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NCI CANCERLIT® Search: Plasma Cell Neoplasm - May 2002
National Cancer Institute®
Last Modified: May 1, 2002
Table of Contents
1
UI - 11955031
AU - Imrie K; Esmail R; Meyer RM; Members of the Hematology Disease Site
TI -
Group of the Cancer Care Ontario Practice Guidelines Initiative
The role of high-dose chemotherapy and stem-cell transplantation in
patients with multiple myeloma: a practice guideline of the Cancer Care
Ontario Practice Guidelines Initiative.
SO - Ann Intern Med 2002 Apr 16;136(8):619-29
AD - Cancer Care Ontario Program in Evidence-Based Care, Ontario, Canada.
The Hematology Disease Site Group of the Cancer Care Ontario Practice
Guidelines Initiative has systematically reviewed the published
literature and, through a consensus process, developed an evidence-based
practice guideline assessing the role of stem-cell transplantation in
patients with multiple myeloma. The conclusions were validated by
solicited feedback from 221 practitioners across Ontario, Canada. The
guideline comprises six recommendations: 1) Autologous transplantation
is recommended for patients with stage II or III myeloma and good
performance status. Evidence of benefit is strongest for patients who
are younger than 55 years of age and have a serum creatinine level less
than 150 micromol/L (<1.7 mg/dL). Physicians must use clinical judgment
in recommending transplantation to other patients. 2) Allogeneic
transplantation is not recommended as routine therapy. 3) Patients
potentially eligible for transplantation should be referred for
assessment early after diagnosis and should not be extensively exposed
to alkylating agents before collection of stem cells. 4) Autologous
peripheral blood stem cells should be harvested early in the patient's
treatment course. The best available data suggest that transplantation
is most advantageous when performed as part of initial therapy. 5) The
comparative data addressing the specifics of the transplantation process
are insufficient to allow definitive recommendations. In the absence of
such data, a single transplant with high-dose melphalan, with or without
total-body irradiation, is suggested for patients undergoing
transplantation outside a clinical trial. 6) At this time, no
conclusions can be reached about the role of interferon therapy after
transplantation.
2
UI - 11771050
AU - Campis P; Frenkiel S; Glikstein R; Mohr G
TI -
Unilateral sixth cranial nerve palsy caused by skull base mass lesions:
case series.
SO - J Otolaryngol 2001 Jun;30(3):184-6
AD - Department of Otolaryngology, Sir Mortimer B. Davis-Jewish General
Hospital, McGill University, Montreal, Quebec.
3
UI - 11920166
AU - San Miguel JF; Lahuerta JJ; Garcia-Sanz R; Alegre A; Blade J; Martinez
TI -
R; Garcia-Larana J; De La Rubia J; Sureda A; Vidal MJ; Escudero A;
Perez-Esquiza E; Conde E; Garcia-Ruiz JC; Cabrera R; Caballero D;
Moraleda JM; Leon A; Besalduch J; Hernandez MT; Rifon J; Hernandez F;
Solano C; Palomera L; Parody R; Gonzalez JD; Mataix R; Maldonado J;
Constela J; Carrera D; Bello JL; De Pablos JM; Perez-Simon JA; Torres
JP; Olanguren J; Prieto E; Acebede G; Penarrubia MJ; Torres P;
Diez-Martin JL; Rivas A; Sanchez JM; Diaz-Mediavilla J
Are myeloma patients with renal failure candidates for autologous stem
cell transplantation?
SO - Hematol J 2000;1(1):28-36
AD - Spanish Registry for Transplant in Multiple Myeloma, Grupo Espanol de
Trasplante Hematopoyetico (GETH), Spain. sanmigiz@gugu.usal.es
INTRODUCTION: Renal function is one of the most important prognostic
factors in multiple myeloma (MM). Patients with renal failure are
generally excluded from high dose therapy even though they display a
poor prognosis with conventional chemotherapy schemes. The aim of this
study was to analyze the outcome of MM patients with renal insufficiency
undergoing autologous stem cell transplantation (ASCT), including the
evaluation of the quality of PB stem cell collections, kinetics of
engraftment, transplant-related mortality, response to high dose
chemotherapy and survival. MATERIALS AND METHODS: From a total of 566
valuable patients included in the MM Spanish ASCT registry, three groups
of patients were defined: group BA, patients with abnormal renal
function at diagnosis but normal at transplant (73 cases); group BB,
patients with abnormal function both at diagnosis and at transplant (14
cases); and group AA (control group, 479 cases), patients who constantly
had normal renal function. RESULTS AND CONCLUSION: Patients from groups
BA and BB presented with a significantly higher number of adverse
prognostic factors, reflecting that we were dealing with high tumor MM
cases, as compared with patients from group AA. The number of
mononuclear cells, CD34+ cells and CFU-GM cells collected in patients
with non-reversible renal insufficiency was similar to those harvested
in MM patients with normal renal function. Moreover, neutrophil and
platelet engraftments were identical in patients with and without renal
failure (days +11 and +12, respectively). By contrast,
transplant-related mortality (TRM) was significantly higher in group BB
patients (29%) than in groups BA (4.1%) and AA (3.3%). In multivariate
analysis only three variables showed independent influence on TRM: poor
performance status (ECOG 3), hemoglobin <9.5 g/dl and serum creatinine >
or =5 mg/dl. The response to high dose therapy was independent of renal
function. Interestingly, 43% of patients from group BB showed an
improvement in renal function (creatinine < 2 mg/dl) after transplant.
