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1. 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
Hazardous Substances Data Bank. THALIDOMIDE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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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2. 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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3. 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.
  • [Cites] N Engl J Med. 1999 Nov 18;341(21):1565-71 [10564685.001]
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  • [Cites] Br J Haematol. 1998 Sep;102(5):1115-23 [9753033.001]
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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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4. 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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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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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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

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  • [ErratumIn] Cancer. 2008 Nov 15;113(10):2835
  • (PMID = 18683218.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Bone Density Conservation Agents; 0 / Diphosphonates; 0 / Imidazoles; 6XC1PAD3KF / zoledronic acid
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6. Asai S, Miyachi H, Kobayashi H, Hotta T, Ando Y: Smoldering myeloma associated with zonisamide treatment. Intern Med; 2002 Feb;41(2):138-41
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Smoldering myeloma associated with zonisamide treatment.
  • Laboratory examination revealed a serum M-protein which consisted of IgG (lambda) and an increased number of plasma cells in the bone marrow, resulting in a diagnosis of smoldering myeloma.
  • Considering his age, zonisamide was suspected to play an etiologic role in the occurrence of smoldering myeloma.
  • [MeSH-major] Agammaglobulinemia / chemically induced. Anticonvulsants / adverse effects. Epilepsy, Generalized / drug therapy. Immunoglobulin lambda-Chains / blood. Isoxazoles / adverse effects. Multiple Myeloma / chemically induced. Myeloma Proteins / analysis
  • [MeSH-minor] Adult. Humans. Intracranial Arteriovenous Malformations / complications. Male. Subarachnoid Hemorrhage / complications. Valproic Acid / therapeutic use

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  • (PMID = 11868602.001).
  • [ISSN] 0918-2918
  • [Journal-full-title] Internal medicine (Tokyo, Japan)
  • [ISO-abbreviation] Intern. Med.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Anticonvulsants; 0 / Immunoglobulin lambda-Chains; 0 / Isoxazoles; 0 / Myeloma Proteins; 459384H98V / zonisamide; 614OI1Z5WI / Valproic Acid
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7. Jakob C, Egerer K, Liebisch P, Türkmen S, Zavrski I, Kuckelkorn U, Heider U, Kaiser M, Fleissner C, Sterz J, Kleeberg L, Feist E, Burmester GR, Kloetzel PM, Sezer O: Circulating proteasome levels are an independent prognostic factor for survival in multiple myeloma. Blood; 2007 Mar 1;109(5):2100-5
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  • [Title] Circulating proteasome levels are an independent prognostic factor for survival in multiple myeloma.
  • The proteasome is a proteolytic complex for intracellular degradation of ubiquitinated proteins which are involved in cell-cycle regulation and apoptosis.
  • A constitutively increased proteasome activity has been found in myeloma cells.
  • We studied circulating proteasome levels and their prognostic significance in sera of 50 control subjects, 20 persons with monoclonal gammopathies of undetermined significance (MGUS), and 141 previously untreated patients with multiple myeloma (MM) by an anti-20S proteasome enzyme-linked immunoabsorbent assay (ELISA).
  • Serum proteasome concentrations were significantly elevated in MM compared with controls (P < .001), in MM versus MGUS (P = .03), and in active (n = 101) versus smoldering (n = 40) MM (P < .001).
  • In patients with active MM, there was a significant (P < .001) decrease from pretreatment to post-treatment proteasome concentrations in responders to chemotherapy, but not in nonresponders.
  • We demonstrate for the first time that increased serum proteasome concentrations correlate with advanced disease and are an independent prognostic factor in MM.
  • [MeSH-major] Multiple Myeloma / blood. Multiple Myeloma / diagnosis. Proteasome Endopeptidase Complex / blood

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  • (PMID = 17095627.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] EC 3.4.25.1 / Proteasome Endopeptidase Complex
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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

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  • (PMID = 14616966.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Myeloma Proteins; 0 / multiple myeloma M-proteins
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9. Rajkumar SV, Dispenzieri A, Fonseca R, Lacy MQ, Geyer S, Lust JA, Kyle RA, Greipp PR, Gertz MA, Witzig TE: Thalidomide for previously untreated indolent or smoldering multiple myeloma. Leukemia; 2001 Aug;15(8):1274-6
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  • [Title] Thalidomide for previously untreated indolent or smoldering multiple myeloma.
  • We conducted a clinical trial of thalidomide as initial therapy for asymptomatic smoldering (SMM) or indolent multiple myeloma (IMM).
  • Six patients had a confirmed response to therapy with at least 50% or greater reduction in serum and urine monoclonal (M) protein.
  • When minor responses (25-49%) decrease in M protein concentration) were included, 11 of 16 patients (69%) responded to therapy.
  • Pre-treatment MVD was not a significant predictor of response to therapy, median MVD 4 and 12 in responders and non-responders respectively, P = 0.09.
  • We conclude that thalidomide has significant activity in the treatment of newly diagnosed SMM/IMM.
  • However, we do not recommend treatment with thalidomide at this stage since some patients with SMM/IMM can be stable for several months or years without any therapy.
  • Additional randomized trials are needed to determine if thalidomide will delay progression to active multiple myeloma.
  • [MeSH-major] Angiogenesis Inhibitors / administration & dosage. Multiple Myeloma / drug therapy. Thalidomide / administration & dosage
  • [MeSH-minor] Administration, Oral. Adult. Aged. Female. Humans. Male. Middle Aged. Treatment Outcome

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  • (PMID = 11480571.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA62242; United States / NCI NIH HHS / CA / CA85818
  • [Publication-type] Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Angiogenesis Inhibitors; 4Z8R6ORS6L / Thalidomide
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10. Danilatou V, Liapi D, Psyllaki M, Chatzivasili A, Chronaki I, Heliakis P: Neurofibromatosis type I and smoldering multiple myeloma: a case report. Hematology; 2006 Feb;11(1):45-8
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  • [Title] Neurofibromatosis type I and smoldering multiple myeloma: a case report.
  • We present a case of a 64-year-old woman with neurofibromatosis (NF1) and smoldering multiple myeloma (SMM).
  • SMM was diagnosed 9 years ago when the asymptomatic patient was found to have mild anemia, IgA paraproteinemia, hypogammaglobulinemia, osteopenia without any lytic bone lesions and bone marrow plasmacytosis.
  • During follow-up period she remained stable in an excellent clinical condition without requiring any therapy for almost 4 years.
  • Forty-two months after diagnosis she had a femoral fracture and since then biphosphonates have been administered intravenously, once monthly.
  • We will discuss the probable pathogenesis of plasma cell dyscrasia in NF1 patients, as well as the likely antimyeloma activity of biphoshonates.
  • [MeSH-major] Bone Density Conservation Agents / administration & dosage. Diphosphonates / administration & dosage. Multiple Myeloma / drug therapy. Multiple Myeloma / etiology. Neurofibromatosis 1 / complications. Neurofibromatosis 1 / drug therapy

