhibitors by decreased levels of 19S proteasomal subunits

    DEFF Research Database (Denmark)

    Acosta-Alvear, Diego; Cho, Min Y; Wild, Thomas

    2015-01-01

    Hallmarks of cancer, including rapid growth and aneuploidy, can result in non-oncogene addiction to the proteostasis network that can be exploited clinically. The defining example is the exquisite sensitivity of multiple myeloma (MM) to 20S proteasome inhibitors, such as carfilzomib. However, MM...

  8. Bortezomib, melphalan, prednisone (VMP) versus melphalan, prednisone, thalidomide (MPT) in elderly newly diagnosed multiple myeloma patients

    DEFF Research Database (Denmark)

    Morabito, Fortunato; Bringhen, Sara; Larocca, Alessandra

    2014-01-01

    Novel agents in combination with melphalan and prednisone (MP) significantly improved progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). Randomized trials comparing MP plus bortezomib (VMP) versus MP plus thalidomide (MPT) are lacking. Nine hundred and fifty-six e...

  9. Epigenetics of multiple myeloma after treatment with cytostatics and gamma radiation

    Czech Academy of Sciences Publication Activity Database

    Krejčí, Jana; Harničarová, Andrea; Štreitová, Denisa; Hájek, R.; Pour, L.; Kozubek, Stanislav; Bártová, Eva

    2009-01-01

    Roč. 33, č. 11 (2009), s. 1490-1498 ISSN 0145-2126 R&D Projects: GA MŠk(CZ) LC06027 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : multiple myeloma * histone methylation * histone acetylation Subject RIV: BO - Biophysics Impact factor: 2.358, year: 2009

  10. In anemia of multiple myeloma hepcidin is induced by increased bone-morphogenetic protein-2

    Science.gov (United States)

    Hepcidin is the principal iron-regulatory hormone and pathogenic factor in anemia of inflammation. Patients with multiple myeloma (MM) frequently present with anemia. We showed that MM patients had increased serum hepcidin, which inversely correlated with hemoglobin, suggesting that hepcidin contrib...

  11. Different aspects of thalidomide treatment and stem cell transplantation in multiple myeloma patients

    NARCIS (Netherlands)

    Marion, A.M.W. van

    2006-01-01

    Multiple myeloma (MM) is an haematological malignancy caused by an unrestrained proliferation of plasma cells (monoclonally differentiated B-cells), and part of the white blood cell count. This proliferation infiltrates the blood forming skeletal bone marrow, producing osteoclastic factors, causing

  12. Multiple myeloma among atomic bomb survivors, Hiroshima and Nagasaki, 1950 - 76

    International Nuclear Information System (INIS)

    Ichimaru, Michito; Ishimaru, Toranosuke; Mikami, Motoko; Matsunaga, Masako.

    1979-10-01

    The relationship between atomic bomb exposure and the occurrence of multiple myeloma has been evaluated in a fixed cohort of approximately 100,000 A-bomb survivors and nonexposed controls during the period from October 1950 to December 1976. Analysis of these data revealed the standardized relative risk adjusted for city, sex, and age at the time of the bombs (ATB) to be significantly greater in the group of individuals who received 100 rad or more of radiation than in their controls. An excess risk became apparent in the high dose group about 20 years after exposure. The excess risk of multiple myeloma in those persons aged 20 - 59 ATB is estimated to be approximately 0.24 per million person-years per rad (PYR) in kerma dose and approximately 0.48 per million PYR in bone marrow dose. The interval between radiation exposure and the occurrence of an excess risk for multiple myeloma in the high dose population is considerably longer than that for leukemia. The cases of multiple myeloma observed in the high dose group showed no unusual clinical features. (author)

  13. Whole-body MRI, dynamic contrast-enhanced MRI, and diffusion-weighted imaging for the staging of multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Dutoit, Julie C.; Verstraete, Koenraad L. [Ghent University Hospital, Department of Radiology, Ghent (Belgium)

    2017-06-15

    Magnetic resonance imaging (MRI) is the most sensitive imaging technique for the detection of bone marrow infiltration, and has therefore recently been included in the new diagnostic myeloma criteria, as proposed by the International Myeloma Working Group. Nevertheless, conventional MRI only provides anatomical information and is therefore only of limited use in the response assessment of patients with multiple myeloma. The additional information from functional MRI techniques, such as diffusion-weighted imaging and dynamic contrast-enhanced MRI, can improve the detection rate of bone marrow infiltration and the assessment of response. This can further enhance the sensitivity and specificity of MRI in the staging of multiple myeloma patients. This article provides an overview of the technical aspects of conventional and functional MRI techniques with practical recommendations. It reviews the diagnostic performance, prognostic value, and role in therapy assessment in multiple myeloma and its precursor stages. (orig.)

  14. MicroRNA Transfer Between Bone Marrow Adipose and Multiple Myeloma Cells.

    Science.gov (United States)

    Soley, Luna; Falank, Carolyne; Reagan, Michaela R

    2017-06-01

    Multiple myeloma remains an incurable disease, largely due to the tumor-supportive role of the bone marrow microenvironment. Bone marrow adipose tissue (BMAT) is one component of the fertile microenvironment which is believed to contribute to myeloma progression and drug resistance, as well as participate in a vicious cycle of osteolysis and tumor growth. MicroRNAs (miRNAs) have recently emerged as instrumental regulators of cellular processes that enable the development and dissemination of cancer. This review highlights the intersection between two emerging research fields and pursues the scientific and clinical implications of miRNA transfer between BMAT and myeloma cells. This review provides a concise and provocative summary of the evidence to support exosome-mediated transfer of tumor-supportive miRNAs. The work may prompt researchers to better elucidate the mechanisms by which this novel means of genetic communication between tumor cells and their environment could someday yield targeted therapeutics.

  15. Influence of Disease and Patient Characteristics on Daratumumab Exposure and Clinical Outcomes in Relapsed or Refractory Multiple Myeloma

    DEFF Research Database (Denmark)

    Yan, Xiaoyu; Clemens, Pamela L; Puchalski, Thomas

    2018-01-01

    OBJECTIVE: The aim of this study was to understand the influence of disease and patient characteristics on exposure to daratumumab, an immunoglobulin Gκ (IgGκ) monoclonal antibody, and clinical outcomes in relapsed or refractory multiple myeloma (MM). PATIENTS AND METHODS: Baseline myeloma type, ...

  16. Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry

    Science.gov (United States)

    Pessoa de Magalhães, Roberto J.; Vidriales, María-Belén; Paiva, Bruno; Fernandez-Gimenez, Carlos; García-Sanz, Ramón; Mateos, Maria-Victoria; Gutierrez, Norma C.; Lecrevisse, Quentin; Blanco, Juan F; Hernández, Jose; de las Heras, Natalia; Martinez-Lopez, Joaquin; Roig, Monica; Costa, Elaine Sobral; Ocio, Enrique M.; Perez-Andres, Martin; Maiolino, Angelo; Nucci, Marcio; De La Rubia, Javier; Lahuerta, Juan-Jose; San-Miguel, Jesús F.; Orfao, Alberto

    2013-01-01

    Multiple myeloma remains largely incurable. However, a few patients experience more than 10 years of relapse-free survival and can be considered as operationally cured. Interestingly, long-term disease control in multiple myeloma is not restricted to patients with a complete response, since some patients revert to having a profile of monoclonal gammopathy of undetermined significance. We compared the distribution of multiple compartments of lymphocytes and dendritic cells in the bone marrow and peripheral blood of multiple myeloma patients with long-term disease control (n=28), patients with newly diagnosed monoclonal gammopathy of undetermined significance (n=23), patients with symptomatic multiple myeloma (n=23), and age-matched healthy adults (n=10). Similarly to the patients with monoclonal gammopathy of undetermined significance and symptomatic multiple myeloma, patients with long-term disease control showed an expansion of cytotoxic CD8+ T cells and natural killer cells. However, the numbers of bone marrow T-regulatory cells were lower in patients with long-term disease control than in those with symptomatic multiple myeloma. It is noteworthy that B cells were depleted in patients with monoclonal gammopathy of undetermined significance and in those with symptomatic multiple myeloma, but recovered in both the bone marrow and peripheral blood of patients with long-term disease control, due to an increase in normal bone marrow B-cell precursors and plasma cells, as well as pre-germinal center peripheral blood B cells. The number of bone marrow dendritic cells and tissue macrophages differed significantly between patients with long-term disease control and those with symptomatic multiple myeloma, with a trend to cell count recovering in the former group of patients towards levels similar to those found in healthy adults. In summary, our results indicate that multiple myeloma patients with long-term disease control have a constellation of unique immune changes

  17. Multiple myeloma and central nervous system involvement: experience of a Brazilian center.

    Science.gov (United States)

    Dias, Ana Luiza Miranda Silva; Higashi, Fabiana; Peres, Ana Lúcia M; Cury, Pricilla; Crusoé, Edvan de Queiroz; Hungria, Vânia Tietsche de Moraes

    The estimated involvement of the central nervous system in patients with multiple myeloma is rare at about 1%. The infiltration can be identified at the time multiple myeloma is diagnosed or during its progression. However, it is more common in refractory disease or during relapse. This retrospective cohort study reviewed data from medical records of patients followed up at the Gammopathy Outpatient Clinic of Santa Casa de Misericórdia de São Paulo from January 2008 to December 2016. Twenty patients were included, with a median follow-up of 33.5 months after central nervous system infiltration. The prevalence was 7%. The median age at diagnosis of multiple myeloma was 56.1 years, with 70% of participants being female. Sixteen patients had central nervous system infiltration at diagnosis of multiple myeloma. Seventeen patients had exclusive osteodural lesions and three had infiltrations of the leptomeninge, of which one had exclusive involvement and two had associated osteodural lesions. The median overall survival was 40.3 months after central nervous system involvement. The median overall survival in the group with central nervous system infiltration at relapse was 7.4 months. The patients with leptomeningeal involvement had a median overall survival of 5.8 months. Central nervous system infiltration is a rare condition, but it should be considered as a possibility in patients with multiple myeloma and neurological symptoms. The best treatment regimen for this condition remains unknown and, in most cases, the prognosis is unfavorable. Copyright © 2017. Published by Elsevier Editora Ltda.

  18. Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration.

    Science.gov (United States)

    Nabissi, Massimo; Morelli, Maria Beatrice; Offidani, Massimo; Amantini, Consuelo; Gentili, Silvia; Soriani, Alessandra; Cardinali, Claudio; Leoni, Pietro; Santoni, Giorgio

    2016-11-22

    Several studies showed a potential anti-tumor role for cannabinoids, by modulating cell signaling pathways involved in cancer cell proliferation, chemo-resistance and migration. Cannabidiol (CBD) was previously noted in multiple myeloma (MM), both alone and in synergy with the proteasome inhibitor bortezomib, to induce cell death. In other type of human cancers, the combination of CBD with Δ9-tetrahydrocannabinol (THC) was found to act synergistically with other chemotherapeutic drugs suggesting their use in combination therapy. In the current study, we evaluated the effects of THC alone and in combination with CBD in MM cell lines. We found that CBD and THC, mainly in combination, were able to reduce cell viability by inducing autophagic-dependent necrosis. Moreover, we showed that the CBD-THC combination was able to reduce MM cells migration by down-regulating expression of the chemokine receptor CXCR4 and of the CD147 plasma membrane glycoprotein. Furthermore, since the immuno-proteasome is considered a new target in MM and also since carfilzomib (CFZ) is a new promising immuno-proteasome inhibitor that creates irreversible adducts with the β5i subunit of immuno-proteasome, we evaluated the effect of CBD and THC in regulating the expression of the β5i subunit and their effect in combination with CFZ. Herein, we also found that the CBD and THC combination is able to reduce expression of the β5i subunit as well as to act in synergy with CFZ to increase MM cell death and inhibits cell migration. In summary, these results proved that this combination exerts strong anti-myeloma activities.

  19. Animal model of human disease. Multiple myeloma

    NARCIS (Netherlands)

    Radl, J.; Croese, J.W.; Zurcher, C.; Enden-Vieveen, M.H.M. van den; Leeuw, A.M. de

    1988-01-01

    Animal models of spontaneous and induced plasmacytomas in some inbred strains of mice have proven to be useful tools for different studies on tumorigenesis and immunoregulation. Their wide applicability and the fact that after their intravenous transplantation, the recipient mice developed bone

  20. Safe and tolerable one-hour pamidronate infusion for multiple myeloma patients

    Directory of Open Access Journals (Sweden)

    Dimitrios Chantzichristos

    2008-09-01

    Full Text Available Dimitrios Chantzichristos, Andréasson Björn, Johansson PeterDepartment of Internal Medicine, Uddevalla Hospital, Uddevalla, SwedenBackground: Once a month, patients with multiple myeloma received an infusion of bisphosphonates, principally to reduce osteoclastic bone resorption. Recommended infusion time for pamidronate is 2 hours in the US and 4 hours in Europe because of its potential nephrotoxicity. From 2003, a 90 mg infusion of pamidronate was provided over 1 hour to patients with no pre-existing renal impairment, in the Daily Care Unit at Uddevalla Hospital.Method: Retrospective analysis of the renal deterioration, serum calcium, and adverse effects in patients with multiple myeloma treated with 1-hour pamidronate 90 mg infusion from January 2003 to April 2007.Results: Seventy-nine patients provided valuable data. A total number of 846 infusions were given and the median number of infusion to each patient was 11. Significant creatinine elevation was seen in 7 patients (8.9%, after 19 infusions (2.2%. Renal deterioration occurred in 5 of these 7 patients, which was related to progress of the myeloma or opportunistic infections. Prevalence of infusion-related events was 0.8% and the mean total S-Ca was 0.05 mmol/L lower than the baseline.Conclusion: Few events of renal deterioration, hypocalcemia, or other adverse effects resulted from a 1-hour pamidronate 90 mg infusion for multiple myeloma patients with no pre-existing renal impairment.Keywords: bisphosphonates, pamidronate, multiple myeloma, infusion time

  1. Clinical Implications of Complex Pharmacokinetics for Daratumumab Dose Regimen in Patients With Relapsed/Refractory Multiple Myeloma

    DEFF Research Database (Denmark)

    Xu, Xu Steven; Yan, Xiaoyu; Puchalski, Thomas

    2017-01-01

    New therapeutic strategies are urgently needed to improve clinical outcomes in patients with multiple myeloma (MM). Daratumumab is a first-in-class, CD38 human immunoglobulin G1κ monoclonal antibody approved for treatment of relapsed or refractory MM. Identification of an appropriate dose regimen...... for daratumumab is challenging due to its target-mediated drug disposition, leading to time- and concentration-dependent pharmacokinetics. We describe a thorough evaluation of the recommended dose regimen for daratumumab in patients with relapsed or refractory MM. This article is protected by copyright. All...

  2. Multiple myeloma presenting with a maxillary lesion as the first sign

    Energy Technology Data Exchange (ETDEWEB)

    Ramaiah, Kiran Kumar Kotagudda; Joshi, Vajendra; Thayi, Shilpa Ravishankar; Sathyanarayana, Pathalapate; Patil, Prashant [Dept. of Oral Medicine and Radiology, Navodaya Dental College and Hospital, Raichur (Korea, Republic of); Ahmed, Zaheer [Dept. of Public Health Dentistry, Navodaya Dental College and Hospital, Raichur (Korea, Republic of)

    2015-03-15

    Multiple myeloma is a clonal neoplastic proliferation of terminally differentiated B-lymphocytes involving the skeletal system in a multifocal fashion. Its oral manifestations are less common in the maxilla than in the mandible due to the lower amount of hemopoietic bone marrow in the maxilla. We report the case of a 50-year-old man who presented with a mass in the left maxillary alveolar region with tooth mobility. The mass had become enlarged after the teeth were extracted 15 days previously. Radiographs demonstrated multiple punched-out radiolucent lesions in the skull and pelvic region. Computed tomography images showed a soft tissue density mass in the left maxilla, eroding the floor and walls of the maxillary sinus. Although several analytical techniques were used to characterize the lesion, it was finally confirmed as multiple myeloma through immunohistochemistry.

  3. Gamabufotalin triggers c-Myc degradation via induction of WWP2 in multiple myeloma cells.

    Science.gov (United States)

    Yu, Zhenlong; Li, Tao; Wang, Chao; Deng, Sa; Zhang, Baojing; Huo, Xiaokui; Zhang, Bo; Wang, Xiaobo; Zhong, Yuping; Ma, Xiaochi

    2016-03-29

    Deciding appropriate therapy for multiple myeloma (MM) is challenging because of the occurrence of multiple chromosomal changes and the fatal nature of the disease. In the current study, gamabufotalin (GBT) was isolated from toad venom, and its tumor-specific cytotoxicity was investigated in human MM cells. We found GBT inhibited cell growth and induced apoptosis with the IC50 values <50 nM. Mechanistic studies using functional approaches identified GBT as an inhibitor of c-Myc. Further analysis showed that GBT especially evoked the ubiquitination and degradation of c-Myc protein, thereby globally repressing the expression of c-Myc target genes. GBT treatment inhibited ERK and AKT signals, while stimulating the activation of JNK cascade. An E3 ubiquitin-protein ligase, WWP2, was upregulated following JNK activation and played an important role in c-Myc ubiquitination and degradation through direct protein-protein interaction. The antitumor effect of GBT was validated in a xenograft mouse model and the suppression of MM-induced osteolysis was verified in a SCID-hu model in vivo. Taken together, our study identified the potential of GBT as a promising therapeutic agent in the treatment of MM.

  4. [Diagnostic and evolutionary profile of multiple myeloma in Senegal: monocentric study conducted from 2005 to 2016].

    Science.gov (United States)

    Fall, Seynabou; Dieng, Fatma; Diouf, Coumba; Djiba, Boundia; Ndao, Awa Cheikh; Ndiaye, Fatou Samba Diago

    2017-01-01

    Accessibility to innovative multiple myeloma therapies is limited in sub-Saharan Africa. This study aimed to describe the diagnostic and evolutionary features observed during treatment of our patients with myeloma. We conducted a retrospective, descriptive, analytical study (2005 - 2016) of patients with myeloma included in the study based on International Myeloma Working Group (IMWG) Criteria (2003,2014) at the Hopital Aristide Le Dantec (Senegal). We collected data from 136 medical records (69 men, 67 women) of patients with an average age of 59 years ± 10.1 years, who were less than 65 years of age in 69.1% of cases. Tell-tale signs included bone pain (96.3%), renal failure (36.8%), infection (23.5%), pathological fracture (17.6%), spinal cord compression (16.9%) and malignant hypercalcaemia (16.2%). Isotopic antiglobulin test showed that anti-IgG could be detected in 61.3% of cases and Kappa in 65% of cases. Patients were classified stage III (59.4%) and I-II (40.6%)of the index staging system. The median survival of patients under conventional traitement (Méphalan-Prédnisone: 67.6%, innovative: 5.9%) was 20 months (1-78 months). Survival rates are better in the absence of neurological and infectious complications and for patients with score I-II of the index Staging System. In our study, multiple myeloma was frequently diagnosed before age 65, at advanced stage of tumor mass. Early detection and access to adequate therapies could improve overall survival.

  5. A Next-Generation Sequencing Strategy for Evaluating the Most Common Genetic Abnormalities in Multiple Myeloma.

    Science.gov (United States)

    Jiménez, Cristina; Jara-Acevedo, María; Corchete, Luis A; Castillo, David; Ordóñez, Gonzalo R; Sarasquete, María E; Puig, Noemí; Martínez-López, Joaquín; Prieto-Conde, María I; García-Álvarez, María; Chillón, María C; Balanzategui, Ana; Alcoceba, Miguel; Oriol, Albert; Rosiñol, Laura; Palomera, Luis; Teruel, Ana I; Lahuerta, Juan J; Bladé, Joan; Mateos, María V; Orfão, Alberto; San Miguel, Jesús F; González, Marcos; Gutiérrez, Norma C; García-Sanz, Ramón

    2017-01-01

    Identification and characterization of genetic alterations are essential for diagnosis of multiple myeloma and may guide therapeutic decisions. Currently, genomic analysis of myeloma to cover the diverse range of alterations with prognostic impact requires fluorescence in situ hybridization (FISH), single nucleotide polymorphism arrays, and sequencing techniques, which are costly and labor intensive and require large numbers of plasma cells. To overcome these limitations, we designed a targeted-capture next-generation sequencing approach for one-step identification of IGH translocations, V(D)J clonal rearrangements, the IgH isotype, and somatic mutations to rapidly identify risk groups and specific targetable molecular lesions. Forty-eight newly diagnosed myeloma patients were tested with the panel, which included IGH and six genes that are recurrently mutated in myeloma: NRAS, KRAS, HRAS, TP53, MYC, and BRAF. We identified 14 of 17 IGH translocations previously detected by FISH and three confirmed translocations not detected by FISH, with the additional advantage of breakpoint identification, which can be used as a target for evaluating minimal residual disease. IgH subclass and V(D)J rearrangements were identified in 77% and 65% of patients, respectively. Mutation analysis revealed the presence of missense protein-coding alterations in at least one of the evaluating genes in 16 of 48 patients (33%). This method may represent a time- and cost-effective diagnostic method for the molecular characterization of multiple myeloma. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  6. "ROLE OF ALLOGENEIC TRANSPLANTATION IN MULTIPLE MYELOMA IN THE ERA OF NEW DRUGS"

    Directory of Open Access Journals (Sweden)

    Benedetto Bruno

    2010-06-01

                Allografting is a potentially curative treatment for a subset of multiple myeloma patients for its well documented graft-vs-myeloma effects. However, its role has been hotly debated. Even though molecular remissions have been reported up to 50% after high-dose myeloablative conditionings, their applications, given the high toxicity, have been for long limited to younger relapsed/refractory patients. These limitations have greatly been reduced through the introduction of non-myeloablative/reduced-intensity conditionings.             The introduction of new drugs, characterised by low risks of early mortality, indeed requires to define role and timing of an allograft to capture the subset of patients who may most benefit from graft-vs-myeloma effects.   Ultimately, new drugs should not be viewed as mutually exclusive with an allograft. They may be employed to achieve profound cytoreduction before and enhance graft-versus-myeloma effects as consolidation/maintenance therapy after an allograft. However, this combination should be explored only in well-designed clinical trials.

  7. S-phase induction by interleukin-6 followed by chemotherapy in patients with refractory multiple myeloma

    DEFF Research Database (Denmark)

    de Nully Brown, P; Jensen, P O; Diamant, M

    1998-01-01

    .0 microg/kg (n = 6) by subcutaneous injection once daily for 5 days and chemotherapy was administered on the last day of rhIL-6 injection. The effect of rhIL-6 treatment on labeling index (LI) was heterogeneous, but no statistically significant change was noted for this particular group as a whole. In two......The plasma cell labeling index (PCLI) in patients with multiple myeloma (MM) is relatively low and this has been associated with the low rate of remission following chemotherapy. Interleukin-6 (IL-6) has been demonstrated to be a major growth factor of myeloma cells. In order to increase the S......-phase proportion of myeloma cells, which might increase the sensitivity to chemotherapy, we gave rhIL-6 followed by chemotherapy to 15 myeloma patients with refractory disease. A total of 25 treatment cycles were administered since ten patients had two cycles. The rhIL-6 dose was 2.5 (n = 3), 5.0 (n = 6) and 10...

  8. Modern imaging techniques in patients with multiple myeloma; Moderne Bildgebungsverfahren beim Multiplen Myelom

    Energy Technology Data Exchange (ETDEWEB)

    Bannas, Peter; Adam, G.; Derlin, T. [Universitaetsklinikum Hamburg-Eppendorf, Hamburg (Germany). Klinik und Poliklinik fuer Diagnostische und Interventionelle Radiologie; Kroeger, N. [Universitaetsklinikum Hamburg-Eppendorf, Hamburg (Germany). Klinik und Poliklinik fuer Stammzelltransplantation

    2013-01-15

    Imaging studies are essential for both diagnosis and initial staging of multiple myeloma, as well as for differentiation from other monoclonal plasma cell diseases. Apart from conventional radiography, a variety of newer imaging modalities including whole-body low-dose-CT, whole-body MRI and 18F-FDG PET/CT may be used for detection of osseous and extraosseous myeloma manifestations. Despite of known limitations such as limited sensitivity and specificity and the inability to detect extraosseous lesions, conventional radiography still remains the gold standard for staging newly diagnosed myeloma, partly due to its wide availability and low costs. Whole-body low-dose CT is increasingly used due to its higher sensitivity for the detection of osseous lesions and its ability to diagnose extraosseous lesions, and is replacing conventional radiography at selected centres. The highest sensitivity for both detection of bone marrow disease and extraosseous lesions can be achieved with whole-body MRI or 18F-FDG PET/CT. Diffuse bone marrow infiltration may be visualized by whole-body MRI with high sensitivity. Whole-body MRI is at least recommended in all patients with normal conventional radiography and in all patients with an apparently solitary plasmacytoma of bone. To obtain the most precise readings, optimized examination protocols and dedicated radiologists and nuclear medicine physicians familiar with the complex and variable morphologies of myeloma lesions are required. (orig.)

  9. Decorin is down-regulated in multiple myeloma and MGUS bone marrow plasma and inhibits HGF-induced myeloma plasma cell viability and migration

    DEFF Research Database (Denmark)

    Kristensen, Ida Bruun; Pedersen, Lise Mariager; Rø, Torstein Baade

    2013-01-01

    pathway in multiple myeloma (MM). METHODS: Decorin levels in paired peripheral blood and bone marrow plasma samples from healthy volunteers (HV) (n=23), and patients with monoclonal gammopathy of undetermined significance (MGUS) (n=41) and MM (n=19) were determined by ELISA. Further, the ability...

  10. Killing multiple myeloma cells with the small molecule 3-bromopyruvate: implications for therapy.

    Science.gov (United States)

    Majkowska-Skrobek, Grażyna; Augustyniak, Daria; Lis, Paweł; Bartkowiak, Anna; Gonchar, Mykhailo; Ko, Young H; Pedersen, Peter L; Goffeau, Andre; Ułaszewski, Stanisław

    2014-07-01

    The small molecule 3-bromopyruvate (3-BP), which has emerged recently as the first member of a new class of potent anticancer agents, was tested for its capacity to kill multiple myeloma (MM) cancer cells. Human MM cells (RPMI 8226) begin to lose viability significantly within 8 h of incubation in the presence of 3-BP. The Km (0.3 mmol/l) for intracellular accumulation of 3-BP in MM cells is 24 times lower than that in control cells (7.2 mmol/l). Therefore, the uptake of 3-BP by MM cells is significantly higher than that by peripheral blood mononuclear cells. Further, the IC50 values for human MM cells and control peripheral blood mononuclear cells are 24 and 58 µmol/l, respectively. Therefore, specificity and selectivity of 3-BP toward MM cancer cells are evident on the basis of the above. In MM cells the transcription levels of the gene encoding the monocarboxylate transporter MCT1 is significantly amplified compared with control cells. The level of intracellular ATP in MM cells decreases by over 90% within 1 h after addition of 100 µmol/l 3-BP. The cytotoxicity of 3-BP, exemplified by a marked decrease in viability of MM cells, is potentiated by the inhibitor of glutathione synthesis buthionine sulfoximine. In addition, the lack of mutagenicity and its superior capacity relative to Glivec to kill MM cancer cells are presented in this study.

  11. New developments in the management of relapsed/refractory multiple myeloma – the role of ixazomib

    Directory of Open Access Journals (Sweden)

    Richardson PG

    2017-08-01

    Full Text Available Paul G Richardson,1 Shaji Kumar,2 Jacob P Laubach,1 Claudia Paba-Prada,1 Neeraj Gupta,3 Deborah Berg,3 Helgi van de Velde,3 Philippe Moreau4 1Division of Hematologic Malignancy, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA; 2Division of Hematology, Mayo Clinic, Rochester, MN, USA; 3Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA; 4Hematology Department, University Hospital Hotel-Dieu, Nantes, France Abstract: Ixazomib is the first oral proteasome inhibitor to be approved, in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was on the basis of results from the phase 3, double-blind, placebo-controlled TOURMALINE-MM1 study, which demonstrated a 35% improvement in progression-free survival with the all-oral combination of ixazomib plus lenalidomide–dexamethasone versus lenalidomide–dexamethasone alone (median: 20.6 vs 14.7 months; hazard ratio: 0.74, p=0.012; median follow-up 14.7 months. The addition of ixazomib to the lenalidomide–dexamethasone regimen was associated with limited additional toxicity and had no adverse impact on patient-reported quality of life. Common grade ≥3 adverse events with ixazomib include gastrointestinal adverse events, rash, and thrombocytopenia. Here, we review the efficacy, safety, pharmacokinetics, and patient-reported quality of life data seen with ixazomib, and discuss the role of this oral agent in the treatment of patients with relapsed/refractory multiple myeloma, including in patients with high-risk cytogenetic abnormalities and those with multiple prior therapies. Keywords: ixazomib, multiple myeloma, proteasome inhibitor, clinical, efficacy, tolerability, pharmacokinetics 

  12. Initial Clinical Experience in Multiple Myeloma Staging by Means of Whole-Body Resonance Techniques

    International Nuclear Information System (INIS)

    Gallego, J. I.; Concepcion, L.; Alonso, S.; Sanchez, B.; Manzi, F.

    2003-01-01

    To develop a magnetic resonance (MR) exploratory technique equivalent to serial bone X-ray, and to compare their precision in the staging of multiple myeloma (MM) patients. Multiple acquisition T1-weights TSE and STIR sequences in the coronal plane were performed. Ten healthy volunteers and 11 multiple myeloma diagnosed patients were included. The visualization of bony structures was particularly noted,with special attention given to those which would normally be included in a serial bone X-ray. In the case of the patients, a comparison was made between diagnostic capacities of the MR sequences. MR highlighters significantly more (p<0.05) bony elements than did the serial bone X-ray. This was greatly due to a sequential displacement of the scanner bed, allowing for field-of-views which were minimally from head to third proximal of the leg. Magnetic resonance detected a significantly higher number (p<0.05) of lesions. It was, in turn, capable of revealing greater lesion extensions, even to the point of implying staging classification changes in 18% of the patients. The utilization of whole-body MR techniques in multiple myeloma patients is feasible and clinically beneficial. MR is both more sensitive and more specific than serial bone X-ray for evaluation of bony lesions in MM. It is currently serving as a valid alternative in a growing numbers of patients. (Author) 10 refs

  13. Multiple myeloma, leukemia, and breast cancer among the US radium dial workers

    International Nuclear Information System (INIS)

    Stebbings, J.H.; Lucas, H.F.; Stehney, A.F.

