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1. Zeldis JB, Knight RD, Jacques C, Tozer A, Bizzari JP: Lenalidomide in multiple myeloma: current role and future directions. Expert Opin Pharmacother; 2010 Apr;11(5):829-42
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  • [Title] Lenalidomide in multiple myeloma: current role and future directions.
  • IMPORTANCE OF THE FIELD: Lenalidomide and other new agents are improving survival of multiple myeloma patients.
  • This review describes current data on lenalidomide in myeloma and how the unique properties of lenalidomide may lend its use in new settings, such as maintenance and preventive therapy.
  • AREAS COVERED IN THIS REVIEW: This review covers the activity of lenalidomide in multiple myeloma, efficacy in both newly diagnosed and relapsed/refractory patients, how to manage effectively common adverse events observed with lenalidomide, and its potential use in new settings based on clinical trials published up to 2009.
  • WHAT THE READER WILL GAIN: This review describes the mechanism of action of lenalidomide in myeloma which provides the basis for its clinical use in newly diagnosed, relapsed/refractory, and high-risk smoldering myeloma in combination with other agents.
  • Strategies to reduce or effectively manage myelosuppression and thromboembolic events, the main adverse events associated with lenalidomide plus dexamethasone therapy, are also described.
  • TAKE HOME MESSAGE: Lenalidomide is an oral immunomodulatory drug that is highly effective in treating multiple myeloma, has a favorable safety profile and is now being evaluated as maintenance therapy, preventive therapy and in combination with other new agents.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Multiple Myeloma / drug therapy
  • [MeSH-minor] Clinical Trials as Topic. Dexamethasone / administration & dosage. Humans. Neoplasm Recurrence, Local. Survival Rate. Thalidomide / administration & dosage. Thalidomide / analogs & derivatives

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  • [ErratumIn] Expert Opin Pharmacother. 2010 Sep;11(13):2273
  • [ErratumIn] Expert Opin Pharmacother. 2011 Mar;12(4):679
  • (PMID = 20210686.001).
  • [ISSN] 1744-7666
  • [Journal-full-title] Expert opinion on pharmacotherapy
  • [ISO-abbreviation] Expert Opin Pharmacother
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 4Z8R6ORS6L / Thalidomide; 7S5I7G3JQL / Dexamethasone; F0P408N6V4 / lenalidomide
  • [Number-of-references] 87
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2. Armellini A, Sarasquete ME, García-Sanz R, Chillón MC, Balanzategui A, Alcoceba M, Fuertes M, López R, Hernández JM, Fernández-Calvo J, Sierra M, Megido M, Orfão A, Gutiérrez NC, González M, San Miguel JF: Low expression of ZHX2, but not RCBTB2 or RAN, is associated with poor outcome in multiple myeloma. Br J Haematol; 2008 Apr;141(2):212-5
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  • [Title] Low expression of ZHX2, but not RCBTB2 or RAN, is associated with poor outcome in multiple myeloma.
  • RAN, ZHX2 and RCBTB2 (CHC1L) expression was evaluated by quantitative real time reverse transcription polymerase chain reaction in plasma cells from 85 monoclonal gammopathies: 58 symptomatic multiple myeloma (MM) (52 untreated, six relapsed), eight smouldering MM, five monoclonal gammopathy of undetermined significance, four plasma cell leukaemias and 10 myeloid cell lines.
  • ZHX2 was weakly expressed in high-risk/proliferative disease compared to low-risk or indolent disease.
  • High ZHX2 expression was associated with better response and longer survival after high-dose therapy.
  • RCBTB2 expression was weaker in hyperdiploid versus non-hyperdiploid cases while RAN was more expressed in symptomatic MM and cell lines.
  • [MeSH-major] Biomarkers, Tumor / metabolism. Homeodomain Proteins / metabolism. Multiple Myeloma / metabolism. Neoplasm Proteins / metabolism. Transcription Factors / metabolism
  • [MeSH-minor] Age Factors. Aged. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Bone Marrow Cells / metabolism. Female. Gene Expression. Gene Expression Profiling / methods. Humans. Male. Middle Aged. Paraproteinemias / drug therapy. Paraproteinemias / metabolism. Plasma Cells / metabolism. Prognosis. Reverse Transcriptase Polymerase Chain Reaction / methods. Treatment Outcome. ran GTP-Binding Protein / genetics. ran GTP-Binding Protein / metabolism