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  • (PMID = 16522549.001).
  • [ISSN] 1024-5332
  • [Journal-full-title] Hematology (Amsterdam, Netherlands)
  • [ISO-abbreviation] Hematology
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Bone Density Conservation Agents; 0 / Diphosphonates; 0 / Immunoglobulin A; 0 / Paraproteins
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11. Kyle RA: New strategies for MGUS and smoldering multiple myeloma. Clin Adv Hematol Oncol; 2004 Aug;2(8):507, 509
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] New strategies for MGUS and smoldering multiple myeloma.
  • [MeSH-major] Multiple Myeloma / prevention & control. Paraproteinemias / drug therapy
  • [MeSH-minor] Diphosphonates / therapeutic use. Disease Management. Disease Progression. Drug Design. Humans. Immunoglobulin kappa-Chains / blood. Immunoglobulin lambda-Chains / blood. Myeloma Proteins / analysis. Paraproteins / analysis. Prognosis. Randomized Controlled Trials as Topic. Risk Factors. Thalidomide / therapeutic use

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  • (PMID = 16163229.001).
  • [ISSN] 1543-0790
  • [Journal-full-title] Clinical advances in hematology & oncology : H&O
  • [ISO-abbreviation] Clin Adv Hematol Oncol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Diphosphonates; 0 / Immunoglobulin kappa-Chains; 0 / Immunoglobulin lambda-Chains; 0 / Myeloma Proteins; 0 / Paraproteins; 4Z8R6ORS6L / Thalidomide
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12. Cortesão E, Espadana A, Laranjeiro P, Jara M, Orfão A: Successful treatment with VAD of a myelodysplastic syndrome occurring during the course of a smoldering multiple myeloma. Leuk Res; 2009 Jan;33(1):195-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Successful treatment with VAD of a myelodysplastic syndrome occurring during the course of a smoldering multiple myeloma.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Multiple Myeloma / drug therapy
  • [MeSH-minor] Aged. Dexamethasone / administration & dosage. Doxorubicin / administration & dosage. Female. Humans. Treatment Outcome. Vincristine / administration & dosage


13. Kyle RA: Multiple Myeloma. Diagnostic challenges and standard therapy. Semin Hematol; 2001 Apr;38(2 Suppl 3):11-4
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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. 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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14. 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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15. Gozzetti A, Gennari L, Merlotti D, Salvadori S, De Paola V, Avanzati A, Franci B, Marchini E, Tozzi M, Campagna MS, Nuti R, Lauria F, Martini G: The effects of zoledronic acid on serum lipids in multiple myeloma patients. Calcif Tissue Int; 2008 Apr;82(4):258-62
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] The effects of zoledronic acid on serum lipids in multiple myeloma patients.
  • The mechanism of action of these drugs has not been completely clarified, but it has been observed that N-BPs may inhibit squalene synthase or farnesyl pyrophosphate synthase.
  • To explore the effects of ZA on serum lipids, we studied 26 patients with smoldering myeloma at diagnosis.
  • In all subjects, total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and C-terminal telopeptide of type I collagen (CTX) were measured at baseline and after 1, 3, and 6 months.
  • In conclusion, ZA given intravenously at high doses in patients with smoldering myeloma seems to be able to modify the lipid profile with an improvement of atherosclerotic risk index.
  • [MeSH-major] Diphosphonates / pharmacology. Imidazoles / pharmacology. Multiple Myeloma / blood. Multiple Myeloma / drug therapy
  • [MeSH-minor] Aged. Aged, 80 and over. Atherosclerosis / metabolism. Bone Density Conservation Agents / therapeutic use. Cholesterol, HDL / metabolism. Collagen / chemistry. Female. Humans. Lipids / chemistry. Male. Middle Aged. Treatment Outcome

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  • (PMID = 18418538.001).
  • [ISSN] 0171-967X
  • [Journal-full-title] Calcified tissue international
  • [ISO-abbreviation] Calcif. Tissue Int.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Bone Density Conservation Agents; 0 / Cholesterol, HDL; 0 / Diphosphonates; 0 / Imidazoles; 0 / Lipids; 6XC1PAD3KF / zoledronic acid; 9007-34-5 / Collagen
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16. 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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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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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17. 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

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  • (PMID = 12430876.001).
  • [ISSN] 0925-5710
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Japan
  • [Number-of-references] 18
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18. 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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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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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19. Rajkumar SV: Thalidomide in newly diagnosed multiple myeloma and overview of experience in smoldering/indolent disease. Semin Hematol; 2003 Oct;40(4 Suppl 4):17-22
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Thalidomide in newly diagnosed multiple myeloma and overview of experience in smoldering/indolent disease.
  • Based on the activity of single-agent thalidomide demonstrated in relapsed or refractory multiple myeloma, investigators have evaluated the role of this agent in the treatment of earlier stage disease.
  • Two key phase II trials of thalidomide plus dexamethasone in patients with previously untreated symptomatic multiple myeloma have yielded overall response rates of 64% to 73%.
  • Comparable response rates, reduced toxicity, and increased patient convenience with oral administration suggest it may offer an alternative to standard infusional chemotherapies, such as vincristine/doxorubicin/dexamethasone (VAD), before stem cell mobilization and high-dose chemotherapy in patients with active disease; further study is warranted.
  • Two key phase II trials of single-agent thalidomide in patients with smoldering/indolent (asymptomatic) disease have yielded overall response rates of approximately 35%, and further study of thalidomide in this setting is also indicated.
  • The primary toxicities of thalidomide-based therapy are neuropathy, sedation/fatigue, constipation, and rash.
  • Phase III trials of thalidomide in newly diagnosed symptomatic multiple myeloma or smoldering/indolent disease are ongoing.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Multiple Myeloma / drug therapy. Thalidomide / therapeutic use
  • [MeSH-minor] Adjuvants, Immunologic / administration & dosage. Adjuvants, Immunologic / adverse effects. Adjuvants, Immunologic / therapeutic use. Adult. Aged. Angiogenesis Inhibitors / administration & dosage. Angiogenesis Inhibitors / adverse effects. Angiogenesis Inhibitors / therapeutic use. Clinical Trials, Phase II as Topic / statistics & numerical data. Clinical Trials, Phase III as Topic / statistics & numerical data. Dexamethasone / administration & dosage. Diphosphonates / administration & dosage. Diphosphonates / therapeutic use. Female. Humans. Imidazoles / administration & dosage. Imidazoles / therapeutic use. Life Tables. Male. Middle Aged. Randomized Controlled Trials as Topic / statistics & numerical data. Survival Analysis. Treatment Outcome

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  • (PMID = 15015892.001).
  • [ISSN] 0037-1963
  • [Journal-full-title] Seminars in hematology
  • [ISO-abbreviation] Semin. Hematol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA100080; United States / NCI NIH HHS / CA / CA62242; United States / NCI NIH HHS / CA / CA85818; United States / NCI NIH HHS / CA / CA93842
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Adjuvants, Immunologic; 0 / Angiogenesis Inhibitors; 0 / Diphosphonates; 0 / Imidazoles; 4Z8R6ORS6L / Thalidomide; 6XC1PAD3KF / zoledronic acid; 7S5I7G3JQL / Dexamethasone
  • [Number-of-references] 33
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20. Waxman AJ, Kuehl M, Balakumaran A, Weiss B, Landgren O: Smoldering (asymptomatic) multiple myeloma: revisiting the clinical dilemma and looking into the future. Clin Lymphoma Myeloma Leuk; 2010 Aug;10(4):248-57
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Smoldering (asymptomatic) multiple myeloma: revisiting the clinical dilemma and looking into the future.
  • Recent studies show that multiple myeloma (MM) is consistently preceded by an asymptomatic precursor state.
  • Smoldering MM (SMM) is a MM precursor defined by an M-protein concentration >or= 3 g/dL and/or >or= 10% bone marrow plasma cells, in the absence of end-organ damage.
  • Furthermore, until recently, potent drugs with reasonable toxicity profiles have not been available for the development of early MM treatment strategies.
  • Consequently, current clinical guidelines emphasize the application of close clinical monitoring followed by treatment when the patient develops symptomatic MM.
  • We also discuss how the integration of novel biologic markers and clinical monitoring of SMM could facilitate the development of early treatment strategies for high-risk SMM patients in the future.
  • [MeSH-major] Multiple Myeloma / diagnosis. Multiple Myeloma / drug therapy

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  • (PMID = 20709660.001).
  • [ISSN] 2152-2669
  • [Journal-full-title] Clinical lymphoma, myeloma & leukemia
  • [ISO-abbreviation] Clin Lymphoma Myeloma Leuk
  • [Language] eng
  • [Grant] United States / Intramural NIH HHS / /
  • [Publication-type] Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] United States
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21. Greipp PR: Smoldering, asymptomatic stage 1, and indolent myeloma. Curr Treat Options Oncol; 2000 Jun;1(2):119-26
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  • [Title] Smoldering, asymptomatic stage 1, and indolent myeloma.
  • Of patients presenting with multiple myeloma, 5% to 15% satisfy criteria for the diagnosis of multiple myeloma but have no or minimal symptoms and do not require chemotherapy (NRC).
  • These patients are classified as having smoldering, asymptomatic stage 1, or indolent multiple myeloma in order of their increasing risk of progression.
  • We avoid chemotherapy, especially with alkylating agents in such patients, and we either closely monitor them or use a nonchemotherapeutic intervention.
  • If significant bone lesions, renal failure, or hypercalcemia occur, chemotherapy or transplant is recommended.
  • Patients with mild anemia or with small or isolated bone lesions who are asymptomatic or minimally symptomatic because of anemia may be monitored and are classified as having indolent multiple myeloma.
  • Unnecessary treatment with melphalan or cyclophosphamide probably has no benefit in multiple myeloma NRC and can cause significant risk.
  • Patients who do not receive chemotherapy must be monitored closely to avoid complications of overt multiple myeloma, including anemia, bone lesions, renal failure, and hypercalcemia.
  • We use dexamethasone alone in NRC multiple myeloma to reduce tumor burden in selected patients who do not yet have overt multiple myeloma or who are not candidates for chemotherapy.
  • We use erythropoietin to correct anemia, and dexamethasone and erythropoietin together in patients with higher tumor burden (eg, indolent multiple myeloma).
  • Future progress in treating multiple myeloma NRC depends on better identification of new therapeutic targets that control progression from the stable asymptomatic to the progressive symptomatic phase of multiple myeloma.
  • We need to better understand the biologic target of new agents like thalidomide to design more effective treatment for this early phase of multiple myeloma.
  • Although these approaches may delay chemotherapy, it is not known whether survival is prolonged.
  • [MeSH-major] Multiple Myeloma / therapy
  • [MeSH-minor] Alkylating Agents / therapeutic use. Antineoplastic Agents / therapeutic use. Clinical Trials as Topic. Dexamethasone / therapeutic use. Diet Therapy. Diphosphonates / therapeutic use. Erythropoietin / therapeutic use. Humans. Neoplasm Staging. Thalidomide / therapeutic use. Treatment Outcome

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  • (PMID = 12057049.001).
  • [ISSN] 1527-2729
  • [Journal-full-title] Current treatment options in oncology
  • [ISO-abbreviation] Curr Treat Options Oncol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Alkylating Agents; 0 / Antineoplastic Agents; 0 / Diphosphonates; 11096-26-7 / Erythropoietin; 4Z8R6ORS6L / Thalidomide; 7S5I7G3JQL / Dexamethasone; OYY3447OMC / pamidronate
  • [Number-of-references] 15
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22. Omoti CE, Enosolease ME: A smoldering/indolent myeloma with extensive abdominal presentation--case report. Niger J Clin Pract; 2006 Jun;9(1):91-3
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] A smoldering/indolent myeloma with extensive abdominal presentation--case report.
  • A case of indolent/smoldering myeloma in a 70-year-old man is reported.
  • He presented with an unusual multiple symptomatic myeloma with extramedulary impairment and absence of bone pain.
  • [MeSH-major] Abdominal Neoplasms / secondary. Antineoplastic Agents, Hormonal / therapeutic use. Dexamethasone / therapeutic use. Multiple Myeloma / pathology
  • [MeSH-minor] Aged. Diagnosis, Differential. Humans. Male. Plasmacytoma / drug therapy. Plasmacytoma / pathology

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  • [ErratumIn] Niger J Clin Pract. 2007 Jun;10(2):183. Enosolease, M E [added]
  • (PMID = 16986300.001).
  • [ISSN] 1119-3077
  • [Journal-full-title] Nigerian journal of clinical practice
  • [ISO-abbreviation] Niger J Clin Pract
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Nigeria
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Hormonal; 7S5I7G3JQL / Dexamethasone
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23. Jagannath S, Kyle RA, Palumbo A, Siegel DS, Cunningham S, Berenson J: The current status and future of multiple myeloma in the clinic. Clin Lymphoma Myeloma Leuk; 2010 Feb;10(1):28-43
The Lens. Cited by Patents in .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] The current status and future of multiple myeloma in the clinic.
  • It is now recognized that all cases of multiple myeloma (MM) are preceded by the premalignant condition of monoclonal gammopathy of undetermined significance (MGUS).
  • Although patients with MGUS are generally asymptomatic and currently managed by "watch and wait," the identification of high-risk patients whose disease will progress more rapidly to smoldering MM (SMM) and MM aids in timely intervention.
  • The immunomodulatory agents thalidomide and lenalidomide and the proteasome inhibitor bortezomib are now routine components of MM therapy in both first-line and relapsed/ refractory settings.
  • These targeted agents are used in various combinations with chemotherapy for the treatment of both transplantation-ineligible and transplantation-eligible patients.
  • More recently, a trend toward evaluation of 3- and 4-drug multiagent combinations before transplantation and prolongation of primary therapy has generated new treatment paradigms.
  • Ultimately, the physician's choice of therapy and treatment strategy requires consideration of regimen-associated toxicities and integration of the patient's risk, comorbid status, and response and tolerability of previous treatment regimens.
  • Particular attention needs to be paid to baseline and/or treatment-emergent peripheral neuropathy, thrombotic risk, changes in renal function, and bone health.
  • This review highlights challenges in the clinic and newer approaches under evaluation for the treatment and/or management of patients with MGUS, SMM, and MM.
  • [MeSH-major] Multiple Myeloma / drug therapy
  • [MeSH-minor] Clinical Trials as Topic. Humans. Monoclonal Gammopathy of Undetermined Significance / drug therapy

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  • (PMID = 20223727.001).
  • [ISSN] 2152-2669
  • [Journal-full-title] Clinical lymphoma, myeloma & leukemia
  • [ISO-abbreviation] Clin Lymphoma Myeloma Leuk
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 148
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24. Kyle RA, Rajkumar SV: Therapeutic application of thalidomide in multiple myeloma. Semin Oncol; 2001 Dec;28(6):583-7
The Lens. Cited by Patents in .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Therapeutic application of thalidomide in multiple myeloma.
  • Treatment with thalidomide and dexamethasone was given to 26 patients with active, previously untreated multiple myeloma (MM).
  • Twenty (77%) of 26 patients with active MM exhibited a therapeutic response.
  • Among the first seven patients treated with a thalidomide dose of 400 mg, grade III to IV skin toxicity developed in two.
  • Drug titration was then stopped and the thalidomide dose maintained at 200 mg/d.
  • Thalidomide alone produced a response in six (38%) of 16 patients with smoldering or indolent myeloma.
  • Thirty-two patients with relapsed myeloma were treated with thalidomide dosed at 200 mg/d, with 200-mg escalations every 2 weeks to a maximum daily dose of 800 mg.
  • Prior chemotherapy had failed and five (16%) patients had experienced relapse following stem cell transplantation.
  • Ten (38%) of the 26 patients who had received at least two cycles of therapy obtained a response.
  • [MeSH-major] Angiogenesis Inhibitors / therapeutic use. Multiple Myeloma / drug therapy. Thalidomide / therapeutic use
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Clinical Trials as Topic. Dexamethasone / therapeutic use. Humans

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  • [Copyright] Copyright 2001 by W.B. Saunders Company.
  • (PMID = 11740813.001).
  • [ISSN] 0093-7754
  • [Journal-full-title] Seminars in oncology
  • [ISO-abbreviation] Semin. Oncol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA 62242; United States / NCI NIH HHS / CA / CA 85818
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Angiogenesis Inhibitors; 4Z8R6ORS6L / Thalidomide; 7S5I7G3JQL / Dexamethasone
  • [Number-of-references] 22
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25. Koski AM, Sikiö A, Forslund T: Teriparatide treatment complicated by malignant myeloma. BMJ Case Rep; 2010;2010
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  • [Title] Teriparatide treatment complicated by malignant myeloma.
  • Recombinant human parathyroid hormone (1-34) (rhPTH 1-34), teriparatide (Forsteo in Europe), is a new compound that has been introduced and shown to be successful in the treatment of osteoporosis.
  • In malignant myeloma there is an imbalance between osteoclast and osteoblast activity with involvement of the RANKL/OPG system among others.
  • We report a case with monoclonal gammopathy of uncertain significance (MGUS) who developed malignant myeloma after teriparatide treatment and we suggest that in addition to malignant myeloma and smouldering myeloma, MGUS should also be considered contraindicated for teriparatide treatment.
  • [MeSH-major] Fractures, Spontaneous / etiology. Fractures, Spontaneous / radiography. Multiple Myeloma / chemically induced. Osteoporosis, Postmenopausal / drug therapy. Teriparatide / adverse effects
  • [MeSH-minor] Dose-Response Relationship, Drug. Drug Administration Schedule. Female. Follow-Up Studies. Fracture Fixation, Internal / methods. Humans. Middle Aged. Monitoring, Physiologic / methods. Risk Assessment

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  • (PMID = 22767690.001).
  • [ISSN] 1757-790X
  • [Journal-full-title] BMJ case reports
  • [ISO-abbreviation] BMJ Case Rep
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 10T9CSU89I / Teriparatide
  • [Other-IDs] NLM/ PMC3027506
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26. Lust JA, Lacy MQ, Zeldenrust SR, Dispenzieri A, Gertz MA, Witzig TE, Kumar S, Hayman SR, Russell SJ, Buadi FK, Geyer SM, Campbell ME, Kyle RA, Rajkumar SV, Greipp PR, Kline MP, Xiong Y, Moon-Tasson LL, Donovan KA: Induction of a chronic disease state in patients with smoldering or indolent multiple myeloma by targeting interleukin 1{beta}-induced interleukin 6 production and the myeloma proliferative component. Mayo Clin Proc; 2009 Feb;84(2):114-22
The Lens. Cited by Patents in .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Induction of a chronic disease state in patients with smoldering or indolent multiple myeloma by targeting interleukin 1{beta}-induced interleukin 6 production and the myeloma proliferative component.
  • OBJECTIVE: To conduct in vitro studies as well as a phase 2 clinical trial in patients with smoldering or indolent multiple myeloma to determine if interleukin 1 (IL-1) inhibitors can delay or prevent active myeloma.
  • PATIENTS AND METHODS: Stromal cells were cocultured with IL-1beta-expressing myeloma cells in the presence of dexamethasone, IL-1 receptor antagonist (IL-1Ra), or both.
  • Seven patients showed a decrease in the plasma cell labeling index that paralleled a decrease in high-sensitivity C-reactive protein (hs-CRP) levels.
  • Disease stability was maintained in 8 patients who received therapy for more than 4 years.
  • CONCLUSION: In patients with smoldering or indolent multiple myeloma who were at risk of progression to active myeloma, treatment with IL-1 inhibitors decreased the myeloma proliferative rate and hs-CRP levels in those who responded, leading to a chronic disease state and an improved PFS.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Interleukin 1 Receptor Antagonist Protein / therapeutic use. Interleukin-6 / biosynthesis. Multiple Myeloma / drug therapy
  • [MeSH-minor] Adult. Aged. Apoptosis / drug effects. Bone Marrow Cells / pathology. C-Reactive Protein / analysis. Cell Line, Tumor. Dexamethasone / pharmacology. Dexamethasone / therapeutic use. Drug Therapy, Combination. Female. Glucocorticoids / pharmacology. Glucocorticoids / therapeutic use. Humans. In Vitro Techniques. Interleukin-1 / blood. Male. Middle Aged. Plasma Cells / pathology

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  • [CommentIn] Mayo Clin Proc. 2009 Feb;84(2):105-7 [19181642.001]
  • (PMID = 19181644.001).
  • [ISSN] 1942-5546
  • [Journal-full-title] Mayo Clinic proceedings
  • [ISO-abbreviation] Mayo Clin. Proc.
  • [Language] eng
  • [Databank-accession-numbers] ClinicalTrials.gov/ NCT00635154
  • [Grant] United States / NCI NIH HHS / CA / P01 CA062242; United States / NCI NIH HHS / CA / P0I CA62242
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Glucocorticoids; 0 / Interleukin 1 Receptor Antagonist Protein; 0 / Interleukin-1; 0 / Interleukin-6; 7S5I7G3JQL / Dexamethasone; 9007-41-4 / C-Reactive Protein
  • [Other-IDs] NLM/ PMC2664581
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27. Rajkumar SV, Gertz MA, Lacy MQ, Dispenzieri A, Fonseca R, Geyer SM, Iturria N, Kumar S, Lust JA, Kyle RA, Greipp PR, Witzig TE: Thalidomide as initial therapy for early-stage myeloma. Leukemia; 2003 Apr;17(4):775-9
The Lens. Cited by Patents in .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Thalidomide as initial therapy for early-stage myeloma.
  • Patients with early-stage myeloma are typically observed without therapy until symptomatic disease occurs.
  • However, they are at high risk of progression to symptomatic myeloma, with a median time to progression of approximately 1-2 years.
  • We report the final results of a phase II trial of thalidomide as initial therapy for early-stage multiple myeloma in an attempt to delay progression to symptomatic disease.
  • In total, 31 patients with smoldering or indolent multiple myeloma were studied at the Mayo Clinic.
  • Two patients were deemed ineligible because they were found to have received prior therapy for myeloma, and were excluded from analyses except for toxicity.
  • Of the 29 eligible patients, 10 (34%) had a partial response to therapy with at least 50% or greater reduction in serum and urine monoclonal (M) protein.
  • Three patients had progressive disease while on therapy.
  • Thalidomide has significant activity in early-stage myeloma and has the potential to delay progression to symptomatic disease.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Multiple Myeloma / drug therapy. Thalidomide / therapeutic use
  • [MeSH-minor] Adult. Aged. Bradycardia / chemically induced. Constipation / chemically induced. Disease Progression. Disease-Free Survival. Edema / chemically induced. Fatigue / chemically induced. Female. Humans. Life Tables. Male. Middle Aged. Remission Induction. Sensation Disorders / chemically induced. Treatment Outcome

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  • [CommentIn] Leukemia. 2003 Nov;17(11):2237-8; author reply 2238 [12931217.001]
  • (PMID = 12682636.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA 85818; United States / NCI NIH HHS / CA / CA 93842; United States / NCI NIH HHS / CA / CA62242
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 4Z8R6ORS6L / Thalidomide
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28. Weber D, Rankin K, Gavino M, Delasalle K, Alexanian R: Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol; 2003 Jan 1;21(1):16-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Thalidomide alone or with dexamethasone for previously untreated multiple myeloma.
  • PURPOSE: To evaluate the activity of thalidomide in patients with asymptomatic multiple myeloma and of thalidomide-dexamethasone in patients with previously untreated symptomatic myeloma.
  • PATIENTS AND METHODS: Twenty-eight patients with previously untreated asymptomatic myeloma were treated with thalidomide 100 to 200 mg orally (PO) at bedtime (qhs) with serial increments of 50 to 100 mg at weekly intervals, as tolerated to a maximum of 600 mg PO qhs.
  • Forty consecutive previously untreated patients with symptomatic myeloma were also treated as above (maximum dose 400 mg) and received dexamethasone 20 mg/m(2) for 4 days beginning on days 1, 9, and 17; the second and third cycles of repeated dexamethasone were begun on day 30.
  • The median time to remission was 4.2 months with thalidomide alone and 0.7 months with thalidomide-dexamethasone.
  • Five deaths have occurred as a result of multiple myeloma (two patients), infection (one patient), unknown cause (one patient), and a possible thromboembolic event (one patient).
  • CONCLUSION: Thalidomide alone was effective in patients with newly diagnosed myeloma.
  • These observations support further studies of this promising combination for patients with newly diagnosed multiple myeloma.
  • [MeSH-major] Angiogenesis Inhibitors / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Multiple Myeloma / drug therapy. Thalidomide / therapeutic use
  • [MeSH-minor] Combined Modality Therapy. Dexamethasone / administration & dosage. Humans. Stem Cell Transplantation

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  • (PMID = 12506164.001).
  • [ISSN] 0732-183X
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Angiogenesis Inhibitors; 4Z8R6ORS6L / Thalidomide; 7S5I7G3JQL / Dexamethasone
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29. Dierlamm T, Laack E, Dierlamm J, Fiedler W, Hossfeld DK: IgM myeloma: a report of four cases. Ann Hematol; 2002 Mar;81(3):136-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] IgM myeloma: a report of four cases.
  • IgM myeloma is a rare disease, accounting for approximately 0.5% of multiple myelomas (MM).
  • Here we report four cases of IgM multiple myeloma.
  • Two were diagnosed in advanced clinical stages with multiple osteolytic lesions, leading to hypercalcemia in one patient.
  • Bone marrow morphology showed a variable degree of infiltration with mainly mature plasma cells.
  • While one patient with a smoldering IgM myeloma did not need specific therapy, the others received cytotoxic treatment based on standard chemotherapy for MM.
  • All four patients were alive 1 year after diagnosis.
  • We conclude that IgM myeloma shares clinical and histological features with other MM rather than with Waldenström's macroglobulinemia, which is most commonly diagnosed in cases with IgM monoclonal gammopathy.
  • Since MM and Waldenström's macroglobulinemia differ in prognosis and treatment strategies, the two disease entities should be distinguished based on clinical criteria, bone marrow morphology, and immunophenotypic analysis.
  • [MeSH-major] Immunoglobulin M / metabolism. Multiple Myeloma / metabolism. Multiple Myeloma / pathology
  • [MeSH-minor] Adult. Aged. Bone Marrow / pathology. Diagnosis, Differential. Female. Humans. Male. Middle Aged. Waldenstrom Macroglobulinemia / diagnosis

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  • (PMID = 11904738.001).
  • [ISSN] 0939-5555
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Immunoglobulin M
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30. Jakob C, Goerke A, Terpos E, Sterz J, Heider U, Kühnhardt D, Ziefle S, Kleeberg L, Mieth M, Metzler Iv, Müller C, Sezer O: Serum levels of total-RANKL in multiple myeloma. Clin Lymphoma Myeloma; 2009 Dec;9(6):430-5
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Serum levels of total-RANKL in multiple myeloma.
  • BACKGROUND: Receptor activator of nuclear factor-kappaB ligand (RANKL) plays a key role in osteoclast activation in myeloma bone disease.
  • The increased expression of RANKL in the bone marrow microenvironment was demonstrated in several studies, but there are only rare data on circulating RANKL levels in patients with multiple myeloma (MM).
  • Furthermore, tRANKL levels were higher in smoldering MM versus MGUS (P = .031) and in symptomatic versus smoldering MM (P < .001).
  • A significantly longer progression-free survival was observed in patients with a > 50% decrease in tRANKL levels after 3 months of combined chemotherapy and bisphosphonate treatment.
  • CONCLUSION: Our study demonstrates for the first time that serum tRANKL reflects advanced disease, lytic bone destruction, and poor prognosis in MM.
  • [MeSH-major] Multiple Myeloma / blood. RANK Ligand / blood

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  • (PMID = 19951882.001).
  • [ISSN] 1938-0712
  • [Journal-full-title] Clinical lymphoma & myeloma
  • [ISO-abbreviation] Clin Lymphoma Myeloma
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Osteoprotegerin; 0 / RANK Ligand; 0 / TNFSF11 protein, human
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31. Hayes MJ, Carey JL, Krauss JC, Hedstrom DL, Gulbranson RL, Keren DF: Low IgE monoclonal gammopathy level in serum highlights 20-yr survival in a case of IgE multiple myeloma. Eur J Haematol; 2007 Apr;78(4):353-7
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  • [Title] Low IgE monoclonal gammopathy level in serum highlights 20-yr survival in a case of IgE multiple myeloma.
  • This report describes the diagnosis, follow-up, and problems measuring serum immunoglobulin E (IgE) levels in a case of IgE myeloma with 20-yr survival.
  • The diagnosis of multiple myeloma in a 56-yr-old man was based on 5.4 g/24 h of monoclonal free lambda chain in urine and bone marrow findings of 23.5% plasma cells (19% mature and 4.5% atypical).
  • The lack of other clinical findings of multiple myeloma places this case in the category of 'smoldering or indolent myeloma'.
  • Following chemotherapy, the patient went into clinical remission, eventually dying of complications of emphysema.
  • This case expands the recognized clinical spectrum of IgE multiple myeloma.
  • [MeSH-major] Hypergammaglobulinemia / blood. Immunoglobulin E / blood. Multiple Myeloma / blood. Paraproteinemias / blood. Paraproteinemias / diagnosis
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Blood Protein Electrophoresis / methods. Emphysema / complications. Fatal Outcome. Follow-Up Studies. Humans. Male. Middle Aged. Time

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  • (PMID = 17378894.001).
  • [ISSN] 0902-4441
  • [Journal-full-title] European journal of haematology
  • [ISO-abbreviation] Eur. J. Haematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Denmark
  • [Chemical-registry-number] 37341-29-0 / Immunoglobulin E
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32. Scudla V, Ordeltova M, Bacovsky J, Vytrasova M, Sumna E, Martinek A, Horak P: A contribution to examination of propidium iodide and annexin V plasma cells indices in multiple myeloma. Neoplasma; 2003;50(5):363-71
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  • [Title] A contribution to examination of propidium iodide and annexin V plasma cells indices in multiple myeloma.
  • The aim of this study was a contemporaneous measurement and a mutual comparison of plasma cells proliferative activity and grade of apoptosis in patients with monoclonal gammopathy of undetermined significance (MGUS) and various phases of MM i.e. smoldering (SMM), stable/plateau and active (progression/relapse) forms of this disease.
  • The analyzed group of 197 patients consisted of 30 MGUS, 21 SMM, 82 patients examined at the time of MM diagnosis and 64 patients analyzed during various phases of the disease after previous chemotherapy.
  • Plasma cell proliferative activity was measured by means of a propidium iodide index (PC-PI) examined by flow cytometry using a DNA/CD138 double staining technique.
  • For detection of plasma cells entering apoptosis (PC-AI) flow cytometry method with annexin V FITC and MoAb CD138 was used.
  • Analysis of plasma cells proliferative activity (PC-PI) was statistically significant in comparison of MGUS or SMM and versus: patients examined at the time of MM diagnosis (p=0.018 or 0.016); patients evaluated during various phases of MM after previous chemotherapy (p=0.021 or 0.019); stable/plateau MM phase in the cohort of all patients (p=0.017 or 0.040); in the plateau phase after chemotherapy (p=0.008 or 0.024) but insignificant in comparison of MGUS and SMM and with the stable group examined at the time of MM diagnosis.
  • Analysis of the apoptotic process revealed significant differences when comparing PC-AI of SMM but not MGUS group versus all cohort of stable/plateau MM patients (p=0.045); there were also insignificant differences in comparison of MGUS and SMM groupsand versus the stable form of MM measured at the time of MM diagnosis or plateau phase after chemotherapy.
  • There was observed a statistically significant difference in the PC-AI in comparison of SMM group versus group of all patients examined at the time of MM diagnosis (p=0.001) or in various phases of this disease (p=0.015) and the group of MGUS patients compared with patients evaluated at the time of MM diagnosis (p=0.03).
  • Very significant statistical differences of plasma cell proliferative (PC-PI) and apoptotic (PC-AI) activity were found when comparing the levels of both the indices of MGUS, SMM and stable/plateau MM group versus the active (progression/relapse) form of MM marked by a higher level of PC-PI (3.2%, p=0.000) and PC-AI (4.8%, p=0.000) in the whole cohort of MM patients, but also in comparison with both the active forms at the time of MM diagnosis or active forms evaluated during various phases of the disease after chemotherapy.
  • These results revealed importance of measurement not only of proliferative but also of apoptotic plasma cells indices for a complex evaluation of the cells kinetics of plasma cells compartments in patients with MGUS or MM.
  • This study confirmed the initial hypothesis of a common 'inverse relationship between the proliferative (PC-PI) and the apoptosis activity (PC-AI) in plasma cells compartments in patients with MGUS, smoldering, stable/plateau and active (progression/ relapse) forms of MM'.
  • [MeSH-major] Annexin A5 / blood. Monoclonal Gammopathy of Undetermined Significance / blood. Multiple Myeloma / blood. Multiple Myeloma / pathology. Plasma Cells / pathology
  • [MeSH-minor] Apoptosis. Cell Division. Coloring Agents. Humans. Propidium


33. Gabay C, Lamacchia C, Palmer G: IL-1 pathways in inflammation and human diseases. Nat Rev Rheumatol; 2010 Apr;6(4):232-41
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  • The effects of IL-1 are tightly controlled by several naturally occurring inhibitors, such as IL-1 receptor antagonist (IL-1Ra), IL-1 receptor type II (IL-1RII), and other soluble receptors.
  • Numerous IL-1 inhibitors have been developed and tested primarily in rheumatoid arthritis, with only modest effects.
  • Successful treatment with IL-1 blockers has also been reported in other hereditary autoinflammatory diseases, as well as in nonhereditary inflammatory diseases, such as Schnizler syndrome, systemic-onset juvenile idiopathic arthritis and adult Still disease.
  • Finally, preliminary results indicating that IL-1 targeting is efficacious in type 2 diabetes and smoldering myeloma have further broadened the spectrum of IL-1-driven diseases.
  • [MeSH-major] Interleukin-1 / antagonists & inhibitors. Interleukin-1 / metabolism. Rheumatic Diseases / blood. Rheumatic Diseases / drug therapy
  • [MeSH-minor] Animals. Cohort Studies. Disease Models, Animal. Drug Delivery Systems. Female. Humans. Inflammation / blood. Inflammation / physiopathology. Inflammation Mediators / blood. Interleukin 1 Receptor Antagonist Protein / therapeutic use. Interleukin-1beta / drug effects. Interleukin-1beta / metabolism. Male. Mice. Prognosis. Receptors, Interleukin / antagonists & inhibitors. Receptors, Interleukin / drug effects. Risk Assessment. Signal Transduction. Treatment Outcome

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  • (PMID = 20177398.001).
  • [ISSN] 1759-4804
  • [Journal-full-title] Nature reviews. Rheumatology
  • [ISO-abbreviation] Nat Rev Rheumatol
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Inflammation Mediators; 0 / Interleukin 1 Receptor Antagonist Protein; 0 / Interleukin-1; 0 / Interleukin-1beta; 0 / Receptors, Interleukin
  • [Number-of-references] 119
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34. 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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35. Chen L, Wang S, Zhou Y, Wu X, Entin I, Epstein J, Yaccoby S, Xiong W, Barlogie B, Shaughnessy JD Jr, Zhan F: Identification of early growth response protein 1 (EGR-1) as a novel target for JUN-induced apoptosis in multiple myeloma. Blood; 2010 Jan 7;115(1):61-70
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  • [Title] Identification of early growth response protein 1 (EGR-1) as a novel target for JUN-induced apoptosis in multiple myeloma.
  • Tumor-bone marrow microenvironment interactions in multiple myeloma (MM) are documented to play crucial roles in plasma-cell growth/survival.
  • In vitro coculture of MM cells with osteoclasts supported cell survival and significantly down-regulated JUN expression.
  • JUN expression in myeloma cells from late-stage and high-risk MM was significantly lower than in plasma cells from healthy donors, monoclonal gammopathy of undetermined significance, smoldering MM, and low-risk MM; patients with low-JUN-expressing MM cells had earlier disease-related deaths.
  • JUN overexpression in MM cells induced cell death and growth inhibition and up-regulated expression of early growth response protein 1 (EGR-1), whose low expression also carried unfavorable clinical implications.
  • EGR-1 knockdown in MM cells abrogated JUN overexpression-induced MM cell death and growth inhibition, indicating that EGR-1 acts directly downstream of JUN.
  • JUN modulates myeloma cell apoptosis through interacting with EGR-1, which down-regulates Survivin and triggers caspase signaling.
  • Importantly, high JUN or EGR-1 expression was associated with improved outcome in Total Therapy 3, in which bortezomib is given throughout therapy, versus Total Therapy 2, in which bortezomib is given only at relapse.

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  • (PMID = 19837979.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / P01 CA055819; United States / NCI NIH HHS / CA / R01 CA113992; United States / NCI NIH HHS / CA / P01 CA55819
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / BIRC5 protein, human; 0 / Boronic Acids; 0 / EGR1 protein, human; 0 / Early Growth Response Protein 1; 0 / Inhibitor of Apoptosis Proteins; 0 / Microtubule-Associated Proteins; 0 / Proto-Oncogene Proteins c-jun; 0 / Pyrazines; 69G8BD63PP / Bortezomib
  • [Other-IDs] NLM/ PMC2803692
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36. 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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37. Sasaki R: [The clinical significance of M proteins]. Rinsho Byori; 2001 Jul;49(7):678-81
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  • M protein refers to a monoclonal gammaglobulin that is produced by the monoclonal proliferation of plasma cells.
  • More than 50% of M proteinemia is classified as MGUS, but lymphoproliferative disorders such as multiple myeloma and Waldenström's macroglobulinemia may also develop from MGUS.
  • MGUS develops in many disorders including chronic infection, autoimmune disease, various type of neoplasm, neurological disease and skin disease.
  • In general, no treatment is required for MGUS and smoldering type myeloma in which the clinical course and laboratory data are stable.
  • However, in progressive myeloma or cases of plasmacytoma chemotherapy, radiation and/or surgery are indicated.
  • Some factors are known to predict the prognosis of multiple myeloma, and poly(A) polymerase may be a useful indicator for predicting the prognosis of multiple myeloma.
  • [MeSH-minor] Aged. Ammonia / blood. Biomarkers / analysis. Hepatitis C. Humans. Male. Middle Aged. Monoclonal Gammopathy of Undetermined Significance / diagnosis. Multiple Myeloma / diagnosis. Polynucleotide Adenylyltransferase / analysis. Prognosis

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  • (PMID = 11519130.001).
  • [ISSN] 0047-1860
  • [Journal-full-title] Rinsho byori. The Japanese journal of clinical pathology
  • [ISO-abbreviation] Rinsho Byori
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article; Review
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Biomarkers; 0 / Paraproteins; 7664-41-7 / Ammonia; EC 2.7.7.19 / Polynucleotide Adenylyltransferase
  • [Number-of-references] 0
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38. Renner S, Weisz J, Krajewski S, Krajewska M, Reed JC, Lichtenstein A: Expression of BAX in plasma cell dyscrasias. Clin Cancer Res; 2000 Jun;6(6):2371-80
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  • [Title] Expression of BAX in plasma cell dyscrasias.
  • Several studies demonstrate that the BCL-2 and BCL-XL antiapoptotic genes are variably expressed in plasma cells of patients with multiple myeloma (MM).
  • However, the plasma cell expression of BAX protein, their major proapoptotic partner, has not been investigated.
  • Our initial Western blot analysis of myeloma cell extracts also suggested patient variability in the expression of BAX, which was not altered by exposure to interleukin 6.
  • Expression was first evaluated in 104 patients with reactive plasmacytosis, monoclonal gammopathy of undetermined significance/smoldering MM, or active MM.
  • Patients with monoclonal gammopathy of undetermined significance/smoldering MM had intermediate values.
  • For correlations with outcome, expression was assessed in 43 patients at diagnosis who were treated with melphalan and prednisone; 30 at diagnosis who were treated with vincristine, Adriamycin, and dexamethasone; and 29 at relapse who were treated with second-line therapy.
  • There was no correlation between BAX or BCL-2 expression and response to chemotherapy or duration of response or between BCL-2 expression and survival.
  • However, patients who demonstrated extremely low plasma cell BAX expression had significantly increased survival.
  • BAX expression did not correlate with expression of proliferating cell nuclear antigen used as a marker of proliferation.
  • These data indicate a myeloma-specific increase in BAX expression in plasma cells and suggest that low BAX expression identifies a cohort of patients with long survival, which is not specifically associated with low proliferating cell nuclear antigen expression.
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Apoptosis. Biopsy. Blotting, Western. Bone Marrow / metabolism. Cell Division / drug effects. Dexamethasone / administration & dosage. Disease-Free Survival. Doxorubicin / administration & dosage. Humans. Immunohistochemistry. Melphalan / administration & dosage. Multiple Myeloma / metabolism. Multiple Myeloma / pathology. Plasma Cells / metabolism. Plasma Cells / pathology. Prednisone / administration & dosage. Proliferating Cell Nuclear Antigen / biosynthesis. Proto-Oncogene Proteins c-bcl-2 / biosynthesis. Recurrence. Time Factors. Vincristine / administration & dosage. bcl-2-Associated X Protein

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  • (PMID = 10873089.001).
  • [ISSN] 1078-0432
  • [Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research
  • [ISO-abbreviation] Clin. Cancer Res.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA 551164; United States / NCI NIH HHS / CA / CA 69381; United States / NCI NIH HHS / CA / U10CA2115
  • [Publication-type] Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / BAX protein, human; 0 / Proliferating Cell Nuclear Antigen; 0 / Proto-Oncogene Proteins; 0 / Proto-Oncogene Proteins c-bcl-2; 0 / bcl-2-Associated X Protein; 5J49Q6B70F / Vincristine; 7S5I7G3JQL / Dexamethasone; 80168379AG / Doxorubicin; Q41OR9510P / Melphalan; VB0R961HZT / Prednisone
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39. Harousseau JL: Optimising patient outcomes in myeloma. Cancer Treat Rev; 2010 May;36 Suppl 2:S33-5
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  • [Title] Optimising patient outcomes in myeloma.
  • Multiple myeloma (MM) is an incurable disease, and the goal of therapy is to prolong survival.
  • Newer therapies (thalidomide, lenalidomide, and bortezomib) have contributed to the recent improvements in survival.
  • Optimal integration of these newer therapies into standard practice may be aided by better methods of risk stratification.
  • Supplementation of existing risk stratification methods with new prognostic information, such as cytogenetic data and gene expression profiles, may improve prognostication and help to identify appropriate treatment.
  • The advent of newer therapies has also prompted a reassessment of traditional endpoints and goals of therapy, such as complete response.
  • While complete response correlates with survival in some cases, the correlation is not consistent across all treatment regimens and patient groups, and is therefore not always the most appropriate goal of therapy.
  • With the aim of prolonging survival, trials are currently evaluating newer therapies as long-term maintenance therapy or as prevention therapy for patients with smouldering myeloma.
  • Given that these patients are often asymptomatic and free of clinically active disease, success in this setting depends highly on long-term tolerability of these agents.
  • Treatment of MM should therefore be tailored to the individual patient based on the goals of therapy, patient condition, expected adverse events, and patient preference.
  • [MeSH-major] Multiple Myeloma / drug therapy
  • [MeSH-minor] Antineoplastic Agents / therapeutic use. Boronic Acids / therapeutic use. Bortezomib. Disease Management. Humans. Prognosis. Pyrazines / therapeutic use. Risk Assessment. Thalidomide / analogs & derivatives. Thalidomide / therapeutic use. Treatment Outcome

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  • [Copyright] Copyright 2010 Elsevier Ltd. All rights reserved.
  • (PMID = 20472187.001).
  • [ISSN] 1532-1967
  • [Journal-full-title] Cancer treatment reviews
  • [ISO-abbreviation] Cancer Treat. Rev.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Boronic Acids; 0 / Pyrazines; 4Z8R6ORS6L / Thalidomide; 69G8BD63PP / Bortezomib; F0P408N6V4 / lenalidomide
  • [Number-of-references] 18
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40. Sorli ML, Gimeno E, Abella E, Besses C, Knobel H: Smoldering myeloma in HIV patient: a complete remission after antiretroviral therapy. Leuk Res; 2008 Sep;32(9):1482-3
HIV InSite. treatment guidelines - Cardiac Cardiac Manifestations of HIV .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Smoldering myeloma in HIV patient: a complete remission after antiretroviral therapy.
  • [MeSH-major] Antiretroviral Therapy, Highly Active. HIV Infections / drug therapy. Multiple Myeloma / drug therapy


41. Sanders J, Crawford B, Gibson J, Joy Ho P, Iland H, Joshua D: Is there a case for the early use of bisphosphonates in smouldering myeloma and MGUS? (Bisphosphonates in SMM & MGUS). Int J Lab Hematol; 2007 Oct;29(5):395-7
MedlinePlus Health Information. consumer health - Osteoporosis.

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Is there a case for the early use of bisphosphonates in smouldering myeloma and MGUS? (Bisphosphonates in SMM & MGUS).
  • [MeSH-major] Bone Density Conservation Agents / therapeutic use. Diphosphonates / therapeutic use. Imidazoles / therapeutic use. Multiple Myeloma / complications. Osteoporosis / drug therapy. Paraproteinemias / complications

  • MedlinePlus Health Information. consumer health - Multiple Myeloma.
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  • (PMID = 17824924.001).
  • [ISSN] 1751-5521
  • [Journal-full-title] International journal of laboratory hematology
  • [ISO-abbreviation] Int J Lab Hematol
  • [Language] eng
  • [Publication-type] Clinical Trial; Letter; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Bone Density Conservation Agents; 0 / Diphosphonates; 0 / Imidazoles; 6XC1PAD3KF / zoledronic acid
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42. Dinarello CA: Targeting the pathogenic role of interleukin 1{beta} in the progression of smoldering/indolent myeloma to active disease. Mayo Clin Proc; 2009 Feb;84(2):105-7
MedlinePlus Health Information. consumer health - Multiple Myeloma.

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Targeting the pathogenic role of interleukin 1{beta} in the progression of smoldering/indolent myeloma to active disease.

  • MedlinePlus Health Information. consumer health - Cancer Chemotherapy.
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  • [CommentOn] Mayo Clin Proc. 2009 Feb;84(2):114-22 [19181644.001]
  • (PMID = 19181642.001).
  • [ISSN] 1942-5546
  • [Journal-full-title] Mayo Clinic proceedings
  • [ISO-abbreviation] Mayo Clin. Proc.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / P30 CA046934; United States / NIAID NIH HHS / AI / R01 AI015614; United States / NIAID NIH HHS / AI / R56 AI015614
  • [Publication-type] Comment; Editorial
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interleukin 1 Receptor Antagonist Protein; 0 / Interleukin-6
  • [Other-IDs] NLM/ PMC2664579
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