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Table of Contents
1
UI - 11818668
AU - Koskela K; Pelliniemi TT; Pelliniemi LJ; Remes K; Sodestrom KO; Punnonen
TI -
K; Kumar R; Ollikainen H; Pulkki K
Autocrine production and synergistic growth-promoting activity of
interleukin-6 and oncostatin M in a new human myeloma cell line TU-1.
SO - Acta Haematol 2002;107(1):23-8
AD - Department of Medicine, Turku University Central Hospital,
Kunnallissairaalantie 20, FIN-20700 Turku, Finland.
kjkoskela@hotmail.com
Human myeloma cell lines are difficult to establish, and they usually
originate from patients with extramedullary disease. We describe a new
human myeloma cell line, TU-1, which was established from the bone
marrow of a patient without extramedullary myeloma. The myeloma cells
were initially maintained in a conditioned medium derived from another
well-known myeloma cell line U-266. This conditioned medium contained
interleukin-6 (IL-6) and oncostatin M (OSM), and possibly other unknown
growth factors as well. In 3 months the TU-1 cell line proliferated
autonomously and secreted IL-6 and OSM with a synergistic growth
response. As we have previously shown the cell line acquired a p53
mutation in vitro, which may be an important factor causing autonomous
proliferation. In patients with multiple myeloma OSM is frequently found
in the serum and OSM has been associated with serum IL-6 and progressive
disease. Our study demonstrates the close relationship of OSM and IL-6
also in vitro. Copyright 2002 S. Karger AG, Basel
2
UI - 11818671
AU - Yagci M; Sucak GT; Akyol G; Haznedar R
TI -
Hepatic failure due to CD3+ plasma cell infiltration of the liver in
multiple myeloma.
SO - Acta Haematol 2002;107(1):38-42
AD - Department of Haematology, Gazi Medical School, Gazi University,
TR-06610 Ankara, Turkey. erhem@med.gazi.edu.tr
We present a case of multiple myeloma who died of liver failure 7.5
months after initial diagnosis. Postmortem liver biopsy revealed diffuse
CD3-expressing plasma cell infiltration and eosinophilic amorphous
material deposition which was considered as light chain deposits. T cell
receptor-gamma rearrangement was not detected in liver biopsy sections
using the polymerase chain reaction despite CD3 positivity. To our
knowledge, this is the first report of CD3-expressing plasma cell
infiltration in tissue sections. The discordance between the phenotype
and the genotype suggests a partial activation of genes encoding the T
cell antigens by the transforming event. We also concluded that CD3
positivity was associated with short survival, which is consistent with
previous data. Copyright 2002 S. Karger AG, Basel
3
UI - 11904117
AU - Badros AZ; Siegel E; Bodenner D; Zangari M; Zeldis J; Barlogie B; Tricot
TI -
G
Hypothyroidism in patients with multiple myeloma following treatment
with thalidomide.
SO - Am J Med 2002 Apr 1;112(5):412-3
AD - Myeloma and Transplantation Research Center, University of Arkansas for
Medical Sciences, Little Rock, Arkansas, USA.
4
UI - 11760563
AU - Traynor AE; Noga SJ; NCCN Multiple Myeloma Practice Guidelines Panel
TI -
NCCN: Multiple myeloma.
SO - Cancer Control 2001 Nov-Dec;8(6 Suppl 2):78-87
AD - Robert H. Lurie Comprehensive Cancer Center of Northwestern University,
USA.
Although multiple myeloma is sensitive to both chemotherapy and RT, it
remains incurable at present. However, treatment algorithms based on
published data, as well as clinical experience, can be developed to
optimize therapy. This includes not only therapy for the underlying
disease but also supportive therapy to enhance quality of life. Because
myeloma is incurable, these guidelines prominently identify the clinical
settings appropriate for treatment of patients on clinical research
protocols.
5
UI - 11896542
AU - Donovan KA; Lacy MQ; Gertz MA; Lust JA
TI -
IL-1beta expression in IgM monoclonal gammopathy and its relationship to
multiple myeloma.
SO - Leukemia 2002 Mar;16(3):382-5
AD - Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN
55905, USA.
We have shown that IL-1beta is not detectable in normal plasma cells but
is produced by plasma cells from virtually all patients with multiple
myeloma (MM). To extend our earlier work, IL-1beta expression was
determined in 13 newly diagnosed patients with IgM monoclonal
gammopathy. Eleven patients with Waldenstrom's macroglobulinemia (WM)
and two patients with IgM MM were investigated for IL-1beta expression
by in situ hybridization (ISH). All patients with WM had bone marrow
biopsies consistent with the diagnosis, an IgM M-protein in the serum,
and subsequently required chemotherapy. Seven of 11 patients with WM had
an M-protein >3 g/dl and five patients had bone surveys performed that
were negative for osteolytic disease. Two patients were diagnosed with
IgM MM because of the presence of significant osteolytic disease on a
metastatic bone survey. ISH for kappa, lambda, and IL-1beta expression
was performed on bone marrow aspirates from each of the 13 patients.
None of the neoplastic cells from the 11 patients with WM showed
detectable IL-1beta expression by ISH. However, the neoplastic cells
from both patients with IgM MM expressed IL-1beta mRNA at high levels.
