• Changes in T cell receptor repertoire associated with graft-versus-tumor effect and graft-versus-host disease in patients with relapsed multiple

• [Signal transduction and biological function of IL-6 in a human myeloma cell line-XG-7]

• Activated protein C resistance in the absence of factor V Leiden mutation is a common finding in multiple myeloma and is associated with

• Evaluating high dose therapy in Multiple Myeloma: use of quality-adjusted survival analysis.

• Correlations between hematopoietic progenitor cell counts as measured by Sysmex and CD34+ cell harvest yields following mobilization with

• The value of looking. Multiple myeloma discovered by an unusual finding in Gram-stained spinal fluid.

• T-cell clonal expansion in patients with B-cell lymphoproliferative disorders.

• Circulating plasma cells in multiple myeloma: characterization and correlation with disease stage.

• Controversies surrounding the clonogenic origin of multiple myeloma.

• Role of the phosphatidylinositol 3-kinase/Akt and mTOR/P70S6-kinase pathways in the proliferation and apoptosis in multiple myeloma.

• Trimolecular complexes of lambda light chain dimers in serum of a patient with multiple myeloma.

• Analysis of durability of response to thalidomide treatment for relapsed myeloma patients.

• Transfacial excision of brainstem plasmacytoma.

• [Myeloma as a bone tumor]

• Anti-idiotypic T-cell activation in multiple myeloma induced by M-component fragments presented by dendritic cells.

• [Plasmocytic lymphoma/multiple myeloma. Association or transformation?]

• Comparison of gene expression profiling between malignant and normal plasma cells with oligonucleotide arrays.

• [Plasmacytoma and AIDS: unusual duodenal localization]

• Confocal microscopy in multiple myeloma crystalline keratopathy.

• Jin Shin Jyutsu outcomes in a patient with multiple myeloma.

• Arsenic trioxide in multiple myeloma: rationale and future directions.

• Ogilvie's syndrome in patient with multiple myeloma.

• Expression of CD66a in multiple myeloma.

• Improved outcome of allogeneic transplantation in high-risk multiple myeloma patients after nonmyeloablative conditioning.

• A molecular compendium of genes expressed in multiple myeloma.

• Polymorphisms of the tumor necrosis factor-alpha gene promoter predict for outcome after thalidomide therapy in relapsed and refractory

• Deep-vein thrombosis in patients with multiple myeloma receiving first-line thalidomide-dexamethasone therapy.

• Interleukin 6 induces monocyte chemoattractant protein-1 expression in myeloma cells.

• Hepatitis C virus infection in patients with B-cell lymphoproliferative disorders.

• Reduced intensity conditioning and allogeneic stem-cell transplantation: determining its role in multiple myeloma.

• Respiratory distress in a patient with multiple myeloma.

• Autologous peripheral blood progenitor cell transplantation for multiple myeloma.

• Resolution of digital necrosis following treatment of multiple myeloma.

• Acute tumor lysis syndrome in a patient with multiple myeloma treated with dexamethasone monotherapy.

• Thromboembolism in patients on thalidomide for myeloma.

• Tumour lysis syndrome in myeloma.

• [The effect of serum from a patient with myeloma and diffuse muscular hypertrophy on the growth of human muscle cells in culture]

• Solitary plasmacytomas of the spine: a review of 84 cases.

• The treatment of multiple myeloma of the cervical spine with a halo vest.

• Solitary spinal plasmacytomas: management and outcome.

• Extraosseous epidural tumor of immunoglobulin D myeloma.

• An acquired cryoglobulinemia which inhibits fibrin polymerization in a patient with IgG kappa myeloma.

• Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of

• Smoldering myeloma associated with zonisamide treatment.

• High-dose 166Ho-DOTMP in myeloablative treatment of multiple myeloma: pharmacokinetics, biodistribution, and absorbed dose estimation.

1
UI - 10734296
AU - Orsini E; Alyea EP; Schlossman R; Canning C; Soiffer RJ; Chillemi A;
TI - Neuberg D; Anderson KC; Ritz J Changes in T cell receptor repertoire associated with graft-versus-tumor effect and graft-versus-host disease in patients with relapsed multiple myeloma after donor lymphocyte infusion.
SO - Bone Marrow Transplant 2000 Mar;25(6):623-32
AD - Center for Hematologic Oncology, Department of Adult Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Recent reports of clinical responses following donor lymphocyte infusions (DLI) in patients with relapsed multiple myeloma (MM) after allogeneic BMT have demonstrated the ability of allogeneic cells to mediate a graft-versus-myeloma (GVM) effect, but the mechanisms involved have not been determined. To identify changes in the T cell compartment associated with DLI, we performed a molecular analysis of the T cell receptor (TCR) repertoire in four patients with relapsed MM who received infusions of CD4+ lymphocytes from HLA-identical sibling donors. Three of the four patients demonstrated a clinical anti-myeloma response following DLI but also developed graft-versus-host disease (GVHD). The TCR repertoire was examined after PCR amplification of 24 Vbeta gene subfamilies. This method determines the relative utilization of each Vbeta gene subfamily and also allows the identification of clonal and oligoclonal T cell populations through analysis of CDR3 regions for each TCR Vbeta gene subfamily. Serial blood samples were obtained over at least a 1 year period before and after DLI and results compared to 10 normal donors. Serial analysis of CDR3 size profiles demonstrated the appearance of clonal T cell populations after DLI in each of the three responding patients. The appearance of some clones was noted within the first 3 months after DLI and coincided with decreasing levels of monoclonal paraprotein indicating an ongoing GVM response. Other T cell clones appeared at later time points and coincided with the development of GVHD. These findings demonstrate that T cell clones with different patterns of onset can be identified in the peripheral blood of MM patients following DLI. Further functional characterization of these distinct clonal expansions will be required to determine whether these T cell clones are mediators of either anti-myeloma or anti-host activity.