    1984-01-01

    The relationships of radium exposure to mortality from multiple myeloma, leukemia, and breast cancer were studied in three cohorts of female dial workers defined by year of first employment. A three-fold excess risk of multiple myeloma occurred in the pre-1930 cohort; however, analyses of body burdens and durations of employment suggest that external radiation was more likely to have been responsible than was internal radium. Leukemia incidence and mortality have not been elevated overall among the female dial workers, either in the pre-1930 or the post-1930 cohorts, but cases have tended to occur early and in subjects with higher body burdens of radium. Extensive analyses of breast cancer data have uncovered several observations weighing against a causal interpretation of the association between radium body burdens and breast cancer

  14. [Effects of pamidronate disodium (Bonin) combined with chemotherapy on bone pain in multiple myeloma].

    Science.gov (United States)

    Leng, Yun; Chen, Shi-lun; Shi, Hong-zhi

    2002-10-01

    Objective. To evaluate the therapeutic effects of Disodium Pamidronate (Bonin) on bone pain in multiple myeloma. Method. 18 patients received only chemotherapy and 16 patients with addition of Bonin were compared. Result. The bone pain was significantly relieved both in chemotherapy alone group and in the combination group of Bonin with chemotherapy after treatment (P<0.01, as compared with before therapy). However, the effects of combination group were more dramatical than that of the other group (P<0.05). No obvious side-effects were observed except mild fever in one patient in the combination group. Conclusion. Bonin, as a safe and effective Bisphosphonates preparation, could relieve bone pain in multiple myeloma more effectively when combined with chemotherapy.

  15. Paraneoplastic addisonian pigmentation and acquired ichthyosis as presenting features of multiple myeloma

    International Nuclear Information System (INIS)

    Dar, N.R.; Raza, N.

    2010-01-01

    Black brown hyperpigmentation of the mucosae, sun exposed skin, palmar creases and frictional sites (Addisonian pigmentation) is characteristic of Addison disease. However, it can also occur as a para neoplastic manifestation of tumours like bronchogenic carcinoma. Acquired ichthyosis starts later in life and can also be a para neoplastic presentation.We report a unique combination of para neoplastic Addisonian pigmentation and acquired ichthyosis as presenting features in a patient with undiagnosed multiple myeloma. To the best of our knowledge this combination of para neoplastic dermatosis has not been documented before in multiple myeloma. It is concluded that the presence of more than one suspicious dermatosis may be an indicator of being para neoplastic requiring necessary work-up. (author)

  16. Systemic amyloidosis due to unknown multiple myeloma in small bowel pseudo-obstruction: case report

    Directory of Open Access Journals (Sweden)

    Giuseppe Caparrotti

    2016-03-01

    Full Text Available Amyloidosis is a pathologic diagnosis characterized by extracellular deposition of insoluble protein fibrils in various organs and tissues. There are two main forms of amyloidosis, primary amyloidosis, and secondary amyloidosis. Gastrointestinal involvement is common in both amyloidosis forms. We describe the case of a 78-year-old woman taken to the operating room for small bowel obstruction, found to have pseudo-obstruction and enteritis. Exploratory laparotomy revealed gastric mass and histological examen showed extensive amyloid deposition consistent with amyloidosis. Hematological evaluation revealed unknown multiple myeloma. This case report and literature data suggest to perform a hematological examination in patients with amyloidosis diagnosis to exclude a multiple myeloma or other plasma cell disorders

  17. Unsuspected multiples myeloma presenting as bilateral pleural effusion – a cytological diagnosis

    Directory of Open Access Journals (Sweden)

    Dhingra Kajal

    2007-01-01

    Full Text Available Abstract Background Multiple Myeloma presenting as a pleural effusion is extremely rare. It is usually a late complication and is associated with a poor prognosis. Case Presentation A 40-year-old male presented with dyspnea and fever of six months duration. Clinical diagnosis of pulmonary tuberculosis was considered. X-ray chest showed bilateral pleural effusion. Pleural cytology revealed numerous plasma cells, some of which were binucleated and atypical. Cytological differential diagnosis included: Myelomatous effusion and Non-Hodgkin's Lymphoma deposit (Immunoblastic type. Bone marrow biopsy, serum protein electrophoresis and bone scan confirmed the diagnosis of multiple myeloma (Plasmablastic type. Conclusion Myelomatous pleural effusion as an initial presentation although extremely rare, should always be considered in presence of atypical plasma cells irrespective of age.

  18. The shaping and functional consequences of the dosage effect landscape in multiple myeloma.

    Science.gov (United States)

    Samur, Mehmet K; Shah, Parantu K; Wang, Xujun; Minvielle, Stéphane; Magrangeas, Florence; Avet-Loiseau, Hervé; Munshi, Nikhil C; Li, Cheng

    2013-10-02

    Multiple myeloma (MM) is a malignant proliferation of plasma B cells. Based on recurrent aneuploidy such as copy number alterations (CNAs), myeloma is divided into two subtypes with different CNA patterns and patient survival outcomes. How aneuploidy events arise, and whether they contribute to cancer cell evolution are actively studied. The large amount of transcriptomic changes resultant of CNAs (dosage effect) pose big challenges for identifying functional consequences of CNAs in myeloma in terms of specific driver genes and pathways. In this study, we hypothesize that gene-wise dosage effect varies as a result from complex regulatory networks that translate the impact of CNAs to gene expression, and studying this variation can provide insights into functional effects of CNAs. We propose gene-wise dosage effect score and genome-wide karyotype plot as tools to measure and visualize concordant copy number and expression changes across cancer samples. We find that dosage effect in myeloma is widespread yet variable, and it is correlated with gene expression level and CNA frequencies in different chromosomes. Our analysis suggests that despite the enrichment of differentially expressed genes between hyperdiploid MM and non-hyperdiploid MM in the trisomy chromosomes, the chromosomal proportion of dosage sensitive genes is higher in the non-trisomy chromosomes. Dosage-sensitive genes are enriched by genes with protein translation and localization functions, and dosage resistant genes are enriched by apoptosis genes. These results point to future studies on differential dosage sensitivity and resistance of pro- and anti-proliferation pathways and their variation across patients as therapeutic targets and prognosis markers. Our findings support the hypothesis that recurrent CNAs in myeloma are selected by their functional consequences. The novel dosage effect score defined in this work will facilitate integration of copy number and expression data for identifying driver

  19. T cells in multiple myeloma display features of exhaustion and senescence at the tumor site

    Directory of Open Access Journals (Sweden)

    Claudia Zelle-Rieser

    2016-11-01

    Full Text Available Abstract Background Multiple myeloma is an incurable plasma cell malignancy that is mostly restricted to the bone marrow. Cancer-induced dysfunction of cytotoxic T cells at the tumor site may be responsible for immune evasion and therapeutical failure of immunotherapies. Therefore, enhanced knowledge about the actual status of T cells in myeloma bone marrow is urgently needed. Here, we assessed the expression of inhibitory molecules PD-1, CTLA-4, 2B4, CD160, senescence marker CD57, and CD28 on T cells of naive and treated myeloma patients in the bone marrow and peripheral blood and collected data on T cell subset distribution in both compartments. In addition, T cell function concerning proliferation and expression of T-bet, IL-2, IFNγ, and CD107a was investigated after in vitro stimulation by CD3/CD28. Finally, data was compared to healthy, age-matched donor T cells from both compartments. Methods Multicolor flow cytometry was utilized for the analyses of surface molecules, intracellular staining of cytokines was also performed by flow cytometry, and proliferation was assessed by 3H-thymidine incorporation. Statistical analyses were performed utilizing unpaired T test and Mann-Whitney U test. Results We observed enhanced T cell exhaustion and senescence especially at the tumor site. CD8+ T cells expressed several molecules associated with T cell exhaustion (PD-1, CTLA-4, 2B4, CD160 and T cell senescence (CD57, lack of CD28. This phenotype was associated with lower proliferative capacity and impaired function. Despite a high expression of the transcription factor T-bet, CD8+ T cells from the tumor site failed to produce IFNγ after CD3/CD28 in vitro restimulation and displayed a reduced ability to degranulate in response to T cell stimuli. Notably, the percentage of senescent CD57+CD28− CD8+ T cells was significantly lower in treated myeloma patients when compared to untreated patients. Conclusions T cells from the bone marrow of myeloma

  20. The therapeutic effect of modified Huangqi Guizhi Wuwu Tang for multiple myeloma

    OpenAIRE

    Tian, Mingmin; Huang, Huang

    2017-01-01

    Abstract Rationale: Multiple myeloma (MM) is a hematologic malignancy characterized by proliferation of clonal plasma cells in the bone marrow. The median survival has increased to 6 years in recent years. But MM remains incurable. Some studies about the effects of Chinese herb medicine on MM have been carried out. Long survival in MM patients through Traditional Chinese Medicine (TCM) therapies has been reported rarely before. Patient concerns: We report a case of a female patient who was di...

  1. Diagnostic x-ray procedures and risk of leukemia, lymphoma, and multiple myeloma

    International Nuclear Information System (INIS)

    Boice, J.D. Jr.; Morin, M.M.; Glass, A.G.; Friedman, G.D.; Stovall, M.; Hoover, R.N.; Fraumeni, J.F. Jr.

    1991-01-01

    Exposure to diagnostic x-rays and the risk of leukemia, non-Hodgkin's lymphoma (NHL), and multiple myeloma were studied within two prepaid health plans. Adult patients with leukemia (n = 565), NHL (n = 318), and multiple myeloma (n = 208) were matched to controls (n = 1390), and over 25,000 x-ray procedures were abstracted from medical records. Dose response was evaluated by assigning each x-ray procedure a score based on estimated bone marrow dose. X-ray exposure was not associated with chronic lymphocytic leukemia, one of the few malignant conditions never linked to radiation (relative risk [RR], 0.66). For all other forms of leukemia combined (n = 358), there was a slight elevation in risk (RR, 1.17) but no evidence of a dose-response relationship when x-ray procedures near the time of diagnosis were excluded. Similarly, patients with NHL were exposed to diagnostic x-ray procedures more often than controls (RR, 1.32), but the RR fell to 0.99 when the exposure to diagnostic x-ray procedures within 2 years of diagnosis was ignored. For multiple myeloma, overall risk was not significantly high (RR, 1.14), but there was consistent evidence of increasing risk with increasing numbers of diagnostic x-ray procedures. These data suggest that persons with leukemia and NHL undergo x-ray procedures frequently just prior to diagnosis for conditions related to the development or natural history of their disease. There was little evidence that diagnostic x-ray procedures were causally associated with leukemia or NHL. The risk for multiple myeloma, however, was increased among those patients who were frequently exposed to x-rays

  2. Bortezomib in multiple myeloma and lymphoma: a systematic review and clinical practice guideline

    OpenAIRE

    Reece, D.; Imrie, K.; Stevens, A.; Smith, C.A.

    2006-01-01

    Questions In patients with multiple myeloma, Waldenström macroglobulinemia, or lymphoma, what is the efficacy of bortezomib alone or in combination as measured by survival, quality of life, disease control (for example, time to progression), response duration, or response rate? What is the toxicity associated with the use of bortezomib? Which patients are more or less likely to benefit from treatment with bortezomib? Perspectives Evidence was selected and reviewed by two members of the Hemato...

  3. Effects of Radiotherapy in the treatment of multiple myeloma: a retrospective analysis of a Single Institution

    International Nuclear Information System (INIS)

    Matuschek, Christiane; Ochtrop, Thomas A; Bölke, Edwin; Ganswindt, Ute; Fenk, Roland; Gripp, Stephan; Kröpil, Patric; Gerber, Peter Arne; Kammers, Kai; Hamilton, Jackson; Orth, Klaus; Budach, Wilfried

    2015-01-01

    Palliative irradiation of osteolytic lesions is a considerable component in the treatment for patients with multiple myeloma. In this study, we analyzed the efficacy of irradiation in these patients. We retrospectively analyzed 153 patients with multiple myeloma who were admitted to our department between 1989 and 2013. According to the staging system of Durie & Salmon 116 patients were classified as stage III. 107/153 patients were treated with radiotherapy of at least one and up to 6 bony lesions at different times. In order to evaluate the effect of local radiotherapy on pain relief and bone recalcification a uni- and multivariate analysis was performed using a binary logistic regression model to correct for multiple measurements. Complete information on dose, fractionation and volume of radiotherapy was available from 81 patients treated in 136 target volumes for pain relief, and from 69 patients treated in 108 target volumes for recalcification. Total radiation doses varied between 8 Gy to 50 Gy (median dose 25 Gy in 2.5 Gy fractions, 5 times a week). Radiotherapy resulted in complete local pain relief in 31% and partial local pain relief in 54% of the patients. In the univariate analysis, higher total radiation doses (p = 0.023) and higher age (p = 0.014) at the time of radiotherapy were significantly associated with a higher likelihood of pain relief, whereas no significant association was detected for concurrent systemic treatment, type and stage of myeloma and location of bone lesions. The same variables were independent predictors for pain relief in the multivariate analysis. Recalcification was observed in 48% of irradiated bone lesions. In the uni- and multivariate analysis higher radiation doses were significantly associated (p = 0.048) with an increased likelihood of recalcification. Side effects of radiotherapy were generally mild. Higher total biological radiation doses were associated with better pain relief and recalcification in this

  4. Role of whole-body 64-slice multidetector computed tomography in treatment planning for multiple myeloma.

    Science.gov (United States)

    Razek, Ahmed Abdel Khalek Abdel; Ezzat, Amany; Azmy, Emad; Tharwat, Nehal

    2013-08-01

    The authors evaluated the role of whole-body 64-slice multidetector computed tomography (WB-MDCT) in treatment planning for multiple myeloma. This was a prospective study of 28 consecutive patients with multiple myeloma (19 men, nine women; age range, 51-73 years; mean age, 60 years) who underwent WB-MDCT and conventional radiography (CR) of the skeleton. The images were interpreted for the presence of bony lesions, medullary lesions, fractures and extraosseous lesions. We evaluated any changes in treatment planning as a result of WB-MDCT findings. WB-MDCT was superior to CR for detecting bony lesions (p=0.001), especially of the spine (p=0.001) and thoracic cage (p=0.006). WB-MDCT upstaged 14 patients, with a significant difference in staging (p=0.002) between WB-MDCT and CR. Medullary involvement either focal (n=6) or diffuse (n=3) had a positive correlation with the overall score (r=0.790) and stage (r=0.618) of disease. Spine fractures were better detected at WB-MDCT (n=4) than at CR (n=2). Extraosseous soft tissue lesions (n=7) were detected only at WB-MDCT. Findings detected at the WB-MDCT led to changes in the patient's treatment plan in 39% of cases. Upstaging of seven patients (25%) altered the medical treatment plan, and four of 28 (14%) patients required additional radiotherapy (7%) and vertebroplasty (7%). We conclude that WB-MDCT has an impact on treatment planning and prognosis in patients with multiple myeloma, as it has high rate of detecting cortical and medullary bone lesions, spinal fracture and extraosseous lesions. This information may alter treatment planning in multiple myeloma due to disease upstaging and detection of spine fracture and extraosseous spinal lesions.

  5. Bone marrow scintigraphy with antigranulocyte antibody in multiple myeloma: comparison with simple radiography and bone scintigraphy

    International Nuclear Information System (INIS)

    Kim, Dong Hwan; Lee, Jae Tae; Baek, Jin Ho

    1998-01-01

    Simple X-ray study and bone scan have limitations for early diagnosis of bone or bone marrow lesions in multiple myeloma. The purpose of this study was to evaluate the diagnostic usefulness of bone marrow immunoscintigraphy using anti-granulocyte monoclonal antibody for the evaluation of bone involvement in multiple myeloma. In 22 patients (Male: 15, Female: 7) with multiple myeloma, we performed whole-body immunoscintigraphy using 99m Tc-labelled antigranulocyte antibody (BW 250/183, Scintimum Granulozyt R CIS, France) and compared the findings with those of simple bone radiography and 99m Tc-MDP bone scan. Abnormal findings in bone marrow scintigraphy were considered to be present in case of expansion of peripheral bone marrow or focal photon defect in axial bones. Marrow expansion was noted in 15 of 22 patients (68%). Focal photon defects were found in 18 patients (82%). While one (33%) of 3 patients with Stage II disease showed focal defects in bone marrow scan, abnormal focal defects were observed in 17 of 19 (90%) patients with Stage III. Among 124 focal abnormal sites which were observed in bone marrow scan, bone scan or simple bone radiography, bone marrow scan detected 92 sites (74%), whereas 82 sites (66%) were observed in simple bone radiogrpahy (58 sites, 47%) or bone scan (40 sites, 32%). Fifty-one(41%) out of 124 bone lesions were detected by bone marrow scan only, and located mostly in thoracolumbar spine. Bone marrow scan using 99m Tc-labelled antigranulocyte antibody seems to be a more sensitive procedure for the detection of pathologic bone lesions than simple bone X-ray or bone scan in patients with multiple myeloma

  6. Clinical efficacy and management of monoclonal antibodies targeting CD38 and SLAMF7 in multiple myeloma

    DEFF Research Database (Denmark)

    van de Donk, Niels W C J; Moreau, Philippe; Plesner, Torben

    2016-01-01

    Immunotherapeutic strategies are emerging as promising therapeutic approaches in multiple myeloma (MM), with several monoclonal antibodies in advanced stages of clinical development. Of these agents, CD38-targeting antibodies have marked single agent activity in extensively pretreated MM...... of therapeutic antibodies with immunofixation and serum protein electrophoresis assays may lead to underestimation of complete response. Strategies to mitigate interference, based on shifting the therapeutic antibody band, are in development. Furthermore, daratumumab, and probably also other CD38-targeting...

  7. Reassessment of the relationship between M-protein decrement and survival in multiple myeloma.

    OpenAIRE

    Palmer, M.; Belch, A.; Hanson, J.; Brox, L.

    1989-01-01

    The relationship between percentage M-protein decrement and survival is assessed in 134 multiple myeloma patients. The correlation did not achieve statistical significance (P = 0.069). Multivariate analysis using the Cox proportional hazards model, including a number of previously recognised prognostic factors, showed only percentage M-protein decrement, creatinine and haemoglobin to be significantly correlated with survival. However, the R'-statistic for each of these variables was low, indi...

  8. Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation

    OpenAIRE

    Raimondi, Lavinia; De Luca, Angela; Amodio, Nicola; Manno, Mauro; Raccosta, Samuele; Taverna, Simona; Bellavia, Daniele; Naselli, Flores; Fontana, Simona; Schillaci, Odessa; Giardino, Roberto; Fini, Milena; Tassone, Pierfrancesco; Santoro, Alessandra; De Leo, Giacomo

    2015-01-01

    Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs ...

  9. Racial disparities in incidence and outcome in multiple myeloma: a population-based study

    OpenAIRE

    Waxman, Adam J.; Mink, Pamela J.; Devesa, Susan S.; Anderson, William F.; Weiss, Brendan M.; Kristinsson, Sigurdur Y.; McGlynn, Katherine A.; Landgren, Ola

    2010-01-01

    Multiple myeloma (MM) is the most common hematologic malignancy in blacks. Some prior studies suggest inferior survival in blacks; others suggest similar survival. Using the original 9 Surveillance, Epidemiology, and End Results registries, we conducted a large-scale population-based study including 5798 black and 28 939 white MM patients diagnosed 1973-2005, followed through 2006. Age-adjusted incidence rates, disease-specific survival, and relative survival rates were calculated by race, ag...

  10. The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma

    OpenAIRE

    Hernández-García, Susana; San-Segundo, Laura; González-Méndez, Lorena; Corchete, Luis A; Misiewicz-Krzeminska, Irena; Martín-Sánchez, Montserrat; López-Iglesias, Ana-Alicia; Algarín, Esperanza Macarena; Mogollón, Pedro; Díaz-Tejedor, Andrea; Paíno, Teresa; Tunquist, Brian; Mateos, María-Victoria; Gutiérrez, Norma C; Díaz-Rodriguez, Elena

    2017-01-01

    [EN]Kinesin spindle protein inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (ARRY-520), an inhibitor of this protein, has demonstrated activity in heavily pre-treated multiple myeloma patients. The aim of the work herein was to investigate the activity of filanesib in combination with pomalidomide plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect. The ability of filanesib to enhance the activity of pomali...

  11. Interleukin-6 counteracts therapy-induced cellular oxidative stress in multiple myeloma by up-regulating manganese superoxide dismutase.

    Science.gov (United States)

    Brown, Charles O; Salem, Kelley; Wagner, Brett A; Bera, Soumen; Singh, Neeraj; Tiwari, Ajit; Choudhury, Amit; Buettner, Garry R; Goel, Apollina

    2012-06-15

    IL (interleukin)-6, an established growth factor for multiple myeloma cells, induces myeloma therapy resistance, but the resistance mechanisms remain unclear. The present study determines the role of IL-6 in re-establishing intracellular redox homoeostasis in the context of myeloma therapy. IL-6 treatment increased myeloma cell resistance to agents that induce oxidative stress, including IR (ionizing radiation) and Dex (dexamethasone). Relative to IR alone, myeloma cells treated with IL-6 plus IR demonstrated reduced annexin/propidium iodide staining, caspase 3 activation, PARP [poly(ADP-ribose) polymerase] cleavage and mitochondrial membrane depolarization with increased clonogenic survival. IL-6 combined with IR or Dex increased early intracellular pro-oxidant levels that were causally related to activation of NF-κB (nuclear factor κB) as determined by the ability of N-acetylcysteine to suppress both pro-oxidant levels and NF-κB activation. In myeloma cells, upon combination with hydrogen peroxide treatment, relative to TNF (tumour necrosis factor)-α, IL-6 induced an early perturbation in reduced glutathione level and increased NF-κB-dependent MnSOD (manganese superoxide dismutase) expression. Furthermore, knockdown of MnSOD suppressed the IL-6-induced myeloma cell resistance to radiation. MitoSOX Red staining showed that IL-6 treatment attenuated late mitochondrial oxidant production in irradiated myeloma cells. The present study provides evidence that increases in MnSOD expression mediate IL-6-induced resistance to Dex and radiation in myeloma cells. The results of the present study indicate that inhibition of antioxidant pathways could enhance myeloma cell responses to radiotherapy and/or chemotherapy.

  12. The expression of p53 protein in patients with multiple myeloma

    Directory of Open Access Journals (Sweden)

    Marković Olivera

    2007-01-01

    Full Text Available Introduction: Although mutations of p53 are one of the most often acquired genetic changes in malignant tumors, these mutations are rare events in patients with newly diagnosed multiple myeloma (MM. Moreover, there are a few literature data about clinical significance of p53 overexpression in multiple myeloma. Objective The aim of our study was to evaluate the clinical significance of p53 immunoexpression in multiple myeloma. Method A total of 58 patients with newly diagnosed MM (26 females and 32 males, mean age 62 years were enrolled in the study. The diagnosis of MM was made according to criteria of Chronic Leukemia-Myeloma Task Force. Clinical staging was done according to Durie and Salmon classification (4 patients had disease stage I, 15 patients stage II and 39 patients stage III. The histological grade and histological stage were determined according to predominant plasma cell morphology and volume of myeloma infiltration, respectively. Standard immunohistochemical analysis with p53 antibody in B5-fixed and paraffin- embedded bone marrow specimens was used to evaluate the expression of p53 in myeloma cells. The specimens were considered positive when ≥5% of plasma cells exhibited clear nuclear positivity. Results Out of 58 patients, p53 expression was detected in 9 (15.52%. No significant correlation was found between p53 expression and clinical stage (I+II vs. III, Я2-microglobulin level (≤6 mg/L vs. >6mg/L, histological grade (I vs. II+III, histological stage (<20% vs. 21-50% vs. >50% and the extent of osteolytic lesions (≤3 vs. >3 lesions. Median survival of patients with p53 immunoreactivity in =>5% of plasma cells was 10 months, whilst median survival of patients with p53 immunoreactivity in <5% of plasma cells was 36 months. However, such difference was not significant (p=0.2. Conclusion The frequency of p53 immunoexpression in our group of newly diagnosed MM was relatively low. Although p53 immunoexpression was not

  13. Efficacy and toxicity profile of carfilzomib based regimens for treatment of multiple myeloma: A systematic review.

    Science.gov (United States)

    Mushtaq, Adeela; Kapoor, Vikas; Latif, Azka; Iftikhar, Ahmad; Zahid, Umar; McBride, Ali; Abraham, Ivo; Riaz, Irbaz Bin; Anwer, Faiz

    2018-05-01

    Standard induction therapy for multiple myeloma is three-drug combination based on following classes of drugs: proteasome inhibitors, immunomodulators and steroids. Despite its notable efficacy, bortezomib has side effects like peripheral neuropathy (PNP) with reported incidence of grade ≥3 PNP between 2%-23% Schlafer et al., 2017. Carfilzomib (CFZ) has high selectivity and minimal off-target adverse effects including lower rates of PNP. CFZ is already approved for treatment of relapsed and refractory multiple myeloma (RRMM) as single agent as well as in combination with lenalidomide and/or dexamethasone. Extensive literature search identified a total of 1839 articles. Twenty-six articles (n = 5980) met the inclusion criteria, 15 in newly diagnosed multiple myeloma (NDMM) and 11 in RRMM group. CFZ demonstrates comparable or even better efficacy to bortezomib with much favorable AE profile. Deep, rapid and sustainable response using KRd with safer toxicity profile supports extension of KRd therapy to frontline therapy for all risk categories of MM. High incidence of grade ≥3 HTN underscores the importance of serial BP monitoring. In RRMM, CFZ has documented efficacy with standard 20-27mg/m2 dose. Further large-scale trials are needed to study benefit-to-risk profile of 20-56 and 20-70 mg/m2 dose of CFZ vs standard 20-27 mg/m2 dose in NDMM and RRMM. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Radiotherapy for solitary plasmacytoma and multiple myeloma; Strahlentherapie bei solitaerem Plasmozytom und multiplem Myelom

    Energy Technology Data Exchange (ETDEWEB)

    Schmaus, M.C. [Universitaetsklinikum Heidelberg, Klinik fuer Radioonkologie und Strahlentherapie, Heidelberg (Germany); Neuhof, D. [MVZ Strahlentherapie und Nuklearmedizin Weinheim, Weinheim (Germany)

    2014-06-15

    Solitary plasmacytoma and multiple myeloma require a differentiated radiotherapy. The irradiation for plasmacytoma with an adequate total dose (medullary 40-50 Gy or extramedullary 50-60 Gy) leads to a high degree of local control with a low rate of side effects. In cases of multiple myeloma radiotherapy will achieve effective palliation, both in terms of recalcification as well as reduction of neurological symptoms and analgesia. In terms of analgesia the rule is the higher the single dose fraction the faster the reduction of pain. As part of a conditioning treatment prior to stem cell transplantation radiotherapy contributes to the establishment of a graft versus myeloma effect (GVM). (orig.) [German] Das solitaere Plasmozytom und das multiple Myelom fordern eine differenzierte Strahlenbehandlung. Bei Plasmozytomen fuehrt eine Bestrahlung mit ausreichender Gesamtdosis (medullaer 40-50 Gy oder extramedullaer 50-60 Gy) zu einer hohen Lokalkontrolle mit einer geringen Rate an Nebenwirkungen. Beim multiplen Myelom kann die Strahlentherapie eine effektive Palliation sowohl hinsichtlich Rekalzifikation als auch Reduktion neurologischer Symptomatik und Analgesie erzielen. Hinsichtlich der Analgesie gilt: Je hoeher die Einzeldosis, desto schneller der Wirkeintritt. Im Rahmen einer Konditionierungstherapie vor Stammzelltransplantation traegt die Strahlentherapie zur Etablierung eines Graft-versus-Myelom-Effekts (GvM) bei. (orig.)

  15. Synchronous Bone Metastasis From Multiple Myeloma and Prostate Adenocarcinoma as Initial Presentation of Coexistent Malignancies

    Directory of Open Access Journals (Sweden)

    Diego Andres Adrianzen Herrera

    2018-04-01

    Full Text Available The radiographic appearance of bone metastases is usually determined by tumor histology and can be osteolytic, osteoblastic, or mixed. We present a patient with coexistent bone metastasis from multiple myeloma and prostate adenocarcinoma who exhibited synchronous bone involvement of both histologies within the same bone lesion, a rare phenomenon that has not been previously reported and led to atypical radiographic findings. The radiograph of a 71-year-old man with thigh swelling and pain demonstrated a lytic femoral lesion. Magnetic resonance imaging (MRI confirmed a destructive process, but showed coexistent metaphyseal sclerosis. Multiple myeloma was suspected by demonstration of monoclonal gammopathy and confirmed by computed tomography (CT-guided biopsy. Incidentally, CT demonstrated areas of sclerosis corresponding to T2 hypointensity on MRI. Further studies revealed osteoblastic spinal metastasis, prostate enhancement on CT and prostate-specific antigen (PSA level of 90 ng/mL, concerning for concomitant prostate neoplasm. After endoprosthetic reconstruction, pathology of the femur identified both plasma cell neoplasm and metastatic prostate adenocarcinoma. An association between prostate cancer and multiple myeloma is hypothesized due to tumor microenvironment similarities and possible common genetic variations, however, coexisting bone metastases have never been reported. This unusual finding explains the discrepant imaging features in our patient and is evidenced that certain clinical situations merit contemplation of atypical presentations of common malignancies even if this leads to additional testing.

  16. GSK3-mediated MAF phosphorylation in multiple myeloma as a potential therapeutic target

    International Nuclear Information System (INIS)

    Herath, N I; Rocques, N; Garancher, A; Eychène, A; Pouponnot, C

    2014-01-01

    Multiple myeloma (MM) is an incurable haematological malignancy characterised by the proliferation of mature antibody-secreting plasma B cells in the bone marrow. MM can arise from initiating translocations, of which the musculoaponeurotic fibrosarcoma (MAF) family is implicated in ∼5%. MMs bearing Maf translocations are of poor prognosis. These translocations are associated with elevated Maf expression, including c-MAF, MAFB and MAFA, and with t(14;16) and t(14;20) translocations, involving c-MAF and MAFB, respectively. c-MAF is also overexpressed in MM through MEK/ERK activation, bringing the number of MMs driven by the deregulation of a Maf gene close to 50%. Here we demonstrate that MAFB and c-MAF are phosphorylated by the Ser/Thr kinase GSK3 in human MM cell lines. We show that LiCl-induced GSK3 inhibition targets these phosphorylations and specifically decreases proliferation and colony formation of Maf-expressing MM cell lines. Interestingly, bortezomib induced stabilisation of Maf phosphorylation, an observation that could explain, at least partially, the low efficacy of bortezomib for patients carrying Maf translocations. Thus, GSK3 inhibition could represent a new therapeutic approach for these patients

  17. Withaferin A Inhibits STAT3 and Induces Tumor Cell Death in Neuroblastoma and Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Lisette P. Yco

    2014-01-01

    Full Text Available Signal transducer and activator of transcription 3 (STAT3 is an oncogenic transcription factor that has been implicated in many human cancers and has emerged as an ideal target for cancer therapy. Withaferin A (WFA is a natural product with promising antiproliferative properties through its association with a number of molecular targets including STAT3. However, the effect of WFA in pediatric neuroblastoma (NB and its interaction with STAT3 have not been reported. In this study, we found that WFA effectively induces dose-dependent cell death in high-risk and drug-resistant NB as well as multiple myeloma (MM tumor cells, prevented interleukin-6 (IL-6–mediated and persistently activated STAT3 phosphorylation at Y705, and blocked the transcriptional activity of STAT3. We further provide computational models that show that WFA binds STAT3 near the Y705 phosphotyrosine residue of the STAT3 Src homology 2 (SH2 domain, suggesting that WFA prevents STAT3 dimer formation similar to BP-1-102, a well-established STAT3 inhibitor. Our findings propose that the antitumor activity of WFA is mediated at least in part through inhibition of STAT3 and provide a rationale for further drug development and clinical use in NB and MM.

