National Cancer Institute®
Ultima Vez Modificado: 1 de agosto del 2002
UI - 12124883
AU - Chung JB; Albert DA
TI - Clinical images: osteosclerotic myeloma associated with the POEMS syndrome.
SO - Arthritis Rheum 2002 Jul;46(7):1968
AD - University of Pennsylvania, Philadelphia, PA, USA.
UI - 11858359
AU - Lamboley V; Zabraniecki L; Sie P; Pourrat J; Fournie B
TI - Myeloma and monoclonal gammopathy of uncertain significance associated with acquired von Willebrand's syndrome. Seven new cases with a literature review.
SO - Joint Bone Spine 2002 Jan;69(1):62-7
AD - Department of rheumatology, CHU Purpan, Toulouse, France.
OBJECTIVES: Acquired von Willebrand's syndrome (AvWS) is an uncommon complication of monoclonal gammopathy of uncertain significance (MGUS) or myeloma. We investigated clinical and laboratory test abnormalities, pathophysiological hypotheses, and treatment options in this poorly known condition. PATIENTS: Five patients with MGUS and two with myeloma who met classic criteria for acquired von Willebrand's syndrome were included in this retrospective study. RESULTS: Acquired von Willebrand's syndrome was diagnosed before the gammopathy in five of the seven patients. The severity of the bleeding events was chiefly dependent on the degree of von Willebrand's factor deficiency and on the presence or absence of gastrointestinal tract angiodysplasia. Bleeding event severity was similar in patients with nonmalignant and malignant disease. An antibody that inhibited von Willebrand's factor was detected in all seven patients. Clotting returned to normal after treatment of the malignancy in one of the two patients with myeloma. In patients with MGUS, treatment is warranted only when bleeding occurs or before surgery. Von Willebrand's factor concentrates were of limited efficacy because of their short half-life. Intravenous immunoglobulins had a longer-lasting effect (about 3 weeks); this treatment was used on a regular basis in two patients with recurrent bleeding. CONCLUSIONS: A diagnosis of von Willebrand's syndrome in adulthood should prompt a search for a monoclonal gammopathy. In patients with gammopathies, simple clotting tests ensure the diagnosis of acquired von Willebrand's syndrome.
UI - 12113124
AU - Rajkumar SV
TI - Thalidomide in the treatment of multiple myeloma.
SO - Expert Rev Anticancer Ther 2001 Jun;1(1):20-8
AD - Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. firstname.lastname@example.org
Thalidomide--banned from clinical use in the 1960s because of severe teratogenicity--is now back in clinical practice as an effective agent in the treatment of relapsed and refractory multiple myeloma. Several clinical trials have determined that thalidomide is active in 25-35% of patients with relapsed myeloma. The role of thalidomide in early-stage myeloma is being actively investigated. Thalidomide has antiangiogenic and immunomodulatory properties and is an effective inhibitor of TNF-alpha. However, the mechanism of its action in myeloma remains unclear. Major toxicities of thalidomide include constipation, sedation, skin rash, fatigue and peripheral neuropathy. This paper summarizes the current status of thalidomide in multiple myeloma.
UI - 12144086
AU - Abdalla IA; Tabbara IA
TI - Nonsecretory multiple myeloma.
SO - South Med J 2002 Jul;95(7):761-4
AD - Bone Marrow Transplant Program, George Washington University Medical Center, Washington, DC 20037, USA.
Nonsecretory multiple myeloma (NSMM) is a rare variant of the classic form of multiple myeloma (MM) and accounts for 1% to 5% of all cases of MM. The clinical presentation and radiographic findings of NSMM and MM are the same. The diagnosis of MM requires the detection of a monoclonal gammopathy in the serum or urine. In NSMM, however, no such gammopathy can be demonstrated, making the diagnosis more difficult. We describe a 43-year-old African American woman who initially had back pain and pathologic vertebral compression fractures that were thought to be due to osteoporosis. Five months later, hypercalcemia developed and NSMM was diagnosed. No monoclonal gammopathy was found in the serum or urine, but skeletal survey showed diffuse osteolytic lesions, and bone marrow biopsy revealed marked plasmacytosis. The immunohistochemical techniques and chromosomal analysis methods that are currently available are discussed.
UI - 12008088
AU - Savage DG; Mears JG; Balmaceda C; Rescigno J; Shendrik I; Mansukhani M;
TI - Orazi A Leptomeningeal relapse of multiple myeloma following allogeneic stem cell transplantation.