2
UI - 11218881
AU - Song L; Shen B
TI - [Signal transduction and biological function of IL-6 in a human myeloma cell line-XG-7]
SO - Zhonghua Yi Xue Za Zhi 2000 Nov;80(11):845-8
AD - Institute of Basic Medical Science, Academy of Military Medical Science, Beijing, 100850, China.
OBJECTIVE: To investigate the relationship between IL-6 signal transduction and its biological function on a human IL-6-dependent myeloma cell line-XG-7. METHODS: Electrophoretic mobility shift (EMSA) and immunopeipitation were used respectively to detect the activation of transcription factors (STAT3 and NF-IL-6) and protein kinases (JAK1 and ERK) in the two IL-6 signal transduction pathways by IL-6 in XG-7 cells. Then the cells were transfected with the sense or anti-sense expression plasmids of the transcription factors, which could up- or down-regulate the activation of the signal transduction pathways specially, the changes of the biological function of IL-6 on XG-7 cells was shown by cell number counting and MTT. RESULTS: IL-6 can promote the proliferation of XG-7 cells and activate one of the IL-6 signal transduction pathway-Ras/NF-IL-6; but Jak/STAT signal transduction pathway was not activated at the same conditions. When the activation of Ras/NF-IL-6 pathway was up- or down-regulated, the growth effect of IL-6 on XG-7 cells was strongthened or weakened. CONCLUSIONS: The proliferation of XG-7 cells in the presence of IL-6 is mediated by the activation of Ras/NF-IL-6 signal transduction pathway.

3
UI - 11943931
AU - Zangari M; Saghafifar F; Anaissie E; Badros A; Desikan R; Fassas A;
TI - Mehta P; Morris C; Toor A; Whitfield D; Siegel E; Barlogie B; Fink L; Tricot G Activated protein C resistance in the absence of factor V Leiden mutation is a common finding in multiple myeloma and is associated with an increased risk of thrombotic complications.
SO - Blood Coagul Fibrinolysis 2002 Apr;13(3):187-92
AD - Central Arkansas Veteran's Healthcare System, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. ZangariMaurizio@uams.edu
Thromboembolism is not uncommon in multiple myeloma (MM) patients on treatment, but its pathogenesis remains poorly understood. We report the results of a prospective randomized trial of 62 newly diagnosed MM patients tested at baseline for hypercoagulability and treated with intensive chemotherapy with or without thalidomide in a randomized fashion. During the induction phase, 12 patients (19%) developed evidence of deep venous thrombosis (DVT), which was significantly more common in the thalidomide arm (36%) than in the control group (3%) (P = 0.001). Fourteen patients (23%) were found to have a baseline-reduced response to activated protein C (APC) in the absence of factor V Leiden mutation. Using a Kaplan-Meier analysis, a significantly higher proportion of patients with APC resistance developed DVT (5/14 versus 7/38; P = 0.04) irrespective of thalidomide administration. The risk of DVT was highest (50%) in patients with APC resistance on thalidomide. None of the patients with normal APC response and not receiving thalidomide developed DVT. In conclusion, in this series, acquired APC resistance was present in almost one-quarter of newly diagnosed myeloma patients and significantly increased the risk of DVT.

4
UI - 12018742
AU - Porche R; Levy V; Fermand JP; Katsahian S; Chevret S; Ravaud P
TI - Evaluating high dose therapy in Multiple Myeloma: use of quality-adjusted survival analysis.
SO - Qual Life Res 2002 Mar;11(2):91-9
AD - Departement de Biostatistique et Informatique Medicale, Hopital Saint Louis, U444-INSERM, Universite Paris, France. porcher@dbim.jussieu.fr
PURPOSE: To incorporate quality-of-life considerations in assessing high dose therapy (HDT) for patients with Multiple Myeloma (MM). PATIENTS AND METHODS: A quality-adjusted survival analysis. using the quality-adjusted time without symptoms or toxicity (Q-TWiST) method, was applied to two randomized clinical trials conducted in patients with MM which compared randomized assignment to HDT vs. conventional chemotherapy (CCT) alone (MAG91) or followed by HDT (MAG90). Treatment benefit in terms of mean Q-TWiST was assessed through threshold utility analyses, i.e., sensitivity analyses of the choice of the utility coefficients over all possible values of utility weights. RESULTS: In both trials, results slightly favored the first-line HDT group over the first-line CCT group, with an average gain in TWiST of about 5.5 months over the 58 month-median follow-up period (27.8 vs. 22.3 months, respectively) in the MAG90 trial and 5.8 months over the 56 month-median follow-up period (19.1 vs. 13.3 months, respectively) in the MAG91 trial. The utility threshold analyses revealed that the first-line HDT group had a statistically increased mean quality-of-life adjusted time compared to the other group for a broad range of utility coefficient values. CONCLUSION: The development of such understandable and intuitive measures of expressing the relative benefit of complex treatment strategies is expected to be used in clinical decision making in the near future.