The three-year overall survival from transplantation was 56, 49 and 61%
for the BB, BA and AA groups, respectively, with a statistically
significant difference favoring group AA (P<0.01). PFS did not differ
significantly between the three groups of patients. In multivariate
analysis the only unfavorable independent prognostic factors for overall
survival were poor performance status either at diagnosis or at
transplant, high beta(2)-microglobulin levels, and no response to
transplant. According to these results, ASCT is an attractive
alternative for MM patients with renal insufficiency, and it should not
constitute a criterion for exclusion from transplant unless patients
display poor performance status and very high creatinine levels (>5
mg/dl).
4
UI - 11920177
AU - Sundblad A; Coutinho A; Bjorkholm M; Holm G
TI -
V-region-specific alterations of serum IgM production in multiple
myeloma of IgG class.
SO - Hematol J 2000;1(2):102-10
AD - Division of Hematology, Department of Medicine, Karolinska Institute and
Hospital, Stockholm, Sweden. anne.sunblad@cmm.ki.se
INTRODUCTION: Multiple myeloma is accompanied by decreased polyclonal
serum immunoglobulin concentrations. This suppression might be due to
non-specific effects on the polyclonal lymphocyte populations as
previously suggested, or it could include specific variable
region-dependent mechanisms. Thus, differentiation, survival and
activation to Ig secretion of B-lineage cells are dependent on the
expression and signalling through the variable Ig receptor. The present
study addresses the question whether such variable region-specific
alterations were present in the peripheral repertoire of IgM antibodies
in patients with IgG-secreting MM. MATERIALS AND METHODS: IgM reactivity
repertoires towards a large panel of antigens in extracts of homologous
tissues (liver, brain, stomach and heart muscle) and bacteria (Bacillus
macquarensis) were analysed in sera from 22 patients diagnosed with IgG1
MM. Healthy, matched volunteers served as control donors. A modified
Western assay was used, and values obtained from area integration by
image analyses were submitted to multiparametric statistics. RESULTS AND
CONCLUSION: The results confirm previous observations on the depression
of serum IgM concentrations in multiple myeloma, and demonstrate
concentration-independent, patient- and V-region-specific alterations in
the polyclonal reactivity repertoires. Since the scoring of IgM
reactivities by this technique is independent of IgG and because the
deviations of IgM reactivity are not coincident with reactivities of
(myeloma) IgG in the individual sera, the results indicate that the
immunological syndrome of MM includes significant V-region-specific
alterations in the polyclonal repertoires of IgM antibodies.
5
UI - 11920187
AU - Troussard X; Avet-Loiseau H; Macro M; Mellerin MP; Malet M; Roussel M;
TI -
Sola B
Cyclin D1 expression in patients with multiple myeloma.
SO - Hematol J 2000;1(3):181-5
AD - Laboratoire d'Hematologie, CHU Caen, France, and UPRES-EA 2128, UFR de
Medecine, Caen, France. troussard-x@chu-caen.fr
INTRODUCTION: Chromosomal abnormalities are detected in 50 to 70% of
patients with multiple myeloma (MM). By conventional cytogenetic
analysis, a t(11;14)(q13;q32) is observed at a frequency of 3 to 14%.
MATERIALS AND METHODS: To demonstrate a cyclin D1 expression in MM
patients or MM cell lines, 14 patients with multiple myeloma (MM) and
nine human multiple myeloma cell lines (HMCL) were screened by a
competitive RT-PCR and/or Northern blot analysis for cyclin D1
expression. Furthermore, we screened 10 MM patients with FISH to
demonstrate a relationship between the cyclin D1 expression and the
presence of the t(11;14). RESULTS: Five HMCL had a cyclin D1
overexpression: three of them had a t(11;14)(q13;q32) and two had extra
copies of chromosome 11. A cyclin D1 expression was found at diagnosis
in seven out of 14 untreated MM patients (50%). Out of 14 MM patients,
FISH studies were performed in 10 patients. A t(11;14) was detected in
three out of 10 patients and extra copies of chromosome 11 were found in
two additional patients. CONCLUSION: Cyclin D1 expression is a common
event in MM patients (50%) and is associated either with a
t(11;14)(q13;q32) or extra copies of chromosome 11. The prognostic role
of the cyclin D1 expression and the level of this expression, as
compared to other B-cell chronic lymphoproliferative disorders such as
mantle cell lymphoma or hairy cell leukemia, remains to be determined in
the pathogenesis of multiple myeloma.
6
UI - 11920188
AU - Yakoub-Agha I; Moreau P; Leyvraz S; Berthou C; Payen C; Dumontet C;
TI -
Grosbois B; Beris P; Duguet C; Attal M; Harousseau JL; Facon T; (on
behalf of the Intergroupe Francophone du Myelome (IFM))
Thalidomide in patients with advanced multiple myeloma.
SO - Hematol J 2000;1(3):186-9
AD - Service des Maladies du Sang, CHU, Lille, France.
INTRODUCTION: Recently, a report has suggested the efficacy and safety
of thalidomide in refractory multiple myeloma. In an attempt to assess
the efficacy and tolerance of thalidomide in advanced multiple myeloma
(on behalf of the Intergroupe Franchophone dy Myelome (IFM)), we report
the preliminary experience of the IFM with this drug. MATERIALS AND
METHODS: Patients with advanced multiple myeloma (n=27) were treated
with an oral dose of thalidomide (median 400 mg/day). At the start of
treatment, all patients had active disease and 20 patients had received
at least one autologous transplantation. RESULTS: Median follow-up was
105 days from the first administration. The serum and/or urine levels of
the M-component were reduced by at least 75% in four patients including
one patient with a >90% reduction, by at least 50% in five patients and
by at least 25% in three patients, giving a total response rate of 45%
(12 out of 27 patients). Nine patients had stable disease and six
patients had progressed disease. Short-term side-effects of thalidomide
were generally moderate. CONCLUSION: This study confirms that
thalidomide is an effective agent in patients with advanced myeloma.
