Table of Contents
1
UI - 11419443
AU - Osman K; Comenzo R; Rajkumar SV
TI -
Deep venous thrombosis and thalidomide therapy for multiple myeloma.
SO - N Engl J Med 2001 Jun 21;344(25):1951-2
2
UI - 11521791
AU - Thomas DA; Kantarjian HM
TI -
The revitalization of thalidomide.
SO - Ann Oncol 2001 Jul;12(7):885-6
3
UI - 11521808
AU - Dimopoulos MA; Zervas K; Kouvatseas G; Galani E; Grigoraki V; Kiamouris
TI -
C; Vervessou E; Samantas E; Papadimitriou C; Economou O; Gika D;
Panayiotidis P; Christakis I; Anagnostopoulos N
Thalidomide and dexamethasone combination for refractory multiple
myeloma.
SO - Ann Oncol 2001 Jul;12(7):991-5
AD - Department of Clinical Therapeutics, University of Athens School of
Medicine, Greece. mdimop@cc.uoa.gr
BACKGROUND: Thalidomide is effective in approximately 30% of patients
with refractory multiple myeloma. Dexamethasone is active in 25% of
patients with disease resistant to alkylating agents. We investigated
the combination of thalidomide with dexamethasone as salvage treatment
for heavily pretreated patients with multiple myeloma, in order to
assess its efficacy and toxicity. PATIENTS AND METHODS: Forty-four
patients with refractory myeloma were treated with thalidomide, 200 mg
p.o. daily at bedtime, with dose escalation to 400 mg after 14 days, and
dexamethasone, which was administered intermittently at a dose of 20
mg/m2 p.o. daily for four days on day 1-4, 9-12, 17-20, followed by
monthly dexamethasone for four days. Patients' median age was 67 years.
All patients were resistant to standard chemotherapy, 77% were resistant
to dexamethasone-based regimens and 32% had previously received
high-dose therapy. RESULTS: On an intention-to-treat basis twenty-four
patients (55%) achieved a partial response with a median time to
response of 1.3 months. The thalidomide and dexamethasone combination
was equally effective in patients with or without prior resistance to
dexamethasone-based regimens and in patients with or without prior
high-dose therapy. Toxicities were mild or moderate and consisted
primarily of constipation, morning somnolence, tremor, xerostomia and
peripheral neuropathy. The median time to progression for responding
patients is expected to exceed 10 months and the median survival for all
patients is 12.6 months. CONCLUSION: The combination of thalidomide with
dexamethasone appears active in patients with refractory multiple
myeloma. If this activity is confirmed, further studies of this
combination as second-line treatment for patients resistant to
conventional chemotherapy, and as primary treatment for patients with
active myeloma, should be considered.
4
UI - 11780390
AU - Song L; Shen B; Li Y
TI -
Association and contribution of ERK to IL-6-induced activation of signal
transducer and activator of transcription in a human myeloma cell line.
SO - Chin Med J (Engl) 2001 Sep;114(9):954-7
AD - Department of Molecular Immunology, Institute of Basic Medical Sciences,
Academy of Military Medical Sciences, Beijing 100850, China.
lunsong@yahoo.com
OBJECTIVE: To investigate the regulation effect of protein kinase ERK on
the activation of transcription factor STAT3 in response to IL-6 in the
Sko-007 human myeloma cell line. METHODS: Electrophoretic mobility shift
assay (EMSA) and immunoprecipitation (IP) were used to show the
activation of STAT3 and ERK in Sko-007 cells in the presence and absence
of IL-6. Antisense oligonucloetides of ERK (ERK-AS) were transfected
into Sko-007 cells to specifically inhibit the expression and activity
of ERK. The changes in the activation of STAT3 in the transfected cells
were also exhibited by EMSA. Direct binding between STAT3 and ERK was
analyzed by co-IP. RESULTS: Both STAT3 and ERK were activated in Sko-007
cells stimulated with IL-6. ERK-AS inhibited STAT3 activation by IL-6.
Moreover, activated ERK could form a complex with STAT3 in Sko-007
cells. CONCLUSION: ERK can bind STAT3 directly and be required for its
maximal activation in Sko-007 cells stimulated by IL-6.
5
UI - 9686053
AU - Schoenlaub P; Lipsker D; Massard G; Christmann D; Grosshans E
TI -
[Lymph node and cutaneous syndrome associated with bone plasmacytoma]
SO - Ann Dermatol Venereol 1997;124(3):228-32
AD - Clinique Dermatologique, Hopitaux Universitaires de Strasbourg.