5
UI - 12136252
AU - Vogel W; Kopp HG; Kanz L; Einsele H
TI - Correlations between hematopoietic progenitor cell counts as measured by Sysmex and CD34+ cell harvest yields following mobilization with different regimens.
SO - J Cancer Res Clin Oncol 2002 Jul;128(7):380-4
AD - Department of Hematology, Oncology, Rheumatology, and Immunology, Medical Center II, Eberhard Karls University, Otfried-Muller-Str. 10, 72076 Tubingen, Germany.
PURPOSE: The Sysmex SE-9000 cell counter provides an estimate of immature cells referred to as hematopoietic progenitor cells (HPC). HPC counts should correlate with CD34+ counts in mobilized peripheral blood and apheresis to allow optimization of apheresis timing. METHODS: We correlated the HPC counts as measured in the immature information channel with CD34+ cell levels as determined by FACS (HPCA-2 antibody, Becton Dickinson) from mobilized peripheral blood in 40 samples (27 patients and three healthy donors) and in aphereses ( n=113, 41 patients and 20 healthy donors). RESULTS: In mobilized blood, HPC counts were correlated with CD34+ cells ( r=0.78, P<0.0001, n=40). The HPC counts were about 1.5-fold higher than CD34+ cell counts with a median (range) of 84 (1-747)/microl and 57 (1-370)/microl, respectively. In CD34+ selected cell preparations ( n=8), HPC counts were about fourfold lower than CD34+ cell counts with a median (range) of 179 (67-693)/microl and 760 (191-4309)/microl, respectively. In apheresis preparations, linear regression analyses were performed for the group of stem cell donors ( n=44), the group of lymphoma patients ( n=23), the multiple myeloma group ( n=21), and the group of solid tumors ( n=25). Interestingly, no correlation between HPC counts and CD34+ cell counts was found in the G-CSF-mobilized healthy donor group ( r=0.23, P=0.13). Pairing of HPC counts and CD34+ counts was effective in the group of patients receiving chemotherapy + G-CSF for stem cell mobilization: lymphoma group ( r=0.67, P=0.0005), multiple myeloma group ( r=0.56, P=0.008), and the group of solid tumors ( r=0.52, P=0.007). CONCLUSIONS: Lymphoma and multiple myeloma patients who were moderately pretreated and mobilized with chemotherapy and G-CSF showed the best results in correlation analyses even at low HPC counts. Therefore, HPC measurement can be used for timing of apheresis in these patients.

6
UI - 12181846
AU - Patel MR; Nikcevich DA
TI - The value of looking. Multiple myeloma discovered by an unusual finding in Gram-stained spinal fluid.
SO - N C Med J 2002 May-Jun;63(3):129-30
AD - Department of Medicine, Duke University Medical Center, Box 31152, Durham, NC 27710, USA. patel017@mc.duke.edu

7
UI - 9789198
AU - Alatrakchi N; Farace F; Frau E; Carde P; Munck JN; Triebel F
TI - T-cell clonal expansion in patients with B-cell lymphoproliferative disorders.
SO - J Immunother 1998 Sep;21(5):363-70
AD - Laboratoire d'Immunologie Cellulaire, INSERM U3331, Villejuif, France.
We investigated whether T-cell clonal expansion could be found in the blood of 14 untreated patients with B-cell lymphoproliferative disorders [5 B-chronic lymphocytic leukemia (CLL), 4 myelomas, 5 non-Hodgkin lymphoma (NHL)]. The putative presence of T-cell clonotypes was analyzed with a polymerase chain reaction-based method determining V-D-J junction size patterns in 24 T-cell receptor (TCR) V beta subfamilies. This high-resolution method, analyzing CDR3 sizes of TCR transcripts, was used in conjunction with cytometric analysis of the corresponding T-cell subpopulations with 18 TCR V beta-specific monoclonal antibody. We found multiple dominant T-cell clonotypes in the blood of most patients with B-CLL or myeloma as well of a patient with stage IV NHL. In some cases, T-cell clonal expansion was so dominant that the percentage of these clonal T-cell subpopulations in blood represented more than the mean +2 SD value determined in a series of healthy controls. We conclude that a systemic antigen-specific (i.e., leading to clonotypic expansion) immune reaction involving few TCR clonotypes is a hallmark of disseminated B-cell malignancies. The nature of the putative antigens recognized is not known presently. Nonetheless, such insights into the T-cell repertoire of these patients may help to reassess the potential of immunotherapeutic strategies in B-cell malignancies.

8
UI - 9136941
AU - Rawstron AC; Owen RG; Davies FE; Johnson RJ; Jones RA; Richards SJ;
TI - Evans PA; Child JA; Smith GM; Jack AS; Morgan GJ Circulating plasma cells in multiple myeloma: characterization and correlation with disease stage.
SO - Br J Haematol 1997 Apr;97(1):46-55
AD - Department of Haematology, The General Infirmary at Leeds.
The aim of this study was to develop a flow cytometric test to quantitate low levels of circulating myeloma plasma cells, and to determine the relationship of these cells with disease stage. Cells were characterized using five-parameter flow cytometric analysis with a panel of antibodies, and results were evaluated by comparison with fluorescent consensus-primer IgH-PCR. Bone marrow myeloma plasma cells, defined by high CD38 and Syndecan-1 expression, did not express CD10, 23, 30, 34 or 45RO, and demonstrated weak expression of CD37 and CD45. 65% of patients had CD19- 56+ plasma cells, 30% CD19- 56(low), and 5% CD19+ 56+, and these two antigens discriminated myeloma from normal plasma cells, which were all CD19+ 56(low). Peripheral blood myeloma plasma cells had the same composite phenotype, but expressed significantly lower levels of CD56 and Syndecan-1, and were detected in 75% (38/51) of patients at presentation, 92% (11/12) of patients in relapse, and 40% (4/10) of stem cell harvests. Circulating plasma cells were not detectable in patients in CR (n = 9) or normals (n = 10), at a sensitivity of up to 1 in 10,000 cells. There was good correlation between the flow cytometric test and IgH-PCR results: myeloma plasma cells were detectable by flow cytometry in all PCR positive samples, and samples with no detectable myeloma plasma cells were PCR negative. Absolute numbers decreased in patients responding to treatment, remained elevated in patients with refractory disease, and increased in patients undergoing relapse. We conclude that flow cytometry can provide an effective aternative to IgH-PCR that will allow quantitative assessment of low levels of residual disease.