7
UI - 11971193
AU - Wang YD; De Vos J; Jourdan M; Couderc G; Lu ZY; Rossi JF; Klein B
TI -
Cooperation between heparin-binding EGF-like growth factor and
interleukin-6 in promoting the growth of human myeloma cells.
SO - Oncogene 2002 Apr 11;21(16):2584-92
AD - INSERM U475 and Unit for Cellular Therapy, CHU Montpellier, 99 Rue Puech
Villa, 34197 Montpellier, France.
Interleukin-6 (IL-6) is a major survival and proliferation factor of
human malignant plasma cells and IL-6 dependent myeloma cell lines can
be obtained from patients with terminal disease. We show here that
mutated diphtheria toxin, a specific inhibitor of heparin-binding
epidermal growth factor-like growth factor (HB-EGF), blocked the
IL-6-induced growth of two myeloma cell lines (XG-1 and XG-14) and did
not significantly affect that of two other cell lines (XG-6 and XG-13).
The IL-6 mediated growth of myeloma cells was also inhibited by
antibodies to ErbB1, a receptor for HB-EGF. The XG-1 and XG-14 cell
lines that are sensitive to HB-EGF inhibitors overexpressed HB-EGF and
EGF receptor (ErbB1) genes. They also overexpressed CD9, a tetraspanin
that binds to the heparin-binding domain of HB-EGF and is critical for
promoting ErbB1 activation by HB-EGF. The XG-6 and XG-13 myeloma cells
that were not significantly sensitive to HB-EGF antagonists, poorly
expressed HB-EGF, ErbB1 and CD9 genes or proteins. We demonstrated that
recombinant HB-EGF supported the long-term growth of myeloma cells, as
did IL-6. The myeloma cell growth factor activity of HB-EGF was
completely inhited by antibodies to ErbB1, but also by antibodies to
gp130 IL-6 transducer or to IL-6. These data indicate that in the XG-1
and XG-14 IL-6-dependent myeloma cell lines, the CD9/HB-EGF/erbB1 and
the IL-6/IL-6R/gp130 pathways cooperate synergistically to trigger
myeloma cell growth. They suggest that inhibitors of the EGF receptor or
HB-EGF may be useful for inducing myeloma cell apoptosis in patients
with multiple myeloma.
8
UI - 11380408
AU - Blade J; Perales M; Rosinol L; Tuset M; Montoto S; Esteve J; Cobo F;
TI -
Villela L; Rafel M; Nomdedeu B; Montserrat E
Thalidomide in multiple myeloma: lack of response of soft-tissue
plasmacytomas.
SO - Br J Haematol 2001 May;113(2):422-4
AD - Institute of Haematology and Oncology, Department of Haematology,
Postgraduate School of Haematology Farreras-Valenti, Barcelona, Spain.
jblade@clinic.ub.es
Thalidomide is active in patients with refractory myeloma. Seventeen
patients (nine men/eight women, median age 73 years) with multiple
myeloma (MM) were treated with thalidomide. Fifteen patients had
refractory disease and two untested relapse. The median dose of
thalidomide was 500 mg (range, 200-800 mg). Nine of the 17 patients
(53%) responded. The response rate was significantly higher in patients
with no extramedullary disease than in those with soft tissue masses
(75% CI: 43-95% versus 0%; P = 0.01)). Of note, no decrease in the size
of soft tissue plasmacytomas was observed in all the five patients who
had extramedullary involvement. This data suggests that the mechanism of
action and effectiveness of thalidomide might depend on the site of the
tumour cells.
9
UI - 11722443
AU - Myers B; Grimley C; Crouch D; Dolan G
TI -
Lack of response to thalidomide in plasmacytomas.
SO - Br J Haematol 2001 Oct;115(1):234
10
UI - 11792416
AU - Semenov I; Akyuz C; Roginskaya V; Chauhan D; Corey SJ
TI -
Growth inhibition and apoptosis of myeloma cells by the CDK inhibitor
flavopiridol.
SO - Leuk Res 2002 Mar;26(3):271-80
AD - Department of Pediatrics (Hematology-Oncology), Children's Hospital of
Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15213, USA.
Although myeloma shows responsiveness in intensive chemotherapy, overall
survival remains less than 40% at 2 years. Since myeloma appears to be
dependent on cytokines, such as IL-6, we hypothesized that targeting
signal transduction molecules could effectively treat myeloma. Two
myeloma cell lines U266 and RPMI-8226 and CD38+ myeloma cells were
studied by immune complex kinase assay or anti-phosphotyrosine blot for
evidence of constitutive activation of tyrosine kinases. Growth arrest
and apoptosis were evaluated in these two cell lines following their
treatment with specific kinase inhibitors. We found that a variety of
Src and Janus kinases were present and constitutively active in U266 and
RPMI-8226 cells. Inhibitors of both Src and Janus kinases were inferior
to the cyclin-dependent kinase inhibitor, flavopiridol, in inducing both
growth arrest with GI50 of 100 nM and apoptosis in both cell lines and
CD38+ myeloma cells. Although, flavopiridol did not affect cyclin D1 and
cyclin A levels, it inhibited Mcl-1 and Bcl-2 protein levels and
cyclin-dependent kinase 2 activity. Flavopiridol is a well-tolerated
drug, currently in phase I-II trials for a variety of tumors. A clinical
trial using flavopiridol should be performed in patients with myeloma.