This aberrant IL-1beta production may explain the presence of bone
lesions in the patients with IgM MM.
6
UI - 11584064
AU - Lynch HT; Sanger WG; Pirruccello S; Quinn-Laquer B; Weisenburger DD
TI -
Familial multiple myeloma: a family study and review of the literature.
SO - J Natl Cancer Inst 2001 Oct 3;93(19):1479-83
AD - Department of Preventive Medicine, Creighton University School of
Medicine, Omaha, NE 68178, USA. htlynch@creighton.edu
BACKGROUND: The etiology of multiple myeloma (MM) remains obscure,
although reports of familial clustering have implicated both a host
susceptibility factor and environmental effects. Here we describe the
medical histories of members of a family prone to MM. METHODS: We
developed a pedigree for an MM-prone family by using information
obtained from a questionnaire. Protein immunoelectrophoresis of serum
and urine from the proband and from 19 family members was performed to
detect monoclonal immunoproteins. Peripheral blood obtained from the
proband and from five relatives was subjected to standard cytogenetic
studies to detect constitutional chromosomal abnormalities.
Multifluor-fluorescence in situ hybridization (M-FISH) and standard FISH
studies were performed on peripheral blood from the proband and from two
other affected living relatives to determine their karyotypes and to
detect clonal chromosomal abnormalities frequently seen in patients with
MM. RESULTS: Within this family, a sibship of seven included three
individuals (including the proband) with histologically verified MM and
two individuals with a monoclonal gammopathy of unknown significance
(MGUS), as determined by immunoelectrophoresis of serum and urine. This
family also had members with acute lymphocytic leukemia, malignant
melanoma, and prostate cancer. In the family members tested, we detected
no constitutional chromosomal abnormality. None of the three individuals
analyzed by FISH had a deletion of the retinoblastoma (Rb-1) locus,
which is frequently deleted in patients with MM, and only one (the
proband) had a translocation involving chromosomes 11 and 14, a clonal
abnormality commonly seen in MM. CONCLUSION: The study of familial MM
may provide insights into the pathogenesis and, ultimately, the control
and prevention of MM and related disorders.
7
UI - 11781643
AU - Lazzarino M; Corso A; Barbarano L; Alessandrino EP; Cairoli R; Pinotti
TI -
G; Ucci G; Uziel L; Rodeghiero F; Fava S; Ferrari D; Fiumano M; Frigerio
G; Isa L; Luraschi A; Montanara S; Morandi S; Perego D; Santagostino A;
Savare M; Vismara A; Morra E
DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) is an
effective regimen for peripheral blood stem cell collection in multiple
myeloma.
SO - Bone Marrow Transplant 2001 Nov;28(9):835-9
AD - Division of Hematology, IRCCS Policlinico S Matteo, University of Pavia,
Italy.
DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) has
proved to be an effective salvage therapy for refractory-relapsed MM
patients. Little is known, however, about its potential as mobilizing
therapy. The aim of this study was to evaluate the efficacy of DCEP in
mobilizing PBSC and to define its toxicity. Fifty-five MM patients
received DCEP followed by G-CSF as part of high-dose programs including
autologous transplantation. At the time of mobilization, 40 patients had
previously received VAD only, and 15 alkylating agents. Mobilization was
successful (minimum number of CD34(+) cells 2 x 10(6)/kg) in 48/55
patients (87%), and 41/55 patients (75%) collected >4 x 10(6)/kg CD34(+)
cells. Of the seven patients who did not mobilize stem cells, five (71%)
had been previously exposed to alkylating agents. The median number of
CD34(+) cells harvested was 5.8 x 10(6)/kg (range 2.1-22.4). There was
no treatment-related mortality. The side-effects of DCEP were always
tolerable. No neutropenia <1000/microl nor thrombocytopenia
<50,000/microl were observed. No patient required transfusion as a
consequence of therapy, or hospitalization for septic complications. In
conclusion, DCEP, in addition to its demonstrated anti-tumor activity,
is an effective regimen for mobilizing peripheral blood progenitor cells
in myeloma patients, with little or no side-effects. These properties
render DCEP a useful regimen for the debulking and mobilization phase of
high-dose programs for multiple myeloma.
8
UI - 11781644
AU - Le Blanc R; Montminy-Metivier S; Belanger R; Busque L; Fish D; Roy DC;
TI -
Kassis J; Boileau J; Lavallee R; Belanger D; Letendre F; Hebert J;
Sauvageau G; Perreault C; Roy J
Allogeneic transplantation for multiple myeloma: further evidence for a
GVHD-associated graft-versus-myeloma effect.
SO - Bone Marrow Transplant 2001 Nov;28(9):841-8
AD - Division of Hematology-Immunology, Hopital Maisonneuve-Rosemont,
Montreal, Quebec, Canada.
We report a series of 37 consecutive patients with multiple myeloma (MM)
who received an allograft between 1990 and 2000 at our institution.
