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Multiple myeloma is a malignant disorder which is characterized by an uncontrolled proliferation of plasma cells in bone marrow. Primary amyloidosis can either arise idiopathically or can be associated with plasma cell discrasia (1,2). Here we present a patient with amyloidosis of the tongue which developed as a complication of multiple myeloma . Case Report A 73-year-old man admitted to our clinic with macroglossia and asymptomatic multiple ulcerated nodular lesions on his tongue which first appeared 4 months ago and enlarged gradually. He complained of difficulty in speech and swallowing solid foods. His past medical history revealed multiple myeloma which was diagnosed one year ago and he was still being treated with pulsed courses of vincristine, adriamycine, dexamethasone and pamidronate disodium. His dermatologic examination revealed ...

Published by the International Myeloma Foundation (UK) April 2003 2nd Floor, 31 York Place Edinburgh EH1 3HP Tel (Admin): (44) 0131 557 3332 Myeloma Freephone Helpline: 0800 980 3332 Fax: (44) 0131 556 9720 E-mail:TheIMF@ myeloma .org.uk Website: www. myeloma .org.uk Charity Registration Number: SC 026116 Company Number: 190563 www. myeloma .org.uk Helpline 0800 980 3332 Page 2 Clinical Studies and Myeloma - Your Essential Guide Page 3 This guide is for people with myeloma , their families and others who care for them. It aims to answer the main questions that people may have about clinical studies, also known as clinical trials. What is a clinical study? Why are clinical studies important? How are clinical studies carried out? What are the different types and phases of clinical ...

MULTIPLE MYELOMA Pennsylvania Department of Health - Pennsylvania Cancer Incidence and Mortality 2000 - Page 196 Incidence rates for multiple myeloma reported from the National Cancer Institute's SEER Program show the highest risks in blacks. The 1996-2000 average annual age-adjusted incidence rates for Pennsylvania showed the same relationship. The average annual rates for black male and black female residents were 13.2 and 9.9, respectively, compared to 5.8 for white males and 4.0 for white females. The 1996-2000 average annual age-adjusted incidence rate for males (6.4 per 100,000) was over 45 percent higher than the rate for females (4.4). Multiple myeloma accounted for 741 cancer cases diagnosed among Pennsylvania residents in 2000. Annual age-adjusted incidence rates between 1991 and 2000 have generally been on the increase for both black males and black females. Among whites, the rates have been somewhat ...

myeloma Supportive Care in Myeloma T.J.LITTLEWOOD London June 2003 Complications of Myeloma Bone pain Anaemia Kidney damage Infection Supportive Care in Myeloma Key aspects Chemotherapy Prevention and treatment of complications Palliative care Emotional support Supportive care in Patients with Myeloma MM Aged 62 RAF officer Presented with back pain and fatigue Supportive care in Patients with Myeloma Investigations Anaemic Hb 9.3g/dl Myeloma protein level (IgG) 45g/l Urine protein (BJP) 1.5g/24h ...

MULTIPLE MYELOMA - FIRST VISIT EVALUATION 1. History and physical examination 2. CBC and differential, Peripheral blood smear 3. Serum biochemistry including creatinine, electrolytes, uric acid, calcium, total protein, alkaline phosphatase, C-reactive Protein, LDH 4. Serum ß 2 microglobulin level and C-Reactive Protein (CRP) 5. Serum protein electrophoresis (SPEP), immunofixation (IFE) and quantitative immunoglobulins (QIG) 6. 24 hour urine collection for creatinine clearance, 24 hour excretion of protein, urine protein electrophoresis (UPEP) and immunofixation (IFE) 7. Bone marrow aspiration and biopsy to be sent for morphology and flowcytometry (and plasma cell labeling index when this becomes available in the future), cytogenetic analysis, and FISH analysis for chromosome 13 8. Complete skeletal survey including skull and long bones ...

Multiple Myeloma and Family History of Cancer among Blacks and Whites in the U.S. Linda Morris Brown, M.P.H. 1 Martha S. Linet, M.D. 1 Raymond S. Greenberg, M.D. 2 Debra T. Silverman, Sc.D. 1 Richard B. Hayes, Ph.D. 1 G. Marie Swanson, Ph.D. 3 Ann G. Schwartz, Ph.D. 4 Janet B. Schoenberg, M.P.H. 5 Linda M. Pottern, Ph.D. 6 Joseph F. Fraumeni, Jr., M.D. 1 1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. 2 Medical University of South Carolina, Charleston, South Carolina. 3 Cancer Center, Michigan ...