Its mechanism of action may involve targets other than the
cyclin-dependent kinases.
11
UI - 11829241
AU - Muzio LL; Pannone G; Bucci P
TI -
Early clinical diagnosis of solitary plasmacytoma of the jaws: a case
report with a six year follow-up.
SO - Int J Oral Maxillofac Surg 2001 Dec;30(6):558-60
AD - Institute of Dental Sciences, University of Ancona, Italy.
lomuziol@tin.it
The authors reported a case of a solitary mandibular plasmacytoma in a
53-year-old male Caucasian patient. The histological examination of the
specimen was positive for a plasmacytoma with anaplastic appearance.
Since the patient refused a demolitive surgical treatment, he was
treated with a local radiation therapy of 4000 rads over a 20-day period
and polychemotherapy with cyclophosphamide, prednisone and melphalan.
Six years after starting radiation treatment the patient is free of
recurrent primary disease and not affected by multiple localization. In
conclusion, the solitary bone plasmacytoma represents an initial stage
of the multiple myeloma rather than a distinct clinical pathology.
Unfortunately, the diagnosis of the plasmacytoma is only rarely carried
out in the early phases of the disease. The importance of the
identification of the initial stage without a clear M component, as in
the reported case, is self-evident, since the prognosis is related to
the mass of plasmacytoma cells that are present at the time of the
diagnosis. The purpose of this study is to report an extremely rare case
of solitary bone plasmacytoma with a mandibular localization treated
with radio- and polychemotherapy.
12
UI - 11948073
AU - Dooley KE; Sinha SR; Haponik E; Conwit R; Sevransky JE
TI -
A 39-year-old man with hip pain and respiratory failure.
SO - Chest 2002 Apr;121(4):1345-9
AD - Department of Medicine, Johns Hopkins University School of Medicine,
Baltimore, MD 21224-6801, USA.
13
UI - 11968583
AU - Adam Z; Pour L; Svobodnik A; Scudla V; Salajka F; Vytrasova M; Bacovsky
TI -
J; Schutzova M; Koza V; Sumna E; Frankova H; Lehanka F; Gumulec J;
Stavarova Y; Cahova S; Vranova M; Dostalova V; Kessler P; Walterova L;
Meluzinova I; Seifertova N; Slama O; Buchler T; Krejci M; Bencikova V;
Nykodymova V; Dusek L; Hajek R; Czech Myeloma Group
[Quality of life and tolerance of maintenance therapy in patients with
multiple myeloma]
SO - Vnitr Lek 2002 Mar;48(3):216-29
AD - Interni hematoonkologicka klinika FN Brno, pracoviste Bohunice, Brno.
Questionnaires on the quality of life and tolerance of different parts
of maintenance treatment were sent to a total of 83 patients with
multiple myeloma. All patients were for more than one year on
maintenance treatment which involved either interferon alpha monotherapy
(I), 3 million u. three times per week till signs of relapse developed
or sequence administration of interferon alpha and dexamethazone 40 mg
on day 1 to 4, 10 to 13 and 20 to 23 and then after a four-week interval
again interferon alpha, again till progression of the disease occurred.
The patients evaluated the presence or absence of different undesirable
effects of treatment during the first two weeks of treatment and
throughout the year and listed their intensity into four categories
defined in the questionnaire. The quality of life was evaluated by means
of a basic module of the questionnaire of the European Organization for
Research and Treatment of Cancer Core Quality of Life Questionnaire
version 3.0 (EORTC QLQ-C30). The results of the questionnaire are to a
certain extent surprising as from the patients' answers ensues that this
maintenance treatment is associated with more numerous undesirable
effects than the physicians realized when in contact with the patient.
In this summary we can list only the most frequent effects
(deterioration of eyesight, impaired sleep, depressions, irritability
and unrest, chill, pain in muscles and joints, general weakness and
dyspnoea). From the questionnaires on the quality of life ensues a
markedly poorer quality of life of these patients as compared with the
healthy population. There are however no basic differences between
individual groups. The questionnaires were handed only to patients who
had maintenance treatment for more than one year and thus patients were
eliminated where maintenance treatment was discontinued because of
undesirable effects. To give a general idea of the tolerance of the
above maintenance treatment the authors mention that to the date of Aug.
31, 2001 113 patients were randomized into one of the branches of
maintenance treatment. Maintenance treatment had to be discontinued in
6% patients (in two instances on account of severe hypothyroidism, in
one case on account of hallucinations, in three instances on account of
severe mental depression caused by this treatment). Reduction of
interferon doses in 20% patients usually because of cytopenia but also
on account of psychic problem. To the question what length of
prolongation of life compensates the undesirable effects of maintenance
treatment the following replies were obtained from patients receiving
ID, possibly I: 3 months--47.6 and 38.3%, 6 months--4.3 and 10.6%, 9
months--0 and 4.3%, 12 months--47.6 and 46.8% of the addressed patients.
In reply to the question whether the patients would prefer, assuming
equal effectiveness, a maintenance monotherapy with interferon alpha or
dexamethazone more patients preferred interferon to dexamethasone. For
practice ensues from this article informing on undesirable effects of
maintenance treatment and the effect of maintenance treatment on the
quality of life: 1. the necessity of thorough knowledge of physicians of
all possible undesirable effects as only a doctor knowing possible
undesirable effects of treatment can recognize them, 2. regular
monitoring not only of the activity of the basic disease, but also
undesirable effects of maintenance treatment and the influence of
treatment on the patients' quality of life, 3. the necessity to assess
the quality of life in clinical trials as an important parameter for
deciding on the way of treatment.
14
UI - 11893981
AU - Wein RO; Topf P; Sham RL
TI -
Subglottic plasmacytoma: a case report and review of the literature.