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  • (PMID = 18353163.001).
  • [ISSN] 1365-2141
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Homeodomain Proteins; 0 / Neoplasm Proteins; 0 / RAN protein, human; 0 / RCBTB2 protein, human; 0 / Transcription Factors; 0 / ZHX2 protein, human; EC 3.6.5.2 / ran GTP-Binding Protein
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3. Ma CX, Lacy MQ, Rompala JF, Dispenzieri A, Rajkumar SV, Greipp PR, Fonseca R, Kyle RA, Gertz MA: Acquired Fanconi syndrome is an indolent disorder in the absence of overt multiple myeloma. Blood; 2004 Jul 1;104(1):40-2
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  • [Title] Acquired Fanconi syndrome is an indolent disorder in the absence of overt multiple myeloma.
  • At diagnosis, most patients had monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM), with a median creatinine level of 176.8 microM (2.0 mg/dL; range, 79.56-327.08 microM [0.9-3.7 mg/dL]) and evidence of osteomalacia.
  • During the average 65 months (range, 2-238 months) of follow-up, 5 patients developed end-stage renal disease (ESRD) and only 1 of 14 patients with MGUS transformed to multiple myeloma (MM).
  • Chemotherapy offered little benefit on renal functions of MGUS or SMM patients.
  • [MeSH-major] Fanconi Syndrome / pathology. Multiple Myeloma / metabolism

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  • (PMID = 15010372.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA-62242
  • [Publication-type] Journal Article; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] AYI8EX34EU / Creatinine
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4. Detweiler-Short K, Hayman S, Gertz MA, Lacy MQ, Dispenzieri A, Kumar S, Zeldenrust SR, Russell SJ, Lust JA, Kyle RA, Greipp PR, Witzig TE, Vincent Rajkumar S: Long-term results of single-agent thalidomide as initial therapy for asymptomatic (smoldering or indolent) myeloma. Am J Hematol; 2010 Oct;85(10):737-40
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  • [Title] Long-term results of single-agent thalidomide as initial therapy for asymptomatic (smoldering or indolent) myeloma.
  • We report the long-term follow-up results of a phase II trial of thalidomide for early-stage multiple myeloma (MM).
  • Patients were eligible if they had smoldering multiple myeloma (SMM) or indolent MM without the need for immediate therapy.
  • Disease progression was defined using modified American Society of Hematology/Food and Drug Administration consensus panel criteria for SMM.
  • Thirty-one patients were enrolled; 29 (19 SMM and 10 indolent MM) were eligible.
  • The median time to progression (TTP) to symptomatic myeloma was 35 months.
  • Median overall survival from diagnosis was 86 months; median survival from onset of symptomatic myeloma was 49 months.
  • Randomized trials are needed to determine the role of early therapy in SMM.

