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March/April 2004, Vol. 11, No. 2 Cancer Control 119 No significant relationship exists between the author and the compa- nies/organizations whose products or services may be referenced in this article. Stem Cell Transplantation for Multiple Myeloma Cristina Gasparetto, MD Background: Multiple myeloma (MM) is the second most common hematologic malignancy, affecting approximately 14,000 new patients in the United State per year. The median overall survival is 5 years, and cure is a realistic goal for only a small minority of patients. Methods: A review of the literature was conducted that focused on treatment strategies for MM involving administration of high doses of chemotherapy followed by autologous or allogeneic hematopoietic stem cell transplant. Results: For over three decades, the standard treatment for MM has been a regimen of melphalan and prednisone ...

. Your Treatment Team Your Treatment Team LEADING THE SEARCH FOR A CANCER CURE Sylvester Comprehensive Cancer Center 1475 NW 12th Avenue • Miami, Florida 33136 305-243-1000 1-800-545-2292 www.sylvester.org An Equal Opportunity/Affirmative Action University . Leukemia, Lymphoma, and Myeloma UM/Sylvester’s leukemia, lymphoma, and myeloma treatment team includes highly trained hematologist/oncologists and radiation oncologists, all widely recognized for their work in the field. The team is supported by a group of basic science and clinical researchers who work diligently to learn more about these diseases—their detection and treatment, as well as options to improve each patient’s quality of life. As is true with all cancer specialties at UM/Sylvester, the blood-related ...

Myeloma Cell Line Preparation Introduction Several different mouse and human myeloma cell lines are available for use in hybridoma formation. However, only a very few are used frequently. The mouse myeloma cell line that is used most often is the same one we will be using in this course. It is designated: P3x63,Ag8.653 ( ATCC CRL-1580 ) Although some specially designed lines are used for unique applications, this line has been used for years to produce most of the monoclonal antibodies used in clinical and research applications. Thus, we are using this cell line to give you experience in handling the line that you are likely to encounter if you do this type of work in Co-op or after graduation. This cell line is a non-secretor (i.e., does not produce antibodies on its own), is 8- azaguanine resistant (important during selection of hybridoma cells), is derived from the Balb/c ...

Fusion of Lymphocytes and Myeloma Cells Procedure 1. Prepare a suspension of spleen cells in Hank's Balanced Salt Solution (HBSS), following the procedures in Preparation of Lymphocyte Cell Suspension , except resuspend the pellet of cells in 5ml of sterile DMEM without serum . 2. Prepare a suspension of myeloma cells as follows: a. Transfer a culture of myeloma cells from a large flask to a 50 ml sterile centrifuge tube (be sure to gently dislodge the myeloma cells from the bottom surface of the flask before transferring). b. Centrifuge for 4-5 minutes at 200 x g (setting of 3 on an IEC centrifuge). c. Discard the supernate. d. Add 5 ml of sterile DMEM without serum to the cell pellet. Resuspend the cells with a sterile pasteur pipette and sterile pipette bulb. 3. Determine the number of viable lymphocytes/ml and the ...

Fusion of B-lymphocytes and Myeloma Cells B-lymphocyte - produces antibodies, but cannot survive in tissue culture beyond 7-10 days myeloma cell - doesn't produce antibodies, but can survive in tissue culture "indefinitely" fusion combines these two characteristics into one cell (a "hybrid") B-lymphocyte (from spleen) + myeloma cell (from cultured cell line) add 50% polyethylene glycol (PEG) (fuses cell membranes) two separate nuclei in one cell membrane two nuclei will join (temporary tetraploid) chromosomes will mix together subsequent cell division (cells "return" to diploid nucleus) some "hybrids" will have the desired mix of chromosomes antibody specificity/antibody production + "immortality" in tissue culture optimum fusion procedure - favors production of desired hybrids cell ratio of 2 lymphocytes/1 myeloma cell (steps 1-4) ...

A Case-control Study of Multiple Myeloma in Decatur, Illinois Authors Celan J. Alo, M.D. Connie Austin, D.V.M., M.P.H., Ph.D. Holly L. Howe, Ph.D. Illinois Department of Public Health Page 2 Suggested Citation: Alo CJ, Austin C, Howe HL . A Case-control Study of Multiple Myeloma in Decatur, Illinois. Epidemiologic Report Series 97:3. Springfield, IL: Illinois Department of Public Health, February 1997. Copyright information: All material in this report is in the public domain and may be reproduced or copied without permission; citation is to source, however, is appreciated. Page 3 Abstract Background: A cancer cluster investigation that was conducted in ZIP code 62521 of the city of Decatur in Macon County, Illinois, showed a statistically significant excess of multiple myeloma cases for residents ...