SO - Leuk Res 2002 Jul;26(7):689-92
AD - Hematology/Oncology Division, Columbia University College of Physicians and Surgeons, 177 Fort Washington Avenue, New York City, NY 10032, USA. email@example.com
Progressive multiple myeloma may manifest features of 'de-differentiation', including a plasmablastic appearance, failure to secrete paraprotein, extramedullary involvement, and resistance to treatment. A 44-year-old woman with kappa-light chain myeloma underwent allogeneic stem cell transplantation (SCT). Twenty months later she developed paraspinal plasmablastic myeloma in the absence of paraprotein in urine or myeloma in the marrow. The paraspinal masses responded to chemotherapy. At 30 months she developed myelomatous meningitis, which proved resistant to intrathecal chemotherapy, irradiation, and donor lymphocyte infusion (DLI). The leptomeningeal disease led to death at 38 months. This is the first report of leptomeningeal relapse of myeloma after allografting.
UI - 12097303
AU - Akiyama M; Hideshima T; Hayashi T; Tai YT; Mitsiades CS; Mitsiades N;
TI - Chauhan D; Richardson P; Munshi NC; Anderson KC Cytokines modulate telomerase activity in a human multiple myeloma cell line.
SO - Cancer Res 2002 Jul 1;62(13):3876-82
AD - Jerome Lipper Multiple Myeloma Center, Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Telomerase is a ribonucleoprotein DNA polymerase that elongates the telomeres of chromosomes to compensate for losses that occur with each round of DNA replication and maintain chromosomal stability. Interleukin 6 (IL-6) and insulin-like growth factor 1 (IGF-1) are proliferative and survival factors for human multiple myeloma (MM) cells. To date, however, the effects of IGF-1 and IL-6 on telomerase activity and associated sequelae in MM cells have not been characterized. In this study, we evaluated the effects of IGF-1 and IL-6 on telomerase activity in MM cell lines (MM.1S, U266, and RPMI 8226), as well as patient MM cells. We show that these cytokines up-regulate telomerase activity without alteration of human telomerase reverse transcriptase (hTERT) protein expression. We also demonstrate that increased telomerase activity triggered by these cytokines is mediated by phosphatidylinositol 3'-kinase (PI3k)/Akt/nuclear factor kappaB (NFkappaB) signaling. We confirm involvement of PI3k/Akt/NFkappaB signaling because the PI3k inhibitors wortmannin and LY294002 or the inhibitor of NFkappaB (IkappaB) kinase inhibitor PS-1145 block constitutive and cytokine-induced up-regulation of telomerase activity. Furthermore, we show that dexamethasone (Dex) reduces telomerase activity through the inhibition of hTERT expression before the induction of apoptosis. Importantly, IGF-1 and IL-6 abrogate Dex-induced down-regulation of telomerase activity and apoptosis. The protective effect of those cytokines against Dex-induced down-regulation of telomerase activity is blocked by both wortmannin and PS-1145, whereas the protection against Dex-induced apoptosis is blocked by wortmannin but not PS-1145. Therefore, our results demonstrate that telomerase activity is related not only to transcriptional regulation of hTERT by NFkappaB but also to posttranscriptional regulation because of phosphorylation of hTERT by Akt kinase. These studies therefore demonstrate that telomerase activity is associated with cell growth, survival, and drug resistance in MM cells.
UI - 10966172
AU - Tsiara SN; Kapsali E; Christou L; Panteli A; Pritsivelis N; Bourantas KL
TI - Administration of a modified chemotherapeutic regimen containing vincristine, liposomal doxorubicin and dexamethasone to multiple myeloma patients: preliminary data.
SO - Eur J Haematol 2000 Aug;65(2):118-22
AD - Haematology Unit, University of Ioannina, Greece. firstname.lastname@example.org
For elderly patients with multiple myeloma (MM), conventional melphalan and prednisone (MP) therapy has been the treatment of choice; the vincristine, doxorubicin and dexamethasone (VAD) regimen is preferred for younger patients who also receive high-dose melphalan in combination with autologous or allogeneic bone marrow transplantation (BMT). Although survival time is similar in both the MP and VAD regimens, the continuous infusion of doxorubicin which the latter treatment entails constitutes a disadvantage along with the 4-day hospitalization required. Doxorubicin also induces cardiotoxicity, particularly in the elderly. A modified form of VAD therapy includes liposomal doxorubicin (Caelyx) (40 mg/m2 for 1 d) [corrected], oncovin (2 mg for 1 d) and dexamethasone 40 mg for 4 d per os. Doxorubicin encapsulated with liposomes has less cardiotoxicity, is more efficient and has fewer side effects than conventional doxorubicin, and it can be administered on an outpatient basis: dexamethasone can be given orally and vincristine in bolus infusion. In order to estimate its efficacy and tolerability, we administered this regimen to 12 patients (first-line treatment in 6 patients, salvage therapy in 6 patients). All patients exhibited good tolerance to liposomal doxorubicin with no severe side effects. Eight patients achieved complete hematological remission and three partial response. One patient died before completing the treatment. In conclusion, compared to other therapies, this modified VAD regimen containing liposomal doxorubicin can be more easily administered to MM patients, without severe side effects and with increased full remission rates, almost similar to those with the conventional VAD treatment.
