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Tipos de Cancer / Mielomas / Recursos de NCI
National Cancer Institute®
Ultima Vez Modificado: 1 de septiembre del 2002
1
UI - 12075197
AU - Ziegler CM; Flechtenmacher C; Muhling J
TI -
Tender preauricular swelling.
SO - Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002 May;93(5):516-20
AD - University of Heidelberg, Heidelberg, Germany.
2
UI - 12126363
AU - Basu S; Gupta N; Malhotra H
TI -
IgA myeloma presenting as diabetes mellitus with refractory anaemia.
SO - J Assoc Physicians India 2002 Jul;50():981-2
AD - Department of Haematology and Transfusion Medicine, Government Medical
College and Hospital, Chandigarh.
3
UI - 11876068
AU - Harmouche H; Cahen-Doidy L; Bourgarit A; Farge D; Sereni D
TI -
[Breast plasmacytoma. A new case]
SO - Rev Med Interne 2002 Feb;23(2):207-9
4
UI - 11830399
AU - Delisle V; Tollis F; Truchan-Graczyk M; Rousselet-Chapeau MC; Ifrah N;
TI -
Zandecki M; Genevieve F
[Plasma cell leukemia: aggressive form of multiple myeloma]
SO - Ann Biol Clin (Paris) 2002 Jan-Feb;60(1):89-95
AD - Centre hospitalier universitaire, 49033 Angers cedex 01.
5
UI - 12043696
AU - Lee FC
TI -
Second response to lower-dose thalidomide in a patient with multiple
myeloma.
SO - Blood 2002 Jun 1;99(11):4248; discussion 4249
6
UI - 12043699
AU - Devine SM; Jahagirdar B; van Besien K
TI -
Reduced duration of cytopenias following melphalan conditioning and
autografting for multiple myeloma.
SO - Blood 2002 Jun 1;99(11):4251-2; discussion 4252
7
UI - 12170429
AU - Ponisch W; Niederwieser D
TI -
Bendamustine in the treatment of multiple myeloma: results and future
perspectives.
SO - Semin Oncol 2002 Aug;29(4 Suppl 13):23-6
AD - East German Study Group for Hematology and Oncology (OSHO), University
of Leipzig, Philipp Rosenthalstrasse 23-25, D-4103 Liepzig, Germany.
Multiple myeloma (MM) is a malignancy of terminally differentiated
plasma cells typically occurring in elderly patients. The clinical
manifestations of this disease result primarily from the accumulation of
monoclonal protein (paraprotein) in the serum and/or urine, anemia,
lytic bone lesions, hypercalcemia, renal insufficiency, and immune
deficiency. Multiple myeloma is incurable with standard chemotherapy.
Melphalan and prednisone has been the mainstay of treatment for MM for
about three decades. This regimen results in a clinical response in
approximately 60% of patients and a median survival of approximately 36
months. A variety of combination therapies have also been used in MM,
but have not been considered to offer a significant benefit compared
with standard therapy. In early trials, bendamustine monotherapy was as
effective as cyclophosphamide and various combination therapies in
achieving remission in MM. This article describes a prospective,
randomized, phase III study designed to compare the efficacy of
bendamustine/prednisolone with a standard melphalan/prednisolone
regimen. Copyright 2002, Elsevier Science (USA). All rights reserved.
8
UI - 12150155
AU - Bezieau S; Avet-Loiseau H; Moisan JP; Bataille R
TI -
Activating Ras mutations in patients with plasma-cell disorders: a
reappraisal.
SO - Blood 2002 Aug 1;100(3):1101-2; discussion 1103
9
UI - 12130482
AU - Kroger N; Schwerdtfeger R; Kiehl M; Sayer HG; Renges H; Zabelina T;
TI -
Fehse B; Togel F; Wittkowsky G; Kuse R; Zander AR
Autologous stem cell transplantation followed by a dose-reduced
allograft induces high complete remission rate in multiple myeloma.
SO - Blood 2002 Aug 1;100(3):755-60
AD - Bone Marrow Transplantation, University Hospital Hamburg, Hamburg,
Germany. nkroeger@uke.uni-hamburg.de
We evaluated toxicity, engraftment, chimerism, graft-versus-host disease
(GVHD), and response to a dose-reduced allograft after cytoreductive
autografting in 17 patients with advanced stage II/III multiple myeloma
(MM). After autografting with melphalan (200 mg/m2) the patients
received after a median interval of 119 days (range 60-210) a
dose-reduced regimen consisting of fludarabine (180 mg/m2), melphalan
(100 mg/m2), and antithymocyte globulin (3 x 10 mg/kg) followed by
allografting from related (n = 7), mismatched related (n = 2), or
unrelated (n = 8) donors to induce a graft-versus-myeloma effect. After
dose-reduced allografting all patients became neutropenic (< 0.2 x
10(9)/L) for at least 8 days. All patients engrafted with a median time
for leukocyte (> 1 x 10(9)/L) and platelet (> 20 x 10(9)/L) counts of 16
(range, 11-24) and 23 days (range, 12-43), respectively. Complete donor
chimerism was detected after a median of 30 days (range, 19-38). Acute
GVHD stage II occurred in 4 patients (25%) and grade III GVHD in 2
patients (13%). Chronic GVHD developed in 40% of the patients, but only
1 patient experienced extensive chronic GVHD requiring further
immunosuppressive therapy. Two patients died of alveolar hemorrhage and
pneumonia, resulting in a day 100 mortality rate of 11%. The rate of
complete remission with negative immunofixation increased from 18% after
autografting to 73% after allografting. After a median follow-up of 17
months after autologous and 13 months after allogeneic transplantation
13 patients are alive and 12 of them free of relapse or progression. The
tandem auto-allotransplant protocol is highly active and provides rapid
engraftment with complete donor chimerism and tolerable toxicity.