SO - Am J Otolaryngol 2002 Mar-Apr;23(2):112-8
AD - Division of Otolaryngology, University of Rochester Medical Center,
Rochester, NY 14642, USA.
15
UI - 11973972
AU - Jarvelainen H; Remes K; Viikari J
TI -
[A severe osteoporosis in a middle-aged man]
SO - Duodecim 1999;115(22):2473-6
AD - TYKS:n sisatautien klinikka Kiinamyllynkatu 4-8 20520 Turku.
hannu.jarvelainen@utu.fi
16
UI - 11594143
AU - Garcia Montesinos R; Avisbal Portillo N; Velasco Garrido JL; Rueda Rios
TI -
C; Bujalance Zafra J; Ramirez Ramirez G
[Pleural effusion as presentation form of multiple myeloma]
SO - Rev Clin Esp 2001 Jul;201(7):424-5
17
UI - 11917503
AU - Kishi Y; Kashiwagi T; Kaneko T; Hayashi M; Shimizu M; Matsunobu S; Iino
TI -
Y; Katayama Y; Ohashi R
[Multiple myeloma light chain deposition with specific pathological
change]
SO - Nippon Naika Gakkai Zasshi 2002 Feb 10;91(2):749-51
AD - Second Department of Internal Medicine, Nippon Medical School, Tokyo.
18
UI - 11861260
AU - Van Ness B
TI -
Defining the genetic chaos in myeloma.
SO - Blood 2002 Mar 1;99(5):1504
AD - University of Minnesota, USA.
19
UI - 11861292
AU - Zhan F; Hardin J; Kordsmeier B; Bumm K; Zheng M; Tian E; Sanderson R;
TI -
Yang Y; Wilson C; Zangari M; Anaissie E; Morris C; Muwalla F; van Rhee
F; Fassas A; Crowley J; Tricot G; Barlogie B; Shaughnessy J Jr
Global gene expression profiling of multiple myeloma, monoclonal
gammopathy of undetermined significance, and normal bone marrow plasma
cells.
SO - Blood 2002 Mar 1;99(5):1745-57
AD - Donna D. and Donald M. Lambert Laboratory of Myeloma Genetics, Myeloma
Institute for Research and Therapy, University of Arkansas for Medical
Sciences, Little Rock, 72205, USA.
Bone marrow plasma cells (PCs) from 74 patients with newly diagnosed
multiple myeloma (MM), 5 with monoclonal gammopathy of undetermined
significance (MGUS), and 31 healthy volunteers (normal PCs) were
purified by CD138(+) selection. Gene expression of purified PCs and 7 MM
cell lines were profiled using high-density oligonucleotide microarrays
interrogating about 6800 genes. On hierarchical clustering analysis,
normal and MM PCs were differentiated and 4 distinct subgroups of MM
(MM1, MM2, MM3, and MM4) were identified. The expression pattern of MM1
was similar to normal PCs and MGUS, whereas MM4 was similar to MM cell
lines. Clinical parameters linked to poor prognosis, abnormal karyotype
(P =.002) and high serum beta(2)-microglobulin levels (P =.0005), were
most prevalent in MM4. Also, genes involved in DNA metabolism and cell
cycle control were overexpressed in a comparison of MM1 and MM4. In
addition, using chi(2) and Wilcoxon rank sum tests, 120 novel candidate
disease genes were identified that discriminate normal and malignant PCs
(P <.0001); many are involved in adhesion, apoptosis, cell cycle, drug
resistance, growth arrest, oncogenesis, signaling, and transcription. A
total of 156 genes, including FGFR3 and CCND1, exhibited highly elevated
("spiked") expression in at least 4 of the 74 MM cases (range, 4-25
spikes). Elevated expression of these 2 genes was caused by the
translocation t(4;14)(p16;q32) or t(11;14)(q13;q32). Thus, novel
candidate MM disease genes have been identified using gene expression
profiling and this profiling has led to the development of a gene-based
classification system for MM.
20
UI - 11861305
AU - San Miguel JF; Almeida J; Mateo G; Blade J; Lopez-Berges C; Caballero D;
TI -
Hernandez J; Moro MJ; Fernandez-Calvo J; Diaz-Mediavilla J; Palomera L;
Orfao A
Immunophenotypic evaluation of the plasma cell compartment in multiple
myeloma: a tool for comparing the efficacy of different treatment
strategies and predicting outcome.
SO - Blood 2002 Mar 1;99(5):1853-6
AD - Servicio de Hematologia, Hospital Clinico Universitario, Salamanca,
Spain. sanmigiz@gugu.usal.es
Multiparametric immunophenotyping can be a sensitive method for
analyzing the plasma cell (PC) compartment in patients with multiple
myeloma because it discriminates between myelomatous and normal PCs.
Using this approach, we compared the efficacy of high-dose chemotherapy
followed by autologous stem cell transplantation (ASCT) with that of
conventional chemotherapy. We found that ASCT provided a significantly
greater reduction in the level of residual tumor PCs and with better
recovery of normal PCs. This profile of coexistence of normal PCs and
myelomatous PCs resembled that observed in monoclonal gammopathy of
undetermined significance. We also found that treatment-induced changes
in the PC compartment correlated with disease outcome. Thus, patients in
whom at least 30% of gated PCs had a normal phenotype after treatment
had a significantly longer progression-free survival (60 +/- 6 months
versus 34 +/- 12 months; P =.02).
21
UI - 11847486
AU - Gado K; Rimanoczi E; Hasitz A; Gigler G; Toth BE; Nagy GM; Paloczi K;
TI -
Domjan G
Elevated levels of serum prolactin in patients with advanced multiple
myeloma.