UI - 11911415
AU - Fassas AB; Rapoport AP; Bolanos-Meade J; Shanholtz C; Cottler-Fox M;
TI - Tricot G Tamoxifen-based treatment induces clinically meaningful responses in multiple myeloma patients with relapsing disease after autotransplantation.
SO - Leuk Lymphoma 2001 Nov-Dec;42(6):1323-8
AD - Department of Internal Medicine, Greenebaum Cancer Center, University of Maryland, Baltimore, USA. email@example.com
Tamoxifen has been shown to induce apoptosis in multiple myeloma cell lines and primary myeloma cells. Daily tamoxifen was given to 12 consecutive multiple myeloma patients who either relapsed following autologous stem cell transplantation (11) or had progressive disease on conventional chemotherapy (1). Methotrexate was also given biweekly to enhance the antiangiogenetic effect. Two patients achieved complete remission lasting 8 and 18 months. Two additional patients had stable disease (SD) for 7 and 11 months. All responders were men and the earliest signs of response were seen after approximately 6-8 weeks of treatment. The regimen was very well tolerated. Speculations about a possible mechanism of action of tamoxifen in multiple myeloma are discussed.
UI - 11911420
AU - Rasmussen T
TI - The presence of circulating clonal CD19+ cells in multiple myeloma.
SO - Leuk Lymphoma 2001 Nov-Dec;42(6):1359-66
AD - Department of Hematology L, Herlev Hospital, University of Copenhagen, Herlev, Denmark. firstname.lastname@example.org
Multiple myeloma (MM) is a B-cell malignancy characterized by the expansion of mature plasma cells (PC) localized in the bone marrow (BM). Several studies have identified circulating clonotypic CD19+ cells at a differentiation stage preceding the PC. The level of circulating clonotypic CD19+ cells is highly variable but generally low. Circulating clonotypic cells respond well to induction therapy, although a small subset within the CD19 compartment is resistant even to high-dose chemotherapy. The clonal CD19+ cells represent an ongoing differentiating population ranging from memory B-cells to plasmablasts. However, a clonal relationship gives no proof of malignant potential, and whether or not clonotypic precursor cells are involved in the disease process is a subject of intense debate. Translocations involving the immunoglobulin locus (14q32) are an early non-transforming event common to both monoclonal gammopathy of undetermined significance (MGUS) and MM introduced at the memory B-cell level. At the plasmablast stage, a phenotypic transformation occurs with downregulation of CD19 and upregulation of myeloma specific markers such as CD56, CD117 and CD28. Translocations involving the isotype-switch machinery and the introduction of tumor-specific markers at the plasmablast stage suggest that the clonal CD19+ memory B-cells and CD19+ plasmablasts are non-malignant, but immortalized relatives that gave rise to myeloma. A final proof of the malignant potential of CD19+ clonotypic cells might await the identification of the molecular events causing the transformation in myeloma.
UI - 12014238
AU - van Soest EJ; de Klerk G
TI - [Diagnostic image (86). A man with thirst and diplopia]
SO - Ned Tijdschr Geneeskd 2002 Apr 27;146(17):803
A 71-year-old man was thirsty, had bone pains and a double vision. Multiple myeloma with hypercalcemia was diagnosed. One tumour in the clivus turned out to be compressing the left N. abducens.
UI - 12004363
AU - Batsakis JG; Medeiros JL; Luna MA; El-Naggar AK
TI - Plasma cell dyscrasias and the head and neck.
SO - Ann Diagn Pathol 2002 Apr;6(2):129-40
AD - Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston 77004, USA.
Structures in the head and neck (bones, soft tissues, lymph nodes, mucosa) are variably affected by plasma cell dyscrasias. Involvement can be manifested by localized lesions (extramedullary plasmacytoma or solitary plasmacytoma of bone) or by more diffuse disease (multiple myeloma). We present a contemporary review of these disorders with emphasis on patient outcomes. Copyright 2002, Elsevier Science (USA). All rights reserved.