10
UI - 12130509
AU - Chiriva-Internati M; Wang Z; Salati E; Bumm K; Barlogie B; Lim SH
TI -
Sperm protein 17 (Sp17) is a suitable target for immunotherapy of
multiple myeloma.
SO - Blood 2002 Aug 1;100(3):961-5
AD - Division of Hematology and Oncology, Texas Tech University Health
Sciences Center, Amarillo 79106, USA.
Sperm protein 17 (Sp17) is a protein recently identified as a novel
cancer-testis (CT) antigen in multiple myeloma (MM). Because this tumor
antigen demonstrates a very restricted normal tissue expression, Sp17
may be an excellent target for tumor vaccine of MM. In this study, we
determined the ability to generate Sp17-specific HLA class I-restricted
cytotoxic T lymphocytes (CTLs) from the peripheral blood of 4 patients
with MM, 3 consecutive Sp17(+) patients, and 1 Sp17(-) patient.
Dendritic cells were generated from monocytes of 4 patients with MM and
used to present a recombinant Sp17 protein to autologous T cells.
Following 4 rounds of antigen stimulation, the CTLs were tested for
their ability to kill autologous targets in an Sp17-dependent and
HLA-class I- restricted manner in standard cytotoxicity assays. Despite
previous chemotherapy and the immunosuppression so often associated with
MM, CTL generation was successful in all 4 patients, irrespective of the
Sp17 status of their tumors. Most importantly, the CTLs were able to
lyse autologous tumor cells that expressed Sp17. Tumor cell lysis in all
cases appeared to be mainly mediated by perforin and could be blocked by
concanamycin A. We conclude that Sp17 is a suitable target for
immunotherapy of MM. Our findings provide the basis for a clinical study
aimed at inducing a cellular immune response directed at Sp17(+) MM.
11
UI - 9787135
AU - Chesi M; Nardini E; Lim RS; Smith KD; Kuehl WM; Bergsagel PL
TI -
The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel
gene, MMSET, resulting in IgH/MMSET hybrid transcripts.
SO - Blood 1998 Nov 1;92(9):3025-34
AD - Department of Medicine, the Division of Hematology and Oncology, Weill
Medical College of Cornell University, New York, NY, USA.
Previously we reported that a karyotypically silent t(4;14)(p16.
3;q32.3) translocation is present in about 25% of multiple myeloma (MM)
tumors, and causes overexpression of FGFR3, which is 50 to 100 kb
telomeric to the 4p16 breakpoints. Frequent FGFR3 kinase activating
mutations in MM with t(4;14) translocations substantiate an oncogenic
role for FGFR3. We now report that the 4p16 breakpoints occur telomeric
to and within the 5' introns of a novel gene, MMSET (Multiple Myeloma
SET domain). In normal tissues, MMSET has a complex pattern of
expression with a short form (647 amino acids [aa]) containing an HMG
box and hath region, and an alternatively spliced long form (1365 aa)
containing the HMG box and hath region plus 4 PHD fingers and a SET
domain. Although t(4;14) translocation results in IgH/MMSET hybrid
transcripts, overexpression of MMSET also occurs from endogenous
promoters on 4p16. Given the homology to HRX/MLL1/ALL1 at 11q23 that is
dysregulated by translocations in acute leukemia, we hypothesize that
dysregulation of MMSET contributes to neoplastic transformation in MM
with t(4;14) translocation. This is the first example of an IgH
translocation that simultaneously dysregulates two genes with oncogenic
potential: FGFR3 on der(14) and MMSET on der(4). Copyright 1998 by The
American Society of Hematology
12
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
13
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
14
UI - 11490638
AU - Chindia ML; Riyat MS; Nyong'o A
TI -
Multiple myeloma presenting as a painful mandibular swelling: a case
report.
SO - Dent Update 2001 Jun;28(5):258-60
AD - Faculty of Dental Sciences, University of Nairobi, Kenya.
Multiple myeloma is a disease characterized by monoclonal proliferation
of plasma cells, the most differentiated stage of B-cells. Primary
manifestation of multiple myeloma in the jawbones is rare. In the case
reported here, a 29-year-old woman who presented with a right mandibular
swelling after extraction of a mobile painful tooth turned out to have
multiple myeloma. Current diagnostic criteria and management strategies
of the disease are discussed.