SO - Neuroimmunomodulation 2001;9(4):231-6
AD - National Institute of Haematology and Immunology, Budapest, Hungary.
gadok@freemail.hu
BACKGROUND AND OBJECTIVE: The role of prolactin in immunoregulation and
normal hemopoiesis is well known. However, prolactin also seems to be
involved in the pathomechanism of malignancies and autoimmune diseases.
Elevated serum prolactin levels were reported in patients with malignant
lymphoma, colon and breast carcinoma, systemic lupus erythematosus and
rheumatoid arthritis. Recently we demonstrated prolactin immunostaining
in bone marrow cells of patients with multiple myeloma. DESIGN AND
METHODS: Serum prolactin levels of 56 patients with multiple myeloma, as
well as serum beta(2)-microglobulin, and interleukin-6 concentrations
were determined in this study. RESULTS: Patients with advanced disease
showed a significant increase in serum prolactin concentration, while
patients with a clinical stage of I and II, and also control patients
had normal values. The concentration of serum beta(2)-microglobulin and
interleukin-6 changed in parallel with that of serum prolactin in
patients with multiple myeloma. Determining serum prolactin levels
several times during the disease process in a given patient clearly
showed that the prolactin concentration was increasing during the
disease progression. INTERPRETATION AND CONCLUSIONS: Our results
indicate a role of prolactin in disease progression in multiple myeloma.
Copyright 2002 S. Karger AG, Basel
22
UI - 11966603
AU - Ajithkumar TV; Sivasankar C; Ramachandran K
TI -
Orbital multiple myeloma: case report and review of computed tomography
features.
SO - Australas Radiol 2002 Mar;46(1):119-20
AD - Regional Cancer Centre, Trivandrum, India. tvajilh@hotmail.com
Orbital involvement at diagnosis in multiple myeloma is rare. Only a few
a cases are reported with computed tomographic features. We report a
case of orbital myeloma, and relevant medical reviews on computed
tomography features are discussed.
23
UI - 11769964
AU - Bergsagel DE
TI -
Myeloma: what have we learned?
SO - Biomed Pharmacother 2001 Nov;55(9-10):548-9
AD - University of Toronto, ON, Canada. daniel.bergsagel@utoronto.ca
24
UI - 11769965
AU - Alexanian R; Weber D
TI -
Recent advances in treatment of multiple myeloma and Waldenstrom's
macroglobulinemia.
SO - Biomed Pharmacother 2001 Nov;55(9-10):550-2
AD - University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
25
UI - 11869932
AU - Tosi P; Cavo M
TI -
Thalidomide in multiple myeloma: state of art.
SO - Haematologica 2002 Mar;87(3):233-4
26
UI - 11869949
AU - Corso A; Lorenzi A; Orlandi E; Astori C; Mangiacavalli S; Lazzarino M
TI -
Advantages of using thalidomide for the management of refractory myeloma
patients.
SO - Haematologica 2002 Mar;87(3):327-8
A group of 11 heavily pretreated patients receiving low-dose thalidomide
was compared with a similar group of 10 patients with refractory myeloma
treated with a convention-al oral chemotherapy. This study shows that
thalidomide is not only effective in controlling the neoplastic clone
but more-over, thanks to its low toxicity, allows out-patient management
of these subjects.
27
UI - 11877256
AU - Zhang B; Gojo I; Fenton RG
TI -
Myeloid cell factor-1 is a critical survival factor for multiple
myeloma.
SO - Blood 2002 Mar 15;99(6):1885-93
AD - University of Maryland Greenebaum Cancer Center, Bressler Research
Building, 655 W Baltimore St., Rm 7-023, Baltimore, MD 21201, USA.
Multiple myeloma (MM) is characterized by the accumulation of malignant
plasma cells in the bone marrow caused primarily by failure of normal
homeostatic mechanisms to prevent the expansion of postgerminal center
plasma cells. We have examined the molecular mechanisms that promote the
survival of MM cells and have identified a key role for myeloid cell
factor-1 (Mcl-1), an antiapoptotic member of the Bcl-2 family. These
experiments were initiated by the observation that MM cells were
exquisitely sensitive to culture in the presence of actinomycin D:
caspase activation occurred within 3 hours of treatment and cells were
not protected by interleukin-6, the main MM cell growth and survival
factor. Actinomycin D-induced apoptosis was blocked by proteasome
inhibitors, suggesting that a labile protein was required for MM cell
survival. Further analysis demonstrated that Mcl-1 was likely to be the
labile factor governing MM cell survival. Mcl-1 protein levels decreased
rapidly after culture in the presence of actinomycin D in concordance
with effector caspase activation, but addition of proteasome inhibitors
reversed the loss of Mcl-1 and maintained cell viability. The levels of
other antiapoptotic proteins, including Bcl-2 and members of the
inhibitors-of-apoptosis family, were unaffected by these interventions.
Furthermore, Mcl-1 antisense oligonucleotides caused a rapid
down-regulation of Mcl-1 protein levels and the coincident induction of
apoptosis, whereas overexpression of Mcl-1 delayed actinomycin D-induced
apoptosis with kinetics that correlated with expression levels of Mcl-1.
These data indicate that Mcl-1 expression is required for the survival
of MM cells and may represent an important target for future
therapeutics.
28
UI - 11877293
AU - Mitsiades N; Mitsiades CS; Poulaki V; Anderson KC; Treon SP
TI -
Intracellular regulation of tumor necrosis factor-related
apoptosis-inducing ligand-induced apoptosis in human multiple myeloma
cells.
SO - Blood 2002 Mar 15;99(6):2162-71
AD - Department of Adult Oncology, Dana Farber Cancer Institute, Harvard
Medical School, 44 Binney Street, Mayer Bldg., Boston, MA 02115, USA.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, Apo2
ligand) effectively kills multiple myeloma (MM) cells in vitro
irrespective of refractoriness to dexamethasone and chemotherapy.
Because clinical trials with this anticancer agent are expected shortly,
we investigated the signaling pathway of TRAIL-induced apoptosis in MM.
We detected rapid cleavage of caspases-8, -9, -3, and -6, as well as the
caspase substrates poly(ADP-ribose) polymerase (PARP) and DNA
fragmentation factor-45 (DFF45), but not caspase-10, upon TRAIL
treatment in sensitive MM cells, pointing to caspase-8 as the apical
caspase of TRAIL signaling in MM cells. These phenomena were not
observed or were significantly delayed in TRAIL-resistant MM cells,
suggesting that resistance may arise from inhibition at the level of
caspase-8 activation. Higher levels of expression for various apoptosis
inhibitors, including FLICE-inhibitory protein (FLIP), and lower
procaspase-8 levels were present in TRAIL-resistant cells and
sensitivity was restored by the protein synthesis inhibitor
cycloheximide (CHX) and the protein kinase C (PKC) inhibitor
bisindolylmaleimide (BIM), which both lowered FLIP and cellular
inhibitor of apoptosis protein-2 (cIAP-2) protein levels. Forced
expression of procaspase-8 or FLIP antisense oligonucleotides also
sensitized TRAIL-resistant cells to TRAIL. Moreover, the cell permeable
nuclear factor (NF)-kappaB inhibitor SN50, which sensitizes
TRAIL-resistant cells to TRAIL, also inhibited cIAP2 protein expression.
Finally, CHX, BIM, and SN50 facilitated the cleavage and activation of
procaspase-8 in TRAIL-resistant cells, confirming that inhibition of
TRAIL-induced apoptosis occurs at this level and that these agents
sensitize MM cells by relieving this block. Our data set a framework for
the clinical use of approaches that sensitize MM cells to TRAIL by
agents that inhibit FLIP and cIAP-2 expression or augment caspase-8
activity.
29
UI - 11877294
AU - Ishikawa H; Tsuyama N; Abroun S; Liu S; Li FJ; Taniguchi O; Kawano MM
TI -
Requirements of src family kinase activity associated with CD45 for
myeloma cell proliferation by interleukin-6.
SO - Blood 2002 Mar 15;99(6):2172-8
AD - Department of Bio-Signal Analysis, Applied Medical Engineering Science,
Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-kogushi,
Ube, Yamaguchi 755-8505, Japan.
Specific intracellular signals mediated by interleukin-6 (IL-6) receptor
complexes, such as signal transducer and activator of transcription 3
(STAT 3) and extracellular signal-regulated kinase (ERK) 1/2, are
considered to be responsible for inducing a variety of cellular
responses. In multiple myeloma, IL-6 only enhanced the proliferation of
CD45+ tumor cells that harbored the IL-6-independent activation of src
family kinases even though STAT3 and ERK1/2 could be activated in
response to IL-6 in both CD45+ and CD45(minus sign) cells. Furthermore,
the IL-6-induced proliferation of CD45+ U266 myeloma cells was
significantly suppressed by Lyn-specific antisense oligodeoxynucleotides
or a selective src kinase inhibitor. These results indicate that the
activation of both STAT3 and ERK1/2 is not enough for IL-6-induced
proliferation of myeloma cell lines that require src family kinase
activation independent of IL-6 stimulation. Thus, the activation of the
src family kinases associated with CD45 expression is a prerequisite for
the proliferation of myeloma cell lines by IL-6. We propose a mechanism
for IL-6-induced cell proliferation that is strictly dependent upon the
cellular context in myelomas.
30
UI - 11877296
AU - Avet-Loiseau H; Facon T; Grosbois B; Magrangeas F; Rapp MJ; Harousseau
TI -
JL; Minvielle S; Bataille R; Intergroupe Francophone du Myelome
Oncogenesis of multiple myeloma: 14q32 and 13q chromosomal abnormalities
are not randomly distributed, but correlate with natural history,
immunological features, and clinical presentation.
SO - Blood 2002 Mar 15;99(6):2185-91
AD - Laboratory and Clinical Department of Hematology, University Hospital, 9
quai Moncousu, 44093 Nantes, France. havetloiseau@chu-nantes.fr
Multiple myeloma (MM) is a plasma-cell malignancy characterized by
marked epidemiological, biological, and clinical heterogeneity. The goal
of this study was to find a genetic basis for this heterogeneity. Using
fluorescence in situ hybridization, we analyzed a prospective cohort of
901 patients with various plasma-cell disorders--monoclonal gammopathies
of undetermined significance, smoldering MM, MM, and primary plasma-cell
leukemia--for genetic abnormalities involving the 13q14 and 14q32
chromosomal regions; the patients were consecutively enrolled in the
Intergroupe Francophone du Myelome clinical trials, We performed
statistical analyses comparing these chromosomal abnormalities in terms
of immunological (ie, immunoglobulin types and light-chain subtypes) and
clinical status and, to some extent, prognostic features. It was found
that 14q32 translocations and del(13) are the most frequent chromosomal
abnormalities, observed in 75% and 45% of the patients, respectively,
and are not randomly distributed, but interconnected. Second,
correlations between them allowed us to define 4 major genetic
categories of patients: (1) patients lacking any 14q32 abnormality (25%)
and generally also lacking del(13); (2) patients presenting either
t(4;14) or t(14;16), almost always associated with a del(13) (15% of
patients); (3) patients with other 14q32 abnormalities and presenting
del(13) (25%); and (4) patients with other 14q32 abnormalities but not
presenting del(13) (35%). Third, we show that this genetic
stratification is highly correlated with immunological status and
clinical presentation and with some major prognostic factors. For the
first time, this study gives genetic support to the heterogeneity
observed in patients with MM and demonstrates that the 14q32 and 13q
chromosomal abnormalities are not randomly distributed. The strong
correlations we found might be the basis for a novel genetic
classification of MM, as has been previously demonstrated for leukemias
and lymphomas. Furthermore, our study supports different models for MM
oncogenesis.