INTRODUCTION: We report two patients in whom a slowly growing
erythematous thoracic lesion led to the diagnosis of an underlying
plasmocytoma. After the treatment of the latter, the cutaneous lesions
disappeared, strongly suggesting a link between the two manifestations.
CASE REPORTS: The two male patients, aged respectively 66 and 73 years
old, had erythematous thoracic plaques. In both cases, extensive
laboratory work-up and a histological examination of a cutaneous biopsy
did not allow a precise diagnosis. The two patients had a solitary bony
plasmocytoma located beneath the cutaneous plaques. The plasmocytomas
were discovered respectively 2 and 4 years after the first cutaneous
manifestations and were associated to histological non-specific lymph
node hyperplasia. Treatment of the plasmocytoma led to the disappearance
of skin lesions in both patients. DISCUSSION: In both cases, an
erythematous scleroderma-like plaque associated to palpable peripheral
and mediastinal lymph nodes, was located over a solitary bony
plasmocytoma. Treatment of the plasmocytoma led to the disappearance of
the cutaneous lesions, strongly suggesting a link between the two
manifestations. Such an association has not been previously reported. We
think this is a new entity, characterised by a scleroderma-like
cutaneous plaque overlying a solitary bony plasmocytoma and associated
to superficial and deep lymph node hyperplasia. We suggest to call it
"plasmocytoma associated cutaneous lymph node syndrome". Its
relationship to the POEMS syndrome and scleromyxedema are discussed. The
pathophysiology remains completely unknown; the syndrome regresses after
the treatment of the plasmocytoma.
6
UI - 10564685
AU - Singhal S; Mehta J; Desikan R; Ayers D; Roberson P; Eddlemon P; Munshi
TI -
N; Anaissie E; Wilson C; Dhodapkar M; Zeddis J; Barlogie B
Antitumor activity of thalidomide in refractory multiple myeloma.
SO - N Engl J Med 1999 Nov 18;341(21):1565-71
AD - Myeloma and Lymphoma Program, South Carolina Cancer Center, University
of South Carolina, Columbia, USA.
BACKGROUND: Patients with myeloma who relapse after high-dose
chemotherapy have few therapeutic options. Since increased bone marrow
vascularity imparts a poor prognosis in myeloma, we evaluated the
efficacy of thalidomide, which has antiangiogenic properties, in
patients with refractory disease. METHODS: Eighty-four previously
treated patients with refractory myeloma (76 with a relapse after
high-dose chemotherapy) received oral thalidomide as a single agent for
a median of 80 days (range, 2 to 465). The starting dose was 200 mg
daily, and the dose was increased by 200 mg every two weeks until it
reached 800 mg per day. Response was assessed on the basis of a
reduction of the myeloma protein in serum or Bence Jones protein in
urine that lasted for at least six weeks. RESULTS: The serum or urine
levels of paraprotein were reduced by at least 90 percent in eight
patients (two had a complete remission), at least 75 percent in six
patients, at least 50 percent in seven patients, and at least 25 percent
in six patients, for a total rate of response of 32 percent. Reductions
in the paraprotein levels were apparent within two months in 78 percent
of the patients with a response and were associated with decreased
numbers of plasma cells in bone marrow and increased hemoglobin levels.
The microvascular density of bone marrow did not change significantly in
patients with a response. At least one third of the patients had mild or
moderate constipation, weakness or fatigue, or somnolence. More severe
adverse effects were infrequent (occurring in less than 10 percent of
patients), and hematologic effects were rare. As of the most recent
follow-up, 36 patients had died (30 with no response and 6 with a
response). After 12 months of follow-up, Kaplan-Meier estimates of the
mean (+/-SE) rates of event-free survival and overall survival for all
patients were 22+/-5 percent and 58+/-5 percent, respectively.
CONCLUSIONS: Thalidomide is active against advanced myeloma. It can
induce marked and durable responses in some patients with multiple
myeloma, including those who relapse after high-dose chemotherapy.
7
UI - 11012329
AU - Rajkumar SV; Gertz MA; Witzig TE
TI -
Life-threatening toxic epidermal necrolysis with thalidomide therapy for
myeloma.
SO - N Engl J Med 2000 Sep 28;343(13):972-3
8
UI - 11173691
AU - Grosshans E; Weber JC; Lange F; Rondeau M; Lipsker D
TI -
[Adenocutaneous syndrome associated with bone plasmocytoma: clinical
course]
SO - Ann Dermatol Venereol 2000 Dec;127(12):1099
9
UI - 11554625
AU - Clough TM
TI -
Spontaneous fracture healing in plasma cell malignancy of bone.
