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Table of Contents
1
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.
2
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.
jagonzalez@medynet.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).
3
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.
4
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. fonseca.rafael@mayo.edu
5
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.
6
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
7
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.
8
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.
9
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.
10
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.
zangarimaurizio@uams.edu
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.
11
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.
12
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.
13
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.
hmura@health.gunma-u.ac.jp
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.
14
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.
15
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. k.neben@dkfz.de
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.
16
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)
17
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. thra@herlevhosp.kbhamt.dk
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)
18
UI - 21239910
AU - Cremer FW; Goldschmidt H; Moos M
TI -
Clonotypic B cells in the peripheral blood of patients with multiple
myeloma.
SO - Blood 2001 May 1;97(9):2913-4
19
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. dimoclin@cimedoc.uniba.it
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 20
UI - 20548525
AU - Tiplady CW; Summerfield GP
TI -
Continuous low-dose dexamethasone in relapsed or refractory multiple
myeloma.
SO - Br J Haematol 2000 Oct;111(1):381
21
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.
22
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
23
UI - 21365357
AU - Myers B; Grimley C; Dolan G
TI -
Thalidomide and low-dose dexamethasone in myeloma treatment.
SO - Br J Haematol 2001 Jul;114(1):245
24
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.
25
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.
26
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.
27
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.
28
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
29
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.
30
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.
thra@herlevhosp.kbhamt.dk
31
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.
32
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.
33
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. cswilson@salud.unm.edu
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.
34
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
35
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.
36
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.
37
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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