Center for Environmental Health Studies (617) 482-9485 44 Farnsworth Street, Boston, MA 02210 http://www.jsi.com * Findings were statistically significant (strong evidence) + Evidence of a dose-response relationship (strongest evidence) Page 67 Multiple Myeloma (MM) and Exposure to Ionizing Radiation Summary : Studies conducted at the Los Alamos National Laboratory and other nuclear facilities, as well as those exposed to radiation from the atomic bomb suggest an increased likelihood of developing multiple myeloma for those who have been exposed to ionizing radiation. These findings are consistent with the determination of the National Research Council’s BEIR V committee that multiple myeloma has been associated with exposure to ionizing radiation. Multiple myeloma is a “specified” cancer under the EEOICPA. ...

Diagnostic radiation and the risk of multiple myeloma (United States) Juliet L. Hatcher 1, *, Dalsu Baris 2 , Andrew F. Olshan 1 , Peter D. Inskip 2 , David A. Savitz 1 , G. Marie Swanson 3 , Linda M. Pottern 4 , Raymond S. Greenberg 5 , Ann G. Schwartz 6 , Janet B. Schoenberg 7 & Linda Morris Brown 2 1 Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA; 2 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA; 3 Michigan Cancer Foundation, Detroit, MI, USA (currently with the Cancer Center, Michigan State University, E. Lansing, MI, USA); 4 National Cancer Institute, Bethesda, MD, USA (currently with the Women's ...

Diet and nutrition as risk factors for multiple myeloma among blacks and whites in the United States Linda Morris Brown 1, *, Gloria Gridley 1 , Linda M. Pottern 2,a , Dalsu Baris 1 , Christine A. Swanson 2,b , Debra T. Silverman 1 , Richard B. Hayes 1 , Raymond S. Greenberg 3,c , G. Marie Swanson 4,d , Janet B. Schoenberg 5 , Ann G. Schwartz 4 & Joseph F. Fraumeni, Jr 1 1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Executive Plaza South, Room 8026, 6120 Executive Blvd. MSC 7244, Bethesda, MD 20892-7244, USA; 2 National Cancer Institute, Bethesda MD, USA; 3 Rollins School of Public Health, Emory University, Atlanta, GA, USA; ...

MULTIPLE MYELOMA BOTH SEXES TABLE 3A. -- Characteristics of persons reported to the Danish Cancer Registry with an initial multiple myeloma , 1943-80+ _ Category Male Female Total _ No. with first primary cancer* 1,867 1,615 3,482 No. who developed a second primary cancer 45 23 68 Average age at diagnosis of first cancer, yr 65 67 66 Average yr of diagnosis of first cancer 1967 1967 1967 Person-yr of follow-up 3,882 3,566 7,448 Average follow-up, yr 2.1 2.2 2.1 Percent given radiotherapy for first cancer 28 28 28 _ + ICD-7 code = 203. * Number excludes all persons who survived less than 2 mo after the diagnosis of their first primary cancer or who developed a simultaneous cancer during this period. First primary cancers diagnosed only at autopsy or by death certificate are also excluded as are in situ cancers. TABLE 3B. -- Microscopic confirmation among persons who developed ...

MULTIPLE MYELOMA BOTH SEXES TABLE 3A. -- Characteristics of persons reported to the Connecticut Tumor Registry with an initial multiple myeloma , 1935-82+ _ Category Male Female Total _ No. with first primary cancer* 1,107 1,142 2,249 No. who developed a second primary cancer 46 27 73 Average age at diagnosis of first cancer, yr 64 67 65 Average yr of diagnosis of first cancer 1968 1969 1969 Person-yr of follow-up 2,258 2,247 4,505 Average follow-up, yr 2.0 2.0 2.0 Percent given radiotherapy for first cancer 39.7 36.6 38.1 _ + ICD-O morphology codes = 9730-9731. * Number excludes all persons who survived less than 2 mo after the diagnosis of their first primary cancer or who developed a simultaneous cancer during this period. First primary cancers diagnosed only at autopsy or by death certificate are also excluded as are in situ cancers. TABLE 3B. -- Microscopic confirmation ...