UI - 12037117
AU - Curley MJ; Hussein SA; Hassoun PM
TI - Disseminated herpes simplex virus and varicella zoster virus coinfection in a patient taking thalidomide for relapsed multiple myeloma.
SO - J Clin Microbiol 2002 Jun;40(6):2302-4
AD - Pulmonary and Critical Care Division, New England Medical Center, Boston, Massachusetts 02111, USA.
Disseminated herpes simplex virus (HSV) and varicella zoster virus (VZV) have been reported individually in immunosuppressed adults. We present a case of coinfection with disseminated HSV and VZV infection in a patient taking thalidomide for relapsed multiple myeloma. This is the first report of opportunistic infection associated with thalidomide.
UI - 12087204
AU - Kwak HS; Jin GY; Lee JM
TI - Radiologic findings of multiple myeloma with gastric involvement: a case report.
SO - Korean J Radiol 2002 Apr-Jun;3(2):133-5
AD - Department of Diagnostic Radiology, Chonbuk National University Hospital, Korea.
We report a case of multiple myeloma with gastric involvement occurring in a patient who underwent an upper gastrointestinal series (UGIS), CT and MRI. UGIS depicted a luminal protruding mass, while contrast-enhanced CT demonstrated marked thickening of the gastric wall, with subtle contrast enhancement. At T1- and T2-weighted MR imaging, the mass showed iso- and intermediate signal intensity, respectively. After the administration of contrast material, subtle homogeneous enhancement was apparent.
UI - 12098098
AU - Sucker C; Dolken G; Preuss J; Schwesinger G; Stockschlader M
TI - [Plasma cell infiltration of the liver in multiple myeloma]
SO - Dtsch Med Wochenschr 2002 Jul 5;127(27):1469-72
AD - Klinik und Poliklinik fur Innere Medizin C, Germany. email@example.com
UI - 12113047
AU - Anonymous
TI - Human Genome Sciences announces clearance of IND application for LymphoRad.
SO - Expert Rev Anticancer Ther 2002 Jun;2(3):246-7
UI - 12107563
AU - Gernone A; Frassanito MA; Pellegrino A; Vacca A; Dammacco F
TI - Multiple myeloma and mycosis fungoides in the same patient: clinical, immunologic, and molecular studies.
SO - Ann Hematol 2002 Jun;81(6):326-31
AD - Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Section of Internal Medicine and Clinical Oncology, Piazza G. Cesare, 11, 70124 Bari, Italy.
The coexistence of multiple myeloma (MM) and mycosis fungoides (MF), and hence of both B- and T-cell neoplastic clones, is a rare event. We describe a case of plaque-stage MF associated with IgG lambda MM. The clinical onset of MF preceded that of MM, supporting the hypothesis that MF predisposed to the development of the B-cell proliferative disorder. The skin tumor cells were found to originate from CD4(+) T-lymphocytes, characterized by a V beta 8 receptor and no proviral human T-lymphotropic virus (HTLV)-I monoclonal integration. They also displayed a polarized Th1-type cytokine profile containing mRNAs for interleukin (IL)-2, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-beta, but not for IL-4, IL-5, or IL-10. The CD8(+)/CD57(+) suppressor-cytotoxic subpopulation was significantly increased in the peripheral blood and was associated with MM progression. Expression of p16INK4A, a gene from the INK family that inhibits cyclin-dependent kinases and regulates the cell cycle, was lacking in MF cells and bone marrow (BM) plasma cells. The p16INK4A gene was silenced by hypermethylation, suggesting that it plays a role in the early phase of the pathogenesis of both diseases. Thus, a lymphoid precursor cell presumably contains aberrations that induce the development of both clonal diseases in a multistep process.
UI - 10089658
AU - Marcos Sanchez F; Solano Ramos F; Juarez Ucelay F; Arranz Nieto MJ;
TI - Duran Perez-Navarro A [An association of multiple myeloma and megaloblastic anemia]
SO - An Med Interna 1999 Jan;16(1):51-2
UI - 10686722
AU - Miramon Lopez J; Ruiz Cantero A; Morales Jimenez J; Lara Fernandez A;
TI - Hita Perez J [A new case of association of multiple myeloma and megaloblastic anemia]
SO - An Med Interna 1999 Dec;16(12):654-5; discussion 656
UI - 11868975
AU - Gupta A; Helm TN
TI - Acquired cutis laxa associated with multiple myeloma.