SO - Clin Oncol (R Coll Radiol) 2001;13(4):276-8
AD - Royal Bolton Hospital, UK. tim.clough@btinternet.com
This report describes a patient in whom sequential pathological
fractures occurred at sites of plasma cell malignant bony deposits, but
in which clinical and radiological healing occurred without treatment at
the site of the initial deposit.
10
UI - 11597035
AU - Abbott KC; Agodoa LY
TI -
Multiple myeloma and light chain-associated nephropathy at end-stage
renal disease in the United States: patient characteristics and
survival.
SO - Clin Nephrol 2001 Sep;56(3):207-10
AD - Nephrology Service, Walter Reed Army Medical Center, Washington, DC
20307-5001, USA. kevin.abbott@na.amedd.army.mil
AIMS: The patient characteristics and clinical course of nephropathy
associated with multiple myeloma/light chain disease (MMN) has not been
described for a national sample of end-stage renal disease patients.
METHODS: 375,152 patients in the United States Renal Data System were
initiated on ESRD therapy between January 1, 1992 and June 30, 1997, and
were analyzed in a retrospective registry study of MMN (PDIS=2030A,
2030B, 2030Z, and 203Z). RESULTS: Of the study population, 3298 (0.88%)
had MMN. Patients with MMN were disproportionately male (59.5% vs.
53.2%) and Caucasian (76.2% vs. 64.1%, p < 0.01 by Chi-square for both
comparisons) and older (68.00+/-11.78 vs. 60.69+/-16.55 years, p < 0.01
by Student's t-test). In logistic regression analysis, patients with MMN
were more likely male and Caucasian, were older, had lower serum
hemoglobin, higher creatinine, and more likely to have been started on
hemodialysis than peritoneal dialysis. The two-year all-cause mortality
of patients with MMN during the study period was 58% vs. 31% in all
other patients (p < 0.01 by log rank test). In Cox regression, MMN was
independently associated with decreased all-cause patient survival (p <
0.01, hazard ratio for mortality=2.52, 95% CI 2.38-2.67). CONCLUSIONS:
MMN was associated with Caucasian race, male gender, and older age,
compared with other ESRD patients. Patients with MMN had evidence of
poorer medical condition on initiation of dialysis compared to other
patients. MMN was associated with decreased patient survival after
initiation of dialysis, although better than in some previous reports,
and patients with MMN may be initiated on dialysis at a lower level of
renal function than other patients with ESRD.
11
UI - 11561682
AU - Varterasian ML; Pemberton PA; Hulburd K; Rodriguez DH; Murgo A; Al-Katib
TI -
AM
Phase II study of bryostatin 1 in patients with relapsed multiple
myeloma.
SO - Invest New Drugs 2001;19(3):245-7
AD - Karmanos Cancer Institute and Wayne State University, Detroit, MI, USA.
mary.varterasian@pfizer.com
Bryostatin 1, a macrocyclic lactone isolated from the marine bryozoan
Bugula neritina, is a protein kinase C (PKC) modulator which has shown
both preclinical and clinical activity in lymphoid malignancies. We
conducted a phase II trial of bryostatin 1 administered at a dose of 120
microg/m2 by 72-h continuous infusion every 2 weeks in patients with
relapsed multiple myeloma. Treatment was well tolerated with myalgias
constituting the primaray toxicity. There were no responses in nine
evaluable patients. The preclinical anti-lymphoid activity is strong
enough to support further exploration of bryostatin 1 in different
schedules and in combination therapy for multiple myeloma.
12
UI - 11577492
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.
13
UI - 11769531
AU - Kawanishi N; Kanisawa Y; Hisai H; Takahari D; Akiyama T; Sumiyoshi Y;
TI -
Araya H
[Myelomatous ascites: an unusual presenting sign of multiple myeloma]
SO - Nippon Naika Gakkai Zasshi 2001 Nov 10;90(11):2295-7
AD - Department of Internal Medicine, Japan Red Cross, Date General Hospital,
Date.
14
UI - 11769532
AU - Hojo N; Kakimoto M; Sakai I; Takada K; Yasukawa M; Fujita S
TI -
[IgG-kappa biclonal myeloma associated with hepatic tumor]
SO - Nippon Naika Gakkai Zasshi 2001 Nov 10;90(11):2298-300
AD - First Department of Internal Medicine, Ehime University School of
Medicine, Onsen-gun.