Median age was 47 years, and nearly 70% of patients were Durie-Salmon
stage III. A median of five cycles of chemotherapy were given before
transplant, with a median interval between diagnosis and transplant of
9.3 months. We report a nonrelapse mortality rate of 22% with a median
follow-up period of 40 months, whereas complete remission (CR) rate at
12 months is estimated at 57%. Treatment failure rate and overall
survival at 40 months are estimated at 52% and 32%, respectively. The
number of chemotherapy cycles prior to allotransplantation achieved
borderline statistical significance as a poor prognosis factor for
overall survival (P = 0.05), while the presence of chronic
graft-versus-host disease (cGVHD) was significantly correlated with CR
achievement (P = 0.036). Our study confirms that early allografting in
MM can yield toxicity rates significantly lower than those associated
with historical cohorts, and supports the hypothesis that cumulative
chemotoxicity has a negative influence on mortality and survival rates.
More importantly, our study clearly demonstrates an association between
cGVHD and CR and brings further evidence in favor of a
graft-versus-myeloma effect.
9
UI - 11904319
AU - Sobol H; Vey N; Sauvan R; Philip N; Noguchi T; Eisinger F
TI -
Re: familial multiple myeloma: a family study and review of the
literature.
SO - J Natl Cancer Inst 2002 Mar 20;94(6):461-2; discussion 463
10
UI - 11904320
AU - Hemminki K
TI -
Re: familial multiple myeloma: a family study and review of the
literature.
SO - J Natl Cancer Inst 2002 Mar 20;94(6):462-3; discussion 463
11
UI - 11870172
AU - Badros A; Barlogie B; Siegel E; Cottler-Fox M; Zangari M; Fassas A;
TI -
Morris C; Anaissie E; Van Rhee F; Tricot G
Improved outcome of allogeneic transplantation in high-risk multiple
myeloma patients after nonmyeloablative conditioning.
SO - J Clin Oncol 2002 Mar 1;20(5):1295-303
AD - Myeloma and Transplantation Research Center, University of Arkansas for
Medical Sciences, Little Rock, AR, USA. abadros@umm.edu
PURPOSE: We present our experience with relapsed and recently diagnosed
patients with high-risk multiple myeloma (MM) receiving
immunosuppressive, nonmyeloablative melphalan (MEL)-based conditioning
regimens (mini-allograft). PATIENTS AND METHODS: Thirty-one MM patients
received allografts from HLA-matched siblings (n = 25) or unrelated
donors (n = 6) using a mini-allograft. Seventeen had progressive disease
(PD) and 14 had responsive disease (RD) (six with primary RD and eight
with responsive relapse). Thirty patients had received one (n = 13) or
two or more (n = 17) prior autologous transplantations (ATs). Median age
was 56 years (range, 38 to 69 years). Twenty-one patients had chromosome
13 abnormality. Two patients were hemodialysis dependent. Blood and bone
marrow grafts were administered to 28 and three patients, respectively.
Donor lymphocyte infusions were given to 18 patients either to attain
full donor chimerism (n = 6) or to eradicate residual disease (n = 12).
RESULTS: By day 100, 25 (89%) of 28 patients were full donor chimeras,
one was a mixed chimera, and two had autologous reconstitution. Acute
graft-versus-host disease (GVHD) developed in 18 patients (58%), and 10
progressed to chronic GVHD (limited in six and extensive in four). At a
median follow-up of 6 months, 19 (61%) of 31 patients achieved
complete/near complete remission. Twelve patients (39%) have died: three
of PD, three of early treatment-related mortality (TRM) (before day
100), and six of late TRM. Median overall survival (OS) was 15 months.
At 1 year, there was a significantly longer event-free survival (86% v
31%, P =.01) and OS (86% v 48%, P =.04) when a mini-allograft was
performed after one versus two or more prior ATs, respectively. When
compared with historical MM controls (n = 93) receiving conventional
allografts, early TRM was significantly lower (10% v 29%, P =.03), and
OS at 1 year was better (71% v 45%; P =.08) in the mini-allograft MM
patients. CONCLUSION: Mini-allograft induced excellent disease control
in MM patients with high-risk disease, but is still associated with a
significant GVHD.
12
UI - 11675911
AU - Ota K; Tsuda T; Katayama N; Sakaguchi R; Hara I; Hayashi H; Okamoto Y
TI -
A therapeutic strategy for isolated plasmacytoma of bone.
SO - J Int Med Res 2001 Jul-Aug;29(4):366-73
AD - Department of Blood Transfusion Medicine and Clinical Haematology,
Wakayama Medical University, Japan. k-ota@wakayama-med.ac.jp
Two cases of solitary plasmacytoma of bone (SPB) were diagnosed. The
first case was a 41-year-old woman, complaining of fatigue from her
lumbar region to her legs. The second case was a 56-year-old man
complaining of poor gait and severe lumbago with numbness in the toes of
both feet. Magnetic resonance imaging showed the osteolytic lesion in
the 12th thoracic bone in the first patient and around the 2nd, 3rd and
4th lumbar bones in the second patient. In both patients serum analysis
revealed the monoclonal component of immunoglobulin G (IgG) protein with
kappa-light chain, and considering this and other findings SPB was
diagnosed. Both patients were first treated with irradiation around the
involved bone and then with a course of chemotherapy. In the first
patient the tumour region of the bone was surgically removed and
replaced with a ceramic spacer. The symptoms of both patients were
ameliorated, and the patients remained in good condition for around 3
years without conversion to multiple myeloma. In view of the overall
effectiveness of treatments for SPB, our therapeutic strategy deserves
careful evaluation.