15
UI - 11435324
AU - Barlogie B; Desikan R; Eddlemon P; Spencer T; Zeldis J; Munshi N; Badros
TI -
A; Zangari M; Anaissie E; Epstein J; Shaughnessy J; Ayers D; Spoon D;
Tricot G
Extended survival in advanced and refractory multiple myeloma after
single-agent thalidomide: identification of prognostic factors in a
phase 2 study of 169 patients.
SO - Blood 2001 Jul 15;98(2):492-4
AD - Myeloma and Transplantation Research Center, University of Arkansas for
Medical Sciences, Little Rock, AR 72205, USA.
This report of a phase 2 trial of thalidomide (THAL) (200 mg/d; 200 mg
increment every 2 weeks to 800 mg) for 169 patients with advanced
myeloma (MM) (abnormal cytogenetics (CG), 67%; prior autotransplant,
76%) extends earlier results in 84 patients. A 25% myeloma protein
reduction was obtained in 37% of patients (50% reduction in 30% of
patients; near-complete or complete remission in 14%) and was more
frequent with low plasma cell labeling index (PCLI) (below 0.5%) and
normal CG. Two-year event-free and overall survival rates were 20% +/-
6% and 48% +/- 6%, respectively, and these were superior with normal CG,
PCLI of less than 0.5%, and beta(2)-microglobulin of 3 mg/L. Response
rates were higher and survival was longer especially in high-risk
patients given more than 42 g THAL in 3 months (median cumulative dose)
(landmark analysis); this supports a THAL dose-response effect in
advanced MM.
16
UI - 11675360
AU - Hsu J; Shi Y; Krajewski S; Renner S; Fisher M; Reed JC; Franke TF;
TI -
Lichtenstein A
The AKT kinase is activated in multiple myeloma tumor cells.
SO - Blood 2001 Nov 1;98(9):2853-5
AD - Department of Medicine and Pathology, West Los Angeles Veterans
Administration Medical Center and Jonsson Comprehensive Cancer Center,
Los Angeles, CA 90073, USA.
Immunohistochemistry (IHC) was performed on archived bone marrow (BM)
with a phosphospecific anti-AKT antibody. IHC on 26 BM biopsies from
patients with multiple myeloma (MM) demonstrated phospho-AKT staining of
malignant plasma cells in a cell membrane-specific pattern, whereas
nonmalignant hematopoietic cells did not stain. Preabsorption of the
antibody with phosphorylated AKT peptide, but not nonphosphorylated
peptide, abrogated staining. Frequency of plasma cell staining in BMs of
patients with stage I or smoldering MM was significantly less than that
of stage III MM marrows. Plasma cells in 10 patients with monoclonal
gammopathy of undetermined significance were not stained by the
antibody. To investigate the significance of AKT activation, 2 cell
lines initiated from cultures of primary MM cells were also studied.
Both demonstrated constitutive AKT activation. Interruption of AKT
activation and activity, achieved by either exposure to wortmannin or by
ectopic expression of a dominant negative AKT mutant, resulted in
inhibition of MM cell growth in vitro. These results indicate that
activation of the AKT kinase is a characteristic of MM cells and suggest
that AKT activity is important for MM cell expansion.
17
UI - 11806971
AU - Moreau P; Facon T; Attal M; Hulin C; Michallet M; Maloisel F; Sotto JJ;
TI -
Guilhot F; Marit G; Doyen C; Jaubert J; Fuzibet JG; Francois S;
Benboubker L; Monconduit M; Voillat L; Macro M; Berthou C; Dorvaux V;
Pignon B; Rio B; Matthes T; Casassus P; Caillot D; Najman N; Grosbois B;
Bataille R; Harousseau JL; Intergroupe Francophone du Myelome
Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus
140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem
cell transplantation in patients with newly diagnosed multiple myeloma:
final analysis of the Intergroupe Francophone du Myelome 9502 randomized
trial.
SO - Blood 2002 Feb 1;99(3):731-5
AD - Service d'Hematologie, University Hospital Hotel-Dieu, Place Alexis
Recordeau, 44093 Nantes cedex 01, France.
High-dose therapy has become a common treatment for myeloma. The
objective of this study (Intergroupe Francophone du Myelome [IFM] 9502
trial) was to compare in a prospective and randomized trial the 2 most
widely used conditioning regimens before autologous stem cell
transplantation in newly diagnosed symptomatic patients younger than 65
years old: 8 Gy total body irradiation plus 140 mg/m(2) melphalan (arm
A) versus 200 mg/m(2) melphalan (arm B). A total of 282 evaluable
patients were compared--140 in arm A and 142 in arm B. Baseline
characteristics and disease response to 4 cycles of the VAD regimen
performed before randomization and autologous stem cell transplantation
were identical in the 2 treatment arms. In arm B, hematologic recovery
was significantly faster for both the duration of neutropenia and
thrombocytopenia, transfusion requirements were also significantly
lower, and the median duration of hospitalization was significantly
shorter. In arm A, the incidence of severe mucositis was significantly
increased. The median duration of event-free survival was similar in
both arms (21 vs 20.5 months, P =.6), but the 45-month survival was
65.8% in arm B versus 45.5% in arm A (P =.05). This difference might be
attributed in part to better salvage regimens after relapse in arm B
compared with arm A. We conclude that 200 mg/m(2) melphalan is a less
toxic and at least as effective conditioning regimen when compared with
8 Gy total body irradiation with 140 mg/m(2) melphalan. This regimen
should be considered as the standard of care before autologous stem cell
transplantation in multiple myeloma.