  18. Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation

    Science.gov (United States)

    Raimondi, Lavinia; De Luca, Angela; Amodio, Nicola; Manno, Mauro; Raccosta, Samuele; Taverna, Simona; Bellavia, Daniele; Naselli, Flores; Fontana, Simona; Schillaci, Odessa; Giardino, Roberto; Fini, Milena; Tassone, Pierfrancesco; Santoro, Alessandra; De Leo, Giacomo; Giavaresi, Gianluca; Alessandro, Riccardo

    2015-01-01

    Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs differentiation. We show that MM cells produce exosomes which are actively internalized by Raw264.7 cell line, a cellular model of osteoclast formation. MM cell-derived exosomes positively modulate pre-osteoclast migration, through the increasing of CXCR4 expression and trigger a survival pathway. MM cell-derived exosomes play a significant pro-differentiative role in murine Raw264.7 cells and human primary osteoclasts, inducing the expression of osteoclast markers such as Cathepsin K (CTSK), Matrix Metalloproteinases 9 (MMP9) and Tartrate-resistant Acid Phosphatase (TRAP). Pre-osteoclast treated with MM cell-derived exosomes differentiate in multinuclear OCs able to excavate authentic resorption lacunae. Similar results were obtained with exosomes derived from MM patient's sera. Our data indicate that MM-exosomes modulate OCs function and differentiation. Further studies are needed to identify the OCs activating factors transported by MM cell-derived exosomes. PMID:25944696

  19. The glutathione synthesis inhibitor buthionine sulfoximine synergistically enhanced melphalan activity against preclinical models of multiple myeloma

    International Nuclear Information System (INIS)

    Tagde, A; Singh, H; Kang, M H; Reynolds, C P

    2014-01-01

    Melphalan (L-PAM) has been an integral part of multiple myeloma (MM) treatment as a conditioning regimen before stem cell transplant (SCT). After initial response, most treated patients experience relapse with an aggressive phenotype. Increased glutathione (GSH) in MM may mediate resistance to L-PAM. We demonstrated that the GSH synthesis inhibitor buthionine sulfoximine (BSO) synergistically enhanced L-PAM activity (inducing 2–4 logs of cell kill) against nine MM cell lines (also in the presence of marrow stroma or cytokines) and in seven primary MM samples (combination indices <1.0). In MM cell lines, BSO significantly (P<0.05) depleted GSH, increased L-PAM-induced single-strand DNA breaks, mitochondrial depolarization, caspase cleavage and apoptosis. L-PAM depleted GSH, but GSH rapidly recovered in a L-PAM-resistant MM cell line unless also treated with BSO. Treatment with N-acetylcysteine antagonized BSO+L-PAM cytotoxicity without increasing GSH. In human MM xenografted into beige-nude-xid mice, BSO significantly depleted MM intracellular GSH and significantly increased apoptosis compared with L-PAM alone. BSO+L-PAM achieved complete responses (CRs) in three MM xenograft models including maintained CRs >100 days, and significantly increased the median event-free survival relative to L-PAM alone. Combining BSO with L-PAM warrants clinical testing in advanced MM

  20. Non-invasive imaging provides spatiotemporal information on disease progression and response to therapy in a murine model of multiple myeloma.

    Directory of Open Access Journals (Sweden)

    Simone S Riedel

    Full Text Available Multiple myeloma (MM is a B-cell malignancy, where malignant plasma cells clonally expand in the bone marrow of older people, causing significant morbidity and mortality. Typical clinical symptoms include increased serum calcium levels, renal insufficiency, anemia, and bone lesions. With standard therapies, MM remains incurable; therefore, the development of new drugs or immune cell-based therapies is desirable. To advance the goal of finding a more effective treatment for MM, we aimed to develop a reliable preclinical MM mouse model applying sensitive and reproducible methods for monitoring of tumor growth and metastasis in response to therapy.A mouse model was created by intravenously injecting bone marrow-homing mouse myeloma cells (MOPC-315.BM that expressed luciferase into BALB/c wild type mice. The luciferase in the myeloma cells allowed in vivo tracking before and after melphalan treatment with bioluminescence imaging (BLI. Homing of MOPC-315.BM luciferase+ myeloma cells to specific tissues was examined by flow cytometry. Idiotype-specific myeloma protein serum levels were measured by ELISA. In vivo measurements were validated with histopathology.Strong bone marrow tropism and subsequent dissemination of MOPC-315.BM luciferase(+ cells in vivo closely mimicked the human disease. In vivo BLI and later histopathological analysis revealed that 12 days of melphalan treatment slowed tumor progression and reduced MM dissemination compared to untreated controls. MOPC-315.BM luciferase(+ cells expressed CXCR4 and high levels of CD44 and α4β1 in vitro which could explain the strong bone marrow tropism. The results showed that MOPC-315.BM cells dynamically regulated homing receptor expression and depended on interactions with surrounding cells.This study described a novel MM mouse model that facilitated convenient, reliable, and sensitive tracking of myeloma cells with whole body BLI in living animals. This model is highly suitable for monitoring

  1. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis.

    Science.gov (United States)

    Morgan, Gareth J; Gregory, Walter M; Davies, Faith E; Bell, Sue E; Szubert, Alexander J; Brown, Julia M; Coy, Nuria N; Cook, Gordon; Russell, Nigel H; Rudin, Claudius; Roddie, Huw; Drayson, Mark T; Owen, Roger G; Ross, Fiona M; Jackson, Graham H; Child, J Anthony

    2012-01-05

    Thalidomide maintenance has the potential to modulate residual multiple myeloma (MM) after an initial response. This trial compared the effect of thalidomide maintenance and no maintenance on progression-free survival (PFS) and overall survival (OS) in MM patients. After intensive or nonintensive induction therapy, 820 newly diagnosed MM patients were randomized to open-label thalidomide maintenance until progression, or no maintenance. Interphase FISH (iFISH) analysis was performed at study entry. Median PFS was significantly longer with thalidomide maintenance (log-rank P < .001). Median OS was similar between regimens (log-rank P = .40). Patients with favorable iFISH showed improved PFS (P = .004) and a trend toward a late survival benefit. Patients with adverse iFISH receiving thalidomide showed no significant PFS benefit and worse OS (P = .009). Effective relapse therapy enhanced survival after progression, translating into a significant OS benefit. Meta-analysis of this and other studies show a significant late OS benefit (P < .001, 7-year difference hazard ratio = 12.3; 95% confidence interval, 5.5-19.0). Thalidomide maintenance significantly improves PFS and can be associated with improved OS. iFISH testing is important in assessing the clinical impact of maintenance therapy. Overview analysis demonstrated that thalidomide maintenance was associated with a significant late OS benefit. This trial was registered at www.isrctn.org as #ISRCTN68454111.

  2. Anti-c-MET Nanobody - a new potential drug in multiple myeloma treatment.

    Science.gov (United States)

    Slørdahl, Tobias Schmidt; Denayer, Tinneke; Moen, Siv Helen; Standal, Therese; Børset, Magne; Ververken, Cedric; Rø, Torstein Baade

    2013-11-01

    c-MET is the tyrosine kinase receptor of the hepatocyte growth factor (HGF). HGF-c-MET signaling is involved in many human malignancies, including multiple myeloma (MM). Recently, multiple agents have been developed directed to interfere at different levels in HGF-c-MET signaling pathway. Nanobodies are therapeutic proteins based on the smallest functional fragments of heavy-chain-only antibodies. In this study, we wanted to determine the anticancer effect of a novel anti-c-MET Nanobody in MM. We examined the effects of an anti-c-MET Nanobody on thymidine incorporation, migration, adhesion of MM cells, and osteoblastogenesis in vitro. Furthermore, we investigated the effects of the Nanobody on HGF-dependent c-MET signaling by Western blotting. We show that the anti-c-MET Nanobody effectively inhibited thymidine incorporation of ANBL-6 MM cells via inhibition of an HGF autocrine growth loop and thymidine incorporation in INA-6 MM cells induced by exogenous HGF. HGF-induced migration and adhesion of INA-6 were completely and specifically blocked by the Nanobody. Furthermore, the Nanobody abolished the inhibiting effect of HGF on bone morphogenetic protein-2-induced alkaline phosphatase activity and the mineralization of human mesenchymal stem cells. Finally, we show that the Nanobody reduced phosphorylation of tyrosine residues in c-MET, MAPK, and Akt. We also compared the Nanobody with anti-c-MET monoclonal antibodies and revealed the similar or better effect. The anti-c-MET Nanobody inhibited MM cell migration, thymidine incorporation, and adhesion, and blocked the HGF-mediated inhibition of osteoblastogenesis. The anti-c-MET Nanobody might represent a novel therapeutic agent in the treatment of MM and other cancers driven by HGF-c-MET signaling. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Acute gouty arthritis and rapidly progressive renal failure as manifestation of multiple myeloma: clinical case description

    Directory of Open Access Journals (Sweden)

    O.V. Gudym

    2017-08-01

    Full Text Available The article describes a clinical case of multiple myeloma in 78-year-old man, its clinical onset was as an acute attack of gout. The patient was admitted to hospital due to the development of the first acute attack of gout. The attack was characterized by polyarthricular joint lesion of the upper and lower extremities, pronounced inflammatory reaction, insufficient response to the use of non-steroidal anti-inflammatory drugs, and a high level of hyperuricemia. The serum uric acid concentration ranged from 636 to 712 μmol/l. The study of the synovial fluid of the inflamed knee joint made it possible to reveal uric acid crystals and to confirm the diagnosis of acute gouty arthritis. Simultaneously, the patient had significant renal impairment: creatinine was 574 μmol/l, urea — 39.9 mmol/l, glomerular filtration rate according to CKD-EPI — 8 ml/min. The daily proteinuria was 1.8 g. A retrospective assessment of laboratory parameters allowed to reveal completely normal indicators of renal function 6 months ago. Considering the development of acute gouty arthritis, its polyarticular nature, persistent course, rapid involvement of new joints, high uric acid levels during an acute attack exceeding 600 μmol/l (10 mg/dL, rapid development of renal failure within 6 months until the terminal stage, it was suggested the secondary nature of gout on the background of kidney damage by another pathological process. Further clinical, laboratory and instrumental studies allowed verifying multiple myeloma with renal damage. Bence Jones protein in the urine was not detected, there was also no evidence of hyperproteinemia. However, pain in the spine, ribs and chest was the basis for carrying out an X-ray study of the bones of the skeleton. Changes in the skeleton typical for multiple myeloma have been identified. Myelogram showed a high content of plasma cells (21.1 %, electrophoresis of blood proteins showed a high M-gradient (30.42 %, and a cytochemical

  4. Old but Still Relevant: High Resolution Electrophoresis and Immunofixation in Multiple Myeloma.

    Science.gov (United States)

    Misra, Aroonima; Mishra, Jyoti; Chandramohan, Jagan; Sharma, Atul; Raina, Vinod; Kumar, Rajive; Soni, Sushant; Chopra, Anita

    2016-03-01

    High resolution electrophoresis (HRE) and immunofixation (IFX) of serum and urine are integral to the diagnostic work-up of multiple myeloma. Unusual electrophoresis patterns are common and may be misinterpreted. Though primarily the responsibility of the hematopathologist, clinicians who are responsible for managing myelomas may benefit from knowledge of these. In this review article we intend to discuss the patterns and importance of electrophoresis in present day scenario. Patterns of HRE and IFX seen in our laboratory over the past 15 years were studied. Monoclonal proteins are seen on HRE as sharply defined bands, sometimes two, lying from γ- to α-globulin regions on a background of normal, increased or decreased polyclonal γ-globulins, showing HRE to be a rapid and dependable method of detecting M-protein in serum or urine. Immunofixation complements HRE and due to its greater sensitivity, is able to pick up small or light chain bands, not apparent on electrophoresis, including biclonal disease even when electrophoresis shows only one M-band. Special features liable to misinterpretation are discussed. Familiarity with the interpretation of the varied patterns seen in health and disease is essential for providing dependable laboratory support in the management of multiple myeloma.

  5. Raman spectroscopy differentiates between sensitive and resistant multiple myeloma cell lines

    Science.gov (United States)

    Franco, Domenico; Trusso, Sebastiano; Fazio, Enza; Allegra, Alessandro; Musolino, Caterina; Speciale, Antonio; Cimino, Francesco; Saija, Antonella; Neri, Fortunato; Nicolò, Marco S.; Guglielmino, Salvatore P. P.

    2017-12-01

    Current methods for identifying neoplastic cells and discerning them from their normal counterparts are often nonspecific and biologically perturbing. Here, we show that single-cell micro-Raman spectroscopy can be used to discriminate between resistant and sensitive multiple myeloma cell lines based on their highly reproducible biomolecular spectral signatures. In order to demonstrate robustness of the proposed approach, we used two different cell lines of multiple myeloma, namely MM.1S and U266B1, and their counterparts MM.1R and U266/BTZ-R subtypes, resistant to dexamethasone and bortezomib, respectively. Then, micro-Raman spectroscopy provides an easily accurate and noninvasive method for cancer detection for both research and clinical environments. Characteristic peaks, mostly due to different DNA/RNA ratio, nucleic acids, lipids and protein concentrations, allow for discerning the sensitive and resistant subtypes. We also explored principal component analysis (PCA) for resistant cell identification and classification. Sensitive and resistant cells form distinct clusters that can be defined using just two principal components. The identification of drug-resistant cells by confocal micro-Raman spectroscopy is thus proposed as a clinical tool to assess the development of resistance to glucocorticoids and proteasome inhibitors in myeloma cells.

  6. Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma

    DEFF Research Database (Denmark)

    Zweegman, Sonja; van der Holt, Bronno; Mellqvist, Ulf-Henrik

    2016-01-01

    The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone, and lenalid......The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone......, and lenalidomide, followed by lenalidomide maintenance therapy, showed promising results without severe neuropathy emerging. We randomly assigned 668 patients between nine 4-week cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen...... with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label, randomized phase 3 trial was undertaken by Dutch-Belgium Cooperative Trial Group for Hematology Oncology and the Nordic Myeloma Study Group (the HOVON87/NMSG18 trial). The primary end point was progression-free survival (PFS...

  7. Antithyroid drugs induced agranulocytosis and multiple myeloma: case report and general considerations.

    Science.gov (United States)

    Dănciulescu Miulescu, R; Carşote, M; Trifănescu, R; Ferechide, D; Poiană, C

    2013-09-15

    Antithyroid drugs as thionamides are largely used in the treatment of the thyrotoxicosis. Side effects were reported in less than 10% of the cases, especially hematological, hepatic or skin allergies. One of the most severe manifestations is agranulocytosis, probably based on an immune mechanism that is exacerbated by the presence of the thyroid autoimmune disease itself. If the presence of the severe leucopenia is actually an epiphenomenon of a preexisting hematological disturbance as multiple myeloma is debated. The myeloma may also be correlated with an autoimmune predisposition. We present the case of a 56 years old female patient diagnosed with Graves' disease, who developed agranulocytosis after 8 months of therapy with thiamazole. Two months after antithyroid drug's withdrawal, the granulocytes number increased and she received therapy with radioiodine. Two years later she came back for diffuse bone pain that turned out to be caused by a multiple myeloma, confirmed by bone marrow biopsy. It might be a connection between the severe form of leucopenia that the patient developed and the medullar malignancy.

  8. Radiography and bone scintigraphy in bone marrow transplant multiple myeloma patients

    International Nuclear Information System (INIS)

    Aagren, B.; Aspelin, P.

    1997-01-01

    Purpose: To compare conventional radiography and bone scintigraphy in relation to clinical outcome in bone marrow transplant multiple myeloma patients. Material and Methods: A total of 70 radiographies and 70 bone scintigraphies were compared in 35 patients. Results: The skull, the extremities, the iliac and public bones were better assessed with radiography. For new vertebral lesions and for lesions in the ribs and sternum, bone scintigraphy proved superior. For the sacrum, the methods were equal. When bone scintigraphy was used as a complement to radiography, 4% more pathological sites were found. No patient had both a normal radiography and a pathological bone scintigraphy, but 5 patients had both a normal bone scintigraphy and a pathological radiography. The results of the radiological examinations did not always correlate with the clinician's grading of the patient's disease. The radiological examinations had no prognostic value for the 7 patients examined on several occasions. Conclusion: The ability of conventional radiography and bone scintigraphy to disclose myeloma lesions varies, depending on location and size of the lesions. Radiography should remain the primary examination modality also for bone marrow transplant multiple myeloma patients. Bone scintigraphy can severe as a complement for investigating unexplained pain, e.g. caused by lesions in vertebrae or ribs. (orig.)

  9. Chalazia development in multiple myeloma: a new complication associated with bortezomib therapy

    Directory of Open Access Journals (Sweden)

    Charles Yun

    2015-06-01

    Full Text Available Multiple myeloma (MM is a neoplasm of plasma cells within the bone marrow. A major impact on improving survival in MM has been the use of the boronic acid-derived proteasome inhibitor bortezomib, a first-in-class selective inhibitor of the 26S proteasome. Ocular side effects of bortezomib are rare. In this report, we present 2 patients with active MM in whom persistent chalazia became a therapy-interfering complication of treatment with bortezomib. Both patients had relapsed ISS III B kappa light chain myeloma, and they were responding to treatment with bortezomib until chalazia − which caused intolerable discomfort − started. In both patients discontinuation of bortezomib was necessary for chalazia to heal, and restarting of bortezomib was associated with relapse of chalazia.

  10. Reassessment of the relationship between M-protein decrement and survival in multiple myeloma.

    Science.gov (United States)

    Palmer, M.; Belch, A.; Hanson, J.; Brox, L.

    1989-01-01

    The relationship between percentage M-protein decrement and survival is assessed in 134 multiple myeloma patients. The correlation did not achieve statistical significance (P = 0.069). Multivariate analysis using the Cox proportional hazards model, including a number of previously recognised prognostic factors, showed only percentage M-protein decrement, creatinine and haemoglobin to be significantly correlated with survival. However, the R'-statistic for each of these variables was low, indicating that their prognostic power is weak. We conclude that neither the percentage M-protein decrement nor the response derived from it can be used as an accurate means of assessing the efficacy of treatment in myeloma. Mature survival data alone should be used for this purpose. PMID:2757916

  11. Reassessment of the relationship between M-protein decrement and survival in multiple myeloma.

    Science.gov (United States)

    Palmer, M; Belch, A; Hanson, J; Brox, L

    1989-01-01

    The relationship between percentage M-protein decrement and survival is assessed in 134 multiple myeloma patients. The correlation did not achieve statistical significance (P = 0.069). Multivariate analysis using the Cox proportional hazards model, including a number of previously recognised prognostic factors, showed only percentage M-protein decrement, creatinine and haemoglobin to be significantly correlated with survival. However, the R'-statistic for each of these variables was low, indicating that their prognostic power is weak. We conclude that neither the percentage M-protein decrement nor the response derived from it can be used as an accurate means of assessing the efficacy of treatment in myeloma. Mature survival data alone should be used for this purpose.

  12. Endocarditis due to Gemella haemolysans in a newly diagnosed multiple myeloma patient

    Directory of Open Access Journals (Sweden)

    Dongyan Liu

    2016-09-01

    Full Text Available An 87-year-old Caucasian woman with hypertension, diabetes mellitus type 2, and COPD was admitted with 1-week duration of back pain and weight gain. The physical examination revealed jugular venous distention, rales in the left lower lung field, and severe pitting edema over lower extremities. As workup for leukocytosis, blood cultures grew Gemella haemolysans. Subsequently, a transthoracic echocardiogram revealed vegetation on the non-coronary aortic leaflet and mild aortic stenosis. She was treated with ampicillin and gentamicin. After further investigation, the patient was diagnosed with plasma cell myeloma, the monoclonal lambda type. This is the first reported case of G. haemolysans endocarditis in a multiple myeloma patient.

  13. POOR HEMOPOIETIC STEM CELL MOBILIZERS IN MULTIPLE MYELOMA : A SINGLE INSTITUTION EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Guillermo Jose Ruiz-Delgado

    2010-06-01

    Full Text Available In a single institution, in a group of 28 myeloma patients deemed eligible for autologous transplant, stem cell mobilization was attempted using filgrastim: 26 individuals were given 31 autografts employing 1-4 (median three apheresis sessions, to obtain a target stem cell dose of 1 x 106 CD34 viable cells / Kg of the recipient. The median number of grafted CD34 cells was 7.56 x 106  / Kg of the recipient; the range being 0.92 to 14.8.  By defining as poor mobilizers individuals in which a cell collection of 1 x 106 CD34 viable cells / Kg was better (80% at 80 months than those grafted with < 1 x 106 CD34 viable cells / Kg (67% at 76 months. Methods to improve stem cell mobilization are needed and may result in obtaining better results when autografting multiple myeloma patients.

  14. BCL2-BH4 antagonist BDA-366 suppresses human myeloma growth.

    Science.gov (United States)

    Deng, Jiusheng; Park, Dongkyoo; Wang, Mengchang; Nooka, Ajay; Deng, Qiaoya; Matulis, Shannon; Kaufman, Jonathan; Lonial, Sagar; Boise, Lawrence H; Galipeau, Jacques; Deng, Xingming

    2016-05-10

    Multiple myeloma (MM) is a heterogeneous plasma cell malignancy and remains incurable. B-cell lymphoma-2 (BCL2) protein correlates with the survival and the drug resistance of myeloma cells. BH3 mimetics have been developed to disrupt the binding between BCL2 and its pro-apoptotic BCL2 family partners for the treatment of MM, but with limited therapeutic efficacy. We recently identified a small molecule BDA-366 as a BCL2 BH4 domain antagonist, converting it from an anti-apoptotic into a pro-apoptotic molecule. In this study, we demonstrated that BDA-366 induces robust apoptosis in MM cell lines and primary MM cells by inducing BCL2 conformational change. Delivery of BDA-366 substantially suppressed the growth of human MM xenografts in NOD-scid/IL2Rγnull mice, without significant cytotoxic effects on normal hematopoietic cells or body weight. Thus, BDA-366 functions as a novel BH4-based BCL2 inhibitor and offers an entirely new tool for MM therapy.

  15. Extraskeletal multiple myeloma presenting with an atrial mass: a case report and a review of the literature

    OpenAIRE

    Vigo, Federica; Ciammella, Patrizia; Valli, Riccardo; Cagni, Elisabetta; Iotti, Cinzia

    2012-01-01

    Abstract Introduction Extraskeletal presentation at diagnosis or during the course of multiple myeloma is a rare event. The prognosis is usually very poor. At the moment there is no agreed gold standard for the treatment of this presentation. Case presentation A 79-year-old Caucasian woman was treated at our hospital for right atrial myeloma localization. Our patient showed the following signs and symptoms of congestive heart failure: dyspnea, hypotension, cyanosis and facial edema. Surgery w...

  16. Development and biological evaluation of 99mTc-tocilizumab as molecular imaging agent in multiple myeloma

    International Nuclear Information System (INIS)

    Gutierrez, M.

    2012-01-01

    Multiple myeloma (M M) is a neoplasm characterized by infiltration of malignant plasma cells in the bone marrow, and is associated with high levels of monoclonal protein component or M. One of the key molecules involved in the pathogenesis of M M is the interleukin I L-6. This is a polypeptide belonging to the class of cytokines helical, having antiinflammatory activity and pro inflammatory and is secreted by a wide variety of cells. It has been found that high levels of I L-6 are directly related to the growth and survival of M M cell proliferation therefore I L antagonists may be of potential use therapeutic and diagnostic purposes. The Tocilizumab (Act emr To®) is a humanized monoclonal antibody directed against the receptor, both soluble and membrane I L-6 blocking cell signaling mediated by this. The possibility of combining Tocilizumab a gamma emitting isotope would determine l to topography where an increased expression of I L, with the consequent possibility that this associated with an infectious or neoplastic process is observed. In this way it could be used as a diagnostic method. Based on the above, the present work aims to develop the marking and evaluation of 99m Tc Tocilizumab, which could be used as diagnostic radiopharmaceutical to determine the location of the lesion and its extension, both debut in monitoring patients with multiple myeloma

  17. The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting in suppression of human myeloma cell growth and survival

    Czech Academy of Sciences Publication Activity Database

    Scuto, A.; Krejčí, Pavel

    2011-01-01

    Roč. 25, č. 3 (2011), s. 538-550 ISSN 0887-6924 Institutional support: RVO:68081707 Keywords : HUMAN MULTIPLE- MYELOMA * BONE-MARROW MICROENVIRONMENT * PROTEIN-KINASE CASCADE Subject RIV: BO - Biophysics Impact factor: 9.561, year: 2011

  18. Conventional chemotherapy and long-term survival in multiple myeloma patients

    International Nuclear Information System (INIS)

    Kraj, M; Poglod, R.; Sokolowska, U.; Kruk, B.; Maj, S.

    2010-01-01

    Objectives. The study was especially focused on the estimation of real frequency of long-term survivals in patients with multiple myeloma and finding common clinical and laboratory features present in long-term surviving patients as possible good prognostic factors. Material and methods. The survey was carried out on 600 multiple myeloma patients diagnosed before the year 2000 and treated with conventional chemotherapy in the Institute of Hematology and Transfusion Medicine in Warsaw in the years 1962-2009. All patients who had fulfilled the requirement of more than seven years of survival from the diagnosis and beginning of treatment for myeloma were included into the study group. Results. Out of 600 studied patients with multiple myeloma 88 (14.7%) survived over 7 years including 45 (7.5%) over 10 years, 11 (1.8 %) over 15 years and 7 (1.1%) over 20 years from the disease diagnosis and beginning of antitumor treatment. Patients with long survival were younger (median age 55 years) at the time of diagnosis than the whole studied group and had normal serum creatinine, calcium and beta2-microglobulin levels. Sixty eight percent of these patients had stage I or II clinical progression, 60% presented with IgG monoclonal protein and 58% with osteolysis. Treatment with melphalan only was given to 18 patients, 30 were treated with melphalan, followed by vincristine, cyclophosphamide, BCNU, doxorubicin and prednisone or dexamethasone. Polychemotherapy was given from the time of the diagnosis to 16 patients, 15 received radiotherapy or 60C o irradiation besides chemotherapy and 9 received new agents: thalidomide, bortezomib, lenalidomide. In 66% of the evaluated cases response to treatment was good and in another 34% stabilization of the proliferative process was achieved. The mean duration of treatment till the achievement of partial response was 10 months, range: 2 - 89 months. The mean duration of good therapeutic response was 70 months. Twelve patients are alive and

  19. Cytogenetic Alterations in Multiple Myeloma: Prognostic Significance and the Choice of Frontline Therapy.

    Science.gov (United States)

    Stella, Flavia; Pedrazzini, Estela; Agazzoni, Mara; Ballester, Oscar; Slavutsky, Irma

    2015-01-01

    Multiple myeloma tumor cells demonstrate multiple and often complex genetic lesions as evaluated by standard cytogenetic/FISH studies. Over the past decade, specific abnormalities have been associated with standard or high-risk clinical behavior and they have become strong prognostic indicators. Further, as evidenced by recent randomized clinical trials, the choice of front-line therapy (transplant vs. no transplant, inclusion of novel drugs such as bortezomib, thalidomide, and lenalidomide) may be able to overcome the adverse effect of high-risk genetic lesions.

  20. Paradoxical expression of INK4c in proliferative multiple myeloma tumors: bi-allelic deletion vs increased expression

    Directory of Open Access Journals (Sweden)

    Hanamura Ichiro

    2006-10-01

    Full Text Available Abstract Background A high proliferative capacity of tumor cells usually is associated with shortened patient survival. Disruption of the RB pathway, which is critically involved in regulating the G1 to S cell cycle transition, is a frequent target of oncogenic events that are thought to contribute to increased proliferation during tumor progression. Previously, we determined that p18INK4c, an essential gene for normal plasma cell differentiation, was bi-allelically deleted in five of sixteen multiple myeloma (MM cell lines. The present study was undertaken to investigate a possible role of p18INK4c in increased proliferation of myeloma tumors as they progress. Results Thirteen of 40 (33% human myeloma cell lines do not express normal p18INK4c, with bi-allelic deletion of p18 in twelve, and expression of a mutated p18 fragment in one. Bi-allelic deletion of p18, which appears to be a late progression event, has a prevalence of about 2% in 261 multiple myeloma (MM tumors, but the prevalence is 6 to10% in the 50 tumors with a high expression-based proliferation index. Paradoxically, 24 of 40 (60% MM cell lines, and 30 of 50 (60% MM tumors with a high proliferation index express an increased level of p18 RNA compared to normal bone marrow plasma cells, whereas this occurs in only five of the 151 (3% MM tumors with a low proliferation index. Tumor progression is often accompanied by increased p18 expression and an increased proliferation index. Retroviral-mediated expression of exogenous p18 results in marked growth inhibition in three MM cell lines that express little or no endogenous p18, but has no effect in another MM cell line that already expresses a high level of p18. Conclusion Paradoxically, although loss of p18 appears to contribute to increased proliferation of nearly 10% of MM tumors, most MM cell lines and proliferative MM tumors have increased expression of p18. Apart from a small fraction of cell lines and tumors that have inactivated

  1. Nucleotide excision repair is a potential therapeutic target in multiple myeloma

    Science.gov (United States)

    Szalat, R; Samur, M K; Fulciniti, M; Lopez, M; Nanjappa, P; Cleynen, A; Wen, K; Kumar, S; Perini, T; Calkins, A S; Reznichenko, E; Chauhan, D; Tai, Y-T; Shammas, M A; Anderson, K C; Fermand, J-P; Arnulf, B; Avet-Loiseau, H; Lazaro, J-B; Munshi, N C

    2018-01-01

    Despite the development of novel drugs, alkylating agents remain an important component of therapy in multiple myeloma (MM). DNA repair processes contribute towards sensitivity to alkylating agents and therefore we here evaluate the role of nucleotide excision repair (NER), which is involved in the removal of bulky adducts and DNA crosslinks in MM. We first evaluated NER activity using a novel functional assay and observed a heterogeneous NER efficiency in MM cell lines and patient samples. Using next-generation sequencing data, we identified that expression of the canonical NER gene, excision repair cross-complementation group 3 (ERCC3), significantly impacted the outcome in newly diagnosed MM patients treated with alkylating agents. Next, using small RNA interference, stable knockdown and overexpression, and small-molecule inhibitors targeting xeroderma pigmentosum complementation group B (XPB), the DNA helicase encoded by ERCC3, we demonstrate that NER inhibition significantly increases sensitivity and overcomes resistance to alkylating agents in MM. Moreover, inhibiting XPB leads to the dual inhibition of NER and transcription and is particularly efficient in myeloma cells. Altogether, we show that NER impacts alkylating agents sensitivity in myeloma cells and identify ERCC3 as a potential therapeutic target in MM. PMID:28588253

  2. Twelve cases of multiple myeloma in Nagasaki (especially seven atomic bombing casualty cases). [In Japanese

    Energy Technology Data Exchange (ETDEWEB)

    Ichimaru, M; Yasuhi, S; Ouchuru, S

    1963-12-01

    Since 1958, there have been 12 cases of multiple myeloma in Nagasaki, and among them were 7 cases representing atomic bombing casualties, with 3 cases being with 2 km distance from the hypocenter. The age of onset was between 51 and 69 years, and the sex ratio was 8:4, it occurring mostly in males. Symptoms were predominantly low back pain and chest pain caused by the bone changes in 8 cases. Two cases complained of general malaise and palpitation which resulted from anemia. One developed persistent epistaris, and another complained of diplopia caused by the paralysis of the oculomotor nerve. Peripheral blood in all cases showed anemia, 9 with hyperchromic and 3 with normochromic or hypochromic anemia. Low platelet counts were seen in 3 cases. All showed leukopenia. All cases showed typical ..gamma..-globulin change with a myeloma peak, and in 4 cases showed an increase of ..beta..-globulin. Bence-Jones proteinuria was present in 5 cases. Average course was 1 year 4 months. Among complications, myeloma nephrosis, aplastic anemia, and pneumonia were the most important ones.