13
UI - 11805699
AU - Durr HR; Wegener B; Krodel A; Muller PE; Jansson V; Refior HJ
TI -
Multiple myeloma: surgery of the spine: retrospective analysis of 27
patients.
SO - Spine 2002 Feb 1;27(3):320-4; discussion 325-6
AD - Department of Orthopaedics and Orthopaedic Surgery, University of
Rostock, Rostock, Germany. hans_roland.duerr@med.uni-rostock.de
STUDY DESIGN: The authors report on the clinical course of 27
consecutive patients surgically treated for solitary or multiple myeloma
of the spine. OBJECTIVES: To evaluate the complications, neurologic
function, life quality, and survival after decompression of the spinal
cord and stabilization of the spinal column in cases of conventionally
untreatable pain, neurologic impairment, or spinal instability. SUMMARY
OF BACKGROUND DATA: The clinical outcome in patients surgically treated
for multiple myeloma of the spine has not been intensively studied.
Because patients with myeloma often live longer than patients with bone
metastases from other malignancies, it is important that these patients
be examined and treated with methods specific to their needs and not
only with those typically used for patients with metastatic disease.
METHODS: The 27 patients had undergone the following surgical
procedures: two dorsal decompressions, seven dorsal decompressions and
stabilizations, 15 ventral decompressions and stabilizations, and three
ventral and dorsal decompressions and stabilizations. Quality of life
was measured by the Karnofsky Index, neurologic impairment according to
Frankel, and survival by the Kaplan-Meier method. RESULTS: Life quality
improved from 48% before surgery to 59% 1 month after surgery and 73% in
24 survivors after the first year. Comparison of their presurgical
scores with the scores obtained 1 month after surgery revealed that 18
patients had improved, five patients stayed the same, and four patients
declined. After 1 year the scores of all 24 surviving patients had
improved from their presurgical levels. In the 21 patients with
unimpaired preoperative neurologic function, one patient developed a
paraparesis as a complication of surgery, while 20 remained unimpaired
until death or 1 year after treatment. All six patients with neurologic
deficits improved, two of them to normal function. Pain relief was
evident in 26 cases. The mean length of postoperative survival was 49.7
months. Local tumor recurrence occurred in three of 27 patients (11.1%).
CONCLUSION: The surgical treatment of myeloma of the spine seems to be
an effective method of treatment with respect to neurologic function and
life quality in selected cases.
14
UI - 11552984
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.
15
UI - 11920510
AU - Wang J; Weiss LM; Chang KL; Slovak ML; Gaal K; Forman SJ; Arber DA
TI -
Diagnostic utility of bilateral bone marrow examination: significance of
morphologic and ancillary technique study in malignant.
SO - Cancer 2002 Mar 1;94(5):1522-31
AD - Division of Pathology, City of Hope National Medical Center, Duarte,
California 91010, USA.
BACKGROUND: To retrospectively evaluate the significance of morphologic
examination and ancillary studies performed on bilateral bone marrow
biopsy specimens, 1864 bone marrow samples were studied. METHODS:
Bilateral bone marrow biopsy specimens included 883 specimens that were
evaluated for involvement by non-Hodgkin lymphoma (NHL); 381 specimens
that were evaluated for involvement by carcinoma (CA); 362 specimens
that were evaluated for involvement by Hodgkin disease (HD); 94
specimens that were evaluated for involvement by sarcoma (SA); 56
specimens that were evaluated for involvement by multiple myeloma (MM);
53 specimens that were evaluated for involvement by acute and chronic
leukemia, myelodysplasia, and/or myeloproliferative disorders (LEUK);
and 35 specimens that were evaluated for other reasons. RESULTS: Of all
1864 specimens, 410 samples (22.0%) were positive for disease, including
77% of MM samples, 58% of LEUK samples, 29.6% of NHL samples, 14% of SA
samples, 9.9% of HD samples, and 6.8% of CA samples. A discrepancy
between the left and right sides was identified in 48 specimens (11.7%
of positive samples). The discrepancy rate was 39% for HD samples, 29%
for SA samples, 23% for CA samples, and 9.2% for NHL samples. No
morphologic discrepancies between bilateral samples were found in MM
samples or LEUK samples. Bilateral flow cytometric studies (n = 113
samples) were positive in 11 samples (9.7%; all morphologically
positive), with two discrepancies detected between bilateral samples.
Bilateral cytogenetic studies (n = 74 samples) were positive in 5
samples (7%), and there were no discrepancies. Bilateral molecular
studies (n = 16 samples) were positive in 7 samples (44%), and there
were 3 discrepancies. CONCLUSIONS: Bilateral morphologic evaluation is
useful in the evaluation of patients with NHL, HD, CA, and SA and is not
indicated for patients with acute or chronic leukemia, myelodysplasia,
MM, and other diseases. Bilateral flow cytometric or cytogenetic studies
of bone marrow did not provide additional information in this population
to justify bilateral samples. The role of bilateral molecular analysis
needs to be defined further, but pooled samples for molecular studies
may be adequate. Copyright 2002 American Cancer Society.