9
UI - 10931011
AU - Davies FE; Rawstron AC; Owen RG; Morgan GJ
TI - Controversies surrounding the clonogenic origin of multiple myeloma.
SO - Br J Haematol 2000 Jul;110(1):240-1

10
UI - 12242656
AU - Pene F; Claessens YE; Muller O; Viguie F; Mayeux P; Dreyfus F; Lacombe
TI - C; Bouscary D Role of the phosphatidylinositol 3-kinase/Akt and mTOR/P70S6-kinase pathways in the proliferation and apoptosis in multiple myeloma.
SO - Oncogene 2002 Sep 26;21(43):6587-97
AD - Departement d'Hematologie, Institut Cochin, INSERM U567, CNRS UMR 8104, IFR 116, Universite Rene Descartes, Paris, France.
Multiple myeloma (MM) is a plasma cell malignancy preliminary localized in the bone marrow and characterized by its capacity to disseminate. IL-6 and IGF-1 have been shown to mediate proliferative and anti-apoptotic signals in plasmocytes. However, in primary plasma-cell leukemia (PCL) and in end-stage aggressive extramedullar disease, the cytokine requirement for both effects may be not mandatory. This suggests that constitutive activation of signaling pathways occurs. One of the signaling pathways whose deregulation may play an oncogenic role in MM is the phosphatidylinositol 3-kinase (PI 3-K) pathway. In human growth factor-independent MM cell lines OPM2 and RPMI8226, we show that the PI 3-K inhibitors LY294002 and Wortmannin strongly inhibited cell proliferation, whereas inhibition of the mammalian Target Of Rapamycin (mTOR)/P70-S6-kinase (P70(S6K)) pathway with rapamycin or of the Mitogen-Activated Protein Kinase (MAPK) pathway with PD98059 had minimal effect on proliferation. In both cell lines, constitutive activation of the PI 3-K/Akt/FKHRL-1, mTOR/P70(S6K) and MAPK pathways was detected. LY294002 inhibited phosphorylation of Akt, FKHRL-1 and P70(S6K) but had no effect on ERK1/2 phosphorylation, indicating that the PI 3-K and MAPK pathways are independent. IGF-1 but not IL-6 increased phosphorylation of Akt, FKHRL-1 and P70(S6K). Purified plasmocytes from four patients with MM and two patients with primary PCL were studied. In three of them including the two patients with PCL, constitutive phosphorylation of Akt, FKHRL-1 and P70(S6K) was present, inhibited by LY294002 and enhanced by IGF-1. In these patients with constitutive Akt activation, normal PTEN expression was detected. PI 3-K inhibition induced caspase-dependent apoptosis as confirmed by inhibition with the large spectrum caspase inhibitor Z-VAD-FMK and cleavage of pro-caspase-3. Both cell lines spontaneously expressed Skp2 and cyclin D1 proteins at high levels but no p27(Kip1) protein. In the presence of LY294002, cell-cycle arrest in G0/G1 was observed, p27(Kip1) protein expression was up-regulated whereas the expression of both Skp2 and cyclin D1 dramatically diminished. PI 3-K-dependent GSK-3alpha/beta constitutive phosphorylation was also detected in OPM2 cells that may contribute to high cyclin D1 expression. Overall, our results suggest that PI 3-K has a major role in the control of proliferation and apoptosis of growth factor-independent MM cell lines. Most of the biological effects of PI 3-K activation in these cell lines may be mediated by the opposite modulation of p27(Kip1) and Skp2 protein expression. Moreover, constitutive activation of this pathway is a frequent event in the biology of MM in vivo and may be more frequently observed in PCL.

11
UI - 12324506
AU - Abraham RS; Charlesworth MC; Owen BA; Benson LM; Katzmann JA; Reeder CB;
TI - Kyle RA Trimolecular complexes of lambda light chain dimers in serum of a patient with multiple myeloma.
SO - Clin Chem 2002 Oct;48(10):1805-11
AD - Division of Clinical Biochemistry and Immunology, Mayo Clinic, Scottsdale, AZ 85259, USA.
BACKGROUND: Patients with multiple myeloma often have Bence Jones proteins composed of free monoclonal light chains of the kappa or lambda type in their urine. Usually, these light chains exist as monomeric or dimeric forms, but rarely, larger molecules, such as tetramers, have been reported in the serum. METHODS AND RESULTS: We report the presence of trimeric complexes of lambda light chain dimers in a patient who was diagnosed with a free lambda light chain multiple myeloma 2 years earlier and subsequently underwent a stem cell transplant. Recently, the patient presented with a large serum M-spike (23 g/L) by protein electrophoresis. The spike consisted of monoclonal lambda light chains without a heavy chain. The urine contained only 8 mg of lambda light chain in a 24-h specimen. Quantitative analysis of the serum and urinary free light chains (FLCs) indicated the probability of larger aggregates of FLCs. Size-exclusion chromatography, electrophoresis, analytical ultracentrifugation, and mass spectrometric studies of the serum revealed almost exclusively the presence of trimolecular aggregates of lambda light chain dimers without other multimeric species. CONCLUSION: Monoclonal lambda light chains may present as hexameric aggregates that cannot be cleared by renal excretion.

12
UI - 12100175
AU - Myers B; Dolan G
TI - Analysis of durability of response to thalidomide treatment for relapsed myeloma patients.
SO - Br J Haematol 2002 Jul;118(1):347

13
UI - 12297819
AU - Ducic Y
TI - Transfacial excision of brainstem plasmacytoma.
SO - Otolaryngol Head Neck Surg 2002 Sep;127(3):243-4
AD - Department of Otolaryngology, University of Texas Southwestern Medical Center, Dallas, USA. yducic@aol.com