1-3 MMRF Presents: MMRF Case Studies in Multiple Myeloma - An Online CME Program for Oncology/Hematology Professionals New Strategies in Transplantation Therapy Jean-Luc Harousseau, MD University of Nantes, Nantes Cedex, France November 25, 2003 Case Presentation: A 62-year gentleman presented with a 6-month history of back pain, initially alleviated with paracetamol, which increased markedly in the last 2 weeks. He has always been healthy, but he indicated some recent fatigue. He had no other symptoms. Physical examination was unremarkable. X-rays of the spine revealed diffuse osteoporosis. Laboratory evaluation revealed him to be anemic (hemoglobin level 9.8 grams per deciliter). The patient was admitted to the hospital and myeloma was diagnosed as evidenced by the patient having 55% plasma cells in the bone marrow; IgA kappa monoclonal protein in the blood, ...

Version 1.1 / February 2003 MYELOMA IX TRIAL PROTOCOL SUMMARY INDICATION Multiple myeloma requiring treatment (International Myeloma Working Group definition) in patients of all age groups. OBJECTIVES For ‘younger/fitter’ patients considered appropriate for high-dose chemotherapy Primary • To compare two induction regimens, CVAD (infusional) v C-Thal-Dex (CTD) (oral) • To compare two bisphosphonates, namely sodium clodronate (2 nd generation) v zoledronic acid (3 rd generation) • To assess the value of giving low-dose thalidomide in maintenance (versus no treatment) • To assess low-intensity conditioning (LIC) (non-ablative) allogeneic stem cell transplantation (‘mini-allograft’) following standard high-dose melphalan with autograft in patients with donors available. For ...

1-3 MMRF Presents: MMRF Case Studies in Multiple Myeloma - An Online CME Program for Oncology/Hematology Professionals Options for Salvage Therapy for Myeloma Patients Mohamad A. Hussein, MD Cleveland Clinic Multiple Myeloma Program October 28, 2003 Case Presentation: A 70-year-old African American diagnosed with stage IIIA multiple myeloma IgA ? type was treated with VAD (vincristine, doxorubicin, dexamethasone) x 4 cycles followed by autologous bone marrow transplant as initial therapy, which achieves a plateau phase. Twelve months following the transplant procedure, the patient complained of generalized weakness and bone pain. Further work-up showed the patient to have relapsed with increasing M protein from (2 gms/dL to 6 gms/dL), new lytic bone lesions, and back pain. An MRI of the spine showed the patient to have developed a compression fracture at the T6 and ...

September/October 2003, Vol.10, No.5 370 Cancer Control Trials of Arsenic Trioxide in Multiple Myeloma Mohamad A.Hussein, MD Background: Several reports on the use of arsenic trioxide (ATO), mainly in acute promyelocytic leukemia, have led to a renewed interest in ATO in the management of malignancies, especially those of hematologic origin such as multiple myeloma (MM). MM remains an incurable disease, with median survival rates of 4-6 years. Thus, newer treatments with good safety profiles are needed to improve the quality of responses, prolong progression, and increase overall survival. Method: The current state of the art regarding the role of ATO in the management of MM and the rationale for this consideration is reviewed. Results: Preclinical evidence suggests that one of the mechanisms in which ATO exerts its antimyeloma effect is by immunologic mechanisms. One such ...

Editorial C a n c e r C o n t r o l September/October 2003, Vol.10, No.5 Cancer Control 357 Multiple myeloma is a malig- nancy characterized by the prolif- eration of clonal plasma cells pref- erentially in the bone marrow. The second most common hematologic malignancy, this diagnosis is newly made in 35,000 persons yearly worldwide. Over 40 years ago, Bergsagel and others showed that a combina- tion of melphalan and prednisone was an effective chemotherapy reg- imen in myeloma , inducing responses in over 50% of newly diagnosed patients. For decades, this simple combination remained the standard treatment for myelo- ma since other chemotherapy regi- mens failed to show improved sur- vival when compared to it. It was not until 1995, when high-dose chemotherapy plus peripheral ...