  3. Evaluation of Revised International Staging System (R-ISS) for transplant-eligible multiple myeloma patients.

    Science.gov (United States)

    González-Calle, Verónica; Slack, Abigail; Keane, Niamh; Luft, Susan; Pearce, Kathryn E; Ketterling, Rhett P; Jain, Tania; Chirackal, Sintosebastian; Reeder, Craig; Mikhael, Joseph; Noel, Pierre; Mayo, Angela; Adams, Roberta H; Ahmann, Gregory; Braggio, Esteban; Stewart, A Keith; Bergsagel, P Leif; Van Wier, Scott A; Fonseca, Rafael

    2018-04-06

    The International Myeloma Working Group has proposed the Revised International Staging System (R-ISS) for risk stratification of multiple myeloma (MM) patients. There are a limited number of studies that have validated this risk model in the autologous stem cell transplant (ASCT) setting. In this retrospective study, we evaluated the applicability and value for predicting survival of the R-ISS model in 134 MM patients treated with new agents and ASCT at the Mayo Clinic in Arizona and the University Hospital of Salamanca in Spain. The patients were reclassified at diagnosis according to the R-ISS: 44 patients (33%) had stage I, 75 (56%) had stage II, and 15 (11%) had stage III. After a median follow-up of 60 months, R-ISS assessed at diagnosis was an independent predictor for overall survival (OS) after ASCT, with median OS not reached, 111 and 37 months for R-ISS I, II and III, respectively (P R-ISS II and having high-risk chromosomal abnormalities (CA) had a significant shorter median OS than those with R-ISS II without CA: 70 vs. 111 months, respectively. Therefore, this study lends further support for the R-ISS as a reliable prognostic tool for estimating survival in transplant myeloma patients and suggests the importance of high-risk CA in the R-ISS II group.

  4. A novel mouse model for multiple myeloma (MOPC315.BM that allows noninvasive spatiotemporal detection of osteolytic disease.

    Directory of Open Access Journals (Sweden)

    Peter O Hofgaard

    Full Text Available Multiple myeloma (MM is a lethal human cancer characterized by a clonal expansion of malignant plasma cells in bone marrow. Mouse models of human MM are technically challenging and do not always recapitulate human disease. Therefore, new mouse models for MM are needed. Mineral-oil induced plasmacytomas (MOPC develop in the peritoneal cavity of oil-injected BALB/c mice. However, MOPC typically grow extramedullary and are considered poor models of human MM. Here we describe an in vivo-selected MOPC315 variant, called MOPC315.BM, which can be maintained in vitro. When injected i.v. into BALB/c mice, MOPC315.BM cells exhibit tropism for bone marrow. As few as 10(4 MOPC315.BM cells injected i.v. induced paraplegia, a sign of spinal cord compression, in all mice within 3-4 weeks. MOPC315.BM cells were stably transfected with either firefly luciferase (MOPC315.BM.Luc or DsRed (MOPC315.BM.DsRed for studies using noninvasive imaging. MOPC315.BM.Luc cells were detected in the tibiofemoral region already 1 hour after i.v. injection. Bone foci developed progressively, and as of day 5, MM cells were detected in multiple sites in the axial skeleton. Additionally, the spleen (a hematopoietic organ in the mouse was invariably affected. Luminescent signals correlated with serum myeloma protein concentration, allowing for easy tracking of tumor load with noninvasive imaging. Affected mice developed osteolytic lesions. The MOPC315.BM model employs a common strain of immunocompetent mice (BALB/c and replicates many characteristics of human MM. The model should be suitable for studies of bone marrow tropism, development of osteolytic lesions, drug testing, and immunotherapy in MM.

  5. Lack of survival improvement with novel anti-myeloma agents for patients with multiple myeloma and central nervous system involvement: the Greek Myeloma Study Group experience.

    Science.gov (United States)

    Katodritou, Eirini; Terpos, Evangelos; Kastritis, Efstathios; Delimpasis, Sossana; Symeonidis, Argiris S; Repousis, Panagiotis; Kyrtsonis, Marie-Christine; Vadikolia, Chrysa; Michalis, Eurydiki; Polychronidou, Genovefa; Michael, Michael; Papadaki, Sofia; Papathanasiou, Maria; Kokoviadou, Kyriaki; Kioumi, Anna; Vlachaki, Eythimia; Hadjiaggelidou, Christina; Kouraklis, Alexandra; Patsias, Ioannis; Gavriatopoulou, Maria; Kotsopoulou, Maria; Verrou, Evgenia; Gastari, Vasiliki; Christoulas, Dimitrios; Giannopoulou, Evlambia; Pouli, Anastasia; Konstantinidou, Pavlina; Anagnostopoulos, Achilles; Dimopoulos, Meletios-Athanasios

    2015-12-01

    Involvement of the central nervous system (CNS) is a rare complication of multiple myeloma (MM). Herein, we have described the incidence, characteristics, prognostic factors for post CNS-MM survival, and outcome of CNS-MM and explored the efficacy of novel agents (NA) (thalidomide, bortezomib, lenalidomide) in this setting. Between 2000 and 2013, 31 (0.9 %) out of 3408 newly diagnosed symptomatic MM patients, consecutively diagnosed and treated during the same period in 12 Greek centers, developed CNS-MM (M/F 15/16, median age 59 years, range 20-96 years; newly diagnosed/relapsed-refractory 2/29; median time to CNS-MM diagnosis 29 months). Clinical and laboratory characteristics were retrospectively recorded. Twenty-six percent of patients had circulating plasma cells (PCs) or plasma cell leukemia (PCL) at CNS-MM and 39 % had skull-derived plasmacytomas, suggesting hematological and contiguous spread. Treatment for CNS-MM was offered in 29/31 patients and 11/29 responded (NA 18/29, additional radiotherapy 9/28, intrathecal chemotherapy 13/29). The median post CNS-MM survival was 3 months (95 % CI 1.9-4.1) and did not differ between patients treated with NA and/or radiotherapy vs. others. In the multivariate analysis, prior treatment of MM with NA, extramedullary disease (EMD) during MM course (i.e., plasmacytomas, circulating PCs, or documented PCL) and abnormally high LDH at MM diagnosis were independent prognostic factors, whereas treatment of CNS-MM with NA did not predict for post CNS-MM survival. Despite the relatively limited number of patients due to the rarity of CNS-MM, our results suggest that NA do not seem to improve post CNS-MM survival. Patients with EMD display shortened post CNS-MM survival and should be followed thoroughly.

  6. Single vs. multiple fraction regimens for palliative radiotherapy treatment of multiple myeloma. A prospective randomised study

    International Nuclear Information System (INIS)

    Rudzianskiene, Milda; Inciura, Arturas; Gerbutavicius, Rolandas; Rudzianskas, Viktoras; Dambrauskiene, Ruta; Juozaityte, Elona; Macas, Andrius; Simoliuniene, Renata; Kiavialaitis, Greta Emilia

    2017-01-01

    To compare the impact of a single fraction (8 Gy x 1 fraction) and multifraction (3 Gy x 10 fractions) radiotherapy regimens on pain relief, recalcification and the quality of life (QoL) in patients with bone destructions due to multiple myeloma (MM). In all, 101 patients were included in a randomised prospective clinical trial: 58 patients were included in the control arm (3 Gy x 10 fractions) and 43 patients into the experimental arm (8 Gy x 1 fraction). The response rate was defined according to the International Consensus on Palliative Radiotherapy criteria. Recalcification was evaluated with radiographs. QoL questionnaires were completed before and 4 weeks after treatment. Pain relief was obtained in 81/101 patients (80.2%): complete response in 56 (69%) and partial in 25 patients (30.9%). No significant differences were observed in analgesic response between the groups. Significant factors for pain relief were female gender, age under 65, IgG MM type, presence of recalcification at the irradiated site. Recalcification was found in 32/101 patients (33.7%): complete in 17 (53.2%) and partial in 15 (46.2%). No significant differences were observed in recalcification between the groups. Significant factors for recalcification were Karnofsky index ≥ 60%, haemoglobin level ≤ 80 g/dl, MM stage II and analgesic response at the irradiated site. The QoL after radiotherapy was improved in the control group. The same analgesic and recalcification response was observed using two different radiotherapy regimens. Higher doses should be used to achieve a better QoL. (orig.) [de

  7. Evaluation of clinical state of patients with acute leukemia, multiple myeloma and malignant lymphoma by means of in vitro T1 and T2 measurements in serum

    International Nuclear Information System (INIS)

    Kuliszkiewicz-Janus, M.; Urbaniak-Kujda, D.; Burczak, K.

    1995-01-01

    A dynamic relaxation times T1 and T2 in vitro study has been performed in the human sera of patients with haematological malignant diseases to monitor their clinical state. Two hundred studies were performed in 20 healthy volunteers and in 180 patients with different malignancies, mostly: acute leukemia, Hodgkin's disease, non-Hodgkin's lymphomas, multiple myeloma. Determinations were performed in active phase of disease and in remission. Measurements were carried out on spectrometer Minispect PC 20B (Bruker; 20 MHz) in 27 C. Additionally, serum proteins of all patients were examined, including total protein content, serum electrophoresis and measurement of Ig classes. Remarkable increase of T1 values in active phase of the disease was found (compared to healthy volunteers) in all malignancies, except multiple myeloma. It was associated with the severeness of the illness, not with diagnose. During remission T1 values did not differ significantly from those of healthy persons. All sera of patients with multiple myeloma in active phase of the disease showed strongly reduced values of T1, associated with the high level of pathological proteins. In 45 patients the measurements were repeated up to 4 times before and during chemotherapy. During treatment resulting in remission, mean T1 values progressively decreased (from 1560 ms to 1394 ms) except of those patients with multiple myeloma. In persons non-responding to therapy these mean values were prolonged (from 1474 ms to 1620 ms) during therapy. In patients with multiple myeloma we noted the reverse changes of mean T1 values in comparison with other malignancies: those responding to the treatment revealed prolonged T1 (from 1165 to 1303 ms) while in those non-responding were decreased (from 1184 ms to 1158 ms). Statistically significant negative correlation was observed between the T1 and total protein content, percentage of gamma-globulin, especially of IgG class. Moreover, a remarkable positive correlation of T1

  8. Entropy and Multifractality for the Myeloma Multiple TET 2 Gene

    Directory of Open Access Journals (Sweden)

    Carlo Cattani

    2012-01-01

    Full Text Available The nucleotide and amino-acid distributions are studied for two variants of mRNA of gene that codes for a protein which is involved in multiple myeloid. Some patches and symmetries are singled out, thus, showing some distinctions between the two variants. Fractal dimensions and entropy are discussed as well.

  9. HIF-1α inhibition blocks the cross talk between multiple myeloma plasma cells and tumor microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Borsi, Enrica, E-mail: enrica.borsi2@unibo.it [Department of Experimental Diagnostic and Specialty Medicine (DIMES), “L. and A. Seràgnoli”, Bologna University School of Medicine, S. Orsola' s University Hospital (Italy); Perrone, Giulia [Fondazione IRCCS Istituto Nazionale dei Tumori, Hematology Department, Via Venezian 1, 20133 Milano (Italy); Terragna, Carolina; Martello, Marina; Zamagni, Elena; Tacchetti, Paola; Pantani, Lucia; Brioli, Annamaria; Dico, Angela Flores; Zannetti, Beatrice Anna; Rocchi, Serena; Cavo, Michele [Department of Experimental Diagnostic and Specialty Medicine (DIMES), “L. and A. Seràgnoli”, Bologna University School of Medicine, S. Orsola' s University Hospital (Italy)

    2014-11-01

    Multiple myeloma (MM) is a malignant disorder of post-germinal center B cells, characterized by the clonal proliferation of malignant plasma cells (PCs) within the bone marrow (BM). The reciprocal and complex interactions that take place between the different compartments of BM and the MM cells result in tumor growth, angiogenesis, bone disease, and drug resistance. Given the importance of the BM microenvironment in MM pathogenesis, we investigated the possible involvement of Hypoxia-Inducible transcription Factor-1 alpha (HIF-1α) in the PCs-bone marrow stromal cells interplay. To test this hypothesis, we used EZN-2968, a 3rd generation antisense oligonucleotide against HIF-1α, to inhibit HIF-1α functions. Herein, we provide evidence that the interaction between MM cells and BM stromal cells is drastically reduced upon HIF-1α down-modulation. Notably, we showed that upon exposure to HIF-1α inhibitor, neither the incubation with IL-6 nor the co-culture with BM stromal cells were able to revert the anti-proliferative effect induced by EZN-2968. Moreover, we observed a down-modulation of cytokine-induced signaling cascades and a reduction of MM cells adhesion capability to the extracellular matrix proteins in EZN-2968-treated samples. Taken together, these results strongly support the concept that HIF-1α plays a critical role in the interactions between bone BM cells and PCs in Multiple Myeloma. - Highlights: • HIF-1α inhibition induces a mild apoptotic cell death. • Down-modulation of cytokine-induced signaling cascades upon HIF-1α inhibition. • Reduced interaction between MM cells and BMSCs upon HIF-1α down-modulation. • Reduced PCs adhesion to the extracellular matrix protein induced by EZN-2968. • HIF-1α inhibition may be an attractive therapeutic strategy for Multiple Myeloma.

  10. Vertebral lesion distribution in multiple myeloma - assessed by reduced-dose whole-body MDCT

    Energy Technology Data Exchange (ETDEWEB)

    Bier, Georg; Kloth, Christopher; Schabel, Christoph; Bongers, Malte; Nikolaou, Konstantin; Horger, Marius [Eberhard-Karls-University Tuebingen, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany)

    2016-01-15

    To observe the distribution and potential distribution patterns of osteolytic and sclerotic vertebral involvement in a representative collective of multiple myeloma patients. A total of 66 consecutive patients with a diagnosis of multiple myeloma at initial diagnosis or during follow-up were examined by multidetector reduced-dose computed tomography to evaluate the distribution of bone lesions along the spine with focus on size, location, and lesion character. Confirmation of diagnosis was performed by comparison to follow-up computed tomography or magnetic resonance tomography. If >50 % of all detected malignant lesions occurred in one spinal segment, the distribution pattern was called cervical, thoracic, lumbar, or sacral, otherwise a ''mixed'' pattern was classified. Of a total number of 933 osseous spine lesions, 632 (67.7 %) were classified as malignant (98.9 % of them osteolytic) and 293 (31.5 %) as benign. The distribution pattern analysis yielded two patients (3.8 %) with a cervical, 26 (50 %) with a thoracic, 4 (7.7 %) with a lumbar, one (1.9 %) with a sacral pattern, and 19 cases (36.6 %) showed a mixed distribution pattern. Segment-wise, the mean lesion size was 6.52 ± 2.76 mm (cervical), 8.97 ± 5.43 mm (thoracic), 11.97 ± 7.11 mm (lumbar), and 17.5 ± 16.465 (sacral), whilst, related to the vertebra size, the lesion/vertebra size ratio is decreasing through the whole spine beginning from the top. Multiple myeloma bone lesions occur preferably and are larger in the thoracic and lumbar spine. Moreover, a specific distribution pattern is present in about 60 %. (orig.)

  11. Vertebral lesion distribution in multiple myeloma - assessed by reduced-dose whole-body MDCT

    International Nuclear Information System (INIS)

    Bier, Georg; Kloth, Christopher; Schabel, Christoph; Bongers, Malte; Nikolaou, Konstantin; Horger, Marius

    2016-01-01

    To observe the distribution and potential distribution patterns of osteolytic and sclerotic vertebral involvement in a representative collective of multiple myeloma patients. A total of 66 consecutive patients with a diagnosis of multiple myeloma at initial diagnosis or during follow-up were examined by multidetector reduced-dose computed tomography to evaluate the distribution of bone lesions along the spine with focus on size, location, and lesion character. Confirmation of diagnosis was performed by comparison to follow-up computed tomography or magnetic resonance tomography. If >50 % of all detected malignant lesions occurred in one spinal segment, the distribution pattern was called cervical, thoracic, lumbar, or sacral, otherwise a ''mixed'' pattern was classified. Of a total number of 933 osseous spine lesions, 632 (67.7 %) were classified as malignant (98.9 % of them osteolytic) and 293 (31.5 %) as benign. The distribution pattern analysis yielded two patients (3.8 %) with a cervical, 26 (50 %) with a thoracic, 4 (7.7 %) with a lumbar, one (1.9 %) with a sacral pattern, and 19 cases (36.6 %) showed a mixed distribution pattern. Segment-wise, the mean lesion size was 6.52 ± 2.76 mm (cervical), 8.97 ± 5.43 mm (thoracic), 11.97 ± 7.11 mm (lumbar), and 17.5 ± 16.465 (sacral), whilst, related to the vertebra size, the lesion/vertebra size ratio is decreasing through the whole spine beginning from the top. Multiple myeloma bone lesions occur preferably and are larger in the thoracic and lumbar spine. Moreover, a specific distribution pattern is present in about 60 %. (orig.)

  12. Dorsal Column Degeneration after Bortezomib Therapy in a Patient with Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Tatsuro Joh

    2009-10-01

    Full Text Available We present here a case of dorsal column degeneration in a female patient with multiple myeloma following exposure to bortezomib. Two days after intravenous administration of a first course of bortezomib 1 mg/m2, the patient developed rapidly-progressive numbness, pain and muscle weakness in the bilateral upper and lower limbs. Following gancyclovir treatment of subsequent cytomegalovirus viremia, the patient went on to receive a course of EPOCH (etoposide 50 mg/m2/day on days 1–4, vincristine 0.4 mg/m2/day on days 1–4, doxorubicin 10 mg/m2/day on days 1–4, cyclophosphamide 750 mg/m2/day on day 6, and prednisolone 60 mg/m2/day on days 1–6. Shortly thereafter, the patient developed bilateral Aspergillus pneumonia. Despite treatment with appropriate antifungal agents, the patient died from respiratory failure due to bilateral diffuse alveolar damage of the lungs and without recovery of severe sensory and motor neuropathy prior to her death. Post mortem examination revealed spongy degeneration of the dorsal column from the medulla oblongata to the cervical spinal cord. Bortezomib-associated peripheral neuropathy in patients with multiple myeloma has been commonly reported but appears to resolve in a majority of these patients after dose reduction or discontinuation. We believe this to be the first report of spinal cord abnormalities in a patient with multiple myeloma treated with bortezomib. Further investigation is required to ascertain the exact mechanism of this central neurotoxic effect and to identify appropriate neuroprotective strategies.

  13. Coexisting multiple myeloma, lymphoma, and non-small cell lung cancer: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Khade P

    2017-11-01

    Full Text Available Parth Khade, Srinivas Devarakonda Department of Internal Medicine, Louisiana State University Health, Shreveport, LA, USA Abstract: Multiple myeloma is a plasma cell dyscrasia characterized by neoplastic proliferation of plasma cells, producing a monoclonal immunoglobulin. Small lymphocytic lymphoma (SLL is a neoplasm consisting of monoclonal B-cell lymphocyte proliferation. We present an extremely rare case of coexisting multiple myeloma, SLL, and squamous cell carcinoma of the lung in a 74-year-old female patient. She initially presented with a midline mass with pain in the lumbar area. Debulking surgery was performed, and pathology showed plasmacytoma. Further evaluation revealed coexistent IgG kappa myeloma. Imaging revealed extensive abdominal lymphadenopathy, and mesenteric lymph node biopsy confirmed the presence of SLL. The patient was also found to have a mass in the left lower lobe of the lung; biopsy showed squamous cell carcinoma. This patient was treated with lenalidomide and dexamethasone for multiple myeloma, and stereotactic body radiotherapy for limited stage lung cancer. Due to the more indolent course of SLL, watchful waiting was applied. Keywords: coexisting, multiple myeloma, lung cancer, non-Hodgkin’s lymphoma

  14. The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group

    DEFF Research Database (Denmark)

    Terpos, E; Dimopoulos, M A; Sezer, O

    2010-01-01

    progression and overall survival. Bone markers have also been used for the early diagnosis of bone lesions. This International Myeloma Working Group report summarizes the existing data for the role of bone markers in assessing the extent of MM bone disease and in monitoring bone turnover during anti...

  15. Donor versus no-donor comparison of newly diagnosed myeloma patients included in the HOVON-50 multiple myeloma study

    NARCIS (Netherlands)

    Lokhorst, Henk M.; van der Holt, Bronno; Cornelissen, Jan J.; Kersten, Marie-José; van Oers, Marinus; Raymakers, Reinier; Minnema, Monique C.; Zweegman, Sonja; Janssen, Jeroen J.; Zijlmans, Mark; Bos, Gerard; Schaap, Nicolaas; Wittebol, Shulamiet; de Weerdt, Okke; Ammerlaan, Rianne; Sonneveld, Pieter

    2012-01-01

    To prospectively evaluate allogeneic stem cell transplantation (allo-SCT) for myeloma as part of first-line therapy, a donor versus no-donor analysis was performed of patients treated in the HOVON-50 study, a study that was originally designed to examine thalidomide combined with intensive therapy.

  16. Role of sequential hemi-body irradiation in multiple myeloma: preliminary observations

    International Nuclear Information System (INIS)

    Kumar, H.S.; Chaudhary, R.K.; Kumar, Vanita

    1993-01-01

    Ten patients with multiple myeloma presenting in a highly painful condition were included in the study. They were treated by sequential hemi-body irradiation. A dose of 600 cGy was delivered to the upper hemi-body and 800 c Gy to the lower hemi-body. All patients has appreciable relief from pain. The maximum effect was achieved within 24 to 48 hours of treatment. 9 out of the 10 patients has an improvement in the performance status. All these patients were later subjected to combination chemotherapy. (author). 9 refs., 3 tabs

  17. Diffuse hepatic and splenic 99mTc MPD tracer uptake in case of multiple myeloma

    International Nuclear Information System (INIS)

    Sood, Ashwani; Seam, Rajeev Kumar; Sethi, Sandeep; Gupta, Manish

    2010-01-01

    99m Tc-methylene diphosphonate (MDP) bone scintigraphy has long been used for the evaluation of benign as well as malignant skeletal conditions. However, non-osseous tracer uptake on a bone scan is an unusual finding. There is a need to understand the pathophysiological basis of the non-osseous uptake, which may have a clinical relevance or deteriorating effect on the quality of the bone scan. We describe a case of multiple myeloma, where extraosseous uptake in the form of diffuse hepatic and splenic uptake, with almost normal skeletal tracer distribution, has been seen on the bone scan. (author)

  18. [Unilateral exophthalmos as the debut of a non-secretory multiple myeloma].

    Science.gov (United States)

    Castro-Rebollo, M; Cañones-Zafra, R; Vleming-Pinilla, E N; Drake-Rodríguez-Casanova, P; Pérez-Rico, C

    2009-12-01

    A 56 year-old male presented blurred vision and diplopia for 2 months, left unilateral exophthalmos, restricted ocular motility and papilledema. The imaging proofs showed osteolytic lesions in the left sphenoid bone, fourth rib and fourth dorsal vertebral body with associated masses of soft tissues. Biopsy was performed and the diagnosis of plasma cell neoplasm was established. The diagnosis of non-secretory multiple myeloma was made by analytical criteria and bone marrow biopsy. Local radiotherapy and polychemotherapy was prescribed. The ophthalmologist can play an important role in the diagnosis of systemic neoplasms that require the intervention of a multidisciplinary team.

  19. Occurrence of breast cancer, renal cancer and multiple myeloma in a Nagasaki atomic bomb survivor

    International Nuclear Information System (INIS)

    Yanagisawa, Tsutomu; Kubota, Kazuo; Tamura, Jun'ichi; Kurabayashi, Hitoshi; Shirakura, Takuo; Hayashida, Masayoshi; Nagayama, Tadao.

    1990-01-01

    A 60-year-old female, who was exposed to the Nagasaki atomic bomb at 18 years old, had renal cancer and subsequently was found to have multiple myeloma (IgGk). She underwent the left mastectomy for breast cancer at 43 years old but was not given chemotherapy or radiotherapy. The karyotype of bone marrow cells was 46, XX. The estimated radiation dose was under 10 rads. While the effect of such a low-dose of radiation is considered to be almost negligible, there would be a possibility that in this case the risk of carcinogenesis was enhanced as her age advanced. (author)

  20. Gemcitabine radiosensitizes multiple myeloma cells to low let, but not high let, irradiation

    International Nuclear Information System (INIS)

    Supiot, Stephane; Thillays, Francois; Rio, Emmanuel; Gouard, Sebastien; Morgenstern, Alfred; Bruchertseifer, Frank; Mahe, Marc-Andre; Chatal, Jean-Francois; Davodeau, Francois; Cherel, Michel

    2007-01-01

    The radiosensitizing properties of gemcitabine in relation to low Linear Energy Transfer (LET) particles (Cobalt 60) and high-LET particles (alpha-RIT 213 Bi-radiolabeled CHX-DTPA-B-B4) were analyzed. Three multiple myeloma cell lines (LP1, RPMI 8226, U266) were irradiated with or without 10 nM gemcitabine 24 h prior to radiation. Gemcitabine led to radiosensitization of LP1 and U266 cells with low-LET (Radiation Enhancement Ratio: 1.55 and 1.49, respectively) but did not radiosensitize any cell line when combined with high-LET

  1. Examination by magnetic resonance in the diagnosis and treatment of multiple myeloma

    International Nuclear Information System (INIS)

    Nekula, J.; Scudla, V.; Bacovsky, J.

    1998-01-01

    A group of 41 patients with a confirmed diagnosis of multiple myeloma (MM) was subjected to MR examination of the lumbar and thoracic spine. Pathological MR changes in the initial stage of MM were found in 88%, whereas in simple images the finding was only positive in 8%. T1 v.o. changes in sagittal planes are most important from the diagnostic point of view. Paraspinal or epidural propagation in 11 patients was a finding of fundamental importance, serving as indication for radiotherapy or surgical intervention. In 16 patients in remission, signs of complete lipid reconstruction of bone marrow were found 11 times, reconversion or mixed changes were observed twice. (author)

  2. Clinical and biological features of multiple myeloma involving the gastrointestinal system.

    Science.gov (United States)

    Talamo, Giampaolo; Cavallo, Federica; Zangari, Maurizio; Barlogie, Bart; Lee, Choon-Kee; Pineda-Roman, Mauricio; Kiwan, Elias; Krishna, Somashekar; Tricot, Guido

    2006-07-01

    We report 24 cases of multiple myeloma (MM) with involvement of the gastrointestinal (GI) system. We found a strong association with high A lactate dehydrogenase levels, plasmablastic morphology, and A unfavorable karyotype. GI involvement at the time of initial diagnosis was much rarer than later in the course of the disease. The A median survival after diagnosis of GI involvement was 7 months. Among 13 patients treated with stem cell transplantation, the response rate was 92%, and median progression-free survival was 4 months. We conclude that MM involving the GI system is associated with adverse biological features and with short-lasting remissions, even after A high-dose chemotherapy.

  3. Personalized therapy in multiple myeloma according to patient age and vulnerability

    DEFF Research Database (Denmark)

    Palumbo, Antonio; Bringhen, Sara; Ludwig, Heinz

    2011-01-01

    Most patients with newly diagnosed multiple myeloma (MM) are aged > 65 years with 30% aged > 75 years. Many elderly patients are also vulnerable because of comorbidities that complicate the management of MM. The prevalence of MM is expected to rise over time because of an aging population. Most...... elderly patients with MM are ineligible for autologous transplantation, and the standard treatment has, until recently, been melphalan plus prednisone. The introduction of novel agents, such as thalidomide, bortezomib, and lenalidomide, has improved outcomes; however, elderly patients with MM are more......, occurrence of serious nonhematologic adverse events during treatment should be carefully taken into account to adjust doses and optimize outcomes....

  4. Biological Activity of Lenalidomide and Its Underlying Therapeutic Effects in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Roberta Martiniani

    2012-01-01

    Full Text Available Lenalidomide is a synthetic compound derived by modifying the chemical structure of thalidomide. It belongs to the second generation of immunomodulatory drugs (IMiDs and possesses pleiotropic properties. Even if lenalidomide has been shown to be active in the treatment of several hematologic malignancies, this review article is mostly focalized on its mode of action in multiple myeloma. The present paper is about the direct and indirect antitumor effects of lenalidomide on malignant plasmacells, bone marrow microenvironment, bone resorption and host’s immune response. The molecular mechanisms and targets of lenalidomide remain largely unknown, but recent evidence shows cereblon (CRBN as a possible mediator of its therapeutical effects.

  5. Multiple myeloma in South Cumbria 1974-80: problems of health analysis in small communities

    International Nuclear Information System (INIS)

    Jessop, E.G.; Horsley, S.D.