16
UI - 11920511
AU - Wilder RB; Ha CS; Cox JD; Weber D; Delasalle K; Alexanian R
TI -
Persistence of myeloma protein for more than one year after radiotherapy
is an adverse prognostic factor in solitary plasmacytoma of bone.
SO - Cancer 2002 Mar 1;94(5):1532-7
AD - Department of Radiation Oncology, M.D. Anderson Cancer Center, Houston,
Texas, USA. rwilder@mdanderson.org
BACKGROUND: Prognostic factors for solitary plasmacytoma of bone (SPB),
whether measured before or after radiotherapy (RT), have not been
established. The authors analyzed multiple factors for myeloma-free
survival (MFS) and cause-specific survival (CSS) in SPB patients treated
with RT alone. METHODS: Between 1965 and 2000, 60 patients with
carefully staged SPB were treated with RT alone at the M. D. Anderson
Cancer Center. Patient ages ranged from 29-77 years (median, 54 years),
and 75% of patients had a myeloma (M) protein in the blood and/or urine.
No patients showed other lesions on skeletal survey or, in recent years,
magnetic resonance imaging (MRI) of the spine; marrow aspirate was
normal in all patients. Radiotherapy to the solitary lesion was given to
a total dose of 30-70 Gy (median, 46 Gy). The authors analyzed the
impact of multiple factors on MFS and CSS, including resolution v.
persistence of M protein after RT, secretory v. nonsecretory disease at
diagnosis, presence v. absence of an associated soft tissue mass on
computed tomography or MRI scan, magnitude of serum M protein elevation
at diagnosis, age, spinal v. nonspinal location, Karnofsky performance
status, total RT dose, and tumor size. RESULTS: Median follow-up was 7.8
years (range, 1.0-25.5 years). On multivariate analysis, persistence of
M protein more than one year after RT was the only independent adverse
prognostic factor for MFS (P = 0.005) and CSS (P = 0.04). Most patients
with M protein that persisted for more than one year after RT were
diagnosed with multiple myeloma within 2.2 years of treatment.
CONCLUSIONS: Patients with M protein that persists for more than one
year after RT should be monitored frequently and considered for standard
chemotherapy followed by intensive consolidation therapy when they
either develop symptoms or show an increasing M protein level. Copyright
2002 American Cancer Society.
17
UI - 11900061
AU - Gregersen H; Pedersen G; Svendsen N; Thulstrup A M; Sorensen H T;
TI -
Schonheyder H C
Multiple myeloma following an episode of community-acquired pneumococcal
bacteraemia or meningitis.
SO - APMIS 2001 Nov;109(11):797-800
AD - Department of Medicine B, Aalborg Hospital, Denmark.
henrik.gregersen@dadlnet.dk
The risk of multiple myeloma subsequent to an episode of serious
pneumococcal infection has not been ascertained. We identified 328
episodes of community-acquired pneumococcal bacteraemia and 77 episodes
of pneumococcal meningitis in 227,000 persons over 40 years of age in
the County of North Jutland, Denmark, in the period 1981 to 1996. The
incidence rate of a subsequent diagnosis of multiple myeloma was
determined by linkage to the Danish Cancer Registry. During 1,218
patient-years of follow-up in the bacteraemia cohort, 7 cases of
multiple myeloma were diagnosed compared with 0.13 cases expected
(standardized incidence ratio (SIR) 53.5, 95% confidence interval
21.4-111.4). During 444 patient-years of follow-up in the meningitis
cohort, 4 cases of multiple myeloma were diagnosed compared with 0.05
cases expected (SIR 83.2, 95% confidence interval 22.6-214.8). Patients
who survive an episode of community-acquired pneumococcal bacteraemia or
meningitis are at increased risk of being diagnosed with multiple
myeloma, but the absolute risk is low.
18
UI - 11730044
AU - Guvenc B; Canataroglu A; Gumurdulu Y; Gumurdulu D; Paydast S
TI -
Multiple myeloma with skin involvement.
SO - J Eur Acad Dermatol Venereol 2001 Jul;15(4):328-9
AD - Department of Internal Medicine, Cukurova University, Medical Faculty,
Adana, Turkey.
Multiple myeloma (MM) is a plasma cell dyscrasia seen in the elderly
that constitutes 10% of all haematopoietic neoplasias. It is a systemic
disorder affecting various organs, in particular the kidneys and bones.
Skin involvement is not a common finding. This report presents a case of
MM with skin involvement.
19
UI - 11898173
AU - Valorie AM
TI -
Thalidomide. A new beginning.
SO - Cancer Pract 2000 Mar-Apr;8(2):101-3
AD - Philadelphia College of Pharmacy and Science, Philadelphia,
Pennsylvania, USA.
20
UI - 11901068
AU - Abraham RS; Clark RJ; Bryant SC; Lymp JF; Larson T; Kyle RA; Katzmann JA
TI -
Correlation of serum immunoglobulin free light chain quantification with
urinary Bence Jones protein in light chain myeloma.