31
UI - 11902142
AU - Alkan S; Izban KF
TI -
Immunohistochemical localization of phosphorylated AKT in multiple
myeloma.
SO - Blood 2002 Mar 15;99(6):2278-9
32
UI - 11990854
AU - Kuehl WM; Bergsagel PL
TI -
Multiple myeloma: evolving genetic events and host interactions.
SO - Nature Rev Cancer 2002 Mar;2(3):175-87
AD - Center for Cancer Research, National Cancer Institute, National
Institutes of Health, Bethesda Naval Hospital, Maryland 20889-5105, USA.
wmk@helix.nih.gov
Multiple myeloma is a neoplasm of terminally differentiated B cells
(plasma cells) in which chromosome translocations frequently place
oncogenes under the control of immunoglobulin enhancers. Unlike most
haematopoietic cancers, multiple myeloma often has complex chromosomal
abnormalities that are reminiscent of epithelial tumours. What causes
full-blown myeloma? And can our molecular understanding of this common
haematological malignancy be used to develop effective preventive and
treatment strategies?
33
UI - 11991600
AU - Michopoulos S; Petraki K; Petraki C; Dimopoulos MA
TI -
Light chain deposition disease of the liver without renal involvement in
a patient with multiple myeloma related to liver failure and rapid fatal
outcome.
SO - Dig Dis Sci 2002 Apr;47(4):730-4
AD - Gastroenterology Unit, Alexandra University Hospital, Athens, Greece.
We describe a 36-year-old man with advanced multiple myeloma (Salmon and
Durie stage III) who developed jaundice and severe cholestasis after a
first cure with systemic chemotherapy of vincristine, doxorubicin, and
oral dexamethasone (VAD). Serology for hepatitis A, B, and C and for CMV
was negative. A liver ultrasound and CT scan showed mild hepatomegaly
without evidence of extrahepatic or intrahepatic biliary tree
dilatation. A percutaneous liver biopsy revealed perisinusoidal deposits
of an abundant slightly eosinophilic, PAS-positive amorphous substance.
Immunohistochemistry showed positivity for kappa-light chains and was
negative for lambda-light chains, for IgA, IgG, IgM, and IgD
immunoglobulins as well as for AA and AL proteins and for amyloid P
component. A diagnosis of light chain deposition disease (LCDD) of the
liver was made. The patient developed rapid deterioration of liver
function, leading to a multisystem dysfunction and death. The occurrence
of LCDD in multiple myeloma is close to 5% and myeloma is the underlying
disease in two thirds of patients with LCDD. The kidneys are involved in
almost all cases of LCDD and renal dysfunction usually reveals the
disease. Only three patients with LCDD of the liver without overt renal
involvement have been reported so far. This is the first observation of
LCDD presenting with jaundice and severe cholestasis shortly after the
diagnosis of high tumor mass myeloma, without overt renal involvement,
leading rapidly to the patient's death.
34
UI - 11279146
AU - Ghosh N; Gyory I; Wright G; Wood J; Wright KL
TI -
Positive regulatory domain I binding factor 1 silences class II
transactivator expression in multiple myeloma cells.
SO - J Biol Chem 2001 May 4;276(18):15264-8
AD - H. Lee Moffitt Cancer Center, Interdisciplinary Oncology Program and the
Department of Biochemistry and Molecular Biology, University of South
Florida, Tampa, Florida 33612, USA.
The major histocompatibility complex (MHC) class II transactivator
(CIITA) acts as a master switch to activate expression of the genes
required for MHC-II antigen presentation. During B-cell to plasma cell
differentiation, MHC-II expression is actively silenced, but the
mechanism has been unknown. In plasma cell tumors such as multiple
myeloma the repression of MHC-II is associated with the loss of CIITA.
We have identified that positive regulatory domain I binding factor 1
(PRDI-BF1), a transcriptional repressor, inhibits CIITA expression in
multiple myeloma cell lines. Repression of CIITA depends on the DNA
binding activity of PRDI-BF1 and its specific binding site in the CIITA
promoter. Deletion of a histone deacetylase recruitment domain in
PRDI-BF1 does not inhibit repression of CIITA nor does blocking histone
deacetylase activity. This is in contrast to PRDI-BF1 repression of the
c-myc promoter. Repression of CIITA requires either the N-terminal
acidic and conserved PR motif or the proline-rich domain. PRDI-BF1 has
been shown to be a key regulator of B-cell and macrophage
differentiation. These findings now indicate that PRDI-BF1 has at least
two mechanisms of repression whose function is dependent on the nature
of the target promoter. Importantly, PRDI-BF1 is defined as the key
molecule in silencing CIITA and thus MHC-II in multiple myeloma cells.
35
UI - 11841448
AU - Nagy M; Chapuis B; Matthes T
TI -
Expression of transcription factors Pu.1, Spi-B, Blimp-1, BSAP and oct-2
in normal human plasma cells and in multiple myeloma cells.
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