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  • [Copyright] © 2010 Wiley-Liss, Inc.
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  • (PMID = 20730790.001).
  • [ISSN] 1096-8652
  • [Journal-full-title] American journal of hematology
  • [ISO-abbreviation] Am. J. Hematol.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / P01 CA062242; United States / NCI NIH HHS / CA / R01 CA107476; United States / NCI NIH HHS / CA / CA107476; United States / NCI NIH HHS / CA / CA62242
  • [Publication-type] Clinical Trial; Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 4Z8R6ORS6L / Thalidomide
  • [Other-IDs] NLM/ NIHMS228591; NLM/ PMC3022372
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5. Musto P, Petrucci MT, Bringhen S, Guglielmelli T, Caravita T, Bongarzoni V, Andriani A, D'Arena G, Balleari E, Pietrantuono G, Boccadoro M, Palumbo A, GIMEMA (Italian Group for Adult Hematologic Diseases)/Multiple Myeloma Working Party and the Italian Myeloma Network: A multicenter, randomized clinical trial comparing zoledronic acid versus observation in patients with asymptomatic myeloma. Cancer; 2008 Oct 1;113(7):1588-95
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  • [Title] A multicenter, randomized clinical trial comparing zoledronic acid versus observation in patients with asymptomatic myeloma.
  • BACKGROUND: Bisphosphonates (BPs) are effective in the prevention and treatment of skeletal-related events (SREs) in patients with symptomatic myeloma who are receiving chemotherapy.
  • Few studies published to date have explored the role of BPs in patients with untreated, asymptomatic myeloma (AM).
  • RESULTS: After a median follow-up of 64.7 person-months, 44.4% of patients in the zoledronic acid group and 45.1% of the control group progressed to 'symptomatic' myeloma requiring chemotherapy (P = .9307).
  • The median time to progression was 67 months and 59 months for the treatment and control groups, respectively (P = .8312).
  • More frequent adverse events observed in the zoledronic acid-treated group were asymptomatic hypocalcemia and fever.
  • One patient developed reversible osteonecrosis of the jaw.
  • [MeSH-major] Bone Density Conservation Agents / therapeutic use. Bone Diseases / prevention & control. Diphosphonates / therapeutic use. Imidazoles / therapeutic use. Multiple Myeloma / drug therapy


6. Kyle RA: Multiple Myeloma. Diagnostic challenges and standard therapy. Semin Hematol; 2001 Apr;38(2 Suppl 3):11-4
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  • [Title] Multiple Myeloma. Diagnostic challenges and standard therapy.
  • In the diagnosis of multiple myeloma (MM), the clinician must exclude other disorders in which a plasma cell reaction may occur such as rheumatoid arthritis and connective tissue disorders, or metastatic carcinoma where the patient may have osteolytic lesions associated with bone metastases.
  • Patients with smoldering multiple myeloma (SMM) or monoclonal gammopathy of undetermined significance (MGUS) have none of the complicating features of MM and do not require treatment with potentially toxic agents.
  • The plasma cell labeling index can help make a differential diagnosis of MM from SMM.
  • In addition, SMM or MGUS patients have few or no circulating plasma cells.
  • High-dose chemotherapy and stem cell support prolong overall survival in contrast to conventional therapy.
  • If stem cell transplantation is considered, it is important to harvest the cells before using alkylating agents to obtain a sufficient number of cells.
  • Supportive treatment consists of the occasional use of erythropoietin to maintain adequate hemoglobin levels and adequate hydration to protect renal function.
  • Vaccination against pneumococcal infections and the prophylactic use of antibiotic therapy during the first 2 months of treatment can be beneficial.
  • Recognizing the symptoms of spinal cord compression and initiating dexamethasone therapy promptly to prevent paraplegia are critical.
  • [MeSH-major] Multiple Myeloma / diagnosis. Multiple Myeloma / therapy
  • [MeSH-minor] Antineoplastic Agents / therapeutic use. Diagnosis, Differential. Hematopoietic Stem Cell Transplantation. Humans

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  • (PMID = 11309703.001).
  • [ISSN] 0037-1963
  • [Journal-full-title] Seminars in hematology
  • [ISO-abbreviation] Semin. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents
  • [Number-of-references] 14
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7. Barlogie B, Zangari M, Spencer T, Fassas A, Anaissie E, Badros A, Cromer J, Tricot G: Thalidomide in the management of multiple myeloma. Semin Hematol; 2001 Jul;38(3):250-9
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  • [Title] Thalidomide in the management of multiple myeloma.
  • Thalidomide has recently been shown to have significant activity in refractory multiple myeloma (MM).
  • The addition of thalidomide to dexamethasone and chemotherapy for the management of post-transplant relapses results in higher response rates.
  • The early results of the Total Therapy II trial for newly diagnosed MM patients show an unprecedented complete remission (CR) and near-CR rate of 69% after two melphalan-based transplants (whether or not receiving thalidomide).
  • In addition, available clinical trial information involving at least 20 patients confirms that thalidomide is active in one third of patients in single-agent trials for refractory disease, with response rates increasing to 50% to 60% in combination with dexamethasone and to as high as 80% in combination with dexamethasone and chemotherapy.
  • When applied as primary therapy in smoldering myeloma, one third of patients experienced 50% paraprotein reduction (PPR); in combination with dexamethasone pulsing, 70% to 80% of symptomatic patients responded.
  • Thus, thalidomide is a major new tool in the treatment armamentarium of MM.
  • The virtual lack of myelosuppression makes it an ideal agent for combination with cytotoxic chemotherapy.
  • [MeSH-major] Angiogenesis Inhibitors / therapeutic use. Multiple Myeloma / drug therapy. Thalidomide / therapeutic use