Cancer Mortality Rates by State Economic Area (Age-adjusted 1970 US Population) Multiple Myeloma : White Males, 1970-94 US = 3.10/100,000 3.70-4.72 (highest 10%) 3.52-3.69 3.40-3.51 3.29-3.39 3.19-3.28 3.07-3.18 2.96-3.06 2.82-2.95 2.63-2.81 1.61-2.62 (lowest 10%) Sparse data (1 SEA; 0.01% of deaths)

Cancer Mortality Rates by State Economic Area (Age-adjusted 1970 US Population) Multiple Myeloma : Black Females, 1970-94 US = 4.43/100,000 5.76-8.48 (highest 10%) 5.18-5.75 4.96-5.17 4.74-4.95 4.54-4.73 4.39-4.53 4.10-4.38 3.84-4.09 3.42-3.83 1.84-3.41 (lowest 10%) Sparse data (309 SEAs; 5.70% of deaths)

Cancer Mortality Rates by State Economic Area (Age-adjusted 1970 US Population) Multiple Myeloma : White Males, 1950-69 US = 1.84/100,000 2.44-4.18 (highest 10%) 2.16-2.43 2.04-2.15 1.90-2.03 1.81-1.89 1.70-1.80 1.60-1.69 1.47-1.59 1.27-1.46 0.69-1.26 (lowest 10%) Sparse data (53 SEAs; 1.40% of deaths)

Cancer Mortality Rates by State Economic Area (Age-adjusted 1970 US Population) Multiple Myeloma : Black Males, 1970-94 US = 6.49/100,000 8.84-20.58 (highest 10%) 7.83- 8.83 7.47- 7.82 7.13- 7.46 6.86- 7.12 6.40- 6.85 5.98- 6.39 5.68- 5.97 5.19- 5.67 3.25- 5.18 (lowest 10%) Sparse data (292 SEAs; 5.00% of deaths)

MOLECULAR PROFILE OF THE ANTI- MYELOMA ACTIVITY OF HISTONE DEACETYLASE (HDAC) INHIBITORS: BIOLOGICAL AND THERAPEUTIC IMPLICATIONS. Constantine S. Mitsiades 1,2 , Nicholas S. Mitsiades 1,2 , Ciaran J. McMullan 1,2 , Vassiliki Poulaki 3 , Reshma Shringarpure 1,2 , Teru Hideshima 1,2 , Masaharu Akiyama 1,2 , Dharminder Chauhan 1,2 , Nikhil Munshi 1,2 , Xuesong Gu 4 , Charles Bailey 4 , Marie Joseph 4 , Towia A. Libermann 4 , Victoria M. Richon 5 , Paul A. Marks 5,6 , Kenneth C. Anderson 1,2 . 1. Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115 2. Department ...

305 Results of Reduced Intensity Conditioning Allogeneic Transplantation in Myeloma – A report from the EBMT C. Crawley, R.Szydlo, M. Lalancette, G.Juliusson, A. Shimoni, A. Nagler, T Ruutu, M.Michallet, J Boiron, K.Peggs, J. Sierra, H.Einsele, R.Chopra, A. Carella, A. Zander, A. Gratwohl, H. Greinix, J. Cavenagh, F. Garban, D. Caballero, D.Niederwieser, G. Gahrton and J.Apperley for the Chronic Leukaemia Working Party of the EBMT. The more widespread use of conventional allogeneic transplant for myeloma has been limited by the substantial procedure related mortality. Reduced intensity conditioning has been widely adopted with the demonstration of its feasibility and apparent lower mortality. Evidence for efficacy is limited, as the majority of series are small and frequently diagnostically heterogeneous. Data were collected for myeloma patients from 38 EBMT centres on a total of 256 transplants ...

303 Long-Term Follow-Up of Previously Untreated Symptomatic Myeloma Patients Treated with Myeloablative Therapy and Sibling-Matched Allogeneic Transplantation of the SWOG Study 9321. Bart Barlogie, Jason McCoy, Hilliard Lazarus, Stephen Forman, Fred Appelbaum, Kenneth C. Anderson, Robert Kyle, John Crowley. Myeloma Institute for Research and Therapy (MIRT), University of Arkansas for Medical Sciences, Little Rock, AR, USA; Cancer Research And Biostatistics (CRAB), Fred Hutchinson Cancer Center, Seattle, WA, USA; Ireland Cancer Center, University Hospitals of Cleveland, Cleveland, Ohio; City of Hope National Medical Center, Duarte, CA, USA; Dana Farber Cancer Institute, Boston, MA, USA; Mayo Clinic, Rochester, MN, USA A long-term follow-up is provided on the myeloablative sibling-matched allotransplant arm of a multi-institutional randomized study which enrolled 38 newly diagnosed patients ...

P10.2.4 SINGLE VS. TANDEM AUTOLOGOUS TRANSPLANTS IN MULTIPLE MYELOMA : ITALIAN EXPERIENCE. Michele Cavo, Elena Zamagni, Claudia Cellini, Patrizia Tosi, Sonia Ronconi, Delia Cangini, Paola Tacchetti, Antonio De Vivo, Roberto Massimo Lemoli, Monica Benni, Francesca Bonifazi, Mauro Fiacchini, Maria Rosa Motta, Simona Rizzi, Michele Baccarani and Sante Tura, writing committee of the “Bologna 96” clinical trial. Institute of Hematology and Medical Oncology “Seràgnoli”, University of Bologna, Italy. Over the last decade, high-dose therapy (HDT) with autologous hematopoietic stem cell support has enjoyed wider application for the management of multiple myeloma (MM). Results of a prospective randomized study by the Intergroupe Francais du Myélome (IFM) (1) and of a retrospective population-based study by the Nordic Myeloma Study Group (2) demonstrated superior outcome with autologous ...

P10.2.1 DOUBLE AUTOLOGOUS TRANSPLANTATION IMPROVES SURVIVAL OF MULTIPLE MYELOMA PATIENTS : FINAL ANALYSIS OF A PROSPECTIVE RANDOMIZED STUDY OF THE "INTERGROUPE FRANCOPHONE DU MYELOME" (IFM 94). Michel Attal, Jean-Luc Harousseau, Thierry Facon, François Guilhot, Chantal Doyen, Jean-Gabriel Fuzibet, Mathieu Monconduit, Cyril Hullen, Denis caillot, Reda Bouabdallah, Laurent Voillat, Jean-Jacques Sotto, Bernard Grosbois and Regis Bataille For the IFM. High dose therapy supported with autologous stem cell transplantation has been introduced in the management of aggressive myeloma and promising survivals from single institutions, case-controlled and randomized studies have been reported. However after a single transplant (ST), almost all patients ultimately relapse. In order to improve these results the role of double transplantation (DT) has been evaluated in uncontrolled studies. ...

P10.2.5 SINGLE VS. TANDEM AUTOLOGOUS TRANSPLANTATION IN MULTIPLE MYELOMA : THE GMMG EXPERIENCE Goldschmidt H On behalf of the German-Speaking Myeloma Multicenter Group, GMMG High-dose (HD) therapy followed by autologous stem cell transplantation (ASCT) has improved event-free (EFS) and overall survival (OS) in multiple myeloma (MM), but nonetheless virtually all patients eventually relapse. Single center experience of the Arkansas group has indicated that total therapy including tandem ASCT improves clinical outcome further, and results of the French IFM-group have shown in a randomized trial that MM patients benefit from tandem ASCT. No significant benefit of double ASCT could be demonstrated in the studies performed by the HOVON-group, the Bologna-group and in the MAG95-study. Melphalan without total body irradiation is currently considered as the best high-dose therapy regimen. Between ...

THE ECONOMIC IMPACTS OF THE MYELOMA INSTITUTE FOR RESEARCH AND THERAPY ACTIVITIES ON THE STATE OF ARKANSAS Dennis P. Robinson, Ph.D. Institute for Economic Advancement University of Arkansas at Little Rock April 4, 2003 This report provides an analysis of the economic impacts of activities at the Myeloma Institute for Research and Therapy on the economy of the state of Arkansas. Report Highlights • The Institute raises almost $2 million per year in philanthropy dollars. • Over the past 14 years, the Institute has brought in over $30 million in out-of- state research grants. • The Institute employs roughly 285 people performing clinical care, research, and administrative functions. • In one year, over 1,600 patients come to the Institute. Very few of these are Little Rock residents. On average, 1.07 people ...

-59- Suggestion: Read the chapter Blood" and "Multiple Myeloma " prior to reading this. WALDENSTROM'S MACROGLOBULINEMIA This disease, like multiple myeloma , is also a monoclonal gammopathy. The abnormal globulin is a large gammaglobulin called IgM. The "M" is a so-called macroglobulin that means that it is about five times the size of other immunoglobulins. The disease is chemically and biologically related to multiple myeloma but is much different in other respects. In multiple myeloma there is usually a great deal of bone disease, but in Waldenstrom's the bones may be normal - without fractures or pain. In Waldenstrom's the liver and spleen are often enlarged, but the kidneys may not be affected as they are in multiple myeloma . Perhaps the most difficult aspect of this disease is that there may be excessive clotting of blood, leading to strokes and clots in important arteries and veins. People with monoclonal ...

P12.1.2 THE ROLE OF ARSENIC TRIOXIDE IN MULTIPLE MYELOMA Mohamad Hussein, MD Multiple Myeloma Research Program, Cleveland Clinic Cancer Center, Cleveland, OH, USA Introduction In recent years the delineation of the different cytokines and cellular interactions influencing plasma cells has provided the drug industry with a rationale to develop target specific molecules. Multiple Myeloma is incurable as a result of the complex, redundant and effective mechanisms maintaining the plasma cell’s survival. Effectively influencing the malignant plasma cell microenvironment to modulate and/or reset to a normal level of activity could change the disease into a chronic process. Molecules that act on different levels of the immune system, or a combination of such agents will be needed to overcome the redundancy and positive feedback loops in the myeloma cell support system. These molecules ...

ROLE OF IMMUNOMODULATORY DRUGS IN MULTIPLE MYELOMA Kenneth C. Anderson, M.D. Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA 02115 We have carried our preclinical and clinical studies of the immunomodulatory drug (IMiD) Revimid. It induces growth arrest or apoptosis of drug resistant multiple myeloma (MM) cell lines and patient cells; abrogates binding of MM cells to bone marrow stromal cells (BMSCs) and extracellular matrix proteins; inhibits production cytokines (IL-6, IGF-1, VEGF) which confer growth, survival, and drug resistance in the BM; and stimulates patient anti-MM NK cell and ADCC. Revimid triggers activation of caspase 8, enhances MM cell sensitivity to Fas-induced apoptosis, and downregulates NF-_B activity as well as expression of cellular inhibitor of apoptosis protein-2 and FLICE inhibitor protein. It potentiates the activity of TRAIL/Apo2L, ...

P2.5 MOLECULAR CYTOGENETICS OF MYELOMA BIOLOGY: CLINICAL AND PROGNOSTIC IMPLICATIONS Rafael Fonseca, and Philip R Greipp Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, 55905 1. INTRODUCTION: Cytogenetic and genetic abnormalities are thought to be critical for the pathogenesis of multiple myeloma (MM). We have embarked on the study of genetic abnormalities in MM to better understand their relationship to pathogenesis and clinical outcome. We have studied these abnormalities using a combination of classical molecular techniques, molecular cytogenetics (cIg-FISH), conventional karyotype analysis and novel genomic platforms (gene expression analysis). We have carefully considered the implications of specific chromosome abnormalities for a) the different stages of the disease, and b) evidence of ongoing genomic evolution and heterogeneity. 2. IgH TRANSLOCATIONS: The work done by ...

326 ThaCyDex in relapsed/refractory multiple myeloma . Gonzalez-Porras, JR; Garcia-Sanz, R; Polo-Zarzuela, M; Sureda, A; Barrenetxea, M; Alegre-Amor, A; Grande-García, C; Pérez R; Gutierrez-Perez, O; Vargas-Pabón, M; Del Campo, M; Hernandez, J; San Miguel; JF. Hematology Departament. University Hospital of Salamanca. Group GEMM. Spain Introduction : The association of Thalidomide, Cyclophosphamide and Dexamethasone (ThaCyDex) has been shown to be effective in a short series of relapsed/refractory multiple myeloma (MM). However, its real efficacy in large series of patients. has not been analysed moreover in some of these schemes cyclophosphamide was used i.v. and toxicity was rather high. In the present work we have evaluated the efficacy and the tolerability of ThaCyDex in oral formulations in a series of 59 patients. Material and methods : The protocol included the administration of thalidomide ...

P12.1.3 THE PROTEASOME INHIBITOR BORTEZOMIB IN MULTIPLE MYELOMA (MM) Paul G. Richardson, MD, Teru Hideshima, MD, and Kenneth C. Anderson MD In MM cell lines and patient (pt) MM cells in vitro, bortezomib (VELCADETM, formerly PS-341) inhibited proliferation, prevented binding to bone marrow stromal cells, induced apoptosis, and produced additive cytotoxicity with conventional treatment, including dexamethasone (Dex).1,2 Additionally, bortezomib inhibited tumor growth, induced apoptosis, and reduced angiogenesis in a murine MM xenograft model in vivo.3 As part of a phase I study, pts with MM (n=8) were treated with bortezomib (0.4– 1.38mg/m2, 2x/w x 4 q6w) and significant antitumor activity was seen, including 1 CR.4 In a phase II trial of bortezomib of heavily pre-treated relapsed and refractory MM pts (n=202, median number of prior regimens=6), bortezomib (1.3mg/m2 2x/w x2 q3w) induced ...