    1985-01-01

    The occurrence of seven cases of multiple myeloma over seven years in a small community 15 miles from a plant reprocessing nuclear fuel caused much local concern. A case control study of 34 confirmed cases in the health district during 1974 to 1980 revealed no excess of known risk factors among the 23 cases for whom informants could be traced. The possible effects of exposure to marine discharges of radioactive material cannot be completely ruled out, but dose estimates make this highly unlikely. Such studies are a necessary response by community physicians to the population they serve but have major practical and theoretical limitations. (author)

  6. Prognostic value of unrelated atypical serum immunofixation patterns during multiple myeloma therapy.

    Science.gov (United States)

    Guimarães, Cristina; Bergantim, Rui; Ramalho, Renata; Couto, Nuno; Guimarães, João T; Trigo, Fernanda

    2012-06-26

    Autologous stem cell transplantation (ASCT) is the gold standard therapy for suitable multiple myeloma (MM) patients after induction with high dose therapy. To date, the evidence of a reliable marker of prognosis in these cases remains scarce. Our aim was to evaluate appearance of unrelated atypical serum immunofixation patterns (ASIPs) as a marker of prognosis in MM patients submitted to ASCT. We retrospectively analysed data from 65 patients. Interestingly, we observed that presence of ASIPs was associated with longer progression-free survival and longer overall survival. Our results suggested that presence of ASIPs could be a novel marker of good prognosis in MM patients submitted to ASCT.

  7. Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma

    DEFF Research Database (Denmark)

    Drent, Esther; Groen, Richard W. J.; Noort, Willy A. Noort

    2016-01-01

    Adoptive transfer of chimeric antigen receptor-transduced T cells is a promising strategy for cancer immunotherapy. The CD38 molecule, with its high expression on multiple myeloma cells, appears a suitable target for antibody therapy. Prompted by this, we used three different CD38 antibody...... sequences to generate second-generation retroviral CD38- chimeric antigen receptor constructs with which we transduced T cells from healthy donors and multiple myeloma patients. We then evaluated the preclinical efficacy and safety of the transduced T cells. Irrespective of the donor and antibody sequence......, CD38-chimeric antigen receptor-transduced T cells proliferated, produced inflammatory cytokines and effectively lysed malignant cell lines and primary malignant cells from patients with acute myeloid leukemia and multi-drug resistant multiple myeloma in a cell-dose, and CD38-dependent manner, despite...

  8. Upper Gastrointestinal Bleeding from Gastric Amyloidosis in a Patient with Smoldering Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Mihajlo Gjeorgjievski

    2015-01-01

    Full Text Available Amyloidosis is a common complication of patients with monoclonal gammopathy of undetermined significance (MGUS, smoldering multiple myeloma (SMM, and multiple myeloma (MM. This proteinaceous material can be deposited intercellularly in any organ system, including the gastrointestinal (GI tract. In the GI tract, amyloidosis affects the duodenum most commonly, followed by the stomach and colorectum. Gastric amyloidosis causes symptoms of nausea, vomiting, early satiety, abdominal pain, and GI bleeding. A case of upper GI bleeding from gastric amyloidosis is presented in a patient with SMM. Esophagogastroduodenoscopy (EGD revealed a gastric mass. Endoscopic biopsies revealed amyloid deposition in the lamina propria, consistent with gastric amyloidosis. Liquid chromatography tandem mass spectrometry performed on peptides extracted from Congo red-positive microdissected areas of paraffin-embedded stomach specimens revealed a peptide profile consistent with AL- (lambda- type amyloidosis. Based on this and multiple other case reports, we recommend that patients with GI bleeding and MGUS, SMM, or MM undergo EGD and pathologic examination of endoscopic biopsies of identified lesions using Congo red stains for amyloidosis for early diagnosis and treatment.

  9. Assessment and monitoring of patients receiving chemotherapy for multiple myeloma: strategies to improve outcomes

    Directory of Open Access Journals (Sweden)

    Faiman B

    2016-05-01

    Full Text Available Beth Faiman, Jason Valent Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA Abstract: Improved understanding as to the biology of multiple myeloma (MM and the bone marrow microenvironment has led to the development of new drugs to treat MM. This explosion of new and highly effective drugs has led to dramatic advances in the management of MM and underscores the need for supportive care. Impressive and deep response rates to chemotherapy, monoclonal antibodies, and small molecule drugs provide hope of a cure or prolonged remission for the majority of individuals. For most patients, long-term, continuous therapy is often required to suppress the malignant plasma cell clone, thus requiring clinicians to become more astute in assessment, monitoring, and intervention of side effects as well as monitoring response to therapy. Appropriate diagnosis and monitoring strategies are essential to ensure that patients receive the appropriate chemotherapy and supportive therapy at relapse, and that side effects are appropriately managed to allow for continued therapy and adherence to the regimen. Multiple drugs with complex regimens are currently available with varying side effect profiles. Knowledge of the drugs used to treat MM and the common adverse events will allow for preventative strategies to mitigate adverse events and prompt intervention. The purpose of this paper is to review updates in the diagnosis and management of MM, and to provide strategies for assessment and monitoring of patients receiving chemotherapy for MM. Keywords: multiple myeloma, treatment, symptoms, assessment, monitoring, symptom management, targeted therapies

  10. Expression of Wnt-Inhibitors and SDF-1 in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma

    DEFF Research Database (Denmark)

    Kristensen, Ida Bruun; Christensen, Jacob Haaber; Lyng, Maria Bibi

    Expression of Wnt-Inhibitors and SDF-1 in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma......Expression of Wnt-Inhibitors and SDF-1 in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma...

  11. Inhibition of STAT3 signaling and induction of SHP1 mediate antiangiogenic and antitumor activities of ergosterol peroxide in U266 multiple myeloma cells

    International Nuclear Information System (INIS)

    Rhee, Yun-Hee; Jeong, Soo-Jin; Lee, Hyo-Jeong; Lee, Hyo-Jung; Koh, Wonil; Jung, Ji Hoon; Kim, Sun-Hee; Sung-Hoon, Kim

    2012-01-01

    Ergosterol peroxide (EP) derived from edible mushroom has been shown to exert anti-tumor activity in several cancer cells. In the present study, anti-angiogenic activity of EP was investigated with the underlying molecular mechanisms in human multiple myeloma U266 cells. Despite weak cytotoxicity against U266 cells, EP suppressed phosphorylation, DNA binding activity and nuclear translocalization of signal transducer and activator of transcription 3 (STAT3) in U266 cells at nontoxic concentrations. Also, EP inhibited phosphorylation of the upstream kinases Janus kinase 2 (JAK2) and Src in a time-dependent manner. Furthermore, EP increased the expression of protein tyrosine phosphatase SHP-1 at protein and mRNA levels, and conversely silencing of the SHP-1 gene clearly blocked EP-mediated STAT3 inactivation. In addition, EP significantly decreased vascular endothelial growth factor (VEGF), one of STAT3 target genes at cellular and protein levels as well as disrupted in vitro tube formation assay. Moreover, EP significantly suppressed the growth of U266 cells inoculated in female BALB/c athymic nude mice and immunohistochemistry revealed that EP effectively reduced the expression of STAT3 and CD34 in tumor sections compared to untreated control. These findings suggest that EP can exert antitumor activity in multiple myeloma U266 cells partly with antiangiogenic activity targeting JAK2/STAT3 signaling pathway as a potent cancer preventive agent for treatment of multiple myeloma cells

  12. Healthcare resource use and costs associated with chronic kidney disease in US private insurance patients with multiple myeloma.

    Science.gov (United States)

    Bhowmik, Debajyoti; Song, Xue; Intorcia, Michele; Kent, Shia T; Shi, Nianwen

    2018-01-01

    Objectives Within a median 1.2 years after patients have an initial diagnosis with multiple myeloma, up to 61% were diagnosed with renal impairment and 50% were diagnosed with chronic kidney disease. This study estimated economic burden associated with chronic kidney disease in multiple myeloma patients in the US. Methods In this retrospective cohort study, patients ≥18 years old with ≥1 inpatient or ≥ 2 outpatient multiple myeloma diagnoses between 1 January 2008 and 31 March 2015 were identified from MarketScan® Commercial and Medicare Supplemental Databases. Chronic kidney disease patients had ≥1 diagnosis of chronic kidney disease Stages 1-5 (first chronic kidney disease diagnosis date = index date) on or after the first multiple myeloma diagnosis, and were propensity score matched 1:1 to multiple myeloma patients without chronic kidney disease, end-stage renal disease, dialysis, or other type of chronically impaired renal function. All patients had ≥six-month continuous enrollment prior to index date and were followed for ≥one month from index date until the earliest of inpatient death, end of continuous enrollment, or end of the study period (30 September 2015). The per-patient per-year healthcare resource utilization and costs were measured during follow-up. Costs were total reimbursed amount in 2016 US dollars. Results A total of 2541 multiple myeloma patients with chronic kidney disease stages 1-5 and 2541 matched controls met the study criteria and were respectively 69.3 and 69.6 years, 54.5% and 55.3% men, and had 572.2 and 533.4 mean days of follow up. Compared to controls, chronic kidney disease patients had significantly (all P chronic kidney disease, end-stage renal disease, or dialysis had $78,455 ( P chronic kidney disease in patients with multiple myeloma was estimated to be between $34,754 and $78,455 per-patient per-year. Given its substantial clinical and economic impact, preservation of renal function is important in

  13. Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic Myeloma Study Group): a double-blind, randomised controlled trial

    DEFF Research Database (Denmark)

    Gimsing, Peter; Carlson, Kristina; Turesson, Ingemar

    2010-01-01

    Compared with placebo, prophylactic treatment with bisphosphonates reduces risk of skeletal events in patients with multiple myeloma. However, because of toxicity associated with long-term bisphosphonate treatment, establishing the lowest effective dose is important. This study compared the effec...

  14. Andrographolide inhibits multiple myeloma cells by inhibiting the TLR4/NF-κB signaling pathway.

    Science.gov (United States)

    Gao, Hui; Wang, Jianrong

    2016-02-01

    Andrographolide is an active component from the extract of Andrographis paniculata [(Burm.f) Nees], a medicinal plant from the Acanthaceae family. Pharmacological studies have revealed that andrographolide possesses anti-bacterial, anti-inflammatory, anti-viral, immune regulatory and hepatoprotective properties, and is efficacious in the treatment of cardiovascular diseases, while exhibiting low toxicity and low cost. The present study aimed to determine the inhibitory effects of andrographolide on the growth of multiple myeloma (MM) cells and its possible impact on the Toll-like receptor (TLR)4/nuclear factor (NF)-κB signaling pathway. Cell proliferation was detected using an MTT assay, cellular apoptosis was measured using flow cytometry, and caspase-9/3 activation were assessed using colorimetric assay kits. Furthermore, TLR4 and NF-κB protein expression was determined by western blot analysis. The results revealed that andrographolide reduced the proliferation, while increasing cellular apoptosis and caspase-9/3 activation of MM cells, in addition to downregulating the expression of TLR4 and NF-κB protein. Of note, TLR4- or NF-κB-targeting small-interfering (si)RNA enhanced the andrographolide-induced inhibition of cell proliferation and induction of apoptosis of MM cells. The results of the present study therefore suggested that andrographolide inhibited multiple myeloma cells via the TLR4/NF-κB signaling pathway.

  15. Management of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM).

    Science.gov (United States)

    Kyle, Robert A; Rajkumar, S Vincent

    2011-06-01

    Monoclonal gammopathy of undetermined significance (MGUS) is defined as a serum M protein level of less than 3 g/dL, less than 10% clonal plasma cells in the bone marrow, and the absence of end-organ damage. The prevalence of MGUS is 3.2% in the white population but is approximately twice that high in the black population. MGUS may progress to multiple myeloma, AL amyloidosis, Waldenström macroglobulinemia, or lymphoma. The risk of progression is approximately 1% per year, but the risk continues even after more than 25 years of observation. Risk factors for progression include the size of the serum M protein, the type of serum M protein, the number of plasma cells in the bone marrow, and the serum free light chain ratio. Smoldering (asymptomatic) multiple myeloma (SMM) is characterized by the presence of an M protein level of 3 g/dL or higher and/or 10% or more monoclonal plasma cells in the bone marrow but no evidence of end-organ damage. The overall risk of progression to a malignant condition is 10% per year for the first 5 years, approximately 3% per year for the next 5 years, and 1% to 2% per year for the following 10 years. Patients with both MGUS and SMM must be followed up for their lifetime.

  16. Monitoring multiple myeloma by idiotype-specific peptide binders of tumor-derived exosomes.

    Science.gov (United States)

    Iaccino, Enrico; Mimmi, Selena; Dattilo, Vincenzo; Marino, Fabiola; Candeloro, Patrizio; Di Loria, Antonio; Marimpietri, Danilo; Pisano, Antonio; Albano, Francesco; Vecchio, Eleonora; Ceglia, Simona; Golino, Gaetanina; Lupia, Antonio; Fiume, Giuseppe; Quinto, Ileana; Scala, Giuseppe

    2017-10-13

    Tumor-derived exosomes (TDEs) play a pivotal role in tumor establishment and progression, and are emerging biomarkers for tumor diagnosis in personalized medicine. To date, there is a lack of efficient technology platforms for exosome isolation and characterization. Multiple myeloma (MM) is an incurable B-cell malignancy due to the rapid development of drug-resistance. MM-released exosomes express the immunoglobulin B-cell receptor (Ig-BCR) of the tumor B-cells, which can be targeted by Idiotype-binding peptides (Id-peptides). In this study, we analyzed the production of MM-released exosomes in the murine 5T33MM multiple myeloma model as biomarkers of tumor growth. To this end, we selected Id-peptides by screening a phage display library using as bait the Ig-BCR expressed by 5T33MM cells. By FACS, the FITC-conjugated Id-peptides detected the MM-released exosomes in the serum of 5T33MM-engrafted mice, levels of which are correlated with tumor progression at an earlier time point compared to serum paraprotein. These results indicate that Id-peptide-based recognition of MM-released exosomes may represent a very sensitive diagnostic approach for clinical evaluation of disease progression.

  17. Peptide vaccination against multiple myeloma using peptides derived from anti-apoptotic protein

    DEFF Research Database (Denmark)

    Jørgensen, Nicolai Grønne Dahlager; Ahmad, Shamaila Munir; Abildgaard, N.

    2016-01-01

    The B-cell lymphoma-2 (Bcl-2) family of proteins play a crucial role in multiple myeloma (MM), contributing to lacking apoptosis which is a hallmark of the disease. This makes the Bcl-2 proteins interesting targets for therapeutic peptide vaccination. We report a phase I trial of therapeutic vacc...... vaccination. Vaccination against Bcl-2 was well tolerated and was able to induce immune responses in patients with relapsed MM. © Stem Cell Investigation. All rights reserved.......The B-cell lymphoma-2 (Bcl-2) family of proteins play a crucial role in multiple myeloma (MM), contributing to lacking apoptosis which is a hallmark of the disease. This makes the Bcl-2 proteins interesting targets for therapeutic peptide vaccination. We report a phase I trial of therapeutic...... vaccination with peptides from the proteins Bcl-2, Bcl-XL and Mcl-1 in patients with relapsed MM. Vaccines were given concomitant with bortezomib. Out of 7 enrolled patients, 4 received the full course of 8 vaccinations. The remaining 3 patients received fewer vaccinations due to progression, clinical...

  18. Quality of life in patients with multiple myeloma treated with percutaneous vertebroplasty

    Directory of Open Access Journals (Sweden)

    Omar Jamit Bohsain

    2014-03-01

    Full Text Available OBJECTIVE: To determine the quality of life in patients with multiple myeloma treated with vertebroplasty. Multiple myeloma has a prevalence of 1% in all neoplastic diseases and 10% of hematological malignancies. Bone pain is the initial symptom in most cases. METHODS: A series of cases study was conducted. Patients were assessed by the Karnofsky scale to measure its functionality, the WHO analgesic scale to assess the type of analgesic and visual analog scale (VAS and the Oswestry questionnaire for pain. RESULTS: Of 24 patients, 10 were cases (vertebroplasty (41.7% and 14 were controls (conservative (58.3%, 13 (54.2% were female and 11 (45.8% male, with an average age of 60 years (SD = 12 and 63 kg of average weight (SD = 12, mean height of 1.59 cm (SD = 9 and mean body mass index of 24.8 (SD = 3.7. Survival was obtained from the time of diagnosis to death, and 2 (8.3% patients died within the first 2 years and 1 (4.2% after 3 years. CONCLUSIONS: Patients with MM who have vertebral fractures are excellent candidates to undergo vertebroplasty, because this represents a greater benefit in their quality of life, which has a direct impact on their level of functionality, giving them greater self-sufficiency and reducing their pain because of the benefits of the thermogenic effect of vertebroplasty.

  19. Hemibody irradiation. An effective second-line therapy in drug-resistance multiple myeloma

    International Nuclear Information System (INIS)

    Singer, C.R.; Tobias, J.S.; Giles, F.; Rudd, G.N.; Blackman, G.M.; Richards, J.D.

    1989-01-01

    The authors report the results of treatment of 41 patients with melphalan-resistant multiple myeloma using single half-body irradiation (HBI) or double half-body irradiation (DHBI). Patients were grouped using prognostic classification reported by the Medical Research Council. Patients in group I and II showed the best response to therapy with reduction in serum of urinary paraprotein and improvement in symptoms, most notably a marked reduction in bone pain. In these groups five patients have survived over 2 years after therapy. The therapeutic response appeared better in those patients who received DHBI as opposed to those whom treated with single HBI. Patients in group III did not achieve prolonged survival but effective relief of bone pain was a consistent finding in these patients also. Thus HBI represents an alternative to combination chemotherapy as second-line treatment of patients with melphalan-resistant multiple myeloma. A comparative study of HBI versus combination chemotherapy is now indicated to establish which therapeutic approach is most effective

  20. Double hemibody irradiation (DHBI) in the management of relapsed and primary chemoresistant multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    McSweeney, E.N.; Tobias, J.S.; Goldstone, A.H.; Richards, J.D.M. (University Coll. Hospital, London (United Kingdom)); Blackman, G. (Middlesex Hospital, London (United Kingdom))

    1993-01-01

    Fifty-five patients with multiple myeloma were treated with both upper and lower hemibody irradiation between January 1985 and January 1991; 42 had relapsed post-plateau and 13 were chemo-resistant to initial therapy. Fifteen patients received [alpha]IFN-2b maintenance therapy post-DHBI, at a dose of 3 Mu three times per week. Ninety-five per cent of patients experienced symptomatic improvement in bone pain post-DHBI, 21% of whom discontinued opiate analgesics altogether; 63% had a minor biochemical response and 38% had a partial biochemical response. The overall survival (OS) and progression free survivals (PFS) in all patients were 11 months and 8 months respectively. No significant difference was noted in either OS or PFS, according to whether patients were chemoresistant or had relapsed post-plateau. [alpha]IFN did not appear to prolong survival (OS or PFS) post-DHBI. We conclude that DHBI is an effective treatment in patients with relapsed multiple myeloma and in those who are chemoresistant to initial therapy. Cytopenia was a significant problem post-DHBI, such that the role of maintenance [alpha]IFN therapy could not be fully evaluated. (author).

  1. Double hemibody irradiation (DHBI) in the management of relapsed and primary chemoresistant multiple myeloma

    International Nuclear Information System (INIS)

    McSweeney, E.N.; Tobias, J.S.; Goldstone, A.H.; Richards, J.D.M.; Blackman, G.

    1993-01-01

    Fifty-five patients with multiple myeloma were treated with both upper and lower hemibody irradiation between January 1985 and January 1991; 42 had relapsed post-plateau and 13 were chemo-resistant to initial therapy. Fifteen patients received αIFN-2b maintenance therapy post-DHBI, at a dose of 3 Mu three times per week. Ninety-five per cent of patients experienced symptomatic improvement in bone pain post-DHBI, 21% of whom discontinued opiate analgesics altogether; 63% had a minor biochemical response and 38% had a partial biochemical response. The overall survival (OS) and progression free survivals (PFS) in all patients were 11 months and 8 months respectively. No significant difference was noted in either OS or PFS, according to whether patients were chemoresistant or had relapsed post-plateau. αIFN did not appear to prolong survival (OS or PFS) post-DHBI. We conclude that DHBI is an effective treatment in patients with relapsed multiple myeloma and in those who are chemoresistant to initial therapy. Cytopenia was a significant problem post-DHBI, such that the role of maintenance αIFN therapy could not be fully evaluated. (author)

  2. Dexamethasone, all trans retinoic acid and interferon alpha 2a in patients with refractory multiple myeloma.

    Science.gov (United States)

    Avilés, A; Rosas, A; Huerta-Guzmán, J; Talavera, A; Cleto, S

    1999-02-01

    Few effective regimen are available for patients with refractory multiple myeloma (RMM). Generally, responses are scarce and disease free survival is very short. We developed a new therapeutic option in these patients using dexamethasone (40 mg/m2, i.v., daily, days 1 to 4), all-trans retinoic acid (45 mg/m2, po, daily, days 5 to 14) and interferon alpha 2a (9.0 MU, daily, subcutaneously, days 5 to 14). The treatment was administered every 21 days for 6 cycles. In a pilot study, 12 patients, heavily treated with chemotherapy and radiotherapy and in some cases with interferon, were allocated to receive the afore mentioned treatment. Response was observed in 10 patients (83%). With a median follow-up of 36.1 months (range 27 to 41), seven patients remain alive and disease-free without any treatment. Two patients were failures and have died due to tumor progression. Toxicity was mild and all patients received treatment according to the planned doses of drugs. The use of biological modifiers in combination with dexamethasone offer a safe and effective therapeutic option in patients with refractory multiple myeloma. More studies are warranted to define the role of this type of treatment.

  3. Multiple myeloma, leukemia, and breast cancer among the US radium dial workers

    International Nuclear Information System (INIS)

    Stebbings, J.H.; Lucas, H.F.; Stehney, A.F.

    1983-01-01

    The relationships of radium exposure to mortality from multiple myeloma, leukemia, and breast cancer were studied in three cohorts of female dial workers defined by year of first employment. Mortality was compared with that expected from US white female rates, with and without adjustment for local mortality rates. Dose-response relationships of these cancers to systemic intake of radium were determined in workers whose body burdens had been measured in vivo since 1955. Incident cases of multiple myeloma occurred in the pre-1930 cohort; however, analyses of body burdens and durations of employment suggest that external radiation was more likely to have been responsible than was internal radium. Leukemia incidence and mortality have not been elevated overall among the female dial workers, either in the pre-1930 or the post-1930 cohorts, but cases have tended to occur early and in subjects with higher body burdens. Extensive analyses of breast cancer data have uncovered several observations weighing against a causal interpretation of the association between radium and breast cancer

  4. Low-dose biplanar skeletal survey versus digital skeletal survey in multiple myeloma

    International Nuclear Information System (INIS)

    Boutry, Nathalie; Dutouquet, Bastien; Cotten, Anne; Leleu, Xavier; Vieillard, Marie-Helene; Duhamel, Alain

    2013-01-01

    To evaluate the low-dose biplanar (LDB) skeletal survey (SS) for the assessment of focal bone involvement in patients with multiple myeloma (MM) as compared with digital SS and to compare the two techniques in terms of image quality, patient comfort and radiation exposure. Fifty-six consecutive patients with newly diagnosed or first relapsed MM underwent LDB and digital SS on the same day. These were assessed by two radiologists for the detection of focal bone lesions. In the case of discordance, whole-body MR imaging was performed. Image quality, patient comfort and radiation dose were also assessed. Fifty-six patients (M:30, F:26, mean age, 62 years) with newly diagnosed (n = 21) or first relapse MM (n = 35) were enrolled. A total of 473 bone lesions in 46 patients (82 %) were detected. Out of that total, digital SS detected significantly more lesions than LDB SS (451 [95.35 %] versus 467 [98.73 %]), especially in osteopenic and obese patients. Overall patient satisfaction was greater with LDB SS (48.6 %) compared with digital SS (2.7 %). The radiation dose was significantly reduced (by a factor of 7.8) with the LDB X-ray device. Low-dose biplanar skeletal surveys cannot replace digital SS in all patients suffering from multiple myeloma. (orig.)

  5. SERUM YKL-40 IS ASSOCIATED WITH BONE DISEASE IN MULTIPLE MYELOMA

    DEFF Research Database (Denmark)

    Mylin, Anne Kjærsgaard; Abildgaard, Niels; Johansen, Julia S.

    2007-01-01

     Introduction. The secreted glycoprotein YKL-40 (CHI3L1, HC gp-39) is a potential player in the tumor-host interactions affecting several aspects of multiple myeloma (MM) including bone destruction. Previous studies support a role for YKL-40 in remodelling of the extracellular matrix, in angiogen...... Introduction. The secreted glycoprotein YKL-40 (CHI3L1, HC gp-39) is a potential player in the tumor-host interactions affecting several aspects of multiple myeloma (MM) including bone destruction. Previous studies support a role for YKL-40 in remodelling of the extracellular matrix...... and followed for up to 30 months. Skeletal related events (SRE) were registered and subdivided in vertebral fractures and osteolytic events including non-vertebral fractures. Results. 57% of the patients had a S-YKL-40 elevated above the upper limit in an age specific 90 per cent reference range for healthy...... adults. Patients with elevated S-YKL-40 had a higher total X-ray score (p=0.005) and higher levels of S-CTX-MMP (p=0.003), U-PYD (p=0.004) and U-DPD (p=0.002), while U-NTX-1 and the markers of bone formation did not differ from the levels seen in patients with normal S-YKL-40. During follow-up 21...

  6. B-cell activating factor in the pathophysiology of multiple myeloma: a target for therapy?

    International Nuclear Information System (INIS)

    Hengeveld, P J; Kersten, M J

    2015-01-01

    Multiple myeloma (MM) is a currently incurable malignancy of plasma cells. Malignant myeloma cells (MMCs) are heavily dependent upon the bone marrow (BM) microenvironment for their survival. One component of this tumor microenvironment, B-Cell Activating Factor (BAFF), has been implicated as a key player in this interaction. This review discusses the role of BAFF in the pathophysiology of MM, and the potential of BAFF-inhibitory therapy for the treatment of MM. Multiple studies have shown that BAFF functions as a survival factor for MMCs. Furthermore, MMCs express several BAFF-binding receptors. Of these, only Transmembrane Activator and CAML Interactor (TACI) correlates with the MMC's capability to ligate BAFF. Additionally, the level of expression of TACI correlates with the level of the MMC's BM dependency. Ligation of BAFF receptors on MMCs causes activation of the Nuclear Factor of κ-B (NF-κB) pathway, a crucial pathway for the pathogenesis of many B-cell malignancies. Serum BAFF levels are significantly elevated in MM patients when compared to healthy controls, and correlate inversely with overall survival. BAFF signaling is thus an interesting target for the treatment of MM. Several BAFF-inhibitory drugs are currently under evaluation for the treatment of MM. These include BAFF-monoclonal antibodies (tabalumab) and antibody-drug conjugates (GSK2857916)

  7. Low-dose biplanar skeletal survey versus digital skeletal survey in multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Boutry, Nathalie [University Hospital of Jeanne de Flandre and University of Lille 2, Departments of Pediatric and Musculoskeletal Imaging, Lille (France); University Hospital of Jeanne de Flandre and University of Lille 2, Department of Pediatric Imaging, Lille (France); Hopital Jeanne de Flandre, Service de Radiopediatrie, Lille (France); Dutouquet, Bastien; Cotten, Anne [University Hospital of Roger Salengro and University of Lille 2, Department of Musculoskeletal Imaging, Lille (France); Leleu, Xavier [University Hospital of Claude Huriez and University of Lille 2, Clinical Hematology Department, Lille (France); Vieillard, Marie-Helene [University Hospital of Roger Salengro and University of Lille 2, Rheumatology Department, Lille (France); Duhamel, Alain [University of Lille 2, Department of Medical Statistics, Lille (France)

    2013-08-15

    To evaluate the low-dose biplanar (LDB) skeletal survey (SS) for the assessment of focal bone involvement in patients with multiple myeloma (MM) as compared with digital SS and to compare the two techniques in terms of image quality, patient comfort and radiation exposure. Fifty-six consecutive patients with newly diagnosed or first relapsed MM underwent LDB and digital SS on the same day. These were assessed by two radiologists for the detection of focal bone lesions. In the case of discordance, whole-body MR imaging was performed. Image quality, patient comfort and radiation dose were also assessed. Fifty-six patients (M:30, F:26, mean age, 62 years) with newly diagnosed (n = 21) or first relapse MM (n = 35) were enrolled. A total of 473 bone lesions in 46 patients (82 %) were detected. Out of that total, digital SS detected significantly more lesions than LDB SS (451 [95.35 %] versus 467 [98.73 %]), especially in osteopenic and obese patients. Overall patient satisfaction was greater with LDB SS (48.6 %) compared with digital SS (2.7 %). The radiation dose was significantly reduced (by a factor of 7.8) with the LDB X-ray device. Low-dose biplanar skeletal surveys cannot replace digital SS in all patients suffering from multiple myeloma. (orig.)

  8. Occurrence and prognostic significance of cytogenetic evolution in patients with multiple myeloma

    Science.gov (United States)

    Binder, M; Rajkumar, S V; Ketterling, R P; Dispenzieri, A; Lacy, M Q; Gertz, M A; Buadi, F K; Hayman, S R; Hwa, Y L; Zeldenrust, S R; Lust, J A; Russell, S J; Leung, N; Kapoor, P; Go, R S; Gonsalves, W I; Kyle, R A; Kumar, S K

    2016-01-01

    Cytogenetic evaluation at the time of diagnosis is essential for risk stratification in multiple myeloma, however little is known about the occurrence and prognostic significance of cytogenetic evolution during follow-up. We studied 989 patients with multiple myeloma, including 304 patients with at least two cytogenetic evaluations. Multivariable-adjusted regression models were used to assess the associations between the parameters of interest and cytogenetic evolution as well as overall survival. The prognostic significance of baseline cytogenetic abnormalities was most pronounced at the time of diagnosis and attenuated over time. In the patients with serial cytogenetic evaluations, the presence of t(11;14) at the time of diagnosis was associated with decreased odds of cytogenetic evolution during follow-up (odds ratio (OR)=0.22, 95% confidence interval (CI)=0.09–0.56, P=0.001), while the presence of at least one trisomy or tetrasomy was associated with increased odds (OR=2.96, 95% CI=1.37–6.42, P=0.006). The development of additional abnormalities during the 3 years following diagnosis was associated with increased subsequent mortality (hazard ratio=3.31, 95% CI=1.73–6.30, P<0.001). These findings emphasize the importance of the underlying clonal disease process for risk assessment and suggest that selected patients may benefit from repeated risk stratification. PMID:26967818

  9. [Multiple myeloma with significant multifocal osteolysis in a dog without a detectible gammopathy].