15
UI - 11797120
AU - Patriarca F; Zaja F; Silvestri F; Sperotto A; Scalise A; Gigli G; Fanin
TI -
R
Meningeal and cerebral involvement in multiple myeloma patients.
SO - Ann Hematol 2001 Dec;80(12):758-62
AD - Division of Hematology and Department of Bone Marrow Transplantation,
Udine University Hospital, P.le S. Maria della Misericordia, 33100
Udine, Italy. Ematologia@uniud.it
Cerebral involvement is an unusual complication in multiple myeloma:
herein four patients who presented myelomatous meningitis with multiple
intraparenchymal lesions or a localized cerebral plasmacytoma are
described. Two of these patients relapsed with meningeal involvement and
a very limited disease outside the central nervous system after an
initial complete remission obtained with induction chemotherapy. In the
other two cases, the cerebral tumor appeared during first-line
treatment. Cytological examination of the cerebrospinal fluid and
magnetic resonance were essential for diagnosis. Different modalities of
treatment were used, including intrathecal chemotherapy, cranial
irradiation, and systemic chemotherapy with high-dose methotrexate and
cytarabine, achieving improvement of neurological symptoms in three of
four patients.
16
UI - 11693896
AU - Rosen LS; Gordon D; Antonio BS; Kaminski M; Howell A; Belch A; Mackey
TI -
JA; Apffelstaedt J; Tfrin M; Hussein M; Coleman RE; Reitsma DJ; Seaman
JJ; Chen BL; Ambros Y
Zoledronic acid versus pamidronate in the treatment of skeletal
metastases in patients with breast cancer or osteolytic lesions of
multiple myeloma: a phase III, double-blind, comparative trial.
SO - Cancer J 2001 Sep-Oct;7(5):377-87
AD - Jonsson Cancer Center, University of California, Los Angeles 90095, USA.
PURPOSE: Zoledronic acid, a new and more potent bisphosphonate, was
compared with pamidronate, the current standard treatment for patients
with osteolytic or mixed bone metastases/lesions. PATIENTS AND METHODS:
A total of 1,648 patients with either Durie-Salmon stage III multiple
myeloma or advanced breast cancer and at least one bone lesion were
randomly assigned to treatment with either 4 or 8 mg of zoledronic acid
via 15-minute intravenous infusion or 90 mg of pamidronate via 2-hour
intravenous infusion every 3 to 4 weeks for 12 months. The primary
efficacy endpoint was the proportion of patients experiencing at least
one skeletal-related event over 13 months. RESULTS: The proportion of
patients with at least one skeletal-related event was similar in all
treatment groups. Median time to the first skeletal-related eventwas
approximately 1 year in each treatment group. The skeletal morbidity
rate was slightly lower in patients treated with zoledronic acid than in
those treated with pamidronate, and zoledronic acid (4 mg) significantly
decreased the incidence and event rate for radiation therapy to bone,
both overall and in breast cancer patients receiving hormonal therapy.
Pain scores decreased in all treatment groups in the presence of stable
or decreased analgesic use. Zoledronic acid (4 mg) and pamidronate were
equally well tolerated; the most common adverse events were bone pain,
nausea, fatigue, and fever and < 5% of serious adverse events were
related to the study drug. The incidence of renal impairment among
patients treated with 4 mg of zoledronic acid via 15-minute infusion was
similar to that among patients treated with pamidronate. CONCLUSIONS:
Zoledronic acid (4 mg) via 15-minute intravenous infusion was as
effective and well tolerated as 90 mg of pamidronate in the treatment of
osteolytic and mixed bone metastases/lesions in patients with advanced
breast cancer or multiple myeloma. (Can-
17
UI - 11827013
AU - Mansour AM; Salti HI
TI -
Multiple myeloma presenting with optic nerve compression.
SO - Eye 2001 Dec;15(Pt 6):802-4
18
UI - 11778969
AU - Sirohi B; Powles R; Mehta J; Treleaven J; Raje N; Kulkarni S; Rudin C;
TI -
Bhagwati N; Horton C; Saso R; Singhal S; Parikh R
The implication of compromised renal function at presentation in
myeloma: similar outcome in patients who receive high-dose therapy: a
single-center study of 251 previously untreated patients.
SO - Med Oncol 2001;18(1):39-50
AD - Leukaemia and Myeloma Units, Royal Marsden NHS Trust, Sutton, Surrey,
United Kingdom.
The purpose of the study was to determine the role of sequential therapy
(ST) in new patients with myeloma presenting with renