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National Cancer Institute®
Ultima Vez Modificado: 21 de noviembre del 2001
UI - 97299263
AU - Fang JT; Kuo MC
TI - IgA myeloma associated with decreased anion gap and renal failure.
SO - Ren Fail 1997 May;19(3):481-3
AD - Division of Nephrology, Chang Gung Memorial Hospital, Chang Gung Medical and Technological College, Taipei, Taiwan, Republic of China.
The anion gap in myeloma patients had been well studied. IgG myeloma usually has decreased anion gap, whereas IgA myeloma always presents with normal anion gap. We report an unusual presentation of IgA myeloma with decreased anion gap and renal failure due to superimposing of acetazolamide-related bicarbonate loss.
UI - 21240489
AU - Gonzalez Ordonez AJ; Fernandez Carreira JM; Fernandez Alvarez CR; Martin
TI - L; Sanchez Garcia J; Medina Rodriguez JM; Alvarez MV; Coto E Normal frequencies of the C677T genotypes on the methylenetetrahydrofolate reductase (MTHFR) gene among lymphoproliferative disorders but not in multiple myeloma.
SO - Leuk Lymphoma 2000 Nov;39(5-6):607-12
AD - Hematology Department; Hospital S. Agustin. Aviles, Spain. email@example.com
The folate availability seems to be critical for the DNA integrity since it is required for the transfer of methyl groups in the biosynthesis of thymidilate. Although the excessive incorporation of uracils to the DNA can be efficiently removed, this mechanism of reparation produces many double-strand breaks from two opposing nicks. Several chromosomal abnormalities (mainly translocations and deletions perhaps not well understood) are involved in the origin of lymphoproliferative disorders. The TT homozygosity at nucleotide 677 in the gene of methylene tetrahydrofolatereductase (MTHFR), a key enzyme in folate metabolism, was recently linked to a significant protection against colon carcinoma and acute lymphoblastic leukaemia in adults. We analysed the genotype frequencies of C677T-MTHFR in a group of 143 patients with lymphoproliferative disorders (REAL classification) and 200 controls. Overally, the frequencies of the polymorphic allele were similar (35.3% and 32.0% respectively)(P=0.6). We did not find differences between patients and controls except for myeloma/plasmacytoma group (n=26) which showed a CC genotype less than expected (19% vs 46%) (p=0.01) with a frequency ratio of 0.28 (0.10-0.77). Even among the IgG myeloma cases only one patient showed a common genotype (CC) (1/15, 7%) (P=0.003). If these preliminary data are validated with prospective studies, the 677C allele of MTHFR gene could be confirmed as an effective multiple myeloma protective factor (specially for the IgG cases).
UI - 21237533
AU - Movshev BE; Kalinin NN; Petrov MM; Petrova VI; Zhuravlev VS; Zakharova
TI - ES; Khoroshko ND [Osmotic activity of plasma in plasmapheresis in patients with multiple myeloma]
SO - Ter Arkh 2001;73(2):57-60
AIM: To control safety and efficiency of therapeutic plasmapheresis (PA) by osmolality, colloido-osmotic pressure (COP), total protein concentration before and after the procedure in patients with paraproteinemic hemoblastosis. MATERIAL AND METHODS: 20 patients with multiple myeloma have undergone 42 PA procedures conducted by two techniques: continuous flow centrifugation on blood fractioners or intermittent centrifugation of blood in plastic containers. The removed plasma volume averaged 1/3 (group 1) or 2/3 of the plasma volume (group 2). The removed protein reached 62-197 g. Isotonic sodium chloride solution and/or reopolyglucin (20-60 g) replaced the removed plasm. Total protein concentration was measured colorimetrically in biuretic reaction, plasma osmolality--cryoscopically and COP--on Knauer osmometer. RESULTS: PA leads to a short decline in osmolality (97.0-99.1%), of total protein concentration (82.8-78.6%) and of COD (79.2% in replacement with saline and 90.2% in replacement with dextran). During recovery after the procedure plasma osmotic activity and protein concentration return to the baseline. CONCLUSION: In elimination of 1/3 of plasma volume and crystalloid infusion, hemodilution promotes release of abnormal proteins from the tissues into the circulation and thereafter removal them from the organism. In removal of 1/2 and more of plasma volume, COP demans correction made by administration of colloids, e.g. solution of low molecular dextran. There is a potential danger of COD lowering several hours after PA due to different speed of dextran elimination and mobilization of protein reserve.
UI - 21303122
AU - Fonseca R; Conte G; Greipp PR
TI - Laboratory correlates in multiple myeloma: how useful for prognosis?
SO - Blood Rev 2001 Jun;15(2):97-102
AD - Department of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA. firstname.lastname@example.org
UI - 21370337
AU - de Weerdt O; van de Donk NW; Veth G; Bloem AC; Hagenbeek A; Lokhorst HM
TI - Continuous low-dose cyclophosphamide-prednisone is effective and well tolerated in patients with advanced multiple myeloma.
SO - Neth J Med 2001 Aug;59(2):50-6
AD - Department of Haematology (G.03.647), University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
BACKGROUND: Multiple myeloma is an incurable disease and after several lines of chemotherapy, patients enter a phase in which no standard treatment options are available. The poor outlook of these patients requires mild, palliative therapy with low toxicity. Previously used regimens either require frequent hospital attendance, lack efficacy or have significant toxicity. METHODS: In the current study, daily low dose, oral cyclophosphamide (100 mg) and prednisone (10-20 mg; CP) were administered to patients with advanced myeloma. Forty-two patients with progressive disease after melphalan-based and VAD treatment were enrolled. RESULTS: Objective responses were observed in 29 of 42 (69%) patients. In responding patients, median overall survival and progression-free survival were 22.2 months and 15.0 months, respectively. In non-responders, median OS was 3.5 months only. Side-effects were limited. Cytopenia was the most frequent event (8/29) prompting dose reduction. CP had to be stopped permanently in four patients (two cytopenia, two infections). CONCLUSION: Orally administered, low dose continuous CP is a feasible, effective and well-tolerated regimen in the management of advanced multiple myeloma.
UI - 21433338
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
UI - 21375998
AU - Isoda H; Kojima H; Shimizu K; Kurokawa H; Ikeda K; Sawada S; Sakaida N;
TI - Okamura A Multiple myeloma: short T2 on MR imaging.
SO - Clin Imaging 2001 Mar-Apr;25(2):141-3
AD - Department of Radiology, Kansai Medical University, 10-15, Fumizono-cho, Moriguchi, Osaka 570-8506, Japan.
We describe a rare case of multiple myeloma with marked hypointense areas on both T1- and T2-weighted images. Amyloid deposition and calcification were not found histologically. Hypointensity on T2-weighted images may be caused by distributed free radicals produced by significant macrophages.
UI - 21389238
AU - Thabard W; Collette M; Mellerin MP; Puthier D; Barille S; Bataille R;
TI - Amiot M IL-6 upregulates its own receptor on some human myeloma cell lines.
SO - Cytokine 2001 Jun 21;14(6):352-6
AD - Institut de Biologie, INSERM U463, 9 quai Moncousu, Nantes cedex 01, 44093, France.
Interleukin 6 (IL-6) is the major survival factor of myeloma cells. In this study, we demonstrate that IL-6, oncostatin M (OSM) and leukemia inhibitory factor (LIF) upregulate membrane IL-6 receptor alpha (IL-6Ralpha) on OPM-2 myeloma cell line at transcriptional level. In OPM-2 cells, IL-6, OSM and LIF induce both signal transducers and activators of transcription (STAT), mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI 3-K) activation. We show that the cytokine-induced upregulation of IL-6Ralpha can be abolished by a janus kinase (JAK)-2 specific inhibitor, i.e. AG490, suggesting an involvement of the JAK/STAT pathway in this process. Finally, IL-6Ralpha upregulation was also inhibited by wortmannin, an inhibitor of the PI 3-kinase pathway. In conclusion, IL-6 can upregulate its own receptor on OPM-2 cells probably through the JAK/STAT and PI 3-kinase pathways. Copyright 2001 Academic Press.
UI - 21411474
AU - Kalakonda N; Rothwell DG; Scarffe JH; Norton JD
TI - Detection of N-Ras codon 61 mutations in subpopulations of tumor cells in multiple myeloma at presentation.
SO - Blood 2001 Sep 1;98(5):1555-60
AD - CRC Gene Regulation Group, Paterson Institute for Cancer Research, and CRC Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, United Kingdom.
Activating point mutations in codons 12, 13, or 61 of the K-ras and N-ras genes have been reported to occur in up to 40% of patients with multiple myeloma at presentation. In a study of 34 presentation myeloma cases using a sensitive polymerase chain reaction-restriction fragment length polymorphism strategy on enriched tumor cell populations, the present study detected N-ras codon 61 mutation-positive cells in all patients. Quantitative plaque hybridization using allele-specific oligonucleotide probes showed that in the majority of patients, ras mutation-positive cells comprise only a subpopulation of the total malignant plasma cell compartment (range, 12%-100%). Using clonospecific point mutations in the 5' untranslated region of the BCL6 gene to quantitate clonal B cells in FACS-sorted bone marrow populations from 2 patients, the representation of ras mutation-positive cells was independent of immunophenotype. These observations imply that mutational activation of N-ras codon 61 is a mandatory event in the pathogenesis of multiple myeloma; such mutations provide a marker of intraclonal heterogeneity that may originate at an earlier ontologic stage than immunophenotypic diversification of the malignant B cell clone.
UI - 21411482
AU - Zangari M; Anaissie E; Barlogie B; Badros A; Desikan R; Gopal AV; Morris
TI - C; Toor A; Siegel E; Fink L; Tricot G Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy.
SO - Blood 2001 Sep 1;98(5):1614-5
AD - Central Arkansas Veterans Healthcare System and the University of Arkansas for Medical Sciences, Little Rock, AR, USA. email@example.com
The occurrence of deep-vein thrombosis (DVT) in patients with newly diagnosed multiple myeloma, who were randomly assigned to receive identical induction chemotherapy with or without thalidomide, are reported in this study. The 2 study arms were comparable with respect to key myeloma prognostic factors and known risk factors for DVT. One hundred patients received induction chemotherapy including 4 cycles of continuous infusion of combinations of dexamethasone, vincristine, doxorubicin, cyclophosphamide, etoposide, and cisplatin, and each patient completed at least one induction cycle. DVT developed in 14 of 50 patients (28%) randomly assigned to receive thalidomide but in only 2 of 50 patients (4%) not given the agent (P =.002). All episodes of DVT occurred during the first 3 cycles of induction. Administration of thalidomide was resumed safely in 75% of patients receiving anticoagulation therapy. Thus, thalidomide given in combination with multiagent chemotherapy and dexamethasone is associated with a significantly increased risk of DVT, which appears to be safely treated with anticoagulation and does not necessarily warrant discontinuation of thalidomide.
UI - 21426230
AU - Villasante De La Puente A; Hormaechea Beldarrain JA; Garcia Aguinaga ML;
TI - Vera Lopez E; Gilsanz Fernandez C [Pustulosis of Sneddon Wilkinson disease and multiple myeloma]
SO - An Med Interna 2001 Jul;18(7):373-5
AD - Medicina Interna I, Hospital General Universitario Gregorio Maranon, Madrid.
A case of subcorneal pustular dermatosis is described, this disease is not very common. Its origin remains unknown, there are some data that indicate an immunological basis because of its associations to hematological disorders and others autoimmune diseases. The diagnosis is based on clinic suspects and the histopathological analysis. The differentiation among other dermatosis like pustular psoriasis, due to its therapeutic implication and evolution. This patient developed an IgA-K myeloma after nine years of evolution, a very common finding in this disease. It has not definitive treatment, being corticosteroids and sulfonamides more effective. The prognosis depends on the appearance of complications and associated processes.
UI - 21447295
AU - Kaufmann H; Urbauer E; Ackermann J; Huber H; Drach J
TI - Advances in the biology and therapeutic management of multiple myeloma.
SO - Ann Hematol 2001 Aug;80(8):445-51
AD - Department of Internal Medicine I, University of Vienna, Austria.
During the past decade, new developments have increased our understanding of the biological features of multiple myeloma (MM), and novel therapeutic approaches have improved the outcome and quality of life. The importance of both the malignant clone and the bone marrow environment for disease evolution and propagation has been recognized, and therapeutic approaches that target both components of the disease process appear to be most promising. Along this line, thalidomide has been observed to exert activity in chemotherapy-refractory MM and thus expands the therapeutic armamentarium against MM. Use of high-dose melphalan with autologous stem cell transplantation has resulted in an improved rate of complete remissions as well as prolonged event-free and overall survival. Novel treatment strategies exploiting anti-myeloma immunity (nonmyeloablative allogeneic transplantation, vaccination) are being investigated and carry the potential to further improve the outcome of patients with MM.
UI - 21447296
AU - Murakami H; Hayashi K; Hatsumi N; Saitoh T; Yokohama A; Matsushima T;
TI - Tsukamoto N; Morita K; Karasawa M; Ogawara H; Sawamura M; Nojima Y Risk factors for early death in patients undergoing treatment for multiple myeloma.
SO - Ann Hematol 2001 Aug;80(8):452-5
AD - School of Health Sciences, Faculty of Medicine, Gunma University, Japan. firstname.lastname@example.org
The survival time of myeloma patients improved from a few months to many years after treatment with melphalan. Perhaps chemotherapy more intensive than melphalan-prednisolone should be administered to patients at risk of early death. Therefore, early death must be accurately predicted. We analyzed 93 patients with recently diagnosed myeloma and found that 13 (14%) died within 6 months (early death). The most common cause of death was bacterial and fungal pneumonia when myeloma became uncontrollable. The response to conventional chemotherapy was poorer in patients at high risk of early death than the control group. Multivariate analysis showed that the serum level of beta-2 microglobulin was the only value that predicted early death.
UI - 21447301
AU - Kaufmann H; Ackermann J; Nosslinger T; Kromer E; Zojer N; Schreiber S;
TI - Urbauer E; Heinz R; Ludwig H; Huber H; Drach J Absence of clonal chromosomal relationship between concomitant B-CLL and multiple myeloma--a report on two cases.
SO - Ann Hematol 2001 Aug;80(8):474-8
AD - University of Vienna, 1st Department of Internal Medicine, Austria.