    Science.gov (United States)

    Souchon, F; Koch, A; Sohns, A

    2013-01-01

    Description of a variant of multiple myeloma in a dog lacking the gammopathy normally associated with this type of neoplasm. A Border Collie mongrel was presented with symptoms of progressive hind-leg weakness, lethargy and tiredness, which had started to appear 6 weeks previously. Radiographic examination showed small osteolytic areas in the spinal column, but also diffuse small areas of increased opacity as well as evidence of decreased bone density in the pelvis and of both femoral necks. Moderate regenerative anaemia, hypogammopathy and hypercalcaemia were diagnosed. Computed tomography scans displayed multifocal osteolysis and bone destruction in the skull, spinal column, scapulae, proximal humeri, pelvis and femoral necks. H&E staining of the biopsies showed bone destruction and monomorphic plasmacyotid cell populations, causing infiltrative bone marrow lesions and osteolysis. In many areas neoplastic plasma cell infiltration of the bone marrow was 70% and in some areas reached 100%. The diagnosis was non-secretory multiple myeloma without apparent secretion of paraproteins into the blood.

  10. Recent progress in the biology of multiple myeloma and future directions in the treatment.

    Science.gov (United States)

    Pico, J L; Castagna, L; Bourhis, J H

    1998-04-01

    A great amount of scientific information, accumulated over recent years on the biology of Multiple Myeloma (MM), has fuelled speculation about the origin of malignant plasma cells, about a purported critical role played by the bone marrow stroma, and further still, on cytokine interactions and in particular that of IL-6 and its relationship with the immune system. Among the growth factors secreted by stroma cells, IL-6 is a potent stimulator of myeloma cells in vitro but does not induce a malignant phenotype in normal plasma cells. Many efforts have been produced to identify the stem cell in MM and probably memory B lymphocytes are the best candidates. The demonstration of a Graft vs Myeloma effect in the allogeneic setting strongly supports the immunotherapy in MM. Recent data also suggest that a virus (Kaposi-associated herpes virus, HHV-8) may be significantly associated with the development of MM. In parallel, progress has been achieved in the treatment of this incurable disease with well defined prognostic factors, more efficient supportive care and its corollary, improved quality of life and dose-intensified chemo-radiotherapy followed by autologous hematopoietic stem cell support. Improving the quality of grafts with the selection of CD34 positive cells is another approach aimed at reducing plasma cell contamination without impairing haematological recovery. An EBMT randomized study assessing the role of CD34 selection has been initiated by our group Increasingly efficient first-line therapy, better quality autografts and improved post-remission treatment with, for example, anti-idiopathic vaccination are the most promising future directions.

  11. In vitro aggregation behavior of a non-amyloidogenic λ light chain dimer deriving from U266 multiple myeloma cells.

    Directory of Open Access Journals (Sweden)

    Paolo Arosio

    Full Text Available Excessive production of monoclonal light chains due to multiple myeloma can induce aggregation-related disorders, such as light chain amyloidosis (AL and light chain deposition diseases (LCDD. In this work, we produce a non-amyloidogenic IgE λ light chain dimer from human mammalian cells U266, which originated from a patient suffering from multiple myeloma, and we investigate the effect of several physicochemical parameters on the in vitro stability of this protein. The dimer is stable in physiological conditions and aggregation is observed only when strong denaturating conditions are applied (acidic pH with salt at large concentration or heating at melting temperature T(m at pH 7.4. The produced aggregates are spherical, amorphous oligomers. Despite the larger β-sheet content of such oligomers with respect to the native state, they do not bind Congo Red or ThT. The impossibility to obtain fibrils from the light chain dimer suggests that the occurrence of amyloidosis in patients requires the presence of the light chain fragment in the monomer form, while dimer can form only amorphous oligomers or amorphous deposits. No aggregation is observed after denaturant addition at pH 7.4 or at pH 2.0 with low salt concentration, indicating that not a generic unfolding but specific conformational changes are necessary to trigger aggregation. A specific anion effect in increasing the aggregation rate at pH 2.0 is observed according to the following order: SO(4(-≫Cl(->H(2PO(4(-, confirming the peculiar role of sulfate in promoting protein aggregation. It is found that, at least for the investigated case, the mechanism of the sulfate effect is related to protein secondary structure changes induced by anion binding.

  12. BRAFV600 mutations in solid tumors, other than metastatic melanoma and papillary thyroid cancer, or multiple myeloma: a screening study

    Directory of Open Access Journals (Sweden)

    Cohn AL

    2017-02-01

    Full Text Available Allen L Cohn,1 Bann-Mo Day,2 Sarang Abhyankar,3 Edward McKenna,2 Todd Riehl,4 Igor Puzanov5 1Medical Research, Rocky Mountain Cancer Centers, Denver, CO, 2US Medical Affairs, 3Global Safety and Risk Management, 4Product Development Oncology, Genentech, Inc., South San Francisco, CA, 5Melanoma Section, Division of Hematology-Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA Background: Mutations in the BRAF gene have been implicated in several human cancers. The objective of this screening study was to identify patients with solid tumors (other than metastatic melanoma or papillary thyroid cancer or multiple myeloma harboring activating BRAFV600 mutations for enrollment in a vemurafenib clinical study.Methods: Formalin-fixed, paraffin-embedded tumor samples were collected and sent to a central laboratory to identify activating BRAFV600 mutations by bidirectional direct Sanger sequencing.Results: Overall incidence of BRAFV600E mutation in evaluable patients (n=548 was 3% (95% confidence interval [CI], 1.7–4.7: 11% in colorectal tumors (n=75, 6% in biliary tract tumors (n=16, 3% in non-small cell lung cancers (n=71, 2% in other types of solid tumors (n=180, and 3% in multiple myeloma (n=31. There were no BRAFV600 mutations in this cohort of patients with ovarian tumors (n=68, breast cancer (n=86, or prostate cancer (n=21.Conclusion: This multicenter, national screening study confirms previously reported incidences of BRAFV600 mutations from single-center studies. Patients identified with BRAFV600 mutations were potentially eligible for enrollment in the VE-BASKET study. Keywords: genetic testing, proto-oncogene proteins B-raf, PLX4032

  13. Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial.

    Science.gov (United States)

    Palumbo, Antonio; Larocca, Alessandra; Genuardi, Mariella; Kotwica, Katarzyna; Gay, Francesca; Rossi, Davide; Benevolo, Giulia; Magarotto, Valeria; Cavallo, Federica; Bringhen, Sara; Rus, Cecilia; Masini, Luciano; Iacobelli, Massimo; Gaidano, Gianluca; Mitsiades, Constantine; Anderson, Kenneth; Boccadoro, Mario; Richardson, Paul

    2010-07-01

    Defibrotide is a novel orally bioavailable polydisperse oligonucleotide with anti-thrombotic and anti-adhesive effects. In SCID/NOD mice, defibrotide showed activity in human myeloma xenografts. This phase I/II study was conducted to identify the most appropriate dose of defibrotide in combination with melphalan, prednisone and thalidomide in patients with relapsed and relapsed/refractory multiple myeloma, and to determine its safety and tolerability as part of this regimen. This was a phase I/II, multicenter, dose-escalating, non-comparative, open label study. Oral melphalan was administered at a dose of 0.25 mg/kg on days 1-4, prednisone at a dose of 1.5 mg/kg also on days 1-4 and thalidomide at a dose of 50-100 mg/day continuously. Defibrotide was administered orally at three dose-levels: 2.4, 4.8 or 7.2 g on days 1-4 and 1.6, 3.2, or 4.8 g on days 5-35. Twenty-four patients with relapsed/refractory multiple myeloma were enrolled. No dose-limiting toxicity was observed. In all patients, the complete response plus very good partial response rate was 9%, and the partial response rate was 43%. The 1-year progression-free survival and 1-year overall survival rates were 34% and 90%, respectively. The most frequent grade 3-4 adverse events included neutropenia, thrombocytopenia, anemia and fatigue. Deep vein thrombosis was reported in only one patient. This combination of melphalan, prednisone and thalidomide together with defibrotide showed anti-tumor activity with a favorable tolerability. The maximum tolerated dose of defibrotide was identified as 7.2 g p.o. on days 1-4 followed by 4.8 g p.o. on days 5-35. Further trials are needed to confirm the role of this regimen and to evaluate the combination of defibrotide with new drugs.

  14. Bacteria as a target of human milk and myeloma IgA

    Czech Academy of Sciences Publication Activity Database

    Přibylová, Jaroslava; Moldoveanu, Z.; Mestecky, J.; Tlaskalová, Helena

    2009-01-01

    Roč. 39, - (2009), s. 760-760 ISSN 0014-2980. [European Congress of Immunology /2./. 13.09.2009-16.09.2009, Berlin] Institutional research plan: CEZ:AV0Z50200510 Keywords : human milk * myeloma IgA Subject RIV: EC - Immunology

  15. Multiple Myeloma

    African Journals Online (AJOL)

    the importance of adequate examination of urine by electrophores's and ... J., 48, 1023 (1974). The demonstration of disordered gamma globulin synthesis .... insufficiency (urea >40 mg/lOO ml, serum creatinine>1,5 mg/lOO ml, creatinine ...

  16. Multiple myeloma

    Science.gov (United States)

    ... may have bone pain, most often in the ribs or back. The cancer cells can weaken bones. As a result: You may develop broken bones (bone fractures) just from doing normal activities. If cancer grows ...

  17. Multiple Myeloma

    African Journals Online (AJOL)

    proteinuria was also a poor prognostic finding,. but only because of its association with renal failure. Patients with. Bence-Jones protcinur;a and normal renal ... chemotherapy. The mean time which elapsed before the criteria of response were achieved, was 7 months. Five ad- ditional patients who are at present being ...

  18. Bortezomib in multiple myeloma and lymphoma: a systematic review and clinical practice guideline.

    Science.gov (United States)

    Reece, D; Imrie, K; Stevens, A; Smith, C A

    2006-10-01

    In patients with multiple myeloma, Waldenström macroglobulinemia, or lymphoma, what is the efficacy of bortezomib alone or in combination as measured by survival, quality of life, disease control (for example, time to progression), response duration, or response rate?What is the toxicity associated with the use of bortezomib?Which patients are more or less likely to benefit from treatment with bortezomib? Evidence was selected and reviewed by two members of the Hematology Disease Site Group and by methodologists from the Program in Evidence-based Care (pebc) at Cancer Care Ontario. The practice guideline report was reviewed and approved by the Hematology Disease Site Group, which comprises hematologists, medical and radiation oncologists, and a patient representative. As part of an external review process, the report was disseminated to practitioners throughout Ontario to obtain their feedback. Outcomes of interest were overall survival, quality of life, response rates and duration, and rates of adverse events. A systematic search was conducted of the medline, embase, HealthStar, cinahl, and Cochrane Library databases for primary articles and practice guidelines. The resulting evidence informed the development of clinical practice recommendations. Those recommendations were appraised by a sample of practitioners in Ontario and modified in response to the feedback received. The systematic review and modified recommendations were approved by a review body w theithin pebc. The literature review found one randomized controlled trial (rct)-the only published rct of bortezomib in relapsed myeloma. A number of phase ii studies were also retrieved, including a randomized phase ii study. No randomized trials were retrieved for lymphoma. The rct found bortezomib to be superior to high-dose dexamethasone for median time to progression and 1-year survival in patients with relapsed myeloma, although grade 3 adverse events were more common in the bortezomib arm. Bortezomib is

  19. Assessing Heterogeneity of Osteolytic Lesions in Multiple Myeloma by 1H HR-MAS NMR Metabolomics

    Directory of Open Access Journals (Sweden)

    Laurette Tavel

    2016-10-01

    Full Text Available Multiple myeloma (MM is a malignancy of plasma cells characterized by multifocal osteolytic bone lesions. Macroscopic and genetic heterogeneity has been documented within MM lesions. Understanding the bases of such heterogeneity may unveil relevant features of MM pathobiology. To this aim, we deployed unbiased 1H high-resolution magic-angle spinning (HR-MAS nuclear magnetic resonance (NMR metabolomics to analyze multiple biopsy specimens of osteolytic lesions from one case of pathological fracture caused by MM. Multivariate analyses on normalized metabolite peak integrals allowed clusterization of samples in accordance with a posteriori histological findings. We investigated the relationship between morphological and NMR features by merging morphological data and metabolite profiling into a single correlation matrix. Data-merging addressed tissue heterogeneity, and greatly facilitated the mapping of lesions and nearby healthy tissues. Our proof-of-principle study reveals integrated metabolomics and histomorphology as a promising approach for the targeted study of osteolytic lesions.

  20. Amelioration of NK cell function driven by Vα24+ invariant NKT cell activation in multiple myeloma.

    Science.gov (United States)

    Iyoda, Tomonori; Yamasaki, Satoru; Hidaka, Michihiro; Kawano, Fumio; Abe, Yu; Suzuki, Kenshi; Kadowaki, Norimitsu; Shimizu, Kanako; Fujii, Shin-Ichiro

    2018-02-01

    NK cells represent a first line of immune defense, but are progressively dysregulated in multiple myeloma (MM) patients. To restore and facilitate their antitumor effect, NK cells are required in sufficient quantities and must be stimulated. We initially assessed the proportions of NKT and NK cells in 34 MM patients. The frequencies of both in PBMC populations correlated with those in BMMNCs irrespective of low BMMNC numbers. We then assessed the adjunctive effect of stimulating NKT cells with CD1d and α-GalCer complexes on the NK cells. The expression of NKG2D on CD56 dim CD16 + NK cells and DNAM-1 on CD56 bright CD16 - NK cells increased after NKT cell activation. Apparently, NK cell-mediated anti-tumor effects were dependent on NKG2D and DNAM-1 ligands on myeloma cells. Thus, NK cell function in patients could be ameliorated, beyond the effect of immunosuppression, by NKT cell activation. This NKT-driven NK cell therapy could represent a potential new treatment modality. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Nuclear medicine imaging of multiple myeloma, particularly in the relapsed setting

    Energy Technology Data Exchange (ETDEWEB)

    Waal, Esther G.M. de; Vellenga, Edo [University of Groningen, University Medical Center Groningen, Department of Hematology, PO Box 30001, Groningen (Netherlands); Glaudemans, Andor W.J.M. [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Schroeder, Carolien P. [University of Groningen, University Medical Center Groningen, Department of Medical Oncology, Groningen (Netherlands); Slart, Riemer H.J.A. [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University of Twente, Department of Biomedical Photonic Imaging, Enschede (Netherlands)

    2017-02-15

    Multiple myeloma (MM) is characterized by a monoclonal plasma cell population in the bone marrow. Lytic lesions occur in up to 90 % of patients. For many years, whole-body X-ray (WBX) was the method of choice for detecting skeleton abnormalities. However, the value of WBX in relapsing disease is limited because lesions persist post-treatment, which restricts the capacity to distinguish between old, inactive skeletal lesions and new, active ones. Therefore, alternative techniques are necessary to visualize disease activity. Modern imaging techniques such as magnetic resonance imaging, positron emission tomography and computed tomography offer superior detection of myeloma bone disease and extramedullary manifestations. In particular, the properties of nuclear imaging enable the identification of disease activity by directly targeting the specific cellular properties of malignant plasma cells. In this review, an overview is provided of the effectiveness of radiopharmaceuticals that target metabolism, surface receptors and angiogenesis. The available literature data for commonly used nuclear imaging tracers, the promising first results of new tracers, and our pilot work indicate that a number of these radiopharmaceutical applications can be used effectively for staging and response monitoring of relapsing MM patients. Moreover, some tracers can potentially be used for radio immunotherapy. (orig.)

  2. [Subcutaneous bortezomib as a new promising way to successful maintenance therapy in multiple myeloma].

    Science.gov (United States)

    Grosicki, Sebastian

    2012-01-01

    Multiple myeloma (MM) despite the introduction to clinical practice of a new drugs in the last years, and still searching of new points of the handle for targeting treatment, remaining incurable disease. Even most intensive and most modern induction-consolidation regimens is not in the state to eradicate of the clone of myeloma, and even complete remission in immunofixation the most often after some time ends progression. Optimal way of maintenance treatment is still searching, which would be maximally effective near acceptable toxicity. Now hypothesis about possible successful maintenance therapy, which may prolong survival of MM patients became more actual in the face of the introduction to the studies with maintenance of a new drugs as: thalidomide, lenalidomide and bortesomib. The expectations on the essential progress to establish the optimal bortesomib-based regimen of the maintenance treatment in MM cause the results of the studies with its subcutaneous administration, which proved comparable efficacy with advantage in toxicity profile, especially neurological in comparison to classic intravenous way.

  3. Patients with Multiple Myeloma Develop SOX2-Specific Autoantibodies after Allogeneic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Sebastian Kobold

    2011-01-01

    Full Text Available The occurrence of SOX2-specific autoantibodies seems to be associated with an improved prognosis in patients with monoclonal gammopathy of undetermined significance (MGUS. However, it is unclear if SOX2-specific antibodies also develop in established multiple myeloma (MM. Screening 1094 peripheral blood (PB sera from 196 MM patients and 100 PB sera from healthy donors, we detected SOX2-specific autoantibodies in 7.7% and 2.0% of patients and donors, respectively. We identified SOX2211–230 as an immunodominant antibody-epitope within the full protein sequence. SOX2 antigen was expressed in most healthy tissues and its expression did not correlate with the number of BM-resident plasma cells. Accordingly, anti-SOX2 immunity was not related to SOX2 expression levels or tumor burden in the patients’ BM. The only clinical factor predicting the development of anti-SOX2 immunity was application of allogeneic stem cell transplantation (alloSCT. Anti-SOX2 antibodies occurred more frequently in patients who had received alloSCT (n=74. Moreover, most SOX2-seropositive patients had only developed antibodies after alloSCT. This finding indicates that alloSCT is able to break tolerance towards this commonly expressed antigen. The questions whether SOX2-specific autoantibodies merely represent an epiphenomenon, are related to graft-versus-host effects or participate in the immune control of myeloma needs to be answered in prospective studies.

  4. Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma

    Science.gov (United States)

    Lahuerta, Juan J.; Pepin, François; González, Marcos; Barrio, Santiago; Ayala, Rosa; Puig, Noemí; Montalban, María A.; Paiva, Bruno; Weng, Li; Jiménez, Cristina; Sopena, María; Moorhead, Martin; Cedena, Teresa; Rapado, Immaculada; Mateos, María Victoria; Rosiñol, Laura; Oriol, Albert; Blanchard, María J.; Martínez, Rafael; Bladé, Joan; San Miguel, Jesús; Faham, Malek; García-Sanz, Ramón

    2014-01-01

    We assessed the prognostic value of minimal residual disease (MRD) detection in multiple myeloma (MM) patients using a sequencing-based platform in bone marrow samples from 133 MM patients in at least very good partial response (VGPR) after front-line therapy. Deep sequencing was carried out in patients in whom a high-frequency myeloma clone was identified and MRD was assessed using the IGH-VDJH, IGH-DJH, and IGK assays. The results were contrasted with those of multiparametric flow cytometry (MFC) and allele-specific oligonucleotide polymerase chain reaction (ASO-PCR). The applicability of deep sequencing was 91%. Concordance between sequencing and MFC and ASO-PCR was 83% and 85%, respectively. Patients who were MRD– by sequencing had a significantly longer time to tumor progression (TTP) (median 80 vs 31 months; P < .0001) and overall survival (median not reached vs 81 months; P = .02), compared with patients who were MRD+. When stratifying patients by different levels of MRD, the respective TTP medians were: MRD ≥10−3 27 months, MRD 10−3 to 10−5 48 months, and MRD <10−5 80 months (P = .003 to .0001). Ninety-two percent of VGPR patients were MRD+. In complete response patients, the TTP remained significantly longer for MRD– compared with MRD+ patients (131 vs 35 months; P = .0009). PMID:24646471

  5. A First Report on [18F]FPRGD2 PET/CT Imaging in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Nadia Withofs

    2017-01-01

    Full Text Available An observational study was set up to assess the feasibility of [F18]FPRGD2 PET/CT for imaging patients with multiple myeloma (MM and to compare its detection rate with low dose CT alone and combined [F18]NaF/[F18]FDG PET/CT images. Four patients (2 newly diagnosed patients and 2 with relapsed MM were included and underwent whole-body PET/CT after injection of [F18]FPRGD2. The obtained images were compared with results of low dose CT and already available results of a combined [F18]NaF/[F18]FDG PET/CT. In total, 81 focal lesions (FLs were detected with PET/CT and an underlying bone destruction or fracture was seen in 72 (89% or 8 (10% FLs, respectively. Fewer FLs (54% were detected by [F18]FPRGD2 PET/CT compared to low dose CT (98% or [F18]NaF/[F18]FDG PET/CT (70% and all FLs detected with [F18]FPRGD2 PET were associated with an underlying bone lesion. In one newly diagnosed patient, more [F18]FPRGD2 positive lesions were seen than [F18]NaF/[F18]FDG positive lesions. This study suggests that [F18]FPRGD2 PET/CT might be less useful for the detection of myeloma lesions in patients with advanced disease as all FLs with [F18]FPRGD2 uptake were already detected with CT alone.

  6. Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma

    International Nuclear Information System (INIS)

    Maes, Ken; Menu, Eline; Van Valckenborgh, Els; Van Riet, Ivan; Vanderkerken, Karin; De Bruyne, Elke

    2013-01-01

    Multiple myeloma (MM) is an incurable B-cell malignancy. Therefore, new targets and drugs are urgently needed to improve patient outcome. Epigenetic aberrations play a crucial role in development and progression in cancer, including MM. To target these aberrations, epigenetic modulating agents, such as DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi), are under intense investigation in solid and hematological cancers. A clinical benefit of the use of these agents as single agents and in combination regimens has been suggested based on numerous studies in pre-clinical tumor models, including MM models. The mechanisms of action are not yet fully understood but appear to involve a combination of true epigenetic changes and cytotoxic actions. In addition, the interactions with the BM niche are also affected by epigenetic modulating agents that will further determine the in vivo efficacy and thus patient outcome. A better understanding of the molecular events underlying the anti-tumor activity of the epigenetic drugs will lead to more rational drug combinations. This review focuses on the involvement of epigenetic changes in MM pathogenesis and how the use of DNMTi and HDACi affect the myeloma tumor itself and its interactions with the microenvironment

  7. Adipokines, adiposity, and bone marrow adipocytes: Dangerous accomplices in multiple myeloma.

    Science.gov (United States)

    Morris, Emma V; Edwards, Claire M

    2018-06-26

    Obesity has become a global epidemic influencing the establishment and progression of a wide range of diseases, such as diabetes, cardiovascular disease, and cancer. In 2016, International Agency for Research on Cancer reported that obesity is now associated with 13 different cancers, one of which is multiple myeloma (MM), a destructive cancer of plasma cells that predominantly reside in the bone marrow. Obesity is the accumulation of excess body fat, which causes metabolic, endocrine, immunologic, and inflammatory-like changes. Obesity is usually associated with an increase in visceral and/or subcutaneous fat; however, an additional fat depot that also responds to diet-induced changes is bone marrow adipose tissue (BMAT). There have been several studies over the past few decades that have identified BMAT as a key driver in MM progression. Adipocytes secrete numerous adipokines, such as leptin, adiponectin, resistin, adipsin, and visfatin, which when secreted at normal controlled levels have protective properties. However, in obesity these levels of secretion change, coupled with an increase in adipocyte number and size causing a profound and lasting effect on the bone microenvironment, contributing to MM cell growth, survival, and migration as well as potentially fueling bone destruction. Obesity is a modifiable risk factor making it an attractive option for targeted therapy. This review discusses the link between obesity, monoclonal gammopathy of undetermined significance (a benign condition that precedes MM), and myeloma, and the contribution of key adipokines to disease establishment and progression. © 2018 Wiley Periodicals, Inc.

  8. Bone marrow scintigraphy vs bone scintigraphy and radiography in multiple myeloma

    International Nuclear Information System (INIS)

    Feggi, M.; Prandini, N.; Orzincolo, C.; Bagni, B.; Scutellari, P.N.; Spanedda, R.; Gennari, M.; Scapoli, C.L.

    1988-01-01

    The radiography patterns of the skeleton of 73 patients affected by multiple myeloma (MM) were compared to the correspondent scintigraphic findings. Whole body scans were performed using Tc-diphosphonates 99m (bone scintigraphy). And Tc-microcolloides 99m (bone marrow scintigraphy). The results indicate that: a) radiography is more sensitive and accurate than scintigraphy in detecting typical myeloma-related bone lesions; b) bone scintigraphy is useful in detecting alterations in particular locations-i.e. sternum, ribs, scapulae, etc.-which are difficult to demonstrate by plain X-rays; moreover, the recovery of the fractures can be visualized; c) bone marrow scintigraphy is employed to demonstrate the presence of marrow expasion, of cold/hot spots, and relative marrow uptake, related to phagocytic activity. Since in adult men red marrow is confined to the epiphysis of long bones and to the spine, all the diseases affecting bone marrow cause medullary expansion/reduction, which are both easily detected by specific radiopharmaceuticals. The peripheral expasions is clearly documented especially in distal humeri and femora since marrow uptake is included, in healthy adults, in the axial and proximal appendicular skeleton. In spite of its yielding unique informetion, bone marrow scintigraphy remains an additional technique of bone scan, because of its low diagnoditc accuracy

  9. Overview of recent trends in diagnosis and management of leptomeningeal multiple myeloma.

    Science.gov (United States)

    Yellu, Mahender R; Engel, Jessica M; Ghose, Abhimanyu; Onitilo, Adedayo A

    2016-03-01

    Neurological complications related to multiple myeloma (MM) are not uncommon; however, direct involvement of the central nervous system (CNS) is extremely rare and represents a diagnostic and therapeutic challenge. Significant survival difference has been noted with the introduction of novel therapy in patients with MM, but their effect on the incidence and their use for management of leptomeningeal myeloma (LMM) is uncertain. Analysis of published data demonstrates its recent increased incidence, median time to CNS presentation, and slight improvement in median survival after diagnosis of LMM. Less common MM isotypes have been overrepresented in LMM. CNS relapse occurred mostly in patients with Durie-Salmon stage III MM. Despite treatments, standard or experimental, the survival rates of LMM remain dismal. Monitoring high risk patients closely, even after achieving complete remission, may be useful in early detection of LMM. As we gain better understanding of LMM, we recommend that future research and clinical care focus on earlier diagnosis and development of more efficient CNS-directed therapy to improve survival in this patient population. Copyright © 2014 John Wiley & Sons, Ltd.

  10. Sequential hemi-body radiotherapy in advanced multiple myeloma. [Side effects of indicated x-ray therapy

    Energy Technology Data Exchange (ETDEWEB)

    Jaffe, J.P.; Bosch, A.; Raich, P.C.

    1979-01-01

    Eleven patients with advanced multiple myeloma refractory to standard chemotherapy were treated with a regimen of sequential hemi-body radiotherapy consisting of 800 rad midplane in a single dose to each half. 9/10 patients experienced significant relief of skeletal pain and there were 5/11 objective tumor responses with one complete remission. Treatment-related morbidity was significant and consisted primarily of nausea and emesis, bone marrow suppression, and pneumonitis. This therapy is helpful in the management of advanced myeloma, and should be studied earlier in the course of the disease.

  11. N-terminal pro-C-type natriuretic peptide in serum associated with bone destruction in patients with multiple myeloma

    DEFF Research Database (Denmark)

    Mylin, Anne K; Goetze, Jens P; Heickendorff, Lene

    2015-01-01

    AIM: To examine whether N-terminal proCNP concentrations in serum is associated with bone destruction in patients with multiple myeloma. MATERIALS & METHODS: N-terminal proCNP and biochemical bone markers were measured in 153 patients. Radiographic bone disease and skeletal-related events were...

  12. DLC1 tumor suppressor gene inhibits migration and invasion of multiple myeloma cells through RhoA GTPase pathway

    Czech Academy of Sciences Publication Activity Database

    Ullmannová-Benson, Veronika; Guan, M.; Zhou, X. G.; Tripathi, V.; Yang, V.; Zimonjic, D. B.; Popescu, C.

    2009-01-01

    Roč. 23, č. 2 (2009), s. 383-390 ISSN 0887-6924 Institutional research plan: CEZ:AV0Z50200510 Keywords : multiple myeloma * tumor suppressor gene * promoter methylation Subject RIV: EC - Immunology Impact factor: 8.296, year: 2009

  13. Overexpression of c-myc is associated with adverse clinical features and worse overall survival in multiple myeloma

    DEFF Research Database (Denmark)

    Szabo, Agoston Gyula; Gang, Anne Ortved; Pedersen, Mette Ølgod

    2016-01-01

    The role of c-myc in multiple myeloma (MM) is controversial. We conducted a retrospective study of 117 patients with MM diagnosed between 2004 and 2010 at Herlev Hospital. Immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) were performed on tissue microarrays (TMAs) made from...

  14. Characteristics and outcomes of patients with multiple myeloma aged 21-40years versus 41-60years

    DEFF Research Database (Denmark)

    Jurczyszyn, Artur; Nahi, Hareth; Avivi, Irit

    2016-01-01

    We compared the outcomes of multiple myeloma (MM) patients aged 21-40 and 41-60years in the novel agent era. This case-control study included 1089 patients between 2000 and 2015. Cases and controls were matched for sex, International Staging System (ISS) stage and institution. There were 173 pati...

  15. Insights on Genomic and Molecular Alterations in Multiple Myeloma and Their Incorporation towards Risk-Adapted Treatment Strategy: Concise Clinical Review

    Directory of Open Access Journals (Sweden)

    Taiga Nishihori

    2017-01-01

    Full Text Available Although recent advances in novel treatment approaches and therapeutics have shifted the treatment landscape of multiple myeloma, it remains an incurable plasma cell malignancy. Growing knowledge of the genome and expressed genomic information characterizing the biologic behavior of multiple myeloma continues to accumulate. However, translation and incorporation of vast molecular understanding of complex tumor biology to deliver personalized and precision treatment to cure multiple myeloma have not been successful to date. Our review focuses on current evidence and understanding of myeloma biology with characterization in the context of genomic and molecular alterations. We also discuss future clinical application of the genomic and molecular knowledge, and more translational research is needed to benefit our myeloma patients.