Thalidomide and Its Derivatives: New Promise for Multiple Myeloma Donna Weber, MD Background: The combination of melphalan and prednisone has been accepted as standard treatment for multiple myeloma (MM) because most studies demonstrate only minimal survival benefit of combination chemotherapy regimens when compared with melphalan and prednisone. Despite modest gains with more intensive myeloablative regimens for certain subgroups, myeloma remains incurable. In 1999, investigators at the University of Arkansas reported the promising results of a phase II study of thalidomide in patients with resistant MM. Since then various trials of thalidomide alone, and in combination, have been tested in patients with resistant, and more recently, untreated MM. In addition, preliminary results of phase I studies of the immunomodulatory derivatives (IMiDs) of thalidomide have recently been reported. ...

September/October 2003, Vol.10, No.5 384 Cancer Control Farnesyltransferase Inhibitors and Their Role in the Treatment of Multiple Myeloma Rodrigo Santucci, MD, Paul A.Mackley, Saïd Sebti, PhD, and Melissa Alsina, MD Background: Ras mutations are among the most common oncogene mutations found in multiple myeloma (MM). Patients with mutated Ras are less likely to respond to chemotherapy and have a shortened median survival. Therefore, targeting Ras farnesylation may be a valuable approach to treatment of MM. R115777 (tipifarnib) is a potent farnesyltransferase inhibitor (FTI) presently undergoing phase II/III clinical trials. Methods: We reviewed the preclinical and clinical experience of FTIs as antineoplastic agents and describe their potential role in the treatment of MM. Results: FTIs are a novel group of agents that selectively inhibit farnesyltransferase, an enzyme responsible ...

1-4 MMRF Presents: MMRF Case Studies in Multiple Myeloma - An Online CME Program for Oncology/Hematology Professionals Novel Immunomodulatory Therapies in the Treatment of Multiple Myeloma Kenneth C. Anderson, MD Dana-Farber Cancer Institute September 16, 2003 Case Presentation: A 41-year-old schoolteacher developed progressive anemia and bone pain in 1989. She was found to have 4 g Bence Jones (BJ) proteinuria, 70% bone marrow plasmacytosis, and extensive lytic bone disease and was diagnosed with stage IIIA multiple myeloma . Although she has 2 siblings, neither one is histocompatible. She received 3 cycles of vincristine-doxorubicin-dexamethasone or (VAD) and pamidronate and then underwent autologous stem cell transplantation after high-dose melphalan therapy in 1990. She achieved partial response and remained progression free on pamidronate only. Due to rising BJ proteinuria ...

Things in the File Xcytrin demonstrated efficacy in preclinical trials against multiple myeloma cells in a report presented at the July meeting of the American Association for Cancer Research held in Washington D.C. The developer, Pharmacyclics, Inc., indicated they are working in collaboration with Northwestern University. The common name of the drug, motexafin gadolinium would be used as an injection. Some of you may recognize that gadolinium is used during the course of MRI investigations of MM patients to aid in the determination of the activity of the MM. Also of interest, a physicist working at the University of Wisconsin had suggested the potential for combining gadolinium with other drugs as having considerable potential in the treatment of cancer about a year ago. (July 2003) Things in the File (continued) The grapefruit and medications warnings have been making the rounds once more with more research ...

1-4 MMRF Presents: MMRF Case Studies in Multiple Myeloma - An Online CME Program for Oncology/Hematology Professionals The Refractory Patient: New Treatment Options Michael W. Schuster, MD Weill Medical College of Cornell University The New York Presbyterian Hospital August 19, 2003 Case Presentation: My name is Dr. Michael Schuster; I am the Director of the Bone Marrow and Blood Stem Cell Transplantation Program and a Professor of Clinical Medicine at the Center for Lymphoma and Myeloma at the New York Presbyterian Hospital/Weill Cornell Medical Center. The case that I am presenting is of a 54 year-old mechanic who was found to have an elevated protein level of 10.6 g/dL on an automated Chemistry 20 panel that was drawn at the time of a routine yearly physical examination at his family physician’s office. He had been having back pain for several months but had attributed ...

myeloma 1581 Case Presentation One 55 y/o African-American female presents with c/o shoulder pain. X-ray shows bony destruction of clavicle. Bx in 1985 with plasmacytoma. Treated w/ XRT(4600 rads) and MP X 3 but developed new lytic lesions in L3,L4 vertebral bodies. Treated with VAD x 4 cycles with good response Case one continued In 1988, she was found to have a sternal mass on CXR. XRT with 3000 cGy and Cytoxan (200 mg/m2 q week and prednisone 100 qod for 5 months. Monthly pamidronate Case one continued No events thru 2000. In fall of 2001, she was hospitalized with worsening creatinine and anemia. Skeletal survey negative, bone marrow biopsy with increased plasma cells but <10%. ?Sx due to CRI from HTN ...