SO - Clin Chem 2002;48(4):655-7
21
UI - 11836178
AU - Piccinini L; Artusi T; Bonacorsi G; Arigliano V
TI -
Acute leukemia of plasmablastic type as terminal phase of multiple
myeloma.
SO - Haematologica 2002 Feb;87(2):EIM04
AD - Divisione di Oncologia Via del Pozzo 71, 41100 Modena, Italy
piccinini@unimo.it
22
UI - 11836179
AU - Dabusti M; Cavazzini F; Della Porta M
TI -
An unusual clinical presentation of multiple myeloma with involvement of
the oro-pharynx.
SO - Haematologica 2002 Feb;87(2):EIM05
AD - Section of Hematology, Department of Biomedical Sciences, Arcispedale
S.Anna, Corso Giovecca 203, 44100 Ferrara, Italy. sse@dns.unife.it
23
UI - 11836184
AU - Pitini V; Arrigo C; Aloi G; Azzarello D; La Gattuta G
TI -
Diabetic foot disease in a patient with multiple myeloma receiving
thalidomide.
SO - Haematologica 2002 Feb;87(2):ELT07
AD - Oncologia Medica e Trapianto di Midollo Osseo, Pad. H 5 piano;
Policlinico Universitario, Via Consolare Valeria, 98125 Messina
(Italy). pitini@ciaoweb.it
24
UI - 11751905
AU - Podar K; Tai YT; Lin BK; Narsimhan RP; Sattler M; Kijima T; Salgia R;
TI -
Gupta D; Chauhan D; Anderson KC
Vascular endothelial growth factor-induced migration of multiple myeloma
cells is associated with beta 1 integrin- and phosphatidylinositol
3-kinase-dependent PKC alpha activation.
SO - J Biol Chem 2002 Mar 8;277(10):7875-81
AD - Jerome Lipper Multiple Myeloma Research Center/Dana-Farber Cancer
Institute and the Department of Medicine, Harvard Medical School,
Boston, Massachusetts 02115, USA.
In multiple myeloma (MM), migration is necessary for the homing of tumor
cells to bone marrow (BM), for expansion within the BM microenvironment,
and for egress into the peripheral blood. In the present study we
characterize the role of vascular endothelial growth factor (VEGF) and
beta(1) integrin (CD29) in MM cell migration. We show that protein
kinase C (PKC) alpha is translocated to the plasma membrane and
activated by adhesion of MM cells to fibronectin and VEGF. We identify
beta(1) integrin modulating VEGF-triggered MM cell migration on
fibronectin. We show that transient enhancement of MM cell adhesion to
fibronectin triggered by VEGF is dependent on the activity of both PKC
and beta(1) integrin. Moreover, we demonstrate that PKC alpha is
constitutively associated with beta(1) integrin. These data are
consistent with PKC alpha-dependent exocytosis of activated beta(1)
integrin to the plasma membrane, where its increased surface expression
mediates binding to fibronectin; conversely, catalytically active PKC
alpha-driven internalization of beta(1) integrin results in MM cell
de-adhesion. We show that the regulatory subunit of phosphatidylinositol
(PI) 3-kinase (p85) is constitutively associated with FMS-like tyrosine
kinase-1 (Flt-1). VEGF stimulates activation of PI 3-kinase, and both MM
cell adhesion and migration are PI 3-kinase-dependent. Moreover, both
VEGF-induced PI 3-kinase activation and beta(1) integrin-mediated
binding to fibronectin are required for the recruitment and activation
of PKC alpha. Time-lapse phase contrast video microscopy (TLVM) studies
confirm the importance of these signaling components in VEGF-triggered
MM cell migration on fibronectin.
25
UI - 11807629
AU - Sevilla J; Rodriguez A; Hernandez-Maraver D; de Bustos G; Aguado J;
TI -
Ojeda E; Arrieta R; Hernandez-Navarro F
Secondary acute myeloid leukemia and myelodysplasia after autologous
peripheral blood progenitor cell transplantation.
SO - Ann Hematol 2002 Jan;81(1):11-5
AD - Banco de Sangre, Hospital Nino Jesus, Av/Menendez Pelayo 65, Madrid
28009, Spain. jsevilla@hnjs.insalud.es
Secondary myelodysplastic syndrome (MDS) and acute leukemia (AL) are
well-known complications of antineoplastic therapy. The incidence of
these serious complications after autologous hematopoietic
transplantation ranges from 1.1% to 24%. Prior chemotherapy is its most
likely cause, but other variables related to these long-term
complications are seriously discussed. There is evidence that priming of
progenitor cells isolated from peripheral blood with chemotherapy is
also related to a higher risk of secondary MDS/AL. Whether progenitor
cells isolated from bone marrow or peripheral blood after mobilization
only with cytokines are related to higher risk is a controversial issue.