  16. Expression of RAN, ZHX-2, and CHC1L genes in multiple myeloma patients and in myeloma cell lines treated with HDAC and Dnmts inhibitors

    Czech Academy of Sciences Publication Activity Database

    Legartová, Soňa; Harničarová, Andrea; Bártová, Eva; Hájek, R.; Pour, L.; Kozubek, Stanislav

    2010-01-01

    Roč. 57, č. 5 (2010), s. 482-487 ISSN 0028-2685 R&D Projects: GA MŠk ME 919; GA ČR(CZ) GAP302/10/1022 Grant - others:GA MŠk(CZ) LC06027; GA MŠk(CZ) LC535 Program:LC; LC Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : multiple myeloma * RAN * ZHX-2 Subject RIV: BO - Biophysics Impact factor: 1.449, year: 2010

  17. Single vs. multiple fraction regimens for palliative radiotherapy treatment of multiple myeloma. A prospective randomised study

    Energy Technology Data Exchange (ETDEWEB)

    Rudzianskiene, Milda; Inciura, Arturas; Gerbutavicius, Rolandas; Rudzianskas, Viktoras; Dambrauskiene, Ruta; Juozaityte, Elona [Lithuanian University of Health Sciences, Oncology Institute, Kaunas (Lithuania); Macas, Andrius [Lithuanian University of Health Sciences, Anaesthesiology Department, Kaunas (Lithuania); Simoliuniene, Renata [Lithuanian University of Health Sciences, Department of Physics, Mathematics and Biophysics, Kaunas (Lithuania); Kiavialaitis, Greta Emilia [University Hospital Zurich, Intitute of Anesthesiology, Zurich (Switzerland)

    2017-09-15

    To compare the impact of a single fraction (8 Gy x 1 fraction) and multifraction (3 Gy x 10 fractions) radiotherapy regimens on pain relief, recalcification and the quality of life (QoL) in patients with bone destructions due to multiple myeloma (MM). In all, 101 patients were included in a randomised prospective clinical trial: 58 patients were included in the control arm (3 Gy x 10 fractions) and 43 patients into the experimental arm (8 Gy x 1 fraction). The response rate was defined according to the International Consensus on Palliative Radiotherapy criteria. Recalcification was evaluated with radiographs. QoL questionnaires were completed before and 4 weeks after treatment. Pain relief was obtained in 81/101 patients (80.2%): complete response in 56 (69%) and partial in 25 patients (30.9%). No significant differences were observed in analgesic response between the groups. Significant factors for pain relief were female gender, age under 65, IgG MM type, presence of recalcification at the irradiated site. Recalcification was found in 32/101 patients (33.7%): complete in 17 (53.2%) and partial in 15 (46.2%). No significant differences were observed in recalcification between the groups. Significant factors for recalcification were Karnofsky index ≥ 60%, haemoglobin level ≤ 80 g/dl, MM stage II and analgesic response at the irradiated site. The QoL after radiotherapy was improved in the control group. The same analgesic and recalcification response was observed using two different radiotherapy regimens. Higher doses should be used to achieve a better QoL. (orig.) [German] Vergleich der einzeitigen vs. fraktionierten palliativen Radiotherapie in Bezug auf Schmerzlinderung, Knochenrekalzifizierung und Lebensqualitaet (QoL) bei Patienten mit multiplem Myelom (MM). In die randomisierte, prospektive Studie wurden 101 Patienten eingeschlossen: Die Kontrollgruppe (n = 58) erhielt eine fraktionierte (3 Gy x 10 Fraktionen) und die Experimentgruppe (n = 43) eine

  18. Infecção em Mieloma Múltiplo Infection in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Ana Luiza Oliveira

    2007-03-01

    Full Text Available Infecção é a principal causa de óbito em pacientes com mieloma múltiplo (MM. Na última década ocorreram mudanças substanciais no espectro de infecções em pacientes com MM, relacionadas com as mudanças no tratamento, ocorridas neste período. Embora as bactérias (particularmente encapsuladas e Gram-negativas continuem a ser os principais agentes etiológicos, infecções fúngicas invasivas causadas por fungos filamentosos (Aspergillus sp. e Fusarium sp. têm sido relatadas com freqüência crescente. Enquanto o aumento na intensidade do tratamento do MM resultou em melhora na sobrevida, novos problemas infecciosos emergiram. Assim, uma abordagem prática às infecções em pacientes com MM deve incluir o reconhecimento dos pat��genos prováveis, de acordo com vários fatores, como a história patológica pregressa, estado da doença de base, e tratamento atual e anterior para o MM. Estratégias específicas de diagnóstico, profilaxia e terapia empírica são direcionadas de acordo com esta abordagem.Infection is the leading cause of death in patients with multiple myeloma. Over the past decade, significant chances have occurred in the spectrum of infections in patients with multiple myeloma, paralleling the changes in the treatment of the disease. Although bacteria (particularly encapsulated and Gram-negative organisms remain the most frequent etiologic agents, invasive fungal infections caused by moulds (Aspergillus sp. and Fusarium sp. have been increasingly reported. While the increase in the intensity of the treatment of multiple myeloma represents a major advance, with a positive impact on survival, new infectious problems have emerged. Therefore, a practical approach to infections in MM patients must include the recognition of the likely pathogens according to several factors, such as past medical history, status of the underlying disease, and past and current treatment for MM. Specific strategies of diagnosis, prophylaxis

  19. The incidence of leukemia, lymphoma, and multiple myeloma among atomic bomb survivors: 1950 – 2001

    Science.gov (United States)

    Hsu, Wan-Ling; Preston, Dale L.; Soda, Midori; Sugiyama, Hiromi; Funamoto, Sachiyo; Kodama, Kazunori; Kimura, Akiro; Kamada, Nanao; Dohy, Hiroo; Tomonaga, Masao; Iwanaga, Masako; Miyazaki, Yasushi; Cullings, Harry M.; Suyama, Akihiko; Ozasa, Kotaro; Shore, Roy E.; Mabuchi, Kiyohiko

    2013-01-01

    A marked increase in leukemia risks was the first and most striking late effect of radiation exposure seen among the Hiroshima and Nagasaki atomic bomb survivors. This paper presents analyses of radiation effects on leukemia, lymphoma, and multiple myeloma incidence in the Life Span Study cohort of atomic bomb survivors updated 14 years since the last comprehensive report on these malignancies. These analyses make use of tumor- and leukemia-registry-based incidence data on 113,011 cohort members with 3.6 million person-years of follow-up from late 1950 through the end of 2001. In addition to a detailed analysis of the excess risk for all leukemias other than chronic lymphocytic leukemia or adult T-cell leukemia (neither of which appear to be radiation-related), we present results for the major hematopoietic malignancy types: acute lymphoblastic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, chronic myeloid leukemia, adult T-cell leukemia, Hodgkin and non-Hodgkin lymphoma, and multiple myeloma. Poisson regression methods were used to characterize the shape of the radiation dose response relationship and, to the extent the data allowed, to investigate variation in the excess risks with sex, attained age, exposure age, and time since exposure. In contrast to the previous report that focused on describing excess absolute rates, we considered both excess absolute rate (EAR) and excess relative risk (ERR) models and found that ERR models can often provide equivalent and sometimes more parsimonious descriptions of the excess risk than EAR models. The leukemia results indicated that there was a non-linear dose response for leukemias other than chronic lymphocytic leukemia or adult T-cell leukemia, which varied markedly with time and age at exposure, with much of the evidence for this non-linearity arising from the acute myeloid leukemia risks. Although the leukemia excess risks generally declined with attained age or time since exposure, there was evidence

  20. Comparative analysis of CD138 antigen targeting for the treatment of multiple myeloma with bismuth-213 and Melphalan chemotherapy

    International Nuclear Information System (INIS)

    Gouard, S.; Gaschet, J.; Maurel, C.; Barbet, J.; Davodeau, F.; Pallardy, A.; Faivre-Chauvet, A.; Kraeber-Bodere, F.; Bruchertseifer, F.; Morgenstern, A.; Cherel, M.

    2015-01-01

    Full text of publication follows. Aim: multiple myeloma (MM) is a B-cell malignancy of terminally differentiated plasma cells within the bone marrow, with the presence of a monoclonal immunoglobulin in serum and/or urine and development of osteolytic bone lesions in human. Despite intense research to develop new treatments, cure is almost never achieved. Alpha-radioimmunotherapy (RIT) has been shown to be effective in vivo in a multiple myeloma model and seems particularly suited for disseminated tumour cells or small clusters of tumour cells. CD138 (Syndecan-1) is found mainly in epithelial cells, but has been shown to be expressed by most myeloma cells, both in human and in mouse. In order to define where alpha RIT stands in MM treatment, the aim of this study was to compare Melphalan, MM standard treatment, with alpha RIT using a bismuth-213-labelled anti-mouse CD138 rat antibody in a syngeneic mouse MM model. Material and Methods: C57BL/KaLwRij mice were grafted with 10 6 5T33 cells (murine myeloma cells). Luciferase transfected 5T33 were used for in vivo localization of the cells during the course of disease. The first step of the study was to assess the dose-response of Melphalan (100, 200 et 300 μg/mouse), 21 days after engraftment. The second step consisted in therapeutic association: Melphalan followed by RIT at d22 et d25 after engraftment. Toxicity (animal weight, blood cell counts) and treatment efficacy were studied in animals receiving no treatment, injected with Melphalan alone (200 μg), RIT alone at d22 and d25 (3.7 MBq of 213 Bi-anti-CD138) and Melphalan combined with alpha RIT. Results: fifty percent of untreated mice died by d64 after MM engraftment. In mice treated with Melphalan alone, only the 200 μg dose improved median survival. No animal was cured after Melphalan treatment whereas 60% of the mice survived with RIT alone at d22 after tumour engraftment. However, the therapeutic window seems to be narrow, indeed no effect was observed with

  1. Extraskeletal multiple myeloma presenting with an atrial mass: a case report and a review of the literature.

    Science.gov (United States)

    Vigo, Federica; Ciammella, Patrizia; Valli, Riccardo; Cagni, Elisabetta; Iotti, Cinzia

    2012-08-10

    Extraskeletal presentation at diagnosis or during the course of multiple myeloma is a rare event. The prognosis is usually very poor. At the moment there is no agreed gold standard for the treatment of this presentation. A 79-year-old Caucasian woman was treated at our hospital for right atrial myeloma localization. Our patient showed the following signs and symptoms of congestive heart failure: dyspnea, hypotension, cyanosis and facial edema. Surgery was not considered feasible due to the extent of the disease. Our patient underwent external-beam radiation therapy using an intensity modulated technique, thus obtaining a persistent complete remission. Our patient has been in continuous complete local remission for 25 months since the end of radiotherapy. The role of radiotherapy is not defined in multiple myeloma with extraskeletal presentation. Our regimen seems to be effective in controlling the disease in this patient.This case report adds to the existing literature as it describes an unusual presentation of the disease and a new therapeutic approach to this rare presentation of multiple myeloma.

  2. Extraskeletal multiple myeloma presenting with an atrial mass: a case report and a review of the literature

    Directory of Open Access Journals (Sweden)

    Vigo Federica

    2012-08-01

    Full Text Available Abstract Introduction Extraskeletal presentation at diagnosis or during the course of multiple myeloma is a rare event. The prognosis is usually very poor. At the moment there is no agreed gold standard for the treatment of this presentation. Case presentation A 79-year-old Caucasian woman was treated at our hospital for right atrial myeloma localization. Our patient showed the following signs and symptoms of congestive heart failure: dyspnea, hypotension, cyanosis and facial edema. Surgery was not considered feasible due to the extent of the disease. Our patient underwent external-beam radiation therapy using an intensity modulated technique, thus obtaining a persistent complete remission. Our patient has been in continuous complete local remission for 25 months since the end of radiotherapy. Conclusion The role of radiotherapy is not defined in multiple myeloma with extraskeletal presentation. Our regimen seems to be effective in controlling the disease in this patient. This case report adds to the existing literature as it describes an unusual presentation of the disease and a new therapeutic approach to this rare presentation of multiple myeloma.

  3. Prognostic impact of circulating plasma cells in patients with multiple myeloma: implications for plasma cell leukemia definition.

    Science.gov (United States)

    Granell, Miquel; Calvo, Xavier; Garcia-Guiñón, Antoni; Escoda, Lourdes; Abella, Eugènia; Martínez, Clara Mª; Teixidó, Montserrat; Gimenez, Mª Teresa; Senín, Alicia; Sanz, Patricia; Campoy, Desirée; Vicent, Ana; Arenillas, Leonor; Rosiñol, Laura; Sierra, Jorge; Bladé, Joan; de Larrea, Carlos Fernández

    2017-06-01

    The presence of circulating plasma cells in patients with multiple myeloma is considered a marker for highly proliferative disease. In the study herein, the impact of circulating plasma cells assessed by cytology on survival of patients with multiple myeloma was analyzed. Wright-Giemsa stained peripheral blood smears of 482 patients with newly diagnosed myeloma or plasma cell leukemia were reviewed and patients were classified into 4 categories according to the percentage of circulating plasma cells: 0%, 1-4%, 5-20%, and plasma cell leukemia with the following frequencies: 382 (79.2%), 83 (17.2%), 12 (2.5%) and 5 (1.0%), respectively. Median overall survival according to the circulating plasma cells group was 47, 50, 6 and 14 months, respectively. At multivariate analysis, the presence of 5 to 20% circulating plasma cells was associated with a worse overall survival (relative risk 4.9, 95% CI 2.6-9.3) independently of age, creatinine, the Durie-Salmon system stage and the International Staging System (ISS) stage. Patients with ≥5% circulating plasma cells had lower platelet counts (median 86×10 9 /L vs 214×10 9 /L, P <0.0001) and higher bone marrow plasma cells (median 53% vs 36%, P =0.004). The presence of ≥5% circulating plasma cells in patients with multiple myeloma has a similar adverse prognostic impact as plasma cell leukemia. Copyright© Ferrata Storti Foundation.

  4. Alterações moleculares no Mieloma Múltiplo Molecular abnormalities in Multiple Myeloma

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    Esteban Braggio

    2007-03-01

    Full Text Available Nos últimos anos tem acontecido uma revolução no conhecimento dos mecanismos moleculares envolvidos na patogênese do mieloma múltiplo, principalmente devido à incorporação de técnicas de citogenética molecular (hibridização in situ fluorescente - FISH e biologia molecular (Reação em cadeia da polimerase - PCR, hibridização genômica comparativa baseada em microarranjos - aCGH e microarranjos de RNA. Estas técnicas permitem estudar as células em interfase e detectar alterações cromossômicas crípticas, superando assim problemas metodológicos relacionados à análise por citogenética convencional. Por outro lado, a complexidade metodológica relacionada com a realização das técnicas de FISH e biologia molecular tem impossibilitado que sejam amplamente utilizadas na rotina laboratorial. Este trabalho tem como objetivo fazer uma revisão das principais vias moleculares alteradas no mieloma múltiplo, o seu valor prognóstico e a sua utilização na estratificação dos pacientes em diferentes grupos de risco. São detalhadas diferentes abordagens metodológicas e uma ênfase especial é dada em relação à importância da análise se restringir exclusivamente às células plasmocitárias. Por último, discutimos uma série de prioridades e estratégias de estudo na rotina laboratorial.In recent years, we have seen an explosion in knowledge on genetic and cytogenetic mechanisms involved in the pathogenesis of multiple myeloma, mainly due to the incorporation of molecular tools in its study (fluorescence in situ hybridization - FISH, Real time PCR and RNA microarrays. These tools have enabled the study of cells in interphase and to detect cryptic chromosomal abnormalities, replacing cytogenetic techniques. The technical complexities associated with the performance of these tests, however, have limited their widespread applicability in routine clinical practice. The aim of this work is to review the present status of our

  5. Novel agents in the treatment of multiple myeloma: a review about the future

    Directory of Open Access Journals (Sweden)

    Leonard Naymagon

    2016-06-01

    Full Text Available Abstract Multiple myeloma (MM is a disease that affects plasma cells and can lead to devastating clinical features such as anemia, lytic bone lesions, hypercalcemia, and renal disease. An enhanced understanding of MM disease mechanisms has led to new more targeted treatments. There is now a plethora of treatments available for MM. In this review article, our aim is to discuss many of the novel agents that are being studied or have recently been approved for the treatment of MM. These agents include the following: immunomodulators (pomalidomide, proteasome inhibitors (carfilzomib, marizomib, ixazomib, oprozomib, alkylating agents (bendamustine, AKT inhibitors (afuresertib, BTK inhibitors (ibrutinib, CDK inhibitors (dinaciclib, histone deacetylase inhibitors (panobinostat, rocilinostat, vorinostat, IL-6 inhibitors (siltuximab, kinesin spindle protein inhibitors (filanesib, monoclonal antibodies (daratumumab, elotuzumab, indatuximab, SAR650984, and phosphoinositide 3-kinase (PI3K inhibitors.

  6. Economic evaluation of therapies for patients suffering from relapsed-refractory multiple myeloma in Greece

    Directory of Open Access Journals (Sweden)

    Fragoulakis V

    2013-04-01

    Full Text Available V Fragoulakis,1 E Kastritis,2 T Psaltopoulou,3 N Maniadakis1 1National School of Public Health, Athens, Greece; 2Department of Clinical Therapeutics, Alexandra Hospital, University of Athens, School of Medicine, Athens, Greece; 3Department of Hygiene, Epidemiology and Medical Statistics, University of Athens, School of Medicine, Athens, Greece Background: Multiple myeloma is a hematologic malignancy that incurs a substantial economic burden in care management. Since most patients with multiple myeloma eventually relapse or become refractory to current therapies (rrMM, the aim of this study was to assess the cost-effectiveness of the combination of lenalidomide–dexamethasone, relative to bortezomib alone, in patients suffering from rrMM in Greece. Methods: An international discrete event simulation model was locally adapted to estimate differences in overall survival and treatment costs associated with the two alternative treatment options. The efficacy data utilized came from three international trials (MM-009, MM-010, APEX. Quality of life data were extracted from the published literature. Data on resource use and prices came from relevant local sources and referred to 2012. The perspective of the analysis was that of public providers. Total costs for monitoring and administration of therapy to patients, management of adverse events, and cost of medication were captured. A 3.5% discount rate was used for costs and health outcomes. A Monte Carlo simulation was used to estimate probabilistic results with 95% uncertainty intervals (UI and a cost-effectiveness acceptability curve. Results: The mean number of quality-adjusted life years (QALYs was 3.01 (95% UI 2.81–3.20 and 2.22 (95% UI 2.02–2.41 for lenalidomide–dexamethasone and bortezomib, respectively, giving an incremental gain of 0.79 (95% UI 0.49–1.06 QALYs in favor of lenalidomide–dexamethasone. The mean cost of therapy per patient was estimated at €77,670 (95% UI €76,509

  7. A Benefit-Risk Analysis Approach to Capture Regulatory Decision-Making: Multiple Myeloma.

    Science.gov (United States)

    Raju, G K; Gurumurthi, Karthik; Domike, Reuben; Kazandjian, Dickran; Landgren, Ola; Blumenthal, Gideon M; Farrell, Ann; Pazdur, Richard; Woodcock, Janet

    2018-01-01

    Drug regulators around the world make decisions about drug approvability based on qualitative benefit-risk analysis. In this work, a quantitative benefit-risk analysis approach captures regulatory decision-making about new drugs to treat multiple myeloma (MM). MM assessments have been based on endpoints such as time to progression (TTP), progression-free survival (PFS), and objective response rate (ORR) which are different than benefit-risk analysis based on overall survival (OS). Twenty-three FDA decisions on MM drugs submitted to FDA between 2003 and 2016 were identified and analyzed. The benefits and risks were quantified relative to comparators (typically the control arm of the clinical trial) to estimate whether the median benefit-risk was positive or negative. A sensitivity analysis was demonstrated using ixazomib to explore the magnitude of uncertainty. FDA approval decision outcomes were consistent and logical using this benefit-risk framework. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  8. Oral Lesion as Unusual First Manifestation of Multiple Myeloma: Case Reports and Review of the Literature

    Directory of Open Access Journals (Sweden)

    A. Romano

    2014-01-01

    Full Text Available Extramedullary plasmacytoma (EMP and solitary bone plasmacytoma (SBP represent a disease continuum through a multistage process of cell differentiation, survival, proliferation, and dissemination, strictly related to multiple myeloma (MM, the second most common hematological malignancy. Herein, we report two cases of recurrent oral plasmacytoma progressed to MM, in which the first clinical sign of a more widespread disease was limited to the mouth. Based on our experience, we recommend a strict workup for the differential diagnosis between EMP, SBP, and MM for patients with oral plasmacytoma, including radiological exam of the skeleton, magnetic resonance imaging (MRI of the bone, and positive emission tomography (FDG-PET. MRI and possibly PET can all be used to more sensitively detect EM plasmacytoma sites.

  9. Interactions between SNPs affecting inflammatory response genes are associated with multiple myeloma disease risk and survival

    DEFF Research Database (Denmark)

    Nielsen, Kaspar René; Rodrigo-Domingo, Maria; Steffensen, Rudi

    2017-01-01

    The origin of multiple myeloma depends on interactions with stromal cells in the course of normal B-cell differentiation and evolution of immunity. The concept of the present study is that genes involved in MM pathogenesis, such as immune response genes, can be identified by screening for single......3L1 gene promoters. The occurrence of single polymorphisms, haplotypes and SNP-SNP interactions were statistically analyzed for association with disease risk and outcome following high-dose therapy. Identified genes that carried SNPs or haplotypes that were identified as risk or prognostic factors......= .005). The 'risk genes' were analyzed for expression in normal B-cell subsets (N = 6) from seven healthy donors and we found TNFA and IL-6 expressed both in naïve and in memory B cells when compared to preBI, II, immature and plasma cells. The 'prognosis genes' CHI3L1, IL-6 and IL-10 were differential...

  10. THE STUDY OF SOME BIOCHEMICAL PARAMETERS IN PATIENTS WITH MULTIPLE MYELOMA

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    Bularda Morozan Mihai

    2010-09-01

    Full Text Available This paper presents the results of some biochemical parameters obtained in the laboratory of “Elena Beldiman” Emergency Hospital Barlad, and in the”Dr. Stoian –Dr. Ungureanu”Private Medical Practice on 10 patients diagnosed with multiple myeloma during 2005-2011. Numerous researches over serum proteins with the help of various methods ( refractometry have shown the presence of some changes in protein fractions of blood serum. These changes express the change of the normal ratio between these fractions, that means disorders in colloidal structure of blood. The results of the electrophoresis analysis, also in accordance with those from the scholarly literature, show that the changes in the condition of the blood serum are due to the increase in the globulins fractions which is linked to the growth of the immunological processes, the antibodies synthesis being especially closely linked to gammaglobulinic fraction

  11. Localized extramedullary relapse after autologous hematopoietic stem cell transplantation in multiple myeloma

    International Nuclear Information System (INIS)

    Erkus, Muhan; Meteoglu, Ibrahim; Bolaman, Zahit; Kadikoylu, Gurhan

    2005-01-01

    Extramedullary plasmacytomas are rare manifestation of plasma cell malignancies. After hematopoietic stem cell transplantation HSCT, presentation of localized plasmacytoma with extramedullary growth is very unusual. We report a case of a 56-year-old woman with Dune-Salmon stage IIIA immunoglobulin A-kappa multiple myeloma, which presented 120 days after autologous HSCT with extramedullary plasmacytoma arising from a lymph node in supraclavicular region. The patient had no pretransplant-history related with extramedullary disease. There was no increase of plasma cells in bone marrow or monoclonal protein in urine or serum. Aspiration smears of lymph node revealed a population of plasmacytoid cells at various stages of maturation. The patient was successfully treated with local radiotherapy and has remained progression-free for more than 20 months. (author)

  12. Application of 99mTc-MIBI for diagnostic evaluation of multiple myeloma and lymphoma

    International Nuclear Information System (INIS)

    Kostadinova, I.; Garcheva, M.; Petrov, T.

    1995-01-01

    An attempt is made to determine the stage of multiple myeloma (MM), Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) after applying 99 mTc-MIBI, as well as to proof the residual vital tissue after chemo- and radiotherapy. 15 patients with these diseases and 3 controls are examined. An increased tracer uptake was found at 7 of the patients along the bones (in MM) or focal intake at typical places (in HL and NHL) as a sign of an active disease. In comparison with X-ray and bone scintigraphy, the whole body examination with 99m Tc-MIBI allows visualization of more pathological sites. The preliminary results show that more patients with MM, HL and NHL can be examined in order to determine activity and stage of the disease and to differentiate between active and fibrous tissues after chemo and radio therapy. 6 refs., 2 figs. (author)

  13. Expression of osteoblast and osteoclast regulatory genes in the bone marrow microenvironment in multiple myeloma

    DEFF Research Database (Denmark)

    Kristensen, Ida B; Christensen, Jacob Haaber; Lyng, Maria Bibi

    2014-01-01

    Multiple myeloma (MM) lytic bone disease (LBD) is caused by osteoclast activation and osteoblast inhibition. RANK/RANKL/OPG play central roles in osteoclast activation and Wnt inhibitor DKK1 in osteoblast inhibition. The role of other Wnt inhibitors is less clear. We evaluated gene expression...... of osteoclast regulators (RANK, RANKL, OPG, TRAIL, MIP1A), Wnt inhibitors (DKK1, SFRP2, SFRP3, sclerostin, WIF1) and osteoblast transcription factors (RUNX2, osterix) by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in the bone marrow (BM) microenvironment using snap-frozen BM biopsies...... radiographs and the bone resorption marker CTX-1. Protein levels were evaluated by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. Among Wnt inhibitors, only SFRP3 and DKK1 were significantly overexpressed in advanced LBD, correlating with protein levels. SFRP3 correlated with CTX-1. Our...

  14. The effect of ranitidine on cellular immunity in patients with multiple myeloma

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Nielsen, H; Moesgaard, F

    1990-01-01

    .19-2.25 nmol/min) (P less than 0.005 between groups). Among ranitidine-treated patients spontaneous NK cell activity was unchanged, while in vitro interleukin-2- and interferon-alpha-stimulated NK cell activity decreased (P less than 0.03, respectively). As production of oxygen radicals constitutes...... after previous cytotoxic therapy were in a stable phase of their disease. All were without clinical signs of infections and at that time had not been treated with other immunomodulating agents. The patients were randomized to oral ranitidine 300 mg twice a day for 21 days or placebo, and several...... immunological parameters related to multiple myeloma were studied. The blood monocyte chemotactic response was improved in patients treated with ranitidine, and superoxide anion production increased from 2.02 nmol/min to 3.86 nmol/min (median values), while it was unchanged in patients given placebo (2...

  15. Cutaneous involvement in multiple myeloma (MM): A case series with clinicopathologic correlation.

    Science.gov (United States)

    Malysz, Jozef; Talamo, Giampaolo; Zhu, Junjia; Clarke, Loren E; Bayerl, Michael G; Ali, Liaqat; Helm, Klaus F; Chung, Catherine G

    2016-05-01

    Disease-specific skin lesions are rare in patients with multiple myeloma (MM). We sought to further characterize the clinical and pathologic features of patients with cutaneous involvement with MM. We identified 13 patients with cutaneous lesions of MM. Cutaneous lesions consisted of pink, red, and violaceous papules, nodules, and/or plaques that varied in size. Histopathology revealed atypical plasma cells with occasional plasmablastic features. MM had aggressive biologic features and was at an advanced stage in the majority of patients. Despite aggressive management, including chemotherapy and stem-cell transplantation, most patients died of progressive disease within a few months after the development of cutaneous lesions. The study group was relatively small. Cutaneous involvement with MM is associated with aggressive biologic behavior and short survival. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  16. Double Relapsed and/or Refractory Multiple Myeloma: Clinical Outcomes and Real World Healthcare Costs.

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    Sarah Gooding

    Full Text Available Double relapsed and/or refractory multiple myeloma (DRMM, MM that is relapsed and/or refractory to bortezomib and lenalidomide, carries a poor prognosis. The healthcare costs of DRMM have not previously been reported. We analyzed detailed medical resource utilization (MRU costs, drug costs and outcomes for 39 UK patients receiving standard DRMM therapy. Median OS in this cohort was 5.6 months. The mean cost of DRMM treatment plus MRU until death was £23,472 [range: £1,411-£90,262], split between drug costs £11,191 and other resource use costs £12,281. The cost per assumed quality-adjusted life year (QALY during DRMM was £66,983. These data provide a standard of care comparison when evaluating the cost-effectiveness of new drugs in DRMM.

  17. Immune Recovery after Cyclophosphamide Treatment in Multiple Myeloma: Implication for Maintenance Immunotherapy

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    Amir Sharabi

    2011-01-01

    Full Text Available Multiple myeloma (MM is a progressive B-lineage neoplasia characterized by clonal proliferation of malignant plasma cells. Increased numbers of regulatory T cells (Tregs were determined in mouse models and in patients with MM, which correlated with disease burden. Thus, it became rational to target Tregs for treating MM. The effects of common chemotherapeutic drugs on Tregs are reviewed with a focus on cyclophosphamide (CYC. Studies indicated that selective depletion of Tregs may be accomplished following the administration of a low-dose CYC. We report that continuous nonfrequent administrations of CYC at low doses block the renewal of Tregs in MM-affected mice and enable the restoration of an efficient immune response against the tumor cells, thereby leading to prolonged survival and prevention of disease recurrence. Hence, distinctive time-schedule injections of low-dose CYC are beneficial for breaking immune tolerance against MM tumor cells.

  18. Medical image of the week: acute encephalopathy in a multiple myeloma patient

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    Ateeli H

    2018-02-01

    Full Text Available No abstract available. A 45-year-old man with new diagnosis of multiple myeloma waiting to start treatment presented with worsening dizziness, blurred vision that progressed to altered mental status over a week. His physical exam revealed confusion but no focal deficit. His extensive work up showed no abnormality except for mildly elevated serum viscosity. The patient was started immediately on plasmapheresis. He also received dexamethasone, thalidomide and cyclophosphamide. His symptoms resolved completely within a few days of therapy. Serum viscosity measurements do not correlate well with symptoms or the clinical findings of hypervicosity syndrome. Plasmapheresis promptly relieves the symptoms and should be performed in symptomatic patients regardless of the viscosity level (1,2.

  19. Sequential analysis of biochemical markers of bone resorption and bone densitometry in multiple myeloma

    DEFF Research Database (Denmark)

    Abildgaard, Niels; Brixen, K; Eriksen, E.F

    2004-01-01

    BACKGROUND AND OBJECTIVES: Bone lesions often occur in multiple myeloma (MM), but no tests have proven useful in identifying patients with increased risk. Bone marker assays and bone densitometry are non-invasive methods that can be used repeatedly at low cost. This study was performed to evaluate...... 6 weeks, DEXA-scans performed every 3 months, and skeletal radiographs were done every 6 months as well as when indicated. RESULTS: Serum ICTP and urinary NTx were predictive of progressive bone events. Markers of bone formation, bone mineral density assessments, and M component measurements were...... changes, and our data do not support routine use of sequential DEXA-scans. However, lumbar DEXA-scans at diagnosis can identify patients with increased risk of early vertebral collapses. Sequential analyses of serum ICTP and urinary NTx are useful for monitoring bone damage....