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  • (PMID = 11486313.001).
  • [ISSN] 0037-1963
  • [Journal-full-title] Seminars in hematology
  • [ISO-abbreviation] Semin. Hematol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA55819
  • [Publication-type] Journal Article; Research Support, U.S. Gov't, P.H.S.; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Angiogenesis Inhibitors; 4Z8R6ORS6L / Thalidomide
  • [Number-of-references] 48
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8. Rosiñol L, Bladé J, Esteve J, Aymerich M, Rozman M, Montoto S, Giné E, Nadal E, Filella X, Queralt R, Carrió A, Montserrat E: Smoldering multiple myeloma: natural history and recognition of an evolving type. Br J Haematol; 2003 Nov;123(4):631-6
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  • [Title] Smoldering multiple myeloma: natural history and recognition of an evolving type.
  • Patients with smoldering multiple myeloma (SMM) meet the diagnostic criteria of multiple myeloma (MM) but are asymptomatic.
  • The median serum M-protein and proportion of bone marrow plasma cells were 36 g/l and 27% respectively.
  • Two subsets of SMM were identified: (i) evolving SMM (n = 22), characterized by a progressive increase in serum M-protein, a previously recognized monoclonal gammopathy of undetermined significance (MGUS) and a significant higher proportion of IgA type and (ii) non-evolving SMM (n = 26) with stable M-protein that abruptly increases when symptomatic MM develops.
  • Thirty-four patients developed symptomatic MM.
  • The median time to progression in the overall series was 3.2 years and the only feature associated with a shorter time to progression was the evolving versus non-evolving type (1.3 vs. 3.9 years respectively, P = 0.007).
  • Fifty-seven per cent of patients that required chemotherapy showed no or minimal response.
  • The median survival from diagnosis and from progression was 8.2 and 3.5 years respectively.
  • [MeSH-major] Multiple Myeloma / diagnosis. Myeloma Proteins / analysis
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Bone Marrow Examination. Disease Progression. Female. Humans. Male. Middle Aged. Plasma Cells / pathology. Prognosis. Survival Rate. Treatment Outcome


9. Yakushijin Y, Sakai I, Takada K, Yasukawa M, Fujita S: [Double B-cell malignancies with simultaneous onset]. Rinsho Ketsueki; 2004 Mar;45(3):218-22
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  • [Title] [Double B-cell malignancies with simultaneous onset].
  • We encountered a case of a 59-year-old female who simultaneously contracted a non-Hodgkin lymphoma (NHL) and a plasma cell neoplasm.
  • She was diagnosed as having NHL (follicular center lymphoma, grade I, stage IIA) after an open tumor biopsy, and treated by cycles of CHOP chemotherapy which resulted in complete remission.
  • A tumor biopsy was performed laparoscopically at that time.
  • When a bone marrow puncture was performed because of a condition of monoclonal gammopathy which had continued for two years, a smoldering myeloma was additionally diagnosed.
  • This diagnosis was made after the presence of IgG-lambda M protein when the marrow showed an increase in the number of plasma cells.
  • In a Southern blot analysis which studied the abdominal tumor and the bone marrow cells, each B-cell tumor had a different IgH gene rearrangement pattern.
  • Therefore, this case was diagnosed as an example of the simultaneous existence of two different B-cell tumors.
  • [MeSH-major] Abdominal Neoplasms. Lymphoma, Follicular. Multiple Myeloma. Neoplasms, Multiple Primary
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. B-Lymphocytes / pathology. Fatal Outcome. Female. Gene Rearrangement, B-Lymphocyte, Heavy Chain. Humans. Middle Aged. Neoplasm Recurrence, Local

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  • (PMID = 15103935.001).
  • [ISSN] 0485-1439
  • [Journal-full-title] [Rinshō ketsueki] The Japanese journal of clinical hematology
  • [ISO-abbreviation] Rinsho Ketsueki
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article; Review
  • [Publication-country] Japan
  • [Number-of-references] 17
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10. Dimopoulos MA, Moulopoulos LA, Maniatis A, Alexanian R: Solitary plasmacytoma of bone and asymptomatic multiple myeloma. Blood; 2000 Sep 15;96(6):2037-44
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  • [Title] Solitary plasmacytoma of bone and asymptomatic multiple myeloma.
  • Most patients with multiple myeloma (MM) present with symptoms, have evidence of generalized disease, and require chemotherapy promptly to reduce the malignant clone.
  • Some patients present with a local symptom from a single plasmacytoma but no myeloma elsewhere.
  • In patients with MM without symptoms, the diagnosis is made on the basis of screening laboratory tests.
  • In patients with either solitary plasmacytoma of bone or asymptomatic MM, systemic treatment should be deferred until there is evidence of disease progression.
  • [MeSH-major] Bone Neoplasms. Multiple Myeloma. Plasmacytoma


11. Adam Z, Zahradová L, Krejcí M, Pour L, Koukalová R, Rehák Z, Feit J, Kren L, Mechl M, Vasků V, Sirotková A, Hájek R, Mayer J: [Diffuse plane normolipemic xanthomatosis and necrobiotic xanthogranuloma associated with monoclonal gammopathy--determining the disease stage with PET-CT and treatment experience. Two case studies and literature review]. Vnitr Lek; 2010 Nov;56(11):1158-68
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  • [Title] [Diffuse plane normolipemic xanthomatosis and necrobiotic xanthogranuloma associated with monoclonal gammopathy--determining the disease stage with PET-CT and treatment experience. Two case studies and literature review].
  • The size of this lymphadenopathy (histologically no malignant infiltration and no confirmed infectious aetiology) has not changed significantly over a 4-year follow-up.
  • Four cycles of treatment with a combination of bortezomib, cyclophosphamide and dexamethasone brought neither reduction in monoclonal immunoglobulin nor change to skin morphology.
  • The second patient is being followed up for more than 10 years, originally for MGUS, later for asymptomatic multiple myeloma.
  • CT imaging showed clearly numerous infiltrates in the skin and subcutaneous tissue of lower limbs, particularly both shanks, reaching up to 2 cm in depth.
  • The largest infiltrate, measuring 3.5 by 2 by 10 cm, was identified in the distal dorsal part of the right shank.
  • Following 40 Gy irradiation, the size of infiltrate in the radiated area decreased and their soreness ceased.
  • Chemotherapy with cyclophosphamide, bortezomib and dexamethasone brought no reduction in monoclonal immunoglobulin concentration, and no reduction in plane normolipemic xanthomas.
  • [MeSH-minor] Humans. Male. Middle Aged. Positron-Emission Tomography. Tomography, X-Ray Computed

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  • (PMID = 21250495.001).
  • [ISSN] 0042-773X
  • [Journal-full-title] Vnitr̆ní lékar̆ství
  • [ISO-abbreviation] Vnitr Lek
  • [Language] cze
  • [Publication-type] Case Reports; English Abstract; Journal Article; Review
  • [Publication-country] Czech Republic
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12. Basić-kes V, Basić-Jukić N, Kes P, Demarin V, Labar B: [Neurologic sequelae of bone changes in multiple myeloma and its therapy]. Acta Med Croatica; 2002;56(3):103-7
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  • [Title] [Neurologic sequelae of bone changes in multiple myeloma and its therapy].
  • Multiple myeloma (MM) is a plasma cell malignancy characterized by infiltration of bone marrow, bone destruction, infiltration of soft tissues with plasma cells, and suppression of normal hematopoiesis.
  • Full spectrum of plasma cell dyscrasias include monoclonal gammapathy of undetermined significance, smouldering myeloma, indolent multiple myeloma, and fully developed, symptomatic multiple myeloma.
  • Multiple vertebral involvement with the evidence of osteolytic changes in other bones is usual, but solitary vertebral myeloma may occur.
  • Myeloma usually involves the bone of the vertebral body and then spreads into the extradural space.
  • However, patients with solitary extradural myeloma have been reported.
  • Skull myeloma is frequently asymptomatic.
  • Diagnostic approach includes plain X-rays of the skeleton, which was found to be the method of choice for demonstration of osteolytic changes, whereas magnetic resonance with gadolinium enhancement most reliably displays the degree of vertebral involvement and demonstrates any associated soft tissue mass.
  • Current treatment of osteolytic changes in multiple myeloma include chemotherapy, radiotherapy in combination with dexamethasone, monthly infusions of bisphosphonates, surgical decompression, and kyphoplasty.
  • Therapeutic approach is dictated by the presenting symptoms.
  • In case of pain as the predominant symptom, treatment with chemotherapy and radiotherapy may be appropriate.
  • Compressive symptoms are relieved with dexamethasone followed by radiotherapy and chemotherapy.
  • Kyphoplasty is a new method used in the treatment of osteolytic changes of vertebral bodies.
  • Bisphosphonates reduce pain associated with osteolytic changes in multiple myeloma, but also significantly reduce skeletal events (pathologic fracture, spinal cord compression, surgery or irradiation of bone) via unknown mechanism.
  • [MeSH-major] Central Nervous System Diseases / etiology. Multiple Myeloma / diagnosis. Spinal Diseases / diagnosis
  • [MeSH-minor] Humans. Osteolysis / diagnosis. Osteolysis / etiology. Pain / etiology. Pain Management. Spine / pathology

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  • (PMID = 12630341.001).
  • [ISSN] 1330-0164
  • [Journal-full-title] Acta medica Croatica : c̆asopis Hravatske akademije medicinskih znanosti
  • [ISO-abbreviation] Acta Med Croatica
  • [Language] hrv
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Croatia
  • [Number-of-references] 36
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13. Nau KC, Lewis WD: Multiple myeloma: diagnosis and treatment. Am Fam Physician; 2008 Oct 1;78(7):853-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Multiple myeloma: diagnosis and treatment.
  • Multiple myeloma, the most common bone malignancy, is occurring with increasing frequency in older persons.
  • 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.
  • 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.
  • [MeSH-major] Multiple Myeloma / diagnosis. Multiple Myeloma / therapy
  • [MeSH-minor] Age Factors. Humans. Myeloma Proteins / physiology. Pain / etiology. Plasma Cells / physiology. Risk Factors

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  • (PMID = 18841734.001).
  • [ISSN] 0002-838X
  • [Journal-full-title] American family physician
  • [ISO-abbreviation] Am Fam Physician
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Myeloma Proteins; 0 / multiple myeloma M-proteins
  • [Number-of-references] 29
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14. Tricot GJ: New insights into role of microenvironment in multiple myeloma. Int J Hematol; 2002 Aug;76 Suppl 1:334-6
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] New insights into role of microenvironment in multiple myeloma.
  • Multiple Myeloma (MM) is a malignant disease of terminally differentiated B cells.
  • It most likely originates in a B cell which has traversed the germinal center and has been exposed there extensively to antigens based on the high number of somatic mutations in the complementarity determining regions.
  • The cell of origin is either a plasmablast, or more likely, a memory B-cell.
  • Typically MM goes through different phases from indolent (MGUS, smoldering myeloma) to overt myeloma and then to a fulminant phase, characterized by extramedullary manifestations, high LDH, immature morphology and increased proliferation rate.
  • In the indolent phase, the disease already has acquired major cytogenetic abnormalities as demonstrated by FISH and DNA flow cytometry.
  • It has a gene pattern very similar to myeloma cells on gene array analysis.
  • In the early stages of overt MM, the myeloma cells are completely dependent upon the micro-environment for their growth and survival.
  • The interaction between myeloma cells and micro-environment causes bone disease, genetic instability and more importantly, drug-resistance, which is caused by upregulation of anti-apoptotic factors, resistance to apoptosis induced by FAS and TRAIL activation, and by cell adhesion-induced growth arrest.
  • In this phase of the disease, MM is susceptible to chemotherapy, if delivered with adequate intensity.
  • In the fulminant phase of MM, myeloma cells have acquired sufficient genetic alternations to become completely independent of the micro-environment which allows them to grow at extramedullary sites.
  • Because of the many DNA breaks necessary for immature B cells to become mature plasma cells, B cells already have inherent genetic instability.
  • DNA breaks are necessary for VDJ recombinations, somatic mutations and isotype switching and it is therefore not surprising that genetic alternations frequently occur at the Ig heavy chain site at 14q32, which is abnormal in three quarters of myeloma patients.
  • The issues of bone disease, drug resistance and cytogenetics will be addressed in detail during this presentation.
  • [MeSH-major] Cell Communication / physiology. Multiple Myeloma / pathology
  • [MeSH-minor] Drug Resistance, Neoplasm. Humans. Osteoclasts / cytology. Osteoclasts / secretion. Stromal Cells / cytology. Stromal Cells / secretion


15. Barlogie B, van Rhee F, Shaughnessy JD Jr, Epstein J, Yaccoby S, Pineda-Roman M, Hollmig K, Alsayed Y, Hoering A, Szymonifka J, Anaissie E, Petty N, Kumar NS, Srivastava G, Jenkins B, Crowley J, Zeldis JB: Seven-year median time to progression with thalidomide for smoldering myeloma: partial response identifies subset requiring earlier salvage therapy for symptomatic disease. Blood; 2008 Oct 15;112(8):3122-5
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  • [Title] Seven-year median time to progression with thalidomide for smoldering myeloma: partial response identifies subset requiring earlier salvage therapy for symptomatic disease.
  • Smoldering multiple myeloma (SMM) is usually followed expectantly without therapy.
  • In the first 2 years, THAL dose reduction was required in 86% and drug was discontinued in 50%.
  • Within 4 years, 63% improved, including 25% qualifying for partial response (PR); by then, 34 patients had progressed and 17 required salvage therapy.
  • Unexpectedly, attaining PR status was associated with a shorter time to salvage therapy for disease progression (P < .001), perhaps reflecting greater drug sensitivity of more aggressive disease.
  • Four-year survival and event-free survival estimates of 91% and 60%, respectively, together with a median postsalvage therapy survival of more than 5 years justify the conduct of a prospective randomized clinical trial to determine the clinical value of preemptive therapy in SMM.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Bone Marrow / pathology. Diphosphonates / administration & dosage. Immunosuppressive Agents / administration & dosage. Multiple Myeloma / drug therapy. Multiple Myeloma / prevention & control. Precancerous Conditions / drug therapy. Thalidomide / administration & dosage
  • [MeSH-minor] Disease Progression. Disease-Free Survival. Humans. Multivariate Analysis. Salvage Therapy. Time Factors. Treatment Outcome

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  • (PMID = 18669874.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Databank-accession-numbers] ClinicalTrials.gov/ NCT00083382
  • [Grant] United States / NCI NIH HHS / CA / P01 CA055819; United States / NCI NIH HHS / CA / CA55819
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Diphosphonates; 0 / Immunosuppressive Agents; 4Z8R6ORS6L / Thalidomide; OYY3447OMC / pamidronate
  • [Other-IDs] NLM/ PMC2569167
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16. Kyle RA: The role of high-dose chemotherapy in the treatment of multiple myeloma: a controversy. Ann Oncol; 2000;11 Suppl 1:55-8
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] The role of high-dose chemotherapy in the treatment of multiple myeloma: a controversy.
  • BACKGROUND: Minimal criteria for the diagnosis of multiple myeloma are provided.
  • Monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, primary systemic amyloidosis and metastatic carcinoma must be included in the differential diagnosis.
  • Patients with multiple myeloma should not be treated unless they have an increasing M-protein in the serum or urine, development of anemia, hypercalcemia, renal insufficiency, lytic lesions, fractures or extra-medullary plasmacytomas.
  • PATIENTS AND METHODS: This is a review of patients treated with chemotherapy, autologous stem-cell transplantation and allogeneic transplantation.
  • RESULTS: Comparisons of melphalan and prednisone with a variety of combinations of therapeutic agents produces a higher response rate than with melphalan and prednisone but no significant difference in overall survival.
  • Autologous stem-cell transplantation produces a higher response rate and some prolongation of survival but is not curative.
  • CONCLUSIONS: If the patient is younger than 70 years, the physician should consider the possibility of an autologous peripheral blood stem-cell transplant.
  • Autologous stem-cell transplantation does not produce a cure and most patients will relapse.
  • The appropriate timing of an autologous stem-cell transplant has not been ascertained.
  • Another major question is whether double (tandem) transplants are superior to a single autologous stem-cell transplant.
  • A current French Myeloma Group Study randomized study should answer this question.
  • Allogeneic transplantation for multiple myeloma must be made safer because the transplant-related mortality is 40%.
  • The relapse of multiple myeloma following allogeneic transplant is a major problem and consequently the preparative regimens must be improved.

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  • (PMID = 10707780.001).
  • [ISSN] 0923-7534
  • [Journal-full-title] Annals of oncology : official journal of the European Society for Medical Oncology
  • [ISO-abbreviation] Ann. Oncol.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / CA62242
  • [Publication-type] Journal Article; Research Support, U.S. Gov't, P.H.S.; Review
  • [Publication-country] England
  • [Number-of-references] 19
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17. Peest D, Ganser A: [Therapy of multiple myeloma: indications and options]. Internist (Berl); 2007 Dec;48(12):1343-8
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [Therapy of multiple myeloma: indications and options].
  • [Transliterated title] Therapie des multiplen Myeloms : Indikationen und Möglichkeiten.
  • The multiple myeloma (MM) has an incidence of 3-4/100,000 in the Caucasian population.
  • MM has to be distinguished from smouldering MM and monoclonal gammopathy of uncertain significance (MGUS).
  • In younger patients (<65 years) a good long-term remission is the aim of therapy, while in the elderly patients with comorbidities the aim is a good partial remission with good quality of life.
  • High-dose chemotherapy, often as a tandem transplantation, is part of standard therapy of MM patients <65 years.
  • However, allogeneic stem cell transplantation is the only curative approach.
  • New substances approved for treatment of relapsed MM include bortezomib, thalidomide, and lenalidomide.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Multiple Myeloma / drug therapy
  • [MeSH-minor] Boronic Acids / administration & dosage. Boronic Acids / adverse effects. Bortezomib. Combined Modality Therapy. Diphosphonates / administration & dosage. Diphosphonates / adverse effects. Dose-Response Relationship, Drug. Hematopoietic Stem Cell Transplantation. Humans. Melphalan / administration & dosage. Melphalan / adverse effects. Neoplasm Staging. Prednisone / administration & dosage. Prednisone / adverse effects. Pyrazines / administration & dosage. Pyrazines / adverse effects. Remission Induction. Thalidomide / administration & dosage. Thalidomide / adverse effects. Thalidomide / analogs & derivatives. Tumor Burden

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  • (PMID = 17960351.001).
  • [ISSN] 0020-9554
  • [Journal-full-title] Der Internist
  • [ISO-abbreviation] Internist (Berl)
  • [Language] ger
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Boronic Acids; 0 / Diphosphonates; 0 / Pyrazines; 4Z8R6ORS6L / Thalidomide; 69G8BD63PP / Bortezomib; F0P408N6V4 / lenalidomide; Q41OR9510P / Melphalan; VB0R961HZT / Prednisone
  • [Number-of-references] 26
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