SO - Cutis 2002 Feb;69(2):114-8
AD - State University of New York at Buffalo School of Medicine, USA.
Cutis laxa is an uncommon condition characterized by loose and redundant skin. Biopsy results are positive for a reduction in or an absence of elastic fibers in the dermis. Cutis laxa is acquired or congenital. The acquired form is either a generalized insidious form (type I) or a form associated with prior inflammation (type II). Cardiovascular, pulmonary, gastrointestinal, and urologic complications may occur. In the past, cutis laxa was associated with plasma cell dyscrasia. We report on a characteristic cause of cutis laxa to alert clinicians to this uncommon manifestation of multiple myeloma.
UI - 12084448
AU - Meyer T; Ludolph AC; Munch C
TI - Ifosfamide encephalopathy presenting with asterixis.
SO - J Neurol Sci 2002 Jul 15;199(1-2):85-8
AD - Department of Neurology, Charite Hospital, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany. firstname.lastname@example.org
CNS toxic effects of the antineoplastic agent ifosfamide (IFX) are frequent and include a variety of neurological symptoms that can limit drug use. We report a case of a 51-year-old man who developed severe, disabling negative myoclonus of the upper and lower extremities after the infusion of ifosfamide for plasmacytoma. He was awake, revealed no changes of mental status and at rest there were no further motor symptoms. Cranial magnetic resonance imaging and extensive laboratory studies failed to reveal structural lesions of the brain and metabolic abnormalities. An electroencephalogram showed continuous, generalized irregular slowing with admixed periodic triphasic waves indicating symptomatic encephalopathy. The administration of ifosfamide was discontinued and within 12 h the asterixis resolved completely. In the patient described, the presence of asterixis during infusion of ifosfamide, normal laboratory findings and imaging studies and the resolution of symptoms following the discontinuation of the drug suggest that negative myoclonus is associated with the use of IFX.
UI - 12166074
AU - Moriyama T; Tozawa T; Matsuno K
TI - [Tumor producing amylase]
SO - Rinsho Byori 2002 Jun;50(6):566-70
AD - Department of Laboratory Technology, College of Medical Technology, Hokkaido University, Sapporo 060-0812.
The phenotype of tumor-producing amylase is usually salivary-type amylase, in contrast, we experienced sialyl salivary-type amylase detected in the sera of the patients with malignancies. Sialyl salivary-type amylase, with an abnormal anodic migration, was detected by isoamylase electrophoretic analysis in the sera of patients with multiple myeloma and with ovarian cancer. The abnormal isoamylase bands migrated toward the anode faster than the salivary isoamylase band(S2) and were stained more strongly than S2 band. The isoamylases could be separated from residual normal isoamylases in the sera of patients by using gel permeation chromatography. The isoamylases were showed sensitive by neuraminidase treatment and were reacted with anti-human salivary monoclonal antibody.
UI - 11821971
AU - Finsterer J; Kladosek A; Gornik A; Birkner T
TI - Transverse syndrome as the dominant feature of solitary cervical plasmocytoma with dissemination.
SO - Spinal Cord 2002 Jan;40(1):44-7
AD - 2nd Neurological Department, Neurological Hospital Rosenhugel, Vienna, Austria.
STUDY DESIGN: A case report of transverse syndrome secondary to compression from an intravertebral plasmocytoma. OBJECTIVES: To report a rare case of cervical cord compression. SETTING: Vienna, Austria. CASE REPORT: A 47-year-old man presented with pain over the left scapula and subsequent development of pain and sensory disturbance. Investigations showed that the entire C7 vertebra was affected by a plasmocytoma. Decompression was carried out but no stabilisation of the spinal column was performed. Seven days after surgery the patient became paraplegic. Chemotherapy produced no improvement. CONCLUSION: Transverse syndrome may be a dominant feature of plasmocytoma and may resolve after immediate decompression but may recur if the spinal column is not stabilised.
UI - 12078798
AU - Deeb ME; Shargal Y; Merin G; Milgalter E
TI - Incidental finding of myeloproliferative disorders during sternotomy.
SO - Ann Thorac Surg 2002 Jun;73(6):1951-2
AD - Department of Cardiothoracic Surgery, Hadassah Medical Center, Hebrew University, Jerusalem, Israel.
We report 2 cases of myeloproliferative disorders discovered incidentally at the time of routine coronary bypass surgery. Suspicion of abnormal bone marrow tissue upon performing sternotomy and subsequent sampling for frozen section made the diagnosis. The surgical plan was changed, and partial revascularization without cardiopulmonary bypass was performed.
UI - 1872566
AU - Hawkins RC
TI - Pseudohyperphosphataemia in multiple myeloma.
SO - Ann Clin Biochem 1991 May;28 ( Pt 3)():226-8
AD - Department of Clinical Chemistry, Auckland Hospital, New Zealand.
Two cases of spurious hyperphosphataemia in patients with multiple myeloma are presented. An unreduced phosphomolybdate method without dialysis was used and the falsely raised values are shown to be due to the formation of a proteinaceous suspension in the reaction mixture. Such interference may be more prevalent than is generally recognized, and care should be taken to identify the problem in patients with myeloma.
UI - 11892717
AU - Bachleitner-Hofmann T; Machold K; Knobler R; Drach J; Grumbeck E;
TI - Gisslinger H Marked and sustained improvement of systemic sclerosis following polychemotherapy for coexistent multiple myeloma.
SO - Clin Exp Rheumatol 2002 Jan-Feb;20(1):85-8
AD - Department of Internal Medicine I, University of Vienna, Austria.
We present the case of a patient who had systemic sclerosis (SSc) with progressive cutaneous and pulmonary involvement and a coexisting monoclonal gammopathy which gradually progressed to overt multiple myeloma. Strikingly, successful VMCP (vincristine, melphalan, cyclophosphamide and prednisolone) polychemotherapy for myeloma was accompanied by a marked and sustained improvement of SSc that has persisted for 2 years after chemotherapy. Most noticeable was a substantial skin softening in our patient, with a > 50% reduction in the skin thickness score following VMCP treatment. Our case suggests that polychemotherapy may represent a promising treatment option in patients with SSc who are refractory to available treatments.
UI - 11510469
AU - Fonesca R; Oken MM; Greipp PR; Eastern Cooperative Oncology Group
TI - Myeloma Group The t(4;14)(p16.3;q32) is strongly associated with chromosome 13 abnormalities in both multiple myeloma and monoclonal gammopathy of undetermined significance.
SO - Blood 2001 Aug 15;98(4):1271-2
UI - 12101201
AU - Xu JL; Lai R; Kinoshita T; Nakashima N; Nagasaka T
TI - Proliferation, apoptosis, and intratumoral vascularity in multiple myeloma: correlation with the clinical stage and cytological grade.
SO - J Clin Pathol 2002 Jul;55(7):530-4
AD - Department of Laboratory Medicine, Nagoya University School of Medicine, Tsurumai-cho 65, Showa-ku, Japan.
AIMS: Abnormalities involving proliferation, apoptosis, and angiogenesis are important in tumorigenesis. The purpose of this study was to examine these three biological processes, and their relation with the clinical stage and cytological grade in multiple myeloma (MM). METHODS: Fifty four newly diagnosed patients with MM were studied by immunohistochemistry using bone marrow clot sections. Proliferation and apoptosis were evaluated for the proportion of MM cells (indicated by morphology and CD138 reactivity) positive for the Ki67 antigen and single stranded DNA (ssDNA), respectively. Angiogenesis was evaluated by measuring the intratumoral microvessel density (IMVD) and by assessing the immunoreactivity of vascular endothelial growth factor (VEGF). RESULTS: There were 30 men and 24 women (median age, 65 years; range, 37-84). At initial presentation, 15 (28%) were in Durie stage I, 15 (28%) in stage II, and 24 (44%) in stage III. Advanced clinical stage correlated with high cytological grade (p < 0.03). The medians for Ki67, ssDNA, and IMVD were 4.4% (range, 0-15%), 0.2% (range, 0-2.8%), and 15.5 (range, 0-63), respectively. Among these three continuous parameters, the only significant correlation was that between Ki67 and IMVD (p < 0.0001). Both Ki67 and IMVD also correlated with the clinical stage, cytological grade, and VEGF positivity (p <0.05). No correlation was found between ssDNA and all of the other parameters. CONCLUSIONS: These data suggest that proliferation is associated with angiogenesis in MM. Furthermore, proliferation and angiogenesis, but not apoptosis, may be important in disease progression. Lastly, increased production of VEGF may be one of the contributing factors to the increase in intratumoral vascularity seen in advanced MM.
UI - 12135668
AU - Gupta D; Podar K; Tai YT; Lin B; Hideshima T; Akiyama M; LeBlanc R;
TI - Catley L; Mitsiades N; Mitsiades C; Chauhan D; Munshi NC; Anderson KC beta-lapachone, a novel plant product, overcomes drug resistance in human multiple myeloma cells.
SO - Exp Hematol 2002 Jul;30(7):711-20
AD - Jerome Lipper Myeloma Center, Department of Adult Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA.
OBJECTIVE: To evaluate the anti-tumor potential of beta-lapachone in multiple myeloma (MM) cell lines (U266, RPMI8226, and MM.1S); MM cell lines resistant to dexamethasone (MM.1R), melphalan (RPMI8226/LR5), doxorubicin (RPMI8226/DOX40), and mitoxantrone (RPMI8226/ MR20); and MM cells from patients (MM1-MM4). MATERIALS AND METHODS: Cytotoxicity of beta-lapachone was assessed by MTT and [3H]-thymidine uptake assays. Apoptosis was analyzed using propidium iodide staining, DNA fragmentation, TUNEL assay, caspase-9 colorimetric assay, and immunoblotting for caspase-3, poly (ADP-ribose) polymerase (PARP), and caspase-8 cleavage products. Paracrine growth of MM cells was assessed by [3H]-thymidine uptake in cultures of bone marrow stromal cells (BMSCs) and MM cells. Interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) secretion in the culture supernatants was measured by specific enzyme-linked immunosorbent assays (ELISAs). RESULTS: beta-lapachone showed significant cytotoxicity in MM cells (IC(50): 4-8 microM). In contrast, normal peripheral blood mononuclear cells (PBMCs) and BMSCs from MM patients were relatively resistant (IC(50): 8-16 microM). IL-6 did not protect against beta-lapachone-induced apoptosis in MM.1S cells, and dexamethasone showed additive cytotoxicity. beta-lapachone also decreased binding of MM.1S cells to BMSCs; abrogated IL-6 and VEGF secretion triggered by adhesion of BMSCs to MM.1S cells; reduced proliferation of MM.1S cells adherent to BMSCs; and decreased intracellular adhesion molecule-1 (ICAM-1) expression on MM.1S cells. Furthermore, beta-lapachone induced typical PARP cleavage, increased caspase-9 proteolytic activity, and activation of caspase-3, without activation of caspase-8 in U266 cells. CONCLUSION: These studies provide a framework for clinical evaluation of beta-lapachone to improve the outcome for patients with MM.
UI - 12173715
AU - Rajkumar SV; Gertz MA; Kyle RA; Greipp PR; Mayo Clinic Myeloma, Amyloid,
TI - and Dysproteinemia Group Current therapy for multiple myeloma.
SO - Mayo Clin Proc 2002 Aug;77(8):813-22
AD - Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, Minn 55905, USA. email@example.com
Multiple myeloma is an incurable plasma cell malignancy that accounts for 10% of all hematologic cancers. For decades the mainstay of therapy has been the use of melphalan and prednisone; with this regimen, the median survival is approximately 3 years. Recently, important advances were made that have substantially altered the manner in which patients with myeloma are treated. Newly diagnosed patients with good performance status are now treated with autologous stem cell transplantation, resulting in improved survival. Because of the increasing use of transplantation as initial therapy, several therapeutic issues have emerged: the role of tandem transplantation, early vs delayed transplantation, and the role of allogeneic transplantation. The pronounced activity of thalidomide in patients with refractory myeloma represents another important advance. This has prompted the study of several novel agents in the treatment of myeloma, at least 2 of which appear promising. Supportive care measures also have improved, including the use of bisphosphonates to prevent osteolytic lesions. The purpose of this review is to summarize recent advances and provide an evidence-based approach to the treatment of multiple myeloma.
UI - 12173332
AU - Mohrbacher AF; Gregory SA; Gabriel DA; Rusk JM; Giles FJ
TI - Liposomal daunorubicin (DaunoXome) plus dexamethasone for patients with multiple myeloma. A phase II International Oncology Study Group study.