  20. Dysregulation of CD47 and the ligands thrombospondin 1 and 2 in multiple myeloma

    DEFF Research Database (Denmark)

    Rendtlew Danielsen, Jannie M; Knudsen, Lene Meldgaard; Dahl, Inger Marie

    2007-01-01

    % of patients with monoclonal gammopathy of undetermined significance (MGUS) expressed CD47; median expression level increased 10-fold with progression from MGUS to MM. Elevated TSP1/TSP2 levels occurred in bone marrow cultures from MM patients compared with healthy donors. CD47 and TSP1/TSP2 may have......CD47 and thrombospondin 1 and 2 (TSP1 and TSP2) expression were analysed by real-time reverse transcription polymerase chain reaction in fluorescence-activated cell sorted plasma cells (PCs) from patients at consecutive stages of multiple myeloma (MM) development. 80% of MM patients, but only 39...... a potential role in the pathophysiology of MM, probably in the interaction between MM PCs and the microenvironment....

  1. Characterization of the infrared spectra of serum from patients with multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Plotnikova, L., E-mail: ljusja@mail.ru; Nosenko, T.; Uspenskaya, M., E-mail: mv-uspenskaya@mail.ru [Saint Petersburg National Research University of Information Technologies, Mechanics and Optics, Kronverksky Pr., Saint Petersburg, 197101 (Russian Federation); Polyanichko, A. [Saint Petersburg State University, Universitetskaya Nab. 7/9, Saint Petersburg, 199034 (Russian Federation); Garifullin, A.; Voloshin, S. [Russian Scientific Research Institute of Hematology and Transfusiology, 2nd Sovetskaya Str. 16, Saint Petersburg, 191024 (Russian Federation)

    2016-08-02

    Multiple myeloma (MM) accounts for about 1% of all types of cancers. MM is characterized by the proliferation of a single clone of plasma cells, which may produce and secrete a homogeneous monoclonal immunoglobulin. The monoclonal immunoglobulin is commonly referred to as an M protein. The M protein acts as a serological “tumor” marker that is useful for diagnosis and disease monitoring. The electrophoretic pattern reveals the M-protein in 80% of MM patients as a single peak or localized band. In our study we applied a combination of high-resolution agarose gel protein electrophoresis (PEL), spectroscopic techniques and thermal analysis to identify the key differences in protein composition, protein structure and their thermal behavior for the samples obtained from the serum of MM patients and healthy donors.

  2. Diffuse Myocardial Uptake of 99mTc-HDP in Multiple Myeloma

    International Nuclear Information System (INIS)

    Demirel, Koray; Sadic, Murat; Korkmaz, Meliha; Comak, Aylin; Atilgan, Hasan Ikbal; Koca, Goekhan

    2013-01-01

    Soft tissue uptake is a rare finding in bone scintigraphy, with an incidence of 2%. Although the mechanism has not yet been fully clarified, several causes have been reported for this unusual uptake pattern. This paper presents a case of diffuse myocardial accumulation of technetium-99m hydroxymethylene diphosphonate ( 99m Tc-HDP) without either solid/visceral organ or soft tissue with multiple myeloma (MM) in skeletal scintigraphy. A 93-year-old man with hypertension and chronic heart failure for 14 years underwent bone scanning due to a 2-month history of back pain within a 1-year period of MM. Three hours later, 99m Tc-HDP late static images showed diffuse myocardial radiotracer accumulation and there were no other sites of abnormal soft tissue or visceral uptake. Myocardial accumulation had disappeared on 24-h delayed static images. This accumulation was thought to be related with AL-type amyloidosis associated with MM

  3. Diffuse Myocardial Uptake of {sup 99m}Tc-HDP in Multiple Myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Demirel, Koray; Sadic, Murat; Korkmaz, Meliha; Comak, Aylin; Atilgan, Hasan Ikbal; Koca, Goekhan [Ministry of Health Ankara Training and Research Hospital, Ankara (Turkmenistan)

    2013-09-15

    Soft tissue uptake is a rare finding in bone scintigraphy, with an incidence of 2%. Although the mechanism has not yet been fully clarified, several causes have been reported for this unusual uptake pattern. This paper presents a case of diffuse myocardial accumulation of technetium-99m hydroxymethylene diphosphonate ({sup 99m}Tc-HDP) without either solid/visceral organ or soft tissue with multiple myeloma (MM) in skeletal scintigraphy. A 93-year-old man with hypertension and chronic heart failure for 14 years underwent bone scanning due to a 2-month history of back pain within a 1-year period of MM. Three hours later, {sup 99m}Tc-HDP late static images showed diffuse myocardial radiotracer accumulation and there were no other sites of abnormal soft tissue or visceral uptake. Myocardial accumulation had disappeared on 24-h delayed static images. This accumulation was thought to be related with AL-type amyloidosis associated with MM.

  4. Multiple Myeloma of the Central Nervous System: 13 Cases and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Gergely Varga

    2018-01-01

    Full Text Available Central nervous system involvement is a rare complication of multiple myeloma with extremely poor prognosis as it usually fails to respond to therapy. We present 13 cases diagnosed at two centers in Budapest and review the current literature. The majority of our cases presented with high-risk features initially; two had plasma cell leukemia. Repeated genetic tests showed clonal evolution in 3 cases. Treatments varied according to the era, and efficacy was poor as generally reported in the literature. Only one patient is currently alive, with 3-month follow-up, and the patient responded to daratumumab-based treatment. Recent case reports show promising effectivity of pomalidomide and marizomib.

  5. SERUM YKL-40 CORRELATES WITH SERUM INTERLEUKIN-6 IN MULTIPLE MYELOMA

    DEFF Research Database (Denmark)

    Mylin, Anne Kjærsgaard; Andersen, Niels Frost; Johansen, Julia S.

    2007-01-01

    Introduction. The secreted glycoprotein YKL-40 (CHI3L1, HC gp-39) is a potential player in the tumor-host interactions affecting several aspects of multiple myeloma (MM) including angiogenesis. YKL-40 expression is seeen in vascular smooth muscle cells, and the protein is suggested to function......, but S-YKL-40 show a strong positive correlation with S-IL-6 consistent with a possible IL-6 mediated regulation of YKL-40 secretion demonstrated in previous studies. Table 1     Normal S-YKL-40 N   Median (range)     Elevated S-YKL-40 N   Median (range)     p-value   S-IL-6, ng/L             PB 23 3 (1...

  6. UPDATE ON THE ROLE OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA

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    Patrizia Tosi

    2012-11-01

    Full Text Available Autologous stem cell transplantation is considered the standard of care for multiple myeloma patients aged < 65 years with no relevant comorbidities. The addition of drugs acting both on bone marrow microenvironment and on neoplastic plasma cells has significantly increased the proportion of patients achieving a complete remission after induction therapy, and these results are mantained after high-dose melphalan, leading to a prolonged disease control. Studies are being carried out in order to evaluate whether short term consolidation or long-term maintenance therapy can result into disease eradication at the molecular level thus increasing also patients survival. The efficacy of these new drugs has raised the issue of deferring the transplant after achivng a second response upon relapse. Another controversial point is the optimal treatment strategy for high-risk patients, that do not benefit from autologous stem cell transplantation and for whom the efficacy of new drugs is still matter of debate.

  7. High-dose therapy improved the bone remodelling compartment canopy and bone formation in multiple myeloma

    DEFF Research Database (Denmark)

    Hinge, Maja; Delaissé, Jean-Marie; Plesner, Torben

    2015-01-01

    transplantation, and from 20 control patients with monoclonal gammopathy of undetermined significance were histomorphometrically investigated. This investigation confirmed that MM patients exhibited uncoupled bone formation to resorption and reduced canopy coverage. More importantly, this study revealed......Bone loss in multiple myeloma (MM) is caused by an uncoupling of bone formation to resorption trigged by malignant plasma cells. Increasing evidence indicates that the bone remodelling compartment (BRC) canopy, which normally covers the remodelling sites, is important for coupled bone remodelling....... Loss of this canopy has been associated with bone loss. This study addresses whether the bone remodelling in MM is improved by high-dose therapy. Bone marrow biopsies obtained from 20 MM patients, before and after first-line treatment with high-dose melphalan followed by autologous stem cell...

  8. Quantitation of multiple myeloma oncogene 1/interferon-regulatory factor 4 gene expression in malignant B-cell proliferations and normal leukocytes.

    Science.gov (United States)

    Yamada, M; Asanuma, K; Kobayashi, D; Moriai, R; Yajima, T; Yagihashi, A; Yamamori, S; Watanabe, N

    2001-01-01

    We studied multiple myeloma oncogene 1/interferon-regulatory factor 4 (MUM1/IRF4) mRNA expression in various malignant human hematopoietic cell lines and normal leukocyte fractions. A quantitative reverse transcription-polymerase chain reaction was used to assess expression and chromosomes were examined for anomalies by fluorescent in situ hybridization. Among 12 cell lines examined, mRNA transcripts were expressed only in B-lymphoblastic and myeloma cell lines. Myeloma cells and malignant cell lines derived from mature B cells expressed more transcript than cell lines derived from immature B cells. Transcript levels, however, showed no association with chromosomal translocations. Expression in B-cell fractions from healthy donors was much less than in the malignant cells. In addition, MUM1/IRF4 mRNA expressed in samples from patients with acute lymphoblastic leukemia derived from B cells but not T cells. Our results suggested that MUM1/IRF4 gene expression is related to stage of differentiation of malignant B cells and they indicated the possibility that the quantitative analysis of MUM1/IRF4 gene is a useful tool for detection of malignant B-cell proliferations in clinical laboratory tests.

  9. Validation of interphase fluorescence in situ hybridization (iFISH for multiple myeloma using CD138 positive cells

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    Renata Kiyomi Kishimoto

    2016-06-01

    Full Text Available ABSTRACT BACKGROUND: Multiple myeloma is a plasma cell neoplasm with acquired genetic abnormalities of clinical and prognostic importance. Multiple myeloma differs from other hematologic malignancies due to a high fraction of low proliferating malignant plasma cells and the paucity of plasma cells in bone marrow aspiration samples, making cytogenetic analysis a challenge. An abnormal karyotype is found in only one-third of patients with multiple myeloma and interphase fluorescence in situ hybridization is the most useful test for studying the chromosomal abnormalities present in almost 90% of cases. However, it is necessary to study the genetic abnormalities in plasma cells after their identification or selection by morphology, immunophenotyping or sorting. Other challenges are the selection of the most informative FISH panel and determining cut-off levels for FISH probes. This study reports the validation of interphase fluorescence in situ hybridization using CD138 positive cells, according to proposed guidelines published by the European Myeloma Network (EMN in 2012. METHOD: Bone marrow samples from patients with multiple myeloma were used to standardize a panel of five probes [1q amplification, 13q14 deletion, 17p deletion, t(4;14, and t(14;16] in CD138+ cells purified by magnetic cell sorting. RESULTS: This test was validated with a low turnaround time and good reproducibility. Five of six samples showed genetic abnormalities. Monosomy/deletion 13 plus t(4;14 were found in two cases. CONCLUSION: This technique together with magnetic cell sorting is effective and can be used in the routine laboratory practice. In addition, magnetic cell sorting provides a pure plasma cell population that allows other molecular and genomic studies.

  10. Pharmacovigilance of patients with multiple myeloma being treated with bortezomib and/or thalidomide

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    T.B.M. Castro

    2016-01-01

    Full Text Available In order to evaluate the main adverse effects of drug protocols using bortezomib and/or thalidomide for the treatment of multiple myeloma, we conducted a prospective study. Data were collected through interviews, clinical observation, and from hospital records. A total of 59 patients were included. There was a predominance of females, 36 (61% vs 23 (39% males, and of whites, 49 (83.1% vs 10 (16.9% blacks. Age ranged from 40 to 94 years, with a median of 65 years (SD=11.6. Regarding staging at diagnosis, 27 (45.7% patients were in stage III-A, with 12 (20.3% patients having serum creatinine ≥2 mg/dL. The main adverse effects in the bortezomib treatment group (n=40 were: neutropenia (42.5%, diarrhea (47.5%, and peripheral neuropathy in 60% of cases, with no difference between the iv (n=26 and sc (n=14 administration routes (P=0.343. In the group treated with thalidomide (n=19, 31.6% had neutropenia, 47.4% constipation, and 68.4% peripheral neuropathy. Neutropenia was associated with the use of alkylating agents (P=0.038. Of the 3 patients who received bortezomib in combination with thalidomide, only 1 presented peripheral neuropathy (33.3%. Peripheral neuropathy was the main adverse effect of the protocols that used bortezomib or thalidomide, with a higher risk of neutropenia in those using alkylating agents. Improving the identification of adverse effects is critical in multiple myeloma patient care, as the patient shows improvements during treatment, and requires a rational and safe use of medicines.

  11. Clinical utility and patient consideration in the use of lenalidomide for multiple myeloma in Chinese patients

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    Wang J

    2015-06-01

    Full Text Available Jing Wang, Hongfeng Guo, Xin Zhou Department of Hematology, Wuxi People’s Hospital, Nanjing Medical University, Wuxi, People’s Republic of China Abstract: Multiple myeloma (MM is an incurable hematologic malignancy caused by the autonomous growth of malignant plasma cells. In the last decade, the introduction of novel targeted agents such as thalidomide, bortezomib, and lenalidomide has dramatically improved the clinical outcome of MM patients in both the frontline and recurrent settings. Lenalidomide is a synthetic derivative of thalidomide, which has been shown to significantly improve overall survival, time to progression, and overall response rates in patients with MM. The China Food and Drug Administration approved the use of lenalidomide in patients with MM in 2013. In a Phase II trial, lenalidomide plus low-dose dexamethasone was associated with a high response rate and acceptable safety profile in heavily pretreated Chinese patients with relapsed/refractory MM, including those with renal impairment and IgD subtype. However, lenalidomide will remain as a second-line antimyeloma drug in the near future because of its high price and the policy of health insurance reimbursement in People’s Republic of China. In this review, we summarize the clinical utility and patient considerations in the use of lenalidomide for MM in Chinese patients. Further studies with larger sample sizes are required to investigate the better quality, longer duration, and more clinically meaningful outcomes of lenalidomide in the treatment of MM in Chinese patients. Keywords: lenalidomide, multiple myeloma, clinical efficacy, Chinese patients

  12. Multiple myeloma of an extremity: must the whole bone be irradiated?

    International Nuclear Information System (INIS)

    Catell, Donna; Kogen, Zeev; Donahue, Bernadine; Steinfeld, Alan

    1996-01-01

    Purpose/Objective: Radiation of the entire shaft of a long bone affected by multiple myeloma is often advocated to prevent recurrent disease in the bone remote from the symptomatic site. Our standard of care has been to irradiate only the symptomatic area. We investigated the pattern of recurrence in patients treated in this manner. Materials and Methods: 163 patients with multiple myeloma were treated between 1971 and 1994. Twenty-seven patients received treatment to a long bone with 43 sites irradiated (17 humeri, 24 femurs, 1 radius, 1 ulna.) The most common long bone treated was the femur. All patients were treated with megavoltage therapy. The symptomatic lesion, plus a margin of 1-2 cm was treated with no attempt to treat the entire shaft. Mean radiation dose was 2782 cGy (range 600-4480 cGy). The length of the field was measured in centimeters and expressed as both an absolute (AL) and relative (RL) length (i.e. percentage of total length of bone). Results: The mean total AL and RL for femur fields was 18 cm and 42% respectively. For the humerus, the AL and RL were 20 cm and 68% respectively. Only 4 patients developed progressive disease in the same bone but outside the previously irradiated field. In 3 of the 4 patients the RL was between 20 and 30%. The dose of radiation given to these patients was 1250, 2100, 3000 and 3500 cGy. In all of these 4 cases, treatment of progressive disease in adjacent sites provided effective palliation of symptoms. Conclusion: Radiation therapy to the symptomatic portion of a long bone affected by MM is effective for palliation. Symptomatic recurrence out of the irradiated field is uncommon and can be effectively treated. Potential benefits of this approach include irradiation of less normal marrow and elimination of use of pairs of fields or extended distance treatment to cover the entire femur

  13. Percutaneous Vertebroplasty for Pain Management in Patients with Multiple Myeloma: Is Radiofrequency Ablation Necessary?

    International Nuclear Information System (INIS)

    Orgera, Gianluigi; Krokidis, Miltiadis; Matteoli, Marco; Varano, Gianluca Maria; La Verde, Giacinto; David, Vincenzo; Rossi, Michele

    2014-01-01

    PurposeThis study was designed to investigate the added role of radiofrequency ablation (RFA) to vertebroplasty on the pain management of patients with multiple myeloma (MM).MethodsThirty-six patients (51–82 years) with vertebral localization of MM were randomly divided into two groups: 18 patients (group A) who underwent RFA and then vertebroplasty, and 18 patients (group B) who underwent only vertebroplasty. Primary endpoints were technical success and pain relief score rate measured by the visual analogue pain scores (VAS) and Roland–Morris Questionnaire (RMQ); secondary endpoint was the amount of administered analgesia. Survival and complications were compared.ResultsTechnical success was 100 % in both groups. The VAS score (at 24 h and 6 weeks postprocedure) decreased in equal manner for both groups from a mean of 9.1–3.4 and 2.0 for group A and from a mean of 9.3–3.0 and 2.3 for group B; RMQ mean score was 19.8 for group A and 19.9 for group B and decreased to a mean of 9.6 and 8.2 for group A and 9.5 and 8.7 for group B. The amount of medication was equally decreased in the two groups. No statistically significant difference was noted. No major complication occurred and two patients died from other causes.ConclusionsThe use of percutaneous vertebroplasty alone appears to be effective for the pain management of the patients with vertebral involvement of multiple myeloma. The use of RFA that includes cost and time does not offer any clear added benefit on the midterm pain management of such patients

  14. Conventional and Molecular Cytogenetic Analyses in Turkish Patients with Multiple Myeloma

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    Beyhan Durak Aras

    2012-06-01

    Full Text Available OBJECTIVE: Multiple myeloma (MM is characterized by the accumulation and proliferation of malignant plasma cells, secreting monoclonal immunoglobulins and genetic abnormalities in MM have implications for disease progression and survival. In the present study, we investigated the frequency of chromosomal abnormalities (CA in Turkish patients with MM, using interphase FISH and CC and evaluated the relationship between the rearrangements detected, prognosis and stage of disease. METHODS: We performed conventional cytogenetic and FISH studies in 50 patients to detect chromosome anomalies associated with MM. FISH probes were used to detect 13q14, 13q34, 17p13 deletions, IGH rearrangements, and monosomy and/or trisomy of chromosomes 5, 9, and 15. RESULTS: CC studies could be performed in 32 of 50 cases and five patients (15.6% showed chromosomal aberrations while 27 (84.3% had normal karyotypes. By FISH, eighteen percent (9/50 of cases were found to be normal for all parameters evaluated. Eighty-two percent (41/50 of the patients were positive for at least one abnormality. Chromosome 13 anomalies were detected in 54% (27/50 of cases. The second most common aberration observed is chromosome 15 aberrations (50%. CONCLUSION: Median survival rate was shorter in patients with one of the abnormalities including chromosome 13 aberrations, IGH rearrangements or P53 deletions. Chromosome 15 aberrations were significantly higher in patients with stage III disease (p=0.02. We conclude that FISH studies should be performed in conjunction with conventional cytogenetic analysis for prognosis in multiple myeloma patients.

  15. Thirteen treated of acute renal failure secondary to multiple myeloma with high cut off filters.

    Science.gov (United States)

    Berni Wennekers, Ana; Martín Azara, María Pilar; Dourdil Sahun, Victoria; Bergasa Liberal, Beatriz; Ruiz Laiglesia, José Esteban; Vernet Perna, Patricia; Alvarez Lipe, Rafael

    2016-01-01

    Multiple myeloma (MM) is a haematological tumour that is characterised by uncontrolled proliferation of plasma cells and a significant volume of serum free light chains (sFLCs), which can cause acute renal failure due to intratubular precipitation, resulting in cast nephropathy. Acute renal failure is a complication that can arise in more than 20% of patients with multiple myeloma, half of which will require dialysis. We report our experience with 13 patients who were treated with dialysis using high cut off filters (HCO) between July 2011 and February 2015. A total of 6 consecutive 6-hour sessions were performed using a 2.1 m(2) HCO filter (Theralite® by Gambro®). Afterwards, further 6-hour sessions were continued on alternate days. A total of 151 sessions were conducted, with an average of 11.6 sessions per patient (range 6-27). The treatment proved to be effective in removing both kappa and lambda sFLCs, resulting in a 93.7% fall in sFLCs by the end of treatment. The average reduction was 57.7% per dialysis session. 10 out of the 13 cases recovered sufficient renal function to become independent of dialysis. There were no major changes in albumin levels using an infusion protocol of 2 50-mL vials of 20% albumin at the end of the dialysis session. Combination treatment with chemotherapy and long dialysis with HCO filters was effective in reducing the sFLC levels and recovering sufficient renal function in 77% of cases. With HCO filters, significant cost savings are achieved, contrary to what was previously believed. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  16. Bone marrow uptake of 99mTc-MIBI in patients with multiple myeloma

    International Nuclear Information System (INIS)

    Fonti, R.; Del Vecchio, S.; Zannetti, A.; Di Gennaro, F.; Pace, L.; Salvatore, M.; De Renzo, A.; Catalano, L.; Califano, C.; Rotoli, B.

    2001-01-01

    In a previous study, we showed the ability of technetium-99m methoxyisobutylisonitrile ( 99m Tc-MIBI) scan to identify active disease in patients with multiple myeloma (Eur J Nucl Med 1998; 25: 714-720). In particular, a semiquantitative score of the extension and intensity of bone marrow uptake was derived and correlated with both the clinical status of the disease and plasma cell bone marrow infiltration. In order to estimate quantitatively 99m Tc-MIBI bone marrow uptake and to verify the intracellular localization of the tracer, bone marrow samples obtained from 24 multiple myeloma patients, three patients with monoclonal gammopathy of undetermined significance (MGUS) and two healthy donors were studied for in vitro uptake. After centrifugation over Ficoll-Hypaque gradient, cell suspensions were incubated with 99m Tc-MIBI and the uptake was expressed as the percentage of radioactivity specifically retained within the cells. The cellular localization of the tracer was assessed by micro-autoradiography. Twenty-two out of 27 patients underwent 99m Tc-MIBI scan within a week of bone marrow sampling. Whole-body images were obtained 10 min after intravenous injection of 555 MBq of the tracer; the extension and intensity of 99m Tc-MIBI uptake were graded using the semiquantitative score. A statistically significant correlation was found between in vitro uptake of 99m Tc-MIBI and both plasma cell infiltration (Pearson's coefficient of correlation r=0.69, P 99m Tc-MIBI inside the plasma cells infiltrating the bone marrow. Therefore, our findings show that the degree of tracer uptake both in vitro and in vivo is related to the percentage of infiltrating plasma cells which accumulate the tracer in their inner compartments. (orig.)

  17. Percutaneous Vertebroplasty for Pain Management in Patients with Multiple Myeloma: Is Radiofrequency Ablation Necessary?

    Energy Technology Data Exchange (ETDEWEB)

    Orgera, Gianluigi [Sapienza Rome University, Department of Radiology, S. Andrea Hospital (Italy); Krokidis, Miltiadis, E-mail: mkrokidis@hotmail.com [Cambridge University Hospitals NHS Trust, Department of Radiology (United Kingdom); Matteoli, Marco; Varano, Gianluca Maria [Sapienza Rome University, Department of Radiology, S. Andrea Hospital (Italy); La Verde, Giacinto [Sapienza Rome University, Department of Medical Oncology, S. Andrea Hospital (Italy); David, Vincenzo; Rossi, Michele [Sapienza Rome University, Department of Radiology, S. Andrea Hospital (Italy)

    2013-05-08

    PurposeThis study was designed to investigate the added role of radiofrequency ablation (RFA) to vertebroplasty on the pain management of patients with multiple myeloma (MM).MethodsThirty-six patients (51–82 years) with vertebral localization of MM were randomly divided into two groups: 18 patients (group A) who underwent RFA and then vertebroplasty, and 18 patients (group B) who underwent only vertebroplasty. Primary endpoints were technical success and pain relief score rate measured by the visual analogue pain scores (VAS) and Roland–Morris Questionnaire (RMQ); secondary endpoint was the amount of administered analgesia. Survival and complications were compared.ResultsTechnical success was 100 % in both groups. The VAS score (at 24 h and 6 weeks postprocedure) decreased in equal manner for both groups from a mean of 9.1–3.4 and 2.0 for group A and from a mean of 9.3–3.0 and 2.3 for group B; RMQ mean score was 19.8 for group A and 19.9 for group B and decreased to a mean of 9.6 and 8.2 for group A and 9.5 and 8.7 for group B. The amount of medication was equally decreased in the two groups. No statistically significant difference was noted. No major complication occurred and two patients died from other causes.ConclusionsThe use of percutaneous vertebroplasty alone appears to be effective for the pain management of the patients with vertebral involvement of multiple myeloma. The use of RFA that includes cost and time does not offer any clear added benefit on the midterm pain management of such patients.

  18. Iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) imaging of multiple myeloma: initial clinical efficiency results

    International Nuclear Information System (INIS)

    Takasu, Miyuki; Tani, Chihiro; Sakoda, Yasuko; Ishikawa, Miho; Tanitame, Keizo; Date, Shuji; Akiyama, Yuji; Awai, Kazuo; Sakai, Akira; Asaoku, Hideki; Kajima, Toshio

    2012-01-01

    To evaluate the effectiveness of the iterative decomposition of water and fat with echo asymmetric and least-squares estimation (IDEAL) MRI to quantify tumour infiltration into the lumbar vertebrae in myeloma patients without visible focal lesions. The lumbar spine was examined with 3 T MRI in 24 patients with multiple myeloma and in 26 controls. The fat-signal fraction was calculated as the mean value from three vertebral bodies. A post hoc test was used to compare the fat-signal fraction in controls and patients with monoclonal gammopathy of undetermined significance (MGUS), asymptomatic myeloma or symptomatic myeloma. Differences were considered significant at P 2 -microglobulin-to-albumin ratio were entered into the discriminant analysis. Fat-signal fractions were significantly lower in patients with symptomatic myelomas (43.9 ±19.7%, P 2 -microglobulin-to-albumin ratio facilitated discrimination of symptomatic myeloma from non-symptomatic myeloma in patients without focal bone lesions. circle A new magnetic resonance technique (IDEAL) offers new insights in multiple myeloma. (orig.)

  19. Bone marrow immunoscintigraphy using technetium-99m anti-granulocyte antibody in multiple myeloma

    International Nuclear Information System (INIS)

    Sohn, Sang-Kyun; Kim, Dong-Hwan; Park, So-Hyang; Ahn, Byeong-Cheol; Lee, Sang-Woo; Chun, Kyung-Ah; Kim, Jung-Gyun; Lee, Kyu Bo; Lee, Jaetae; Song, Hong-Suk

    2002-01-01

    Conventional skeletal radiography and bone scan have certain limitations in the initial evaluation of bone and bone marrow lesions in multiple myeloma (MM). In this study we investigated the value of bone marrow immunoscintigraphy (BMIS) using anti-granulocyte monoclonal antibody (AGA) for the diagnosis of bone involvement of MM, in comparison with bone scan and skeletal radiography. Whole-body BMIS using technetium-99m-labelled AGA was performed in 22 MM patients (15 male, 7 female) and the imaging findings compared with those of skeletal radiography and 99m Tc-methylene diphosphonate bone scan. The findings of bone marrow aspiration and serum biochemical findings were also compared with BMIS findings. Abnormal findings of BMIS were defined as presence of a focal photon defect in the axial skeleton or expansion of peripheral bone marrow. A total of 124 focal lesions were detected in 19 subjects (86%) by skeletal radiography, bone scan or BMIS. BMIS detected 92 lesions (74%) in 19 subjects, whereas skeletal radiography detected 58 focal lesions (47%) in 14 and bone scan 40 lesions (32%) in 11. Fifty-one (41%) of the 124 lesions were only seen on BMIS. Spine and pelvic lesions were better visualised by BMIS, whereas skull lesions were better seen with skeletal radiography, and bone scan detected more lesions in the ribs. Marrow expansion was noted in 15 subjects (68%) on BMIS, and its grade correlated with marrow cellularity and myeloma cell percentage in bone marrow aspirates (P=0.0055 and P=0.0541, respectively). BMIS revealed abnormal lesions in one of three stage II patients and 17 out of 19 stage III patients. The number of lesions of the thoracolumbar vertebrae on BMIS was correlated with cellularity (P=0.0393), but not with myeloma cell percentage (P=0.1262). These findings suggest that the results of BMIS with 99m Tc-labelled AGA correlate with clinical stage, and thus reflect the functional status of bone marrow in MM patients. BMIS might be useful for the

  20. Multiple myeloma in Niger Delta, Nigeria: complications and the outcome of palliative interventions

    Science.gov (United States)

    Nwabuko, Ogbonna Collins; Igbigbi, Elizabeth Eneikido; Chukwuonye, Innocent Ijezie; Nnoli, Martin Anazodo

    2017-01-01

    Background Multiple myeloma (MM) is one of the hematological malignancies that require palliative care. This is because of the life-threatening nature and the suffering associated with the illness. The aim of this study is to bring to the fore the complications experienced by people living with MM in the Niger-Delta region of Nigeria and the outcome of various palliative interventions. Methods This was a 10-year multi-center retrospective study of 26 patients diagnosed and managed in three major centers in the Niger-Delta region of Nigeria from January 2003 to December 2012. Information on the clinical, laboratory, radiological data, and palliative treatment was obtained at presentation and subsequently at intervals of 3 months until the patient was lost to follow-up. Result The mean duration from onset of symptoms to diagnosis was 13.12 months (95% CI, 6.65–19.58). A total of 16 (61.5%), eight (30.8%), and two subjects (7.7%) presented in Durie–Salmon (DS) stages III, II, and I, respectively. The complications presented by patients at diagnoses included bone pain (84.6%), anemia (61.5%), nephropathy (23.1%), and hemiplegia (35%). All the patients received analgesics, while 50.0% received blood transfusion, 56.7% had surgery performed, 19% had hemodialysis, and 3.8% received radiotherapy. A total of 10 (38%) patients benefited from bisphosphonates (BPs). A total of 57.6% of patients were on melphalan–prednisone (MP) double regimen, while 19% and 8% patients were on MP–thalidomide and MP–bortezomib triple regimens, respectively. A total of 3.8% of patients at DS stage IIIB disease had autologous stem-cell transplantation (ASCT). Only 7.6% of the myeloma patients survived up to 5 years post diagnosis. The overall mean survival interval was 39.7 months (95% CI, 32.1–47.2). Conclusion Late diagnosis and inadequate palliative care account for major complications encountered by MM patients in the Niger-Delta region of Nigeria. This could be responsible for