18
UI - 11901667
AU - Speer SA; Semenza JC; Kurosaki T; Anton-Culver H
TI -
Risk factors for acute myeloid leukemia and multiple myeloma: a
combination of GIS and case-control studies.
SO - J Environ Health 2002 Mar;64(7):9-16; quiz 35-6
AD - Epidemiology Division, Department of Medicine, University of California,
Irvine, 224 Irvine Hall, Irvine, CA 92697-7550, USA.
Risk factors for acute myeloid leukemia (AML) and multiple myeloma (MM)
include exposure to toxic chemicals present in tobacco smoke, as well as
to emissions from industrial operations and petroleum refinery waste
dumps. The study reported here identified these risk factors among case
patients and control patients in Orange County, California, from 1984 to
1993 and determined the significance of the risk factors in the study
population. A case-control study was performed for 604 cases of AML and
643 cases of MM; there were 7,112 control subjects who had colon cancer.
The model included the variables smoking history, occupational history,
and residence in a census tract with a petroleum refinery waste dump. A
geographic information system (GIS) analysis also was performed to
correlate the incidence of AML and MM with proximity to the six dump
sites that received large amounts of petroleum refinery waste. Current
smokers were found to be at an increased risk of AML with an odds ratio
of 2.0. Laborer/equipment cleaners and transportation workers/movers
were at risk of AML with odds ratios of 3.5 and 2.4, respectively.
Construction/resource extraction workers were at risk of MM with an odds
ratio of 2.8. GIS analysis determined that the risk for MM was 1.6 cases
per mile for 10 or more years of residence near a large chemical dump.
The authors were able to identify census tracts with a high incidence of
AML and MM, and to perform distance analysis using a statistical measure
of spatial randomness. The case-control study identified occupational
and lifestyle risk factors for AML and MM that were not apparent from
census-tract-level data.
19
UI - 11961205
AU - Miller WH Jr
TI -
Molecular targets of arsenic trioxide in malignant cells.
SO - Oncologist 2002;7 Suppl 1():14-9
AD - Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish
General Hospital and McGill University Department of Oncology, Montreal,
Quebec, Canada. Wmiller@ldi.jgh.mcgill.ca
Arsenic trioxide (As2O3; ATO) has considerable efficacy in the treatment
of relapsed acute promyelocytic leukemia (APL), inducing partial
differentiation and promoting apoptosis of malignant promyelocytes.
Although initial studies focused on the role of the characteristic APL
fusion protein, PML-RARalpha, in mediating response to ATO, subsequent
investigations have revealed that ATO acts on numerous intracellular
targets. ATO broadly affects signal transduction pathways and causes a
wide range of alterations leading to apoptosis. Key mediators of
sensitivity to ATO-induced apoptosis include intracellular glutathione
and hydrogen peroxide (H2O2). The loss of inner mitochondrial membrane
potential is also an important step in ATO-mediated cell killing.
Cellular and physiologic pathways affected by ATO provide some clues as
to the mechanisms for the biologic effects of ATO. Recent research has
shown that hematologic cancers other than APL and solid tumors derived
from several tissue types may be responsive to monotherapy or
combination therapy with ATO. A better understanding of the mechanisms
of action of ATO may help guide the use of ATO for the treatment of a
wide variety of malignancies and allow its potential in cancer therapy
to be fully realized.
20
UI - 11961206
AU - Hussein MA
TI -
Nontraditional cytotoxic therapies for relapsed/refractory multiple
myeloma.
SO - Oncologist 2002;7 Suppl 1():20-9
AD - Cleveland Clinic Myeloma Research Program, Cleveland Clinic Taussig
Cancer Center, Cleveland, Ohio 44195, USA. husseim@ccf.org
Multiple myeloma remains an incurable disease, with median survival
rates of 4-6 years even with aggressive, high-dose chemotherapy, bone
marrow transplantation, and intensive supportive care. Additionally,
multiple myeloma is primarily a disease of the elderly, many of whom
cannot tolerate aggressive chemotherapy. Thus, newer treatments with
good safety profiles are needed to improve the quality of responses and,
hopefully, to translate into prolonged progression and overall survival.
The pathophysiology of multiple myeloma is complex, involving many
pathways and interactions among cytokines, adhesion molecules,
angiogenesis, and mechanisms of resistance, which, taken together,
provide multiple targets for novel therapeutic modalities. Agents
currently under investigation for treating multiple myeloma include
thalidomide and its successors, PS-341, and arsenic trioxide.
Thalidomide and immunomodulatory drugs both exhibit activity against
multiple myeloma by affecting different levels of the immune system.
PS-341 is a proteasome inhibitor that halts the cell cycle, resulting in
apoptosis; it also inhibits a key transcription factor and may have
antiangiogenic activity. Arsenic trioxide activates multicellular
mechanisms to induce apoptosis, inhibit angiogenesis, and stimulate
immune responses. Preclinical and early clinical data suggest that
combination regimens should be pursued, given the different mechanisms
of action of these compounds on the immune system and their
non-overlapping toxicities at low dosages.
21
UI - 12072017
AU - Bayer-Garner IB; Smoller BR
TI -
AL amyloidosis is not present as an incidental finding in cutaneous
biopsies of patients with multiple myeloma.
SO - Clin Exp Dermatol 2002 May;27(3):240-2
AD - Department of Pathology, University of Arkansas for Medical Sciences,
Little Rock 72205, USA.
Multiple myeloma (MM) is a monoclonal B-cell neoplasm characterized by
autonomous proliferation of immunoglobulin-secreting plasma cells that
are capable of synthesizing amyloidogenic light chains resulting in AL
amyloidosis. Clinically occult AL amyloid deposition may occur in up to
31% of patients with MM. The prognosis of combined amyloidosis and MM is
improving with new therapeutic options. Thus it is imperative that
patients with MM be screened for amyloidosis. Sixty-six consecutive skin
biopsies from patients with MM and the diagnosis of graft vs. host
disease (GVHD) were stained with Congo red and assessed for the presence
of amyloid deposition. Twelve cases that had amyloid deposition in other
tissue and had a cutaneous biopsy were also stained with Congo red and
assessed for the presence of amyloid deposition. None of the 66 biopsies
of GVHD, and none of the 12 cases that had documented amyloid deposition
in other tissue showed evidence of amyloid deposition in the cutaneous
biopsies. In the absence of specific cutaneous manifestations of
amyloidosis, it is unlikely that amyloidogenic light chain deposition in
the skin would be found. Type I collagen may appear similar to amyloid,
both by light microscopy and fluorescence, after staining with Congo
red. Thus care must be taken not to confuse type I collagen
autofluorescence with positivity for amyloid when assessing skin
biopsies stained with Congo red.
22
UI - 12060120
AU - Zojer N; Schuster-Kolbe J; Assmann I; Ackermann J; Strasser K; Hubl W;
TI -
Drach J; Ludwig H
Chromosomal aberrations are shared by malignant plasma cells and a small
fraction of circulating CD19+ cells in patients with myeloma and
monoclonal gammopathy of undetermined significance.
SO - Br J Haematol 2002 Jun;117(4):852-9
AD - First Department of Internal Medicine and Medical Oncology,
Wilhelminenspital, University of Vienna, Montleartstrasse 37, 1160
Vienna, Austria.
In the present study, we aimed to identify distinct structural and
numerical chromosomal aberrations in peripheral blood B cells of
patients with myeloma and monoclonal gammopathy of undetermined
significance (MGUS), which reflect changes thought to occur at different
stages of the disease process. Peripheral blood from 12 patients with
multiple myeloma and three patients with MGUS was investigated for the
occurrence of retinoblastoma-1 gene deletions, p53 gene deletions and
numerical aberrations demonstrated previously to be present in the
patients' bone marrow CD138+ cells. By combining immunocytochemical
staining for light chains and interphase fluorescence in situ
hybridization (FISH), aberrant light-chain +ve cells were detected in
the circulating CD19+ cell fraction. Each kind of chromosomal change
present in the myeloma tumour cells was found to be shared by a small
fraction of CD19+ cells (0.1-1.8%; median 0.36%, n = 6). In one MGUS
patient, aberrant cells could be identified with a frequency of 0.34%
within the CD19-sorted cell fraction. Clonotypic cells were detected
with a frequency of 0.01-0.07% of peripheral blood nucleated cells by
m-RNA in situ hybridization with patient-specific probes in three
investigated patients. These results provide evidence that the
circulating clonotypic B cells are closely related to the malignant
plasma cells in myeloma and MGUS.
23
UI - 12060125
AU - Sahara N; Takeshita A; Shigeno K; Fujisawa S; Takeshita K; Naito K;
TI -
Ihara M; Ono T; Tamashima S; Nara K; Ohnishi K; Ohno R
Clinicopathological and prognostic characteristics of CD56-negative
multiple myeloma.
SO - Br J Haematol 2002 Jun;117(4):882-5
AD - Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1
Handayama, Hamamatsu-shi, 431-3192 Japan. sahara@hama-med.ac.jp
We analysed CD56 expression in 70 patients with multiple myeloma (MM) to
determine its clinicopathological and prognostic significance.
Fifty-five (79%) patients were CD56+. CD56- patients (n = 15) had higher
beta2 microglobulin levels and a higher incidence of extramedullary
disease, Bence Jones protein, renal insufficiency and thrombocytopenia
than CD56+ patients. Their myelomas more frequently had a plasmablastic
morphology. Overall survival was significantly lower in CD56- than CD56+
patients (22 vs 63 months, P = 0.0002). We conclude that CD56- MM is a
discrete entity associated with more aggressive disease. The higher
incidence of plasmablastic cases suggested that CD56- MM may develop
from a less mature plasma cell than CD56+ MM.
24
UI - 12060127
AU - Gonzalez-Fraile MI; Garcia-Sanz R; Mateos MV; Balanzategui A; Gonzalez
TI -
M; Vaquez L; San Miguel JF
Methylenetetrahydrofolate reductase genotype does not play a role in
multiple myeloma pathogenesis.
SO - Br J Haematol 2002 Jun;117(4):890-2
AD - Servicio de Hematologia, Hospital Clinico Universitario de Salamanca,
Centro de Investigacion del Cancer (CIC), Paseo de San Vicente 58-182,
37007 Salamanca, Spain.
Methylenetetrahydrofolate reductase (MTHFR) plays an important role in
carcinogenesis. A decreased incidence of cancer has been reported in the
presence of MTHFR 677TT, 1298AC and 1298CC polymorphic variants. We have
analysed the MTHFR genotype in 107 multiple myeloma (MM) patients and 86
controls. The MM and control polymorphisms frequencies were: 34% and 48%
for 677CC, 53% and 41% for 677CT, 12% and 11% for 677TT; 36% and 43% for
1298AA, 51% and 44% for 1298AC; and 12% and 13% for 1298CC respectively.
No statistically significant differences were observed. In addition, no
differences were seen according to MM stage, presence of p16 gene
hypermethylation or response to treatment.
25
UI - 12171498
AU - Yin H; Alhasan N; Ciervo A; Zinterhofer L
TI -
Soft tissue amyloidoma with features of plasmacytoma: a case report and
review.
SO - Arch Pathol Lab Med 2002 Aug;126(8):969-71
AD - Department of Pathology, Monmouth Medical Center, Long Branch, NJ 07740,
USA.
Soft tissue amyloidoma is rare, and soft tissue amyloidoma associated
with plasmacytoma and without evidence of systemic amyloidosis is even
more rare. We report a case of soft tissue amyloidoma associated with an
apparently localized monoclonal proliferation of plasma cells
(plasmacytoma).
26
UI - 12173037
AU - Mitsiades CS; Mitsiades N; Poulaki V; Schlossman R; Akiyama M; Chauhan
TI -
D; Hideshima T; Treon SP; Munshi NC; Richardson PG; Anderson KC
Activation of NF-kappaB and upregulation of intracellular anti-apoptotic
proteins via the IGF-1/Akt signaling in human multiple myeloma cells:
therapeutic implications.
SO - Oncogene 2002 Aug 22;21(37):5673-83
AD - Jerome Lipper Multiple Myeloma Center, Department of Adult Oncology,
Dana Farber Cancer Institute, Harvard Medical School, Boston,
Massachusetts, MA 02115, USA.
Interleukin-6 (IL-6) and insulin-like growth factor-1 (IGF-1) promote
the proliferation of multiple myeloma (MM) cells and protect them
against dexamethasone (Dex)-induced apoptosis. We have previously shown
that Apo2 ligand/TNF-Related apoptosis inducing ligand (Apo2L/TRAIL)
induces apoptosis of MM cells, including cells either sensitive or
resistant to Dex and cytotoxic drugs, and overcomes the growth and
survival effect of IL-6; conversely, NF-kappaB transcriptional activity
attenuates their Apo2L/TRAIL-sensitivity. In the current study, we
demonstrate that IGF-1 stimulates sustained activation of NF-kappaB and
Akt; induces phosphorylation of the FKHRL-1 Forkhead transcription
factor; upregulates a series of intracellular anti-apoptotic proteins
including FLIP, survivin, cIAP-2, A1/Bfl-1, and XIAP; and decreases
Apo2L/TRAIL-sensitivity of MM cells. In contrast, IL-6 does not cause
sustained NF-kappaB activation, induces less pronounced Akt activation
and FKHRL-1 phosphorylation than IGF-1, and increases the expression of
only survivin. Forced overexpression of constitutively active Akt in
MM-1S cells reduced their sensitivity to Apo2L/TRAIL and to doxorubicin
(Doxo). In contrast, the Akt inhibitor IL-6-Hydroxymethyl-chiro-inositol
2-(R)-2-O-methyl-3-O-octadecylcarbonate induced cell death of both Dex-
and Doxo-sensitive and -resistant cells; opposed the protective effect
of constitutive Akt activity against Apo2L/TRAIL; and abrogated the
NF-kappaB activation, increase of anti-apoptotic proteins and protection
against Apo2L/TRAIL induced by IGF-1. These findings therefore define an
important role of the Akt pathway in modulating tumor cell
responsiveness to Apo2L/TRAIL, delineate molecular mechanisms for the
survival effects of IGF-1, and characterize differential
pathophysiologic sequelae of IGF-1 vs IL-6 on MM cells. Importantly,
they provide the basis for future clinical trials in MM combining
conventional or novel agents with strategies designed to neutralize
IGF-1.
27
UI - 12151702
AU - Gonen C; Oksuzoglu B; Yalcin S
TI -
Abdominal pain in a diabetic myeloma patient with cirrhosis.
SO - Postgrad Med J 2002 Jun;78(920):375, 379
AD - Department of Internal Medicine, Hacettepe University, Samanpazari,
06100 Ankara, Turkey.
28
UI - 12100137
AU - Mitterbauer M; Kalhs P; Keil F; Prinz E; Moser K; Mannhalter C;
TI -
Mitterbauer G; Brugger S; Gisslinger H; Lechner K; Greinix HT
Continuous complete clinical and molecular remission in two patients
with refractory lymphoid malignancies after autografting followed by
allogeneic stem cell transplantation with reduced intensity
conditioning.
SO - Br J Haematol 2002 Jul;118(1):132-5
AD - Department of Medicine I, Bone Marrow Transplantation, University
Hospital of Vienna, Vienna, Austria. Margit.Mitterbauer@akh-wien.ac.at
We present a 60-year-old patient with primary refractory non-Hodgkin's
lymphoma and a 58-year-old patient with multiple myeloma with relapse
after first autologous stem cell transplantation (ASCT), who underwent
ASCT followed by allogeneic stem cell transplantation (alloSCT) with
reduced intensity conditioning consisting of fludarabine and a single
dose of total body irradiation. For graft-versus-host disease
prophylaxis cyclosporine and mycophenolate mofetyl were given. Complete
donor chimaerism was observed on d 28 after SCT. Both patients achieved
sustained complete haematological and molecular remission of the
immunoglobulin kappa light chain (Igkappa) rearrangement and are alive
and well 17 and 16 months after SCT respectively.
29
UI - 12100143
AU - Frassanito MA; Cusmai A; Piccoli C; Dammacco F
TI -
Manumycin inhibits farnesyltransferase and induces apoptosis of
drug-resistant interleukin 6-producing myeloma cells.
SO - Br J Haematol 2002 Jul;118(1):157-65
AD - Department of Biomedical Sciences and Human Oncology, Section of
Internal Medicine and Clinical Oncology, University of Bari Medical
School, Bari, Italy.
Interleukin 6 (IL-6) is an important survival and growth factor for
myeloma cells and exerts its effects by activating several transduction
pathways, including the Ras cascade. As farnesylation of the activated
Ras oncogene product by protein farnesyltransferase (FTase) is a
critical step for Ras functional activity, FTase has emerged as a
potential target for the development of new anti-cancer agents. Based on
our previous demonstration that IL-6-producing myeloma cells are
refractory to drug-induced apoptosis, we have analysed the effect of
manumycin, a natural FTase inhibitor, on IL-6-producing myeloma cells
resistant to Fas-, dexamethasone- and doxorubicin-induced apoptosis.
Treatment of myeloma cells with manumycin prevented cell proliferation
and induced apoptosis. Western blotting experiments demonstrated that
this effect was related to inhibition of the post-translational Ras
processing.Further analysis showed that manumycin-induced apoptosis
involved caspase-3. Activation of caspase-3, in fact, was observed in 6
h-treated myeloma cells expressing Apo 2.7 antigen, the marker of early
apoptosis, whereas their treatment with cell-permeable DEVD-fmk, that
irreversibly inhibits caspase-3 activity, prevented their apoptosis.
Over-expression of caspase-3 was also demonstrated by reverse
transcription-polymerase chain reaction. Finally, over-expression of
Bcl-2 and its homologue Bcl-xL was observed in manumycin-treated cells
as well as in control myeloma cells, implying that the Bcl-2 family is
not involved. FTase inhibitors may thus be proposed as a potential
pharmacological weapon, as they block the Ras pathway and induce the
apoptosis of drug-resistant IL-6-producing myeloma cells.
30
UI - 12100153
AU - Martin A; Garcia-Sanz R; Hernandez J; Blade J; Suquia B; Fernandez-Calvo
TI -
J; Gonzalez M; Mateo G; Orfao A; San Miguel JF
Pamidronate induces bone formation in patients with smouldering or
indolent myeloma, with no significant anti-tumour effect.
SO - Br J Haematol 2002 Jul;118(1):239-42
AD - Hospital Universitario de Salamanca, Salamanca, Spain.
Twelve patients with smouldering or indolent multiple myeloma (MM)
received 12 courses of intravenous pamidronate as a single agent to
evaluate both the antitumour and bone metabolism effects. One patient
achieved minor response, eight had stable disease, and three - all
indolent MM - showed disease progression. Serum interleukin 6 (IL-6),
IL-1beta and Oncostatin-M remained stable throughout the study, while
tumour necrosis factor-alpha increased. Bone density significantly
increased after four and 12 courses compared with baseline. Markers for
bone resorption and bone formation decreased with treatment. These
results suggest that pamidronate treatment reduces bone turnover in
smouldering or indolent MM, but has no significant antitumour effect.
31
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
32
UI - 11503969
AU - Shinagawa A; Kojima H; Kobayashi T; Kawada K; Nagasawa T
TI -
Lupus anticoagulant-like activity observed in a dimeric lambda protein
produced by myeloma cells.
SO - Int J Hematol 2001 Jun;73(4):526-31
AD - Division of Hematology, Institute of Clinical Medicine, University of
Tsukuba, Ibaraki, Japan.
We report here a lupus anticoagulant (LA)-like activity observed in a
45-year-old man with Bence-Jones protein (BJP) lambda-type multiple
myeloma. This patient showed no clinical symptoms of thrombosis or
bleeding diathesis. Laboratory examination on admission showed mild
anemia, prolongation of activated partial thromboplastin time (APTT)
(APTT, 56.2 seconds; control, 29.1 seconds), normal prothrombin time,
normal thrombin time, and massive proteinuria (2.3 g/d). The mix test
with normal plasma showed the presence of circulating anticoagulant.
Based on the assumption that the lambda-type BJP may have been
responsible for the prolongation of APTT, we purified the BJP from the
patient's urine using column works. Sodium dodecyl
sulfate-polyacrylamide gel electrophoresis and immunoblotting showed
that the purified protein was a 48-kd homodimer of immunoglobulin
lambda-chains. Addition of the purified dimeric lambda-type BJP to the
normal plasma prolonged both APTT and dilute Russell's viper venom time
(DRVVT) in a dose-dependent manner, and the negatively charged
phospholipid-dependent prothrombinase activity was significantly
inhibited in the presence of this protein. Furthermore, both the
prolongation of DRVVT and the inhibition of the prothrombinase activity
were almost completely abrogated under the condition of high ionic
strength. These findings collectively suggest that the dimeric
lambda-type BJP showed LA-like activity via the mechanism of ionic
charge.
33
UI - 11594523
AU - Shimizu K; Nagura E; Hirabayashi N; Wakita A; Takeyama H; Sao H; Nitta
TI -
M; Kawashima K; Saito H
Posttreatment nadir M-protein level is a stronger discriminator of
survival following plateau attainment than is percent reduction in
M-protein in patients with IgG myeloma.
SO - Int J Hematol 2001 Aug;74(2):205-8
AD - Department of Medicine, Nagoya City Higashi General Hospital, Nagoya,
Japan.
We conducted a retrospective study of patients with IgG or IgA myeloma
who attained plateau to evaluate the relationships between survival and
posttreatment nadir M-protein levels and between survival and the
response to treatment evaluated by the percent reduction in M-protein.
Of the 127 patients comprising 92 IgG and 35 IgA myeloma patients with
disease stages II or III, 51 (40.2%) attained plateau. For IgG myeloma
patients who attained plateau, survival time was not affected by the
percent reduction in M-protein (median survival, 59.5 months for
responding patients versus 54.4 months for nonresponding patients, P =
.6910). Posttreatment nadir M-protein level, however, did affect
survival time (median survival, 61.2 months for <3000 mg/dL versus 25.7
months for >3000 mg/dL, P = .0439). These findings suggest that the
posttreatment nadir M-protein level is a stronger discriminator of
survival following plateau attainment than the percent reduction of
M-protein in patients with IgG myeloma.
34
UI - 12149181
AU - Van Ness B
TI -
New technologies in the myeloma gene mine.
SO - Blood 2002 Aug 15;100(4):1109
AD - University of Minnesota, USA.
35
UI - 12149193
AU - Zangari M; Siegel E; Barlogie B; Anaissie E; Saghafifar F; Fassas A;
TI -
Morris C; Fink L; Tricot G
Thrombogenic activity of doxorubicin in myeloma patients receiving
thalidomide: implications for therapy.
SO - Blood 2002 Aug 15;100(4):1168-71
AD - Central Arkansas Veterans Healthcare System and University of Arkansas
for Medical Sciences, Little Rock, AR, USA. zangarimaurizio@uams.edu
Ten percent of newly diagnosed myeloma patients treated with any type of
chemotherapy develop deep venous thrombosis (DVT). Thalidomide has
proven activity in refractory multiple myeloma (MM), and although
single-agent thalidomide has minimal prothrombogenic activity, its
combination with cytotoxic chemotherapy is associated with a
significantly increased risk of DVT. We analyzed the inci
Dr. Mao talks about complementary and alternative medicine and the importance of being open about their use with cancer caregivers. Read more.
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Calcium Leucovorin, Citrovorum Factor, Folinic Acid
Cladribine (2-CDA, Leustatin®)
Cyclophosphamide (Cytoxan®, Neosar®, Endoxan®)
Cyclosporine (Neoral®, Sandimmune®, Restasis®, Gengraf®)
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Irinotecan (Camptosar®, CPT-11)
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Leucovorin (Calcium Leucovorin, Citrovorum Factor, Folinic Acid)
Leuprolide Acetate (Lupron®, Lupron Depot®, Eligard®, Prostap®, Viadur®) - For Men
Leuprolide Acetate (Lupron®, Lupron Depot®, Eligard®, Prostap®, Viadur®) - For Women
Lupron®, Lupron Depot®, Eligard®, Prostap®, Viadur®
Lupron®, Lupron Depot®, Eligard®, Prostap®, Viadur®
Busulfan (Myleran®, Busulfex®)
Intravesicular Mitomycin (Mutamycin®, Mitomycin-C, given into the bladder)
Mechlorethamine (Mustargen®, Nitrogen Mustard)
mechlorethamine, mustine, Mustargen®
Megestrol (Megace®, Megace-ES®)
Mercaptopurine (Purinethol®, 6-MP)
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Mexate®, Folex®, Rheumatrex®, Amethopterin, MTX
Mitomycin (Mutamycin®, Mitomycin-C)
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Morphine Sulfate (MS Contin®, Avinza®, Kadian®, Oramorph SR®)
MS Contin®, Avinza®, Kadian®, Oramorph SR®
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Toposar®, VePesid®, Etopophos®,VP-16
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