14
UI - 12232986
AU - Oivanen T; Palva I
TI - [Myeloma as a bone tumor]
SO - Duodecim 2002;118(5):481-2

15
UI - 9531329
AU - Dabadghao S; Bergenbrant S; Anton D; He W; Holm G; Yi Q
TI - Anti-idiotypic T-cell activation in multiple myeloma induced by M-component fragments presented by dendritic cells.
SO - Br J Haematol 1998 Mar;100(4):647-54
AD - Centre for Molecular Medicine, Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
The monoclonal immunoglobulin (Ig) (M-component) secreted by the tumour plasma cells in multiple myeloma (MM) has specific antigenic determinants (idiotypes; id) that can serve as tumour-specific antigens. The intact Ig molecule is a weak antigen, and small fragments of id protein might be more immunogenic for the induction of id-specific immunity. Dendritic cells (DC) have attracted attention as the most efficient antigen-presenting cells and promising adjuvants for immunotherapy in tumours. In this study the in vitro T-cell response against F(ab')2 and Fab fragments, heavy and light chains of the M-component was examined in five patients with MM clinical stage I. All fragments were able to stimulate T cells but F(ab')2 or Fab fragments and heavy chains induced a stronger response than light chains. DC induced a significantly stronger id-specific immune response than monocytes. Moreover, with DC as antigen-presenting cells, a predominant interferon (IFN)-gamma (type-1 T-cell) response was seen in all patients. Both IFN-gamma and interleukin (IL)-4 (type-1 and type-2 T-cell) responses were noted when monocytes were used. Our study suggests that DC pulsed with idiotypic fragments such as F(ab')2 fragment and heavy chain can be used for the induction of type-1 anti-idiotypic T-cell response for immunotherapy in MM.

16
UI - 12355645
AU - Kochbati S; Ben Dahmen F; Boussema F; Kammassi N; Ben Amor G; Shili S;
TI - Cherif O; Daghfous MH; Rokbani L [Plasmocytic lymphoma/multiple myeloma. Association or transformation?]
SO - Tunis Med 2002 Mar;80(3):155-7
AD - Service de radiologie, hopital Habib Thameur, Tunis.
Extramedullary plsmocytoma (plasmocytic lymphoma) is very rare, it seems to have an indolent course and the progression to a multiple myeloma is very rare (about 30 cases are reported in the literature). We report the case of 68-old-woman who presented in 1997 with an axillary left node. Physical examination, biologic and radiologic tests were normal. The histologic examination (of this mass) revealed a primary extramedullary plasmocytoma. She was treated with the combination of chemiotherapy and radiotherapy. 18 months later, at the follow up, the patient developed an Ig A lambda multiple myeloma. She was treated by chemiotherapy with favorable course.

17
UI - 12360412
AU - De Vos J; Thykjaer T; Tarte K; Ensslen M; Raynaud P; Requirand G; Pellet
TI - F; Pantesco V; Reme T; Jourdan M; Rossi JF; Orntoft T; Klein B Comparison of gene expression profiling between malignant and normal plasma cells with oligonucleotide arrays.
SO - Oncogene 2002 Oct 3;21(44):6848-57
AD - INSERM U475, CHU Montpellier, 34 000 France.
The DNA microarray technology enables the identification of the large number of genes involved in the complex deregulation of cell homeostasis taking place in cancer. Using Affymetrix microarrays, we have compared the gene expression profiles of highly purified malignant plasma cells from nine patients with multiple myeloma (MM) and eight myeloma cell lines to those of highly purified nonmalignant plasma cells (eight samples) obtained by in vitro differentiation of peripheral blood B cells. Two unsupervised clustering algorithms classified these 25 samples into two distinct clusters: a malignant plasma cell cluster and a normal plasma cell cluster. Two hundred and fifty genes were significantly up-regulated and 159 down-regulated in malignant plasma samples compared to normal plasma samples. For some of these genes, an overexpression or downregulation of the encoded protein was confirmed (cyclin D1, c-myc, BMI-1, cystatin c, SPARC, RB). Two genes overexpressed in myeloma cells (ABL and cystathionine beta synthase) code for enzymes that could be a therapeutic target with specific drugs. These data provide a new insight into the understanding of myeloma disease and prefigure that the development of DNA microarray could help to develop an 'a la carte' treatment in cancer disease.

18
UI - 11917640
AU - Juglard R; Vidal V; Calvet P; Dussaut JP; Barea D; Colineau X; Tourrette
TI - JH; Solacroup JC [Plasmacytoma and AIDS: unusual duodenal localization]
SO - J Radiol 2001 Dec;82(12 Pt 1):1729-31
AD - Service de Radiologie, HIA Sainte Anne, Boulevard Sainte Anne, 83800 Toulon Naval.
We report an uncommon presentation of plasmocytoma in an AIDS patient. AIDS is associated with an increased risk of neoplasms. The incidence of Plasma Cell tumors in HIV-positive patients is greater than in non-infected patients. Multiple factors contribute to B cell neoplasms development.

19
UI - 12131045
AU - Buerk BM; Tu E
TI - Confocal microscopy in multiple myeloma crystalline keratopathy.
SO - Cornea 2002 Aug;21(6):619-20
AD - Department of Ophthalmology and Visual Sciences, UIC Eye Center, University of Illinois at Chicago, 1855 W. Taylor, Chicago, IL 60612, U.S.A.
PURPOSE: To report confocal microscopy findings of a patient with multiple myeloma crystalline keratopathy and the response to treatment. METHODS: Confocal microscopy images of the cornea were taken OU and the corneal crystals analyzed using the Cell Counter software. RESULTS: Numerous hyperreflective globules 6-11 nm in size were located within the corneal epithelium and anterior stroma. These crystals obscured normal architectural detail of the cornea. After 6 months of chemotherapy, confocal microscopy was repeated and demonstrated decrease in the size and number of hyperreflective globules. CONCLUSION: Confocal microscopy can enable the clinician to monitor the clinical response of multiple myeloma crystalline keratopathy to chemotherapeutic agents.

20
UI - 12233795
AU - Shannon AR
TI - Jin Shin Jyutsu outcomes in a patient with multiple myeloma.
SO - Altern Ther Health Med 2002 Sep-Oct;8(5):128, 126-7
AD - Kaiser Permanente Northwest Center for Health Research in Portland, Ore, USA.