In this paper, we analyze the incidence and variables related to these
complications in a series of 99 patients diagnosed with lymphoma or
multiple myeloma who underwent autologous transplantation using
hematopoietic progenitors isolated from peripheral blood mobilized with
granulocyte colony-stimulating factor (G-CSF). The probability of MDS/AL
in patients alive 5 years after transplant in our series is 8.58%,
similar to that reported in other series using bone marrow grafts. The
total dose of cyclophosphamide ( p=0.099), the number of chemotherapy
cycles ( p=0.04) received before transplant, and the total dose of
mononuclear cells infused at the time of transplant were the only
variables associated with secondary MDS/AL. Autologous transplantation
with progenitor cells isolated from peripheral blood after mobilization
with cytokines has probability and risk factors for secondary MDS/AL
development similar to bone marrow grafts when compared with other
published series.
26
UI - 11807633
AU - Kaneko M; Kanda Y; Oshima K; Nannya Y; Suguro M; Yamamoto R; Chizuka A;
TI -
Hamaki T; Matsuyama T; Takezako N; Miwa A; Togawa A
Simple prognostic model for patients with multiple myeloma: a
single-center study in Japan.
SO - Ann Hematol 2002 Jan;81(1):33-6
AD - Department of Hematology, International Medical Center of Japan, Japan.
The range of survival duration in myeloma patients is wide and several
percent of patients live longer than 10 years. Therefore, a precise
prediction of survival for the individual patient is required to decide
treatment. We evaluated possible prognostic factors at diagnosis for 116
Japanese patients with multiple myeloma. Twelve parameters reported to
affect survival were analyzed using a log rank test and stepwise Cox
proportional hazards regression. Factors identified as adversely
affecting survival were age over 60 years, male sex, blood hemoglobin
less than 8.5 g/dl, platelets less than 100 x 10(9)/l, serum creatinine
level more than 2.0 mg/dl, serum C-reactive protein (CRP) level more
than 6.0 mg/l, and serum beta2-microglobulin level more than 6.0 mg/l.
Among them, only high age and high serum CRP level were independently
prognostic for poor survival. In conclusion, we have established a
simple prognostic model for Japanese myeloma patients only, using
factors that can be determined in routine examinations without the need
of subjective information.
27
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.
28
UI - 11703354
AU - Biagi JJ; Prince HM
TI -
Thalidomide is effective for extramedullary relapse of multiple myeloma
post-allogeneic bone marrow transplantation.
SO - Br J Haematol 2001 Nov;115(2):484-5
29
UI - 11896113
AU - Cesana C; Klersy C; Barbarano L; Nosari AM; Crugnola M; Pungolino E;
TI -
Gargantini L; Granata S; Valentini M; Morra E
Prognostic factors for malignant transformation in monoclonal gammopathy
of undetermined significance and smoldering multiple myeloma.
SO - J Clin Oncol 2002 Mar 15;20(6):1625-34
AD - Department of Hematology, Bone Marrow Transplantation Centre, Niguarda
Ca Granda Hospital, Milan, Italy.
PURPOSE: To evaluate the natural history of monoclonal gammopathy of
undetermined significance (MGUS) and smoldering multiple myeloma (SMM),
identify early predictors of evolution, and assess whether associated
conditions correlate with disease progression. PATIENTS AND METHODS: A
total of 1,231 consecutive patients with either MGUS (n = 1,104) or SMM
study. Cumulative survival probability and cumulative probability of
transformation into lymphoproliferative disease were calculated by means
of the Kaplan-Meier estimator. Univariate and multivariate Cox models
were used to identify possible predictors of malignant evolution.
RESULTS: Cumulative transformation probability at 10 and 15 years was
14% and 30%, respectively. At a median follow-up of 65 months (range, 12
to 239 months), 64 MGUS cases (5.8%) evolved to multiple myeloma (MM) (n
= 43), extramedullary plasmacytoma (n = 1), primary amyloidosis (n = 1),
Waldenstrom's macroglobulinemia (n = 12), non-Hodgkin's lymphoma (n =
6), and B-chronic lymphocytic leukemia (n = 1). At a median follow-up of
72 months (range, 12 to 247 months), 25 SMMs (19.7%) evolved to overt
MM. A lower evolution risk was observed in MGUS than in SMM (P <.0001).
Greater than 5% marrow plasmacytosis, detectable Bence Jones
proteinuria, polyclonal serum immunoglobulin reduction, and high
erythrocyte sedimentation rate (ESR) were independent factors
influencing MGUS transformation. SMM progression correlated with greater
than 10% marrow plasma cells, detectable Bence Jones proteinuria, and
immunoglobulin (Ig) A isotype. Neither concomitant diseases nor
immunosuppression correlated with progression. CONCLUSION: Careful
evaluation of marrow plasmacytosis, urinary paraprotein, background
immunoglobulins, ESR, and paraprotein isotype might help identify at
presentation patients with benign monoclonal gammopathies requiring
stricter monitoring.
30
UI - 11815713
AU - Vacca A; Ribatti D; Roccaro AM; Ria R; Palermo L; Dammacco F
TI -
Bone marrow angiogenesis and plasma cell angiogenic and invasive
potential in patients with active multiple myeloma.