If you are a multiple myeloma patient or caregiver, we would like you to join us as we attempt to help each other. Our meetings are held in London, usually on Wednesday afternoons. Please contact us for times and locations. Watch for meeting notices posted on the bulletin boards at the LRCC or on the LRCC website: www.lrcc.on.ca For more information or to be put in touch with other myeloma patients, please call: Becky Ross (London) (519) 641-7080 bucky03@hotmail.com Jim Barnes (Midwestern Ontario) (519) 887-6163 barnes@scsinternet.com or, to be placed on our mailing list, write: Jim Barnes, 40824 Cardiff Rd., RR#5, Brussels, ON N0G 1H0 Information and support for Multiple Myeloma patients and their caregivers provided through: BI-MONTHLY MEETINGS PEER SUPPORT CONTACT ...

Strategic Plan For Addressing the Recommendations of the Leukemia, Lymphoma, and Myeloma Progress Review Group LLM-PRG Strategic Plan October 2002 1 Page 2 Message From the Director October 2002 In 2001, hematologic cancers-- as a group the fourth most common cancer -- claimed the lives of 60,300 Americans, drained the financial and emotional resources of hundreds of thousands, and continued to resist our best efforts to find a cure. Despite these tragic consequences, we are nevertheless increasing our scientific knowledge of this group of blood-related cancers and are using that knowledge to help reduce the burden. This year the death toll from hematologic cancers is expected to be 58,300 Americans. Continued scientific inquiry will yield unprecedented amounts of vital information essential to eliminating these diseases. ...

1-4 MMRF Presents: MMRF Case Studies in Multiple Myeloma --an Online CME Program for Oncology/Hematology Professionals Prognostic Indicators for the Diagnosis of Multiple Myeloma Philip Greipp, MD Mayo Clinic, Rochester, MN May 13, 2003 Case Presentation: I'm Dr. Philip Greipp from the Mayo Clinic. I'm going to talk to you today about prognostic factors in multiple myeloma . First, I'd like to present to you a patient. A 48-year-old menopausal woman reports to her physician with symptoms of fatigue. She has been previously healthy except for osteopenia, for which she is taking Fosamax, 70 mg once a week, and also estrogen replacement therapy. She reports no back pain, no polydipsia, polyuria, no slurred speech, and no lethargy. Her family history is negative for hematologic malignancy. Examination revealed mild pallor. The rest of the exam was normal, including ...

1-3 MMRF Presents: MMRF Case Studies in Multiple Myeloma - An Online CME Program for Oncology/Hematology Professionals Supportive Therapies in the Management of Myeloma Heinz Ludwig, MD Wilhelminenspital, Vienna, Austria April 15, 2003 Case Presentation: I'm Heinz Ludwig, MD and I'm the director of the Department of Medicine and Medical Oncology at the Wilhelminenspital Hospital in Vienna, Austria. I am going to present you a case of a 63-year-old female patient with IgA myeloma . The patient presents with progressive disease, with diffuse bone pain, and weakness, fatigue, and exertional dyspnea. Her history is as follows: The patient presented with increasing pain in her lumbar sacral spine, and variable pain in her thoracic cage in 1998. Clinical investigation at that time revealed multiple myelomas, stage 3A, IgA kappa paraprotein. Bone marrow examination ...

Multiple Myeloma Page 2 Multiple Myeloma is a B-cell malignancy characterized by accumulation of monclonal plasma cells. The multiple myeloma colon produces a monolonal Ig (M protein) of specific heavy and light chain subtype that can be identified on serum or urine protein electrophoresis Page 3 Diagnostic Criteria I I Multiple Multiple Myeloma Myeloma Major Criteria Major Criteria 1. 1. Plasmacytoma Plasmacytoma on tissue biopsy on tissue biopsy 2. Bone Marrow 2. Bone Marrow plasmacytosis plasmacytosis with more than 30% plasma cells. with more than 30% plasma cells. 3. Monoclonal globulin spike on serum electrophoresis exceeding 3. Monoclonal globulin spike on serum electrophoresis exceeding 3.5 gm/dl for ...

1-4 MMRF Presents: MMRF Case Studies in Multiple Myeloma - An Online CME Program for Oncology/Hematology Professionals Treatment Strategies for Myeloma Bone Disease James R. Berenson, MD Cedars-Sinai Medical Center, Los Angeles, CA March 18, 2003 Case Presentation: My name is James Berenson, MD; I'm an attending physician here at Cedars-Sinai Medical Center and also the current director of the Multiple Myeloma and Bone Metastasis Program. The case that I will present is that of a 63-year-old black retired nurse who developed severe mid and low back pain in July of 2000. Evaluation later that month revealed extensive lytic bone disease, in addition to compression fractures at T8, L1, and L2. She was found to have a light- chain lambda monoclonal gammopathy with a total 24-hour urine protein of 4,700 milligrams, the majority of which was monoclonal light chain. ...

1-4 MMRF Presents: MMRF Case Studies in Multiple Myeloma - An Online CME Program for Oncology/Hematology Professionals Novel Strategies in Treatment of Relapsed/Refractory Multiple Myeloma Paul Richardson, MD Dana-Farber Cancer Institute, Boston, MA February 18, 2003 Case Presentation: My name is Dr. Paul Richardson; I'm an attending physician here at the Dana-Farber Cancer Institute and a member of the Jerome Lipper Multiple Myeloma Center. The case I'm going to present to everybody today is that of a 39-year-old gentleman who was in his usual state of health until 2000 when he developed some flu-like symptoms and presented to his primary care provider dehydrated with a history of nausea and vomiting. Laboratory evaluation revealed him to be hypercalcemic and in acute renal failure. Evaluation confirmed that he had kappa light-chain multiple myeloma ...

1-5 MMRF Presents: MMRF - Case Studies in Multiple Myeloma - An Online CME Program for Oncology/Hematology Professionals Strategies in Treating Newly Diagnosed or Untreated Multiple Myeloma Patients Donna Weber, MD The University of Texas M.D. Anderson Cancer Center, Houston TX January 14, 2003 Case Presentation: A 55-year-old gentleman has a 2- to 3-year history of back pain, which has generally been alleviated with ibuprofen. He presents to the emergency room because he developed moderate- to-severe back, mid-back, pain after lifting a box while cleaning out the garage. He has always been healthy except in the last 5 years; he has developed diabetes and high blood pressure. On further questioning, he indicates he has had some minor fatigue during the past 2 months and occasionally he will become more short of breath if he has to climb several flights of ...

Old and new drugs may fight myeloma Two therapies may improve survival chances of people with a bone marrow cancer called multiple myeloma . At the least, they could delay the day when patients need to undergo a bone marrow transplant, a harsh procedure that carries lethal risks, say researchers. A team at the Mayo Clinic in Rochester, Minn., reports that 6 of 16 patients with no out- ward symptoms of their multiple myeloma improved after treatment with the drug thalido- mide. Moreover, 20 of 26 patients with worsening cases of the disease showed gains after receiving thalidomide with dexamethasone, a steroid often administered in such cases, reports S. Vincent Rajkumar, a hematologist at the clinic. The researchers classified patients as improved if, after four monthly treatments, they showed normal concentrations of the white blood cells called plasma cells. Most countries banned thalidomide decades ago because, ...

Singapore Med J 2000 Vol 41(10) : 500-503 C a s e R e p o r t Immunoglobulin D Multiple Myeloma in Our Hospital - A Rare Occurrence L KTan, R Suri, H L Lim, S K Ong Department of Laboratory Medicine National University Hospital 5 Lower Kent Ridge Road Singapore 119074 L K Tan, MB ChB Leics), MRCP, DipRCPath, MRCPath, CCST Consultant S K Ong, MSc, MAACB, FAACB Section Supervisor Department of Medicine R Suri, MBBS, MMed (Int Med), MRCP Associate Professor Department of Haematology- Oncology H L Lim, MBBS, MMed (Int Med) Consultant Correspondence to: Dr Tan Lip Kun ABSTRACT Immunoglobulin (Ig) D multiple myeloma is a rare presentation, usually with an aggressive course and a poorer prognosis. It accounts for about ...

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 among ...

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 second ...

Although recently developed drugs have made many cancers survivable, multiple myeloma has resisted scientists’ best efforts. The likelihood of a patient withstanding this blood-cell cancer for 5 years remains less than 1 in 3—as it has been for 3 decades. Now, the notorious antinausea drug thalidomide is demonstrating power that outclasses standard chemotherapy against myeloma . Banned in the 1960s for causing birth defects, thalidomide more recently has been shown to cure mouth ulcers and relieve complications of leprosy (SN: 11/11/95, p. 311; SN: 8/15/98, p. 111) . Thalidomide prescribed in gradually increasing doses brought about improvements in 27 of 84 multiple myeloma patients in whom standard treatments had failed, scientists report in the Nov. 18 N EW E NGLAND J OURNAL OF M EDICINE . The researchers at the University of Arkansas for ...