21
UI - 11895198
AU - Anderson KC; Boise LH; Louie R; Waxman S
TI - Arsenic trioxide in multiple myeloma: rationale and future directions.
SO - Cancer J 2002 Jan-Feb;8(1):12-25
AD - Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA.
Multiple myeloma remains an incurable malignancy with a median survival that does not exceed 3 years. At least one third of patients with multiple myeloma fail to respond to induction chemotherapy, and those who initially achieve remission eventually relapse and require additional therapy. Recent reports demonstrating the efficacy of arsenic trioxide in acute promyelocytic leukemia have prompted a revival in the clinical use of this compound. The achievement of clinical responses marked by molecular conversion of the malignant phenotype and remissions in patients who had failed to respond to multiple courses of conventional chemotherapy provided the impetus to explore its use in multiple myeloma. Properties that favor the use of arsenic trioxide are its ability to target selectively malignant cells for apoptosis through enhancementof reactive oxygen species, to induce differentiation, and to inhibit angiogenesis. Multiple events involved in the pathogenesis of multiple myeloma coincide with pathways targeted by arsenic trioxide, and early results have suggested that clinical responses and safety in patients are promising with advanced disease.

22
UI - 11926578
AU - Goral V; Uyar A; Muftuoglu E
TI - Ogilvie's syndrome in patient with multiple myeloma.
SO - Dig Liver Dis 2002 Jan;34(1):85

23
UI - 11948796
AU - Satoh Y; Hayashi T; Takahashi T; Itoh F; Adachi M; Fukui M; Kuroki M;
TI - Kuroki M; Imai K; Hinoda Y Expression of CD66a in multiple myeloma.
SO - J Clin Lab Anal 2002;16(2):79-85
AD - First Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
CD66a is a member of the carcinoembryonic antigen family and has been suggested to function as an intercellular adhesion molecule and cell growth regulator. Expression of CD66a in myeloma cells was examined with mAb TS135 against CD66a transfectants of murine-transformed fibroblasts. The reactivity of mAb TS135 with CD66a, CD66c, and CD66e was revealed. CD66a in myeloma cells was considered to be detectable with this mAb, since CD66c and CD66e are not expressed in them. CD66a was detected in three myeloma cell lines and an IgM-producing B-cell line. In clinical bone marrow specimens, including 18 multiple myeloma, two primary macroglobulinemia, and a case of CLL-like chronic lymphoproliferation with monoclonal IgG production, CD66a and three conventional myeloma cell markers (PCA-1, CD38, and CD56) were examined by indirect immunofluorescence assay. The results showed that 18 out of 21 cases (86%) were CD66a+, and PCA-1 showed the highest correlation with CD66a among conventional markers. Primary macroglobulinemia and chronic lymphoproliferation were also CD66a+. Two-dimensional flow cytometry with mAbs TS135 and CD38 confirmed the reactivity of TS135 with myeloma cells in those bone marrow specimens. The findings suggest that CD66a is expressed in multiple myeloma with high frequency. Copyright 2002 Wiley-Liss, Inc.

24
UI - 11870172
AU - Badros A; Barlogie B; Siegel E; Cottler-Fox M; Zangari M; Fassas A;
TI - Morris C; Anaissie E; Van Rhee F; Tricot G Improved outcome of allogeneic transplantation in high-risk multiple myeloma patients after nonmyeloablative conditioning.
SO - J Clin Oncol 2002 Mar 1;20(5):1295-303
AD - Myeloma and Transplantation Research Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA. abadros@umm.edu
PURPOSE: We present our experience with relapsed and recently diagnosed patients with high-risk multiple myeloma (MM) receiving immunosuppressive, nonmyeloablative melphalan (MEL)-based conditioning regimens (mini-allograft). PATIENTS AND METHODS: Thirty-one MM patients received allografts from HLA-matched siblings (n = 25) or unrelated donors (n = 6) using a mini-allograft. Seventeen had progressive disease (PD) and 14 had responsive disease (RD) (six with primary RD and eight with responsive relapse). Thirty patients had received one (n = 13) or two or more (n = 17) prior autologous transplantations (ATs). Median age was 56 years (range, 38 to 69 years). Twenty-one patients had chromosome 13 abnormality. Two patients were hemodialysis dependent. Blood and bone marrow grafts were administered to 28 and three patients, respectively. Donor lymphocyte infusions were given to 18 patients either to attain full donor chimerism (n = 6) or to eradicate residual disease (n = 12). RESULTS: By day 100, 25 (89%) of 28 patients were full donor chimeras, one was a mixed chimera, and two had autologous reconstitution. Acute graft-versus-host disease (GVHD) developed in 18 patients (58%), and 10 progressed to chronic GVHD (limited in six and extensive in four). At a median follow-up of 6 months, 19 (61%) of 31 patients achieved complete/near complete remission. Twelve patients (39%) have died: three of PD, three of early treatment-related mortality (TRM) (before day 100), and six of late TRM. Median overall survival (OS) was 15 months. At 1 year, there was a significantly longer event-free survival (86% v 31%, P =.01) and OS (86% v 48%, P =.04) when a mini-allograft was performed after one versus two or more prior ATs, respectively. When compared with historical MM controls (n = 93) receiving conventional allografts, early TRM was significantly lower (10% v 29%, P =.03), and OS at 1 year was better (71% v 45%; P =.08) in the mini-allograft MM patients. CONCLUSION: Mini-allograft induced excellent disease control in MM patients with high-risk disease, but is still associated with a significant GVHD.

25
UI - 12200383
AU - Claudio JO; Masih-Khan E; Tang H; Goncalves J; Voralia M; Li ZH; Nadeem
TI - V; Cukerman E; Francisco-Pabalan O; Liew CC; Woodgett JR; Stewart AK A molecular compendium of genes expressed in multiple myeloma.
SO - Blood 2002 Sep 15;100(6):2175-86
AD - Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network, 610 University Avenue, Toronto, Ontario, M5G 2M9 Canada.
We have created a molecular resource of genes expressed in primary malignant plasma cells using a combination of cDNA library construction, 5' end single-pass sequencing, bioinformatics, and microarray analysis. In total, we identified 9732 nonredundant expressed genes. This dataset is available as the Myeloma Gene Index (www.uhnres.utoronto.ca/akstewart_lab).Predictably, the sequenced profile of myeloma cDNAs mirrored the known function of immunoglobulin-producing, high-respiratory rate, low-cycling, terminally differentiated plasma cells. Nevertheless, approximately 10% of myeloma-expressed sequences matched only entries in the database of Expressed Sequence Tags (dbEST) or the high-throughput genomic sequence (htgs) database. Numerous novel genes of potential biologic significance were identified. We therefore spotted 4300 sequenced cDNAs on glass slides creating a myeloma-enriched microarray. Several of the most highly expressed genes identified by sequencing, such as a novel putative disulfide isomerase (MGC3178), tumor rejection antigen TRA1, heat shock 70-kDa protein 5, and annexin A2, were also differentially expressed between myeloma and B lymphoma cell lines using this myeloma-enriched microarray. Furthermore, a defined subset of 34 up-regulated and 18 down-regulated genes on the array were able to differentiate myeloma from nonmyeloma cell lines. These not only include genes involved in B-cell biology such as syndecan, BCMA, PIM2, MUM1/IRF4, and XBP1, but also novel uncharacterized genes matching sequences only in the public databases. In summary, our expressed gene catalog and myeloma-enriched microarray contains numerous genes of unknown function and may complement other commercially available arrays in defining the molecular portrait of this hematopoietic malignancy. GenBank Accession numbers include BF169967-BF176369, BF185966-BF185969, and BF177280-BF177455.

26
UI - 12200397
AU - Neben K; Mytilineos J; Moehler TM; Preiss A; Kraemer A; Ho AD; Opelz G;
TI - Goldschmidt H Polymorphisms of the tumor necrosis factor-alpha gene promoter predict for outcome after thalidomide therapy in relapsed and refractory multiple myeloma.
SO - Blood 2002 Sep 15;100(6):2263-5
AD - Department of Internal Medicine V, University of Heidelberg, Hospitalstrasse 3, 69115 Heidelberg, Germany.
Thalidomide (Thal) is a drug with antiangiogenic, anti-inflammatory, and immunomodulatory properties that was found to inhibit the production of tumor necrosis factor-alpha (TNF-alpha) in vitro. We studied single nucleotide polymorphisms at positions -308 and -238 of the TNF-alpha gene promoter and measured the corresponding TNF-alpha cytokine levels in 81 patients (pts) with refractory and relapsed multiple myeloma (MM) who were treated with Thal. In myeloma pts carrying the TNF-238A allele (n = 8), we found a correlation with higher pretreatment TNF-alpha levels in peripheral blood (P =.047). After Thal administration, this TNF-238A group had a prolonged 12-month progression-free and overall survival of 86% and 100% versus 44% and 84% (P =.003 and P =.07) in pts with the TNF-238G allele, respectively. These findings suggest that regulatory polymorphisms of the TNF-alpha gene can affect TNF-alpha production and predict the outcome after Thal therapy, particularly in those MM pts who are genetically defined as "high producers" of TNF-alpha.

27
UI - 12229885
AU - Cavo M; Zamagni E; Cellini C; Tosi P; Cangini D; Cini M; Valdre L;
TI - Palareti G; Masini L; Tura S; Baccarani M Deep-vein thrombosis in patients with multiple myeloma receiving first-line thalidomide-dexamethasone therapy.
SO - Blood 2002 Sep 15;100(6):2272-3

28
UI - 12357369
AU - Arendt BK; Velazquez-Dones A; Tschumper RC; Howell KG; Ansell SM; Witzig
TI - TE; Jelinek DF Interleukin 6 induces monocyte chemoattractant protein-1 expression in myeloma cells.
SO - Leukemia 2002 Oct;16(10):2142-7
AD - Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic/Foundation, Rochester, MN 55905, USA.
Interleukin 6 (IL-6) is known to play an important role in the biology of the malignant plasma cells in multiple myeloma. In an effort to better understand IL-6 stimulated myeloma cell growth, we have performed gene expression profiling to identify IL-6 early response genes. Using the KAS-6/1 IL-6-dependent human myeloma cell line, IL-6 stimulation dramatically induced expression of monocyte chemoattractant protein-1 (MCP-1) mRNA. To verify this result, we used reverse transcriptase PCR and RNAse protection assays and demonstrated using both assays that MCP-1 is indeed an IL-6 responsive gene in a variety of IL-6-responsive myeloma cell lines. Moreover, we also demonstrated IL-6 stimulated MCP-1 secretion by the myeloma cell lines as well as by fresh patient tumor cells. Lastly, we present evidence that fresh patient tumor cells express mRNA for the MCP-1 receptor, CCR2, as do myeloma cell lines along with a second MCP-1 receptor, CCR11. Although MM cell chemotaxis in response to MCP-1 was only minimal, we were able to demonstrate that MCP-1 stimulated activation of MAPK. Because of the important role that this chemokine plays in both angiogenesis and bone homeostasis, and the ability of MCP-1 to activate myeloma cells, these results suggest a new mechanism by which IL-6 may contribute to disease pathogenesis.