SO - Cancer 2002 May 15;94(10):2645-52
AD - Department of Hematology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA. firstname.lastname@example.org
BACKGROUND: Liposomal daunorubicin is an effective cytotoxic agent in patients with Kaposi sarcoma and hematologic malignancies. Anthracycline-based chemotherapy regimens, such as vincristine/doxorubicin/dexamethasone (VAD), are standard in the treatment of patients with multiple myeloma (MM). Cardiotoxicity remains a limiting factor in dose escalation of anthracyclines, and multidrug resistance (MDR) develops rapidly on exposure to anthracyclines. Liposomal daunorubicin was designed in an attempt to overcome MDR and to reduce anthracycline-related toxicities. Thus, an open-label, Phase II clinical study was conducted by the International Oncology Study Group to assess the efficacy and safety of intravenous liposomal daunorubicin at a dose of 100 mg/m2 given every 3 weeks for a maximum of 6 cycles in patients with recently diagnosed MM (n = 4 patients) or recurrent/refractory MM (n = 37 patients). METHODS: Liposomal daunorubicin was administered as a single agent for the initial two cycles of therapy, and dexamethasone was added to all subsequent cycles. The primary study end point was response rates. Thirty-eight patients were treated, 35 of whom were evaluable for response. RESULTS: A partial response was achieved in six patients (17%), including one patient with disease that previously was refractory to VAD therapy. Stable disease was observed in 22 patients (63%). The principal toxicity was myelosuppression. Grade 3 or 4 hematologic toxicities included granulocytopenia (26%), anemia (Grade 3 only; 11%), thrombocytopenia (11%), and febrile neutropenia (13%). The median survival in 35 patients with recurrent disease was 7.6 months. CONCLUSIONS: Liposomal daunorubicin had activity in this population of poor-risk patients that was comparable to the activity of standard regimens. Further studies of this agent in combination with other anti-MM agents are warranted.
UI - 12091368
AU - Brander C; Raje N; O'Connor PG; Davies F; Davis J; Chauhan D; Hideshima
TI - T; Martin J; Osmond D; Kedes DH; Walker BD; Scadden DT; Anderson KC Absence of biologically important Kaposi sarcoma-associated herpesvirus gene products and virus-specific cellular immune responses in multiple myeloma.
SO - Blood 2002 Jul 15;100(2):698-700
AD - Partners AIDS Research Center, Massachusetts General Hospital, Charlestown, MA, USA.
Kaposi sarcoma-associated herpesvirus (KSHV) has been associated with several diseases, but the association between KSHV and multiple myeloma (MM) remains controversial. To address this issue, we studied patients with MM for the presence of viral RNA transcripts as well as KSHV-specific cellular immune responses. Highly sensitive reverse transcription-polymerase chain reaction assays for detection of viral transcripts of KSHV open reading frame (ORF) 26, ORF72, and ORF74 did not detect viral gene transcripts in long-term cultures of bone marrow stromal cells from 23 patients with MM. Moreover, sensitive assays for KSHV ORF65-specific and ORF73-specific cytotoxic T-lymphocyte (CTL) activity that readily and routinely detect CTLs specific for ORF65 and ORF73 in patients positive for human immunodeficiency virus and KSHV did not show any specific responses in 16 patients with MM, despite the presence of positive Epstein-Barr virus-specific CTLs in all cases. These data therefore do not show a biologically important association between ongoing KSHV infection and MM.
UI - 12187809
AU - Kikuchi M; Inagaki T; Ueda R
TI - [A case of multiple myeloma with infiltration into skeletal muscle after injections of a granulocyte-colony stimulating-factor]
SO - Nippon Ronen Igakkai Zasshi 2002 Jul;39(4):433-8
AD - Second Department of Internal Medicine, Nagoya City University Medical School.
Multiple myelomas often occur in elderly people with complications due to aging. A 54-year-old man was first admitted with cerebral infarction, that was followed by partial remission after chemotherapy. The karyotype of the bone marrow cells was 46, XY, and no p53 gene mutations were detected by polymerase chain reaction and single-strand conformation polymorphism analysis. Chemotherapy (melphalan 10 mg, vindesine 3 mg, ranimustine 150 mg, prednisolone 60 mg for 4 days) was performed in subcutaneous injection of 50 micrograms of nartograstim for six days to treat neutropenia, soft tissues around the right eye were swelled gradually without redness, accompanied by elevation of the serum creatine-kinase concentration. The swelling disappeared, and the enzyme level normalized after discontinuation of nartograstim. In July, on the sixth day of daily subcutaneous injection of 75 micrograms of filgrastim after the same chemotherapy, similar swelling of the soft tissues around the left eye became evident, and again this proved reversible. In July 2000, 40 mg of dexamethasone was infused, and after 5-day subcutaneous-injection of 75 micrograms of filgrastim daily, the right subclavicular soft tissue became swollen. He died of myocardial infarction, and autopsy revealed infiltration of myeloma cells into the right subclavicular muscle and bone marrow packed with myeloma cells. This case suggests that myeloma cells can proliferate and infiltrate into soft tissues on exposure to granulocyte-colony stimulating factors.
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