B-cell chronic lymphocytic leukemia (B-CLL) and multiple myeloma (MM) are chronic B-cell malignancies that represent different stages of B-cell maturation. Occasionally, both diseases are present in the same patient, and this raises the question of clonal associations between the two neoplasms. We here report on two patients with concomitant B-CLL and MM. Clonal chromosomal abnormalities in both lymphocytic cells and plasma cells were studied by interphase fluorescence in situ hybridization (FISH) using a panel of 24 chromosome- and region-specific DNA probes. In the first patient, cytogenetics revealed 47, X, t(Y;22)(p11;q10), +12, dell4(q21q32). By FISH, +12 was present in lymphoid cells, but not in plasma cells. MM cells were characterized by multiple chromosomal gains (1, 11q23) and losses (5q, 10, 13q14, 15, 17p13, Y), which were all undetectable in lymphoid cells. The second patient, in whom no clonal abnormalities were obtained by conventional cytogenetic analysis, had lymphoid cells with loss of 8q24 by FISH. In contrast, evidence for a gain of 8q24 (consistent with amplification of c-myc) was obtained in 13% of plasma cells. Plasma cells were further characterized by gains of chromosomes 1, 3, 11, 18, and Y. We thus conclude that this comprehensive molecular cytogenetic analysis demonstrates the existence of two clonally distinct B-cell malignancies in both patients.
UI - 21439116
AU - Neben K; Moehler T; Egerer G; Kraemer A; Hillengass J; Benner A; Ho AD;
TI - Goldschmidt H High plasma basic fibroblast growth factor concentration is associated with response to thalidomide in progressive multiple myeloma.
SO - Clin Cancer Res 2001 Sep;7(9):2675-81
AD - Department of Internal Medicine V, University of Heidelberg, 69115 Heidelberg, Germany. email@example.com
The aim of this study was to define prognostic factors that might be predictive for response to thalidomide (Thal) in progressive multiple myeloma (n = 54). We examined the concentration of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), two potent heparin-binding mediators of angiogenesis in peripheral blood (PB; PB-VEGF and PB-bFGF) and bone marrow (BM; BM-VEGF and BM-bFGF), in combination with well-characterized predictors for response and survival to chemotherapy. After a median follow-up time of 15 months (range, 0.3-20), 29 patients (pts.) showed at least a minimal response to Thal therapy, whereas 25 pts. were nonresponsive. As shown by univariate analysis, responsive pts. had statistically significant higher concentrations of PB-bFGF (P = 0.009) and beta2-microglobulin (P = 0.03) before therapy, as well as lower hemoglobin (P = 0.008) and albumin (P = 0.02) levels, whereas no statistically significant difference was found for PB-VEGF (P = 0.93). When a multiple logistic regression analysis was performed, PB-bFGF was the only statistically significant predictor for response to therapy (P = 0.01). None of these variables was associated with a prolonged progression-free survival. In conclusion, our findings indicate that high pretreatment plasma bFGF levels in pts. with progressive multiple myeloma are associated with unfavorable parameters of response and survival but nevertheless predict for response to Thal therapy.
UI - 20346882
AU - Kunzmann V; Bauer E; Feurle J; Weissinger F; Tony HP; Wilhelm M
TI - Stimulation of gammadelta T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma.
SO - Blood 2000 Jul 15;96(2):384-92
AD - Medizinische Poliklinik Wuerzburg, Julius-Maximilians Universitat Wuerzburg, Wuerzburg, Germany.
Bisphosphonates are well-known inhibitors of osteoclastic bone resorption, but recent clinical reports support the possibility of direct or indirect antitumor effects by these compounds. Because bisphosphonates share structural homologies with recently identified gamma delta T-cell ligands, we examined the stimulatory capacity of bisphosphonates to gamma delta T cells and determined whether gamma delta T-cell stimulation by bisphosphonates could be exploited to generate antiplasma cell activity in multiple myeloma (MM). All tested aminobisphosphonates (alendronate, ibandronate, and pamidronate) induced significant expansion of gamma delta T cells (V gamma 9V delta 2++ subset) in peripheral blood mononuclear cell cultures of healthy donors at clinically relevant concentrations (half-maximal activity, 0.9-4 mcmol/L). The proliferative response of gamma delta T cells to aminobisphosphonates was IL-2 dependent, whereas activation of gamma delta T cells (up-regulation of CD25 and CD69) occurred in the absence of exogenous cytokines. Pamidronate-activated gamma delta T cells produced cytokines (ie, interferon [IFN]-gamma) and exhibited specific cytotoxicity against lymphoma (Daudi) and myeloma cell lines (RPMI 8226, U266). Pamidronate-treated bone marrow (BM) cultures of 24 patients with MM showed significantly reduced plasma cell survival compared with untreated cultures, especially in cultures in which activation of BM-gamma delta T cells was evident (14 of 24 patients with MM). gamma delta T-cell depletion from BM cultures completely abrogated the cytoreductive effect on myeloma cells in 2 of 3 tested patients with MM. These results show that aminobisphosphonates stimulating gamma delta T cells have pronounced effects on the immune system, which might contribute to the antitumor effects of these drugs. (Blood. 2000;96:384-392)
UI - 20563958
AU - Rasmussen T; Jensen L; Honore L; Johnsen HE
TI - Frequency and kinetics of polyclonal and clonal B cells in the peripheral blood of patients being treated for multiple myeloma.
SO - Blood 2000 Dec 15;96(13):4357-9
AD - Department of Hematology L, Herlev Hospital, University of Copenhagen, Herlev, Denmark. firstname.lastname@example.org
Recent studies concerning the numbers of circulating clonal B cells in patients with multiple myeloma (MM) have reported conflicting data regarding the exact level and phenotype of clonal B cells and their response to treatment. In this report we document that the peripheral blood tumor burden at presentation was reduced by induction therapy to a low level, regardless of the initial tumor burden. However, the residual clonal compartment persisted before and after transplant. The level of clonal cells showed no correlation with CD19(+) cell levels. In a single patient with MM, high numbers of phenotypically aberrant clonal cells with altered CD19 expression were identified. (Blood. 2000;96:4357-4359)
UI - 21226352
AU - Dammacco F; Castoldi G; Rodjer S
TI - Efficacy of epoetin alfa in the treatment of anaemia of multiple myeloma.
SO - Br J Haematol 2001 Apr;113(1):172-9
AD - Department of Internal Medicine and Clinical Oncology, University of Bari, Bari, Italy. email@example.com
Effects of epoetin alfa on transfusions, haemoglobin (Hb) and quality of life (QOL) were evaluated in a placebo-controlled study of 145 patients with multiple myeloma and anaemia (Hb < 11 g/dl). During the 12-week, double-blind phase, patients received 150 IU/kg epoetin alfa or a matching volume of placebo subcutaneously three times weekly; the dose (or volume) was doubled at week 4 if Hb response was inadequate. Patients completing this phase could enter the subsequent optional 12-week phase of open-label epoetin alfa treatment. During double-blind treatment, epoetin alfa significantly decreased the incidence of transfusion compared with placebo (28% vs. 47%, P = 0.017), regardless of patients' transfusion history, and increased mean Hb (1.8 g/dl vs. 0.0 g/dl, P < 0.001). Univariate analysis showed significant (P = 0.05) improvement in more QOL measures with epoetin alfa than with placebo; multivariate analysis discerned no between-treatment differences. Significantly (P = 0.038) more epoetin alfa vs. placebo patients had improved performance scores. At the end of the open-label treatment phase, patients who had continued epoetin alfa maintained Hb status, and placebo patients who were switched to epoetin alfa had mean Hb increases of 2.4 g/dl. Adverse events were similar between treatment groups. Epoetin alfa proved effective and well tolerated for treating anaemia in patients with multiple myeloma.
UI - 21241659
AU - Varkonyi J; Kovalszky I; Nemeth A; Demeter J; Raposa T
TI - Increased risk for cancer in multiple myeloma patients and their first-degree relatives.
SO - Haematologia (Budap) 2001;31(1):45-50
AD - 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
Analyzing data of 125 multiple myeloma patients, the authors found a 40-fold increased tumor incidence among the patients and their first-degree relatives as compared to the average population. These tumors were the same as those usually found among Hungarians. There was no difference as to the patient's blood group antigens in the families of myeloma patients with or without other tumor. IgA-type disease was found to be relatively more frequent in the group of patients who had tumor besides myeloma. In a prospective study, authors could not find mutation of suppressor gene p53 in 14 patients and their 16 healthy first-degree relatives. This may indicate that there is no p53 suppressor gene alteration responsible for the high-risk condition for tumorgenesis in this population.
UI - 21317100
AU - Rossi L; Cardarelli F; Vampa ML; Buzio C; Olivetti G
TI - Membranous glomerulonephritis after haematopoietic cell transplantation for multiple myeloma.
SO - Nephron 2001 Jul;88(3):260-3
AD - Dipartimenti di Clinica Medica, Nefrologia e Scienze della Prevenzione e, Sezione di Anatomia Patologica, Universita degli Studi, Parma, Italia.
Renal involvement during graft-versus-host disease following haematopoietic cell transplantation for multiple myeloma has never been described. We report a case of a recipient who developed nephrotic syndrome and membranous glomerulonephritis 22 months after the graft and 6 months after cyclosporine withdrawal. Symptoms resolved when immunosuppressive therapy was reinstituted. Copyright 2001 S. Karger AG, Basel
UI - 21378253
AU - Wan X; Tarantolo S; Orton DF; Greiner TC
TI - Primary extramedullary plasmacytoma in the atria of the heart.
SO - Cardiovasc Pathol 2001 May-Jun;10(3):137-9
AD - Department of Pathology and Microbiology, University of Nebraska Medical Center, 983332 Nebraska Medical Center, 68198-3332, Omaha, NE, USA.
A rare case of primary extramedullary plasmacytoma of the heart is described. The large space-occupying tumor in the atrial wall and its associated significant pericardial effusion caused marked impairment of cardiovascular function. The diagnosis was made via intravenous biopsy. Immunohistochemistry demonstrated CD45 and kappa light chain expression. Other B-cell- and T-cell-specific lymphoid markers were negative. Elevated kappa light chain was detected in serum by immunofixation electrophoresis. The differential diagnosis of plasmacytoma should be considered in cardiac tumors when routine screening is negative with lymphoid (CD20, CD3) and soft tissue immunohistochemical markers.
UI - 21400381
AU - Bilgrami S; Bona RD; Edwards RL; Li Z; Naqvi B; Shaikh A; Furlong F; Fox
TI - J; Clive J; Tutschka PJ Dexamethasone, paclitaxel, etoposide, cyclophosphamide (d-TEC) and G-CSF for stem cell mobilisation in multiple myeloma.
SO - Bone Marrow Transplant 2001 Jul;28(2):137-43
AD - Bone Marrow Transplant Program, University of Connecticut Health Center, Farmington, CT 06030, USA.
Forty-one patients with multiple myeloma were treated with a novel stem cell mobilisation regimen. The primary end points were adequate stem cell mobilising ability (>1% circulating CD34-positive cells) and collection (> or = 4 x 10(6) CD34-positive cells/kg), and safety. The secondary end point was activity against myeloma. The regimen (d-TEC) consisted of dexamethasone, paclitaxel 200 mg/m(2) i.v., etoposide 60 mg/kg i.v., cyclophosphamide 3 g/m(2) i.v., and G-CSF 5-10 microg/kg/day i.v. A total of 84 cycles were administered to these 41 individuals. Patient characteristics included a median age of 53 years, a median of five prior chemotherapy cycles, and a median interval of 10 months from diagnosis of myeloma to first cycle of d-TEC. Seventy-five percent of the patients had stage II or III disease, 50% had received carmustine and/or melphalan previously, and 25% had received prior radiation therapy. Eighty-eight percent of patients mobilised adequately after the first cycle of d-TEC and 91% mobilized adequately after the second cycle. An adequate number of stem cells were collected in 32 patients. Of the remaining nine patients, three mobilised, but stem cells were not collected, two mobilised but stem cell collection was < 4 x 10(6) CD34-positive cells/kg, three did not mobilise, and one died of disease progression. Major toxicities included pancytopenia, alopecia, fever and stomatitis. One patient died from multi-organ failure and progressive disease. Fifty percent of evaluable patients demonstrated a partial response and 28.6% of patients had a minor response. This novel dose-intense regimen was safe, capable of stem cell mobilisation and collection, even in heavily pre-treated patients, and active against the underlying myeloma.
UI - 21411346
AU - Lim JC; de Luna RH; Eldibany MM
TI - Pathologic quiz case: an 86-year-old woman with refractory anemia.
SO - Arch Pathol Lab Med 2001 Sep;125(9):1249-50
AD - Department of Pathology, University of Illinois-Metropolitan Group Hospitals, Illinois Masonic Medical Center, Chicago, USA.
UI - 21423323
AU - Kahara T; Nagai Y; Yamashita H; Nohara E; Kobayashi K; Takamura T
TI - Extramedullary plasmacytoma in the adrenal incidentaloma.
SO - Clin Endocrinol (Oxf) 2001 Aug;55(2):267-70
AD - First Department of Internal Medicine, School of Medicine, Kanazawa University, Kanazawa, Ishikawa, Japan.
High-resolution imaging has led to the increasingly frequent discovery of adrenal incidentalomas. Most are nonfunctioning tumours and adenomas, but it is difficult to distinguish benign from malignant tumours using only morphological and laboratory data, and the diagnosis often remains uncertain without histological examination. Here we report the case of a 52-year-old Japanese man who had a right adrenal incidentaloma 4 cm in diameter. The tumour was removed by laparoscopic adrenalectomy. The pathology specimen revealed the typical histology of plasmacytoma. Extramedullary plasmacytoma is a very rare type of plasma cell proliferative disorder. This is the first documented case of an extramedullary plasmacytoma in the adrenal gland.
UI - 21418710
AU - Abe R; Ishibashi T; Shichishima T; Maruyama Y
TI - Ten-year survivor with multiple myeloma in first complete remission following treatment with conventional chemotherapy. Case report and a review of the literature.
SO - Acta Haematol 2001;105(4):241-3
AD - First Department of Internal Medicine, Fukushima Medical University, 1-Hikarigaoka, Fukushima, 960-1295, Japan.
A 62-year-old woman with multiple myeloma, who has been in complete remission (CR) for 10 years, is reported. The patient was treated with conventional chemotherapy, including nitrosourea derivatives. Five patients with myeloma, including the present case, who have survived for 10 years or more in CR and on whom detailed clinical descriptions were published, are reviewed. Their disease condition represented "a cure" or "a state extremely close to cure". The review indicates the following favorable prognostic factors common to these patients: age < or =65 years and a rapid response to treatment. Progressive bone destruction and/or lytic changes at disease onset is perhaps not a bad prognostic factor in myeloma patients with excellent outcome. Copyright 2001 S. Karger AG, Basel
UI - 21418712
AU - Cunha A; Costa SC; Lima CS; Ortega M; Costa FF
TI - Low incidence of human herpesvirus 8 in bone marrow samples from Brazilian patients with multiple myeloma.
SO - Acta Haematol 2001;105(4):247-8
AD - Department of Internal Medicine and Department of Clinical Pathology, University of Campinas (UNICAMP), CEP Campinas, SP, 13083-970, Brazil.
UI - 21456416
AU - Rasmussen T
TI - [Gene expression analysis of myelomatosis]
SO - Ugeskr Laeger 2001 Sep 3;163(36):4851-2
AD - Amtssygehuset i Herlev, haematologisk afdeling L. firstname.lastname@example.org
UI - 21437192
AU - Yata K; Sadahira Y; Otsuki T; Sakaguchi H; Isozaki Y; Uno M; Kurebayashi
TI - J; Fujii T; Eda S; Ueki A; Yawata Y; Yamada O; Sugihara T Cell cycle analysis and expression of cell cycle regulator genes in myeloma cells overexpressing cyclin D1.
SO - Br J Haematol 2001 Sep;114(3):591-9
AD - Division of Haematology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Among the recently discovered myeloma-specific gene alterations associated with chromosomal translocations, cyclin D1/PRAD1/Bcl-1 overexpression caused by t(11;14)(q13;q32) is considered to be the most frequent in myeloma patients and cell lines, and may be a prognostic factor clinically. To elucidate the cellular biological role of overexpressed cyclin D1 in myeloma cells, we examined the mRNA expression levels of cell cycle regulators including three cyclin Ds, cyclin-dependent kinase inhibitors (CDK-Is) and accelerators. Cyclin D1 overexpression was clearly demonstrated in the lines with abnormal 11q13 and associated with overexpression of S and G2 accelerator genes. The cyclin D1-overexpressing lines tended to have a shortened G1 phase compared with the non-expressing lines. In addition, artificial silencing using antisense oligonucleotides for cyclin D1 suppressed the growth rate of some but not all cyclin D1-overexpressing cells. These results indicate that overexpression of cyclin D1 caused by cytogenetic abnormalities may make cells progress through the cell cycle rapidly, but it seems that other factors such as cyclin D2 and translocation-related genes affect the cell cycle progression in myeloma cells.
UI - 21437193
AU - Badros A; Barlogie B; Siegel E; Morris C; Desikan R; Zangari M; Fassas
TI - A; Anaissie E; Munshi N; Tricot G Autologous stem cell transplantation in elderly multiple myeloma patients over the age of 70 years.
SO - Br J Haematol 2001 Sep;114(3):600-7
AD - Myeloma and Transplantation Research Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA. AZB@earthlink.net
The feasibility and efficacy of autologous stem cell transplantation (auto-SCT) in patients aged > or = 70 years was analysed. Newly diagnosed (n = 34) and refractory multiple myeloma (n = 36) patients were studied. The median age was 72 years (range: 70-82.6). CD34+ cells were mobilized with chemotherapy and granulocyte colony-stimulating factor (G-CSF) (n = 35) or G-CSF alone (n = 35), yielding medians of 11.8 x 10(6) versus 8 x 10(6) cells/kg respectively (P = 0.007). Because of excessive mortality (16%) in the first 25 patients who received melphalan 200 mg/m2 (MEL-200), the dose was subsequently decreased to 140 mg/m2 (MEL-140). Median times to absolute neutrophil count (ANC) > 0.5 x 10(9)/l and to platelets > 20 x 10(9)/l were 11 and 13 d respectively. Thirty-one patients (44%) received tandem auto-SCT. Complete remission (CR) was 20% after the first SCT and 27% after tandem SCT. Median CR duration was 1.5 years and was significantly longer for patients with < or = 12 months of prior chemotherapy (2.6 versus 1.0 years, P = 0.0008). The 3-year event-free survival (EFS) and overall survival (OS) (+ standard error, SE) were projected at 20% + 9% and 31% + 10% respectively. Tandem SCTs positively affected EFS (4.0 versus 0.7 years; P = 0.003) and OS (4.0 versus 1.4 years; P = 0.02) compared with single auto-SCT. In conclusion, MEL-140 is less toxic and appears equally as efficacious as MEL-200 in elderly patients. The benefits of tandem SCT in this patient population need further evaluation in a randomized trial.
UI - 21441839
AU - Wilson CS; Medeiros LJ; Lai R; Butch AW; McCourty A; Kelly K; Brynes RK
TI - DNA topoisomerase IIalpha in multiple myeloma: a marker of cell proliferation and not drug resistance.
SO - Mod Pathol 2001 Sep;14(9):886-91
AD - Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. email@example.com
DNA topoisomerase IIalpha (topo IIalpha) is the target for a number of antineoplastic agents. Down-regulation of this enzyme is one form of drug resistance. Topo IIalpha is also involved in DNA replication and transcription and serves as an indicator of proliferation rate in many human malignancies. This study examines whether topo IIalpha is one of the mechanisms of chemoresistance commonly observed in multiple myeloma (MM) or alternatively, whether topo IIalpha is associated with tumor cell proliferation. Bone marrow (BM) biopsy sections from 72 cases of MM, stratified according to proliferative activity (bromodeoxyuridine uptake), were immunostained for topo IIalpha. Immunoreactivity with an additional marker of drug resistance, glutathione-S-transferase pi, and the proliferation marker Ki-67 were also examined. Topo IIalpha was expressed in 26 (36%) cases and correlated strongly with proliferative activity (P <.001). A role for drug resistance could not be supported, given this strong relationship with proliferation and the finding that glutathione-S-transferase pi expression in 57 (78%) cases was independent of topo IIalpha immunoreactivity. Topo IIalpha was identified in 91 to 100% of highly proliferative tumors, as evaluated by bromodeoxyuridine uptake or Ki-67 reactivity, respectively. Proliferation also correlated with the histologic grade of the MM. Therefore, topo IIalpha immunoreactivity is primarily a marker of cell proliferation in MM and as such is likely to have prognostic significance. Highly proliferative tumors are most likely to be sensitive to chemotherapeutic protocols using anti-topo IIalpha agents.
UI - 21455865
AU - Rivet J; Moreau D; Daneshpouy M; Schlemmer B; Leleu G; Baumelou E; Rio
TI - B; Brison O; Janin A T-cell lymphoma with eosinophilia of donor origin occurring 12 years after allogeneic bone marrow transplantation for myeloma.
SO - Transplantation 2001 Sep 15;72(5):965
UI - 21461969
AU - Durie BG
TI - Multiple myeloma: what's new.
SO - CA Cancer J Clin 2001 Sep-Oct;51(5):271-2, 263
With conventional therapy, only 5% of multiple myeloma patients achieve complete response. But in recent clinical trials of high-dose therapy with autologous hematopoietic stem cell transplant, complete remission rates of 25-30% can be affected with median survival exceeding 5 years. Newer approaches in clinical trials, including more potent induction regimens utilizing thalidomide, alone or in combination with dexamethasone, are improving treatment outcomes. The authors suggest that potential for a cure now appears to be within reach.
UI - 21461970
AU - Zaidi AA; Vesole DH
TI - Multiple myeloma: an old disease with new hope for the future.
SO - CA Cancer J Clin 2001 Sep-Oct;51(5):273-85; quiz 286-9
AD - Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, USA.
Multiple myeloma is a currently incurable malignancy of terminally differentiated plasma cells. It typically occurs in older patients (median age 71 years). Clinical manifestations result from monoclonal protein (immunoglobulin) production and its accumulation in the serum and/or urine, anemia, lytic bone disease, hypercalcemia, renal insufficiency, and immune deficiency. Myeloma cells have low proliferative activity--most myeloma experts opine that the initial oncogenic event occurs 10-15 years before clinical disease manifestation. In addition, myeloma cells develop multiple chromosomal abnormalities, which may explain the native resistance of myeloma patients to conventional therapy and our inability to completely eradicate the disease. Indeed, with conventional therapy, only 5% of patients achieve complete response. Minimal improvement has been observed with conventional therapies over the past 20-30 years; the median duration of initial response remains approximately 18 months with median survival in the 36-month range. However, recent clinical trials have established high-dose therapy with autologous hematopoietic stem cell transplant as superior to conventional therapy: complete remission rates of 25-30% can be affected with median survival exceeding 5 years. Newer approaches to improve treatment outcomes are in active clinical trials including: more potent induction regimens utilizing thalidomide, alone or in combination with dexamethasone; tandem transplants to improve complete remission rates; newer approaches to maintenance therapy using thalidomide with corticosteroids; non-myeloablative therapy with allogeneic transplant; and post-transplant vaccinations.
UI - 21464086
AU - Chou T
TI - [Multiple myeloma--advances in disease biology and implications for therapy]
SO - Gan To Kagaku Ryoho 2001 Sep;28(9):1206-12
AD - Department of Internal Medicine, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Niigata 951-8566, Japan.
Multiple myeloma (MM) is a systemic malignancy of pathologic plasma cells that is treatable with various chemotherapeutic agents and irradiation, but rarely curable. The mean age of affected patients is the mid-60s. Since the clinical presentation of multiple myeloma varies from asymptomatic to aggressive progression, there are many therapeutic options, such as follow-up without any treatment, and high-dose chemotherapy with stem cell transplantation. Recent advances in disease biology and implications for therapy are reviewed and summarized.
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