29
UI - 12357374
AU - Guida M; D'Elia G; Benvestito S; Casamassima A; Micelli G; Quaranta M;
TI - Moschetta R; De Lena M; Lorusso V Hepatitis C virus infection in patients with B-cell lymphoproliferative disorders.
SO - Leukemia 2002 Oct;16(10):2162-3

30
UI - 12377972
AU - Peggs KS; Mackinnon S; Yong K
TI - Reduced intensity conditioning and allogeneic stem-cell transplantation: determining its role in multiple myeloma.
SO - J Clin Oncol 2002 Oct 15;20(20):4268; discussion 4268-9

31
UI - 12187933
AU - Bush NJ; Griffin-Sobel JP
TI - Respiratory distress in a patient with multiple myeloma.
SO - Oncol Nurs Forum 2002 Aug;29(7):1041-3
AD - njbush@sonnet.ucla.edu

32
UI - 11000991
AU - Attal M; Harousseau JL
TI - Autologous peripheral blood progenitor cell transplantation for multiple myeloma.
SO - Baillieres Best Pract Res Clin Haematol 1999 Mar-Jun;12(1-2):171-91
AD - Service d'Hematologie, CHU Purpan, Place du Docteur Baylac, Toulouse, France.
Autologous stem cell transplantation (ASCT) is increasingly used in the treatment of cases of multiple myeloma (MM) where there has been no significant improvement in the patient's condition following conventional chemotherapy. Peripheral blood progenitor cells (PBPC) have replaced bone marrow as a source of stem cells and offer easier accessibility and availability, faster haematopoietic recovery and possibly lower tumour contamination. The IFM 90 randomized trial has shown that autologous bone marrow transplantation significantly improves response rate, event-free survival (EFS) and overall survival (OS) in younger patients with MM. For MM, this review discusses the role of ASCT, the use of PBPC for autologous transplantation, and current developments of ASCT.

33
UI - 11035146
AU - Courtney PA; Sandhu S; Gardiner PV; Bell AL
TI - Resolution of digital necrosis following treatment of multiple myeloma.
SO - Rheumatology (Oxford) 2000 Oct;39(10):1163-4

34
UI - 11550657
AU - van de Kerkhof JJ; Peters WG; Visser J; Creemers GJ
TI - Acute tumor lysis syndrome in a patient with multiple myeloma treated with dexamethasone monotherapy.
SO - Neth J Med 2001 Aug;59(2):83-5

35
UI - 12171777
AU - Bowcock SJ; Rassam SM; Ward SM; Turner JT; Laffan M
TI - Thromboembolism in patients on thalidomide for myeloma.
SO - Hematology 2002 Feb;7(1):51-3
AD - Department of Haematology, Queen Mary's Sidcup NHS Trust, Sidcup, Kent, DA14 6LT, UK. stella.bowcock@qms-tr.sthames.nhs.uk
Seven cases of thromboembolism were found amongst 23 patients treated with thalidomide for myeloma over a total of 141.5 patient treatment months. Five thromboembolic events were venous (two severe) and two arterial. A historical control of 18 similar patients not given thalidomide had one thromboembolism over 289 months. We found no underlying thrombophilic tendency in the affected patients. We suggest that the thalidomide may predispose to thromboembolism at even lower doses than previously reported (mean dose 150 mg). The two most severe thromboses occurred on 100 mg thalidomide alone, not associated with chemotherapy or glucocorticoids. We raise the possibility that arterial thromboembolism may also occur in association with thalidomide. Some patients continued thalidomide after the event, together with warfarin, with no further thromboembolism.

36
UI - 12365472
AU - Sonneveld P
TI - Tumour lysis syndrome in myeloma.
SO - Neth J Med 2002 Jul;60(6):263

37
UI - 6424890
AU - Delaporte C; Fardeau M
TI - [The effect of serum from a patient with myeloma and diffuse muscular hypertrophy on the growth of human muscle cells in culture]
SO - C R Acad Sci III 1984;298(3):49-54
On normal human muscle cells, the serum of a patient with myeloma producing IgG free kappa light chains and with muscle hypertrophy accelerated the myoblast fusion and the myotubes formed were abnormally large. This serum did not enhance cell proliferation.

38
UI - 2520065
AU - McLain RF; Weinstein JN
TI - Solitary plasmacytomas of the spine: a review of 84 cases.
SO - J Spinal Disord 1989 Jun;2(2):69-74
AD - Department of Orthopaedic Surgery, University of Iowa Hospitals and Clinics, Iowa City 52242.
In order to document the differences in survival between patients with solitary plasmacytoma and those with multiple myeloma involving the spine, we have reviewed the cases of 12 patients with solitary plasmacytoma of the vertebral column treated at the University of Iowa and an additional 72 cases reported in the literature. All patients were followed for 2 years or more without evidence of disseminated disease. The mean disease-free interval for 84 patients was 76 months; 44% of the patients developed disseminated disease, 2-13 years after diagnosis. The 5-year, disease-free survival was 60%. In our study group, survival following dissemination was limited, with a mean of 17 months. This review of 84 cases of solitary plasmacytoma of the spine confirms the significantly greater survival of patients with solitary plasmacytoma, and supports the use of radiotherapy as the treatment modality of choice.

39
UI - 2520084
AU - Abitbol JJ; Botte MJ; Garfin SR; Akeson WH
TI - The treatment of multiple myeloma of the cervical spine with a halo vest.
SO - J Spinal Disord 1989 Dec;2(4):263-7
AD - Division of Orthopaedics and Rehabilitation, University of California, San Diego 92103.
Two patients with multiple myeloma involving the cervical spine and causing instability were treated in a halo vest while radiotherapy and chemotherapy were instituted. Further instability and neurological loss were prevented while continuing this treatment. The bony lesions eventually healed and mechanical stability was restored in both patients. Temporary halo vest placement with concurrent chemo- and/or radiotherapy can be a reasonable and safe alternative to surgery in those patients with multiple myeloma involving the cervical spine, and often results in bone reconstitution and stability.

40
UI - 2980978
AU - Poor MM; Hitchon PW; Riggs CE Jr
TI - Solitary spinal plasmacytomas: management and outcome.
SO - J Spinal Disord 1988;1(4):295-300
AD - Division of Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City 52242.
Nine patients with solitary plasmacytoma of the spine were reviewed. Four of these patients progressed to multiple myeloma within 9 +/- 4 months (mean +/- SD) from diagnosis, and died from their disease in 23 +/- 15 months. In contrast to this, the five remaining patients free of systemic disease or local recurrence survived 78 +/- 66 months. No correlation was found between age at diagnosis, lesion location, symptomatology, laboratory studies, surgical treatment, or radiation dosage and progression to systemic disease. Solitary plasmacytoma will progress to s

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