SO - Acta Haematol 2001;106(4):162-9
AD - Department of Biomedical Sciences and Human Oncology, University of Bari
Medical School, Bari, Italy. avacca@hotmail.com
Factor VIII-related antigen-positive microvessel areas were measured by
both immunohistochemistry and computerized image analysis in patients
with active multiple myeloma (MM), nonactive MM and monoclonal
gammopathies of undetermined significance (MGUS). A 5- to 6-fold larger
area was found in patients with active MM compared to the other two
groups. The conditioned medium (CM) of their bone marrow plasma cells
stimulated endothelial cell proliferation and chemotaxis, monocyte
chemotaxis and angiogenesis in vivo [chick embryo chorioallantoic
membrane (CAM) system] more strongly and frequently than the CM of
patients with nonactive MM and MGUS. An immunoassay of plasma cell
lysates gave significantly higher levels of fibroblast growth factor-2
(FGF-2) in patients with active MM than in the other two groups, and a
neutralizing anti-FGF-2 antibody inhibited by 54-68% the biological
activity exerted by the CM in vitro and in the CAM. In situ
hybridization of bone marrow plasma cells and gelatin zymography of CM
showed that patients with active MM express higher levels of matrix
metalloproteinase-2 (MMP-2) mRNA and protein than those with nonactive
MM and MGUS, whereas MMP-9 expression and secretion overlapped in all
groups. Overall data suggest that patients with active MM represent the
vascular phase of plasma cell tumors that is triggered by bone marrow
plasma cells, at least partly, through FGF-2 and MMP-2. Both
angiogenesis and MMP-2 secretion can account for intramedullary and
extramedullary spreading of plasma cells during the active MM. Copyright
2001 S. Karger AG, Basel
31
UI - 11815718
AU - Tosi P; Tura S
TI -
Antiangiogenic therapy in multiple myeloma.
SO - Acta Haematol 2001;106(4):208-13
AD - Institute of Hematology and Medical Oncology 'Seragnoli', Bologna
University, Bologna, Italy. ptosi@med.unibo.it
In the recent years, several pieces of evidence have pointed out that
disease progression in multiple myeloma (MM) is characterized by an
increased bone marrow neovascularization. Targeting the mechanisms that
control angiogenesis could thus represent an innovative therapeutic
approach to MM. Thalidomide, a glutamic acid derivative with sedative
properties, is able to inhibit angiogenesis in murine models; this
compound has recently demonstrated to be effective in
relapsed/refractory MM, leading to a 30-40% response, coupled with mild
systemic toxicity. Inhibition of angiogenesis is probably just one of
the mechanisms by which thalidomide exerts its action in MM, as
immunomodulation and inhibition of cytokine production by bone marrow
stroma could also be involved. At present, several studies are ongoing,
aiming at testing thalidomide-based drug combinations, mainly with
dexamethasone, but also with conventional chemotherapy; the results that
have been obtained so far show a synergistic effect of the drug
combinations, with a response rate ranging from 50 to 70% in pretreated
patients. There is now growing interest in novel compounds with
potential antiangiogenic effects, among them a promising activity both
in vitro and in animal models has been displayed by thalidomide analogs,
inhibitors of vascular endothelial growth factor receptor-2 and
endostatin. Copyright 2001 S. Karger AG, Basel
32
UI - 11896336
AU - Badros A; Tricot G; Toor A; Morris C; Guo C; Munshi N; Barlogie B;
TI -
Cottler-Fox M
ABO mismatch may affect engraftment in multiple myeloma patients
receiving nonmyeloablative conditioning.
SO - Transfusion 2002 Feb;42(2):205-9
AD - Myeloma and Transplantation Research Center, University of Arkansas for
Medical Sciences, Little Rock, Arkansas, USA. abadros@umm.edu
BACKGROUND: Blood group incompatibility does not appear to affect the
overall outcome in patients undergoing myeloablative conditioning before
allogeneic BMT. Data on ABO-mismatched transplantation in the
nonmyeloablative setting are limited. STUDY DESIGN AND METHODS: A
retrospective analysis of the effects of ABO mismatches in multiple
myeloma patients who received a nonmyeloablative conditioning regimen
was conducted. RESULTS: Three of 27 patients received a minor
ABO-mismatched graft, all with evidence of hemolysis before converting
to donor ABO group on Days 10, 15, and 6. Six patients received a major
ABO-mismatched graft; of these, three developed GVHD of more than grade
2 and subsequently converted to the ABO blood group of the donor on Days
38, 33, and 43. Of the three patients without GVHD, one rejected the
allograft and had autologous reconstitution. One remained a mixed
chimera to Day 100 despite three donor lymphocyte infusions, and one
developed pure RBC aplasia. None of the ABO-matched patients rejected
the graft, whether they developed GVHD or not. RBC transfusions were
significantly higher in the major and minor ABO-mismatched patients than
in the ABO-matched patients, with medians of 12 units (range, 2-35), 13
units (range, 5-18), and 4 units (range, 2-15), respectively (p = 0.02).
ABO-matched patients had a similar incidence of GVHD, with 5 of 9
ABO-mismatched patients (56%) having more than grade 2 versus 10 of 18
(56%). Four of 9 ABO-mismatched patients (44%) were mixed chimeras up to
Day 100 versus 2 of 18 ABO-matched patients (11%), and the difference
was significant (p = 0.01). CONCLUSION: Patients with ABO mismatch had
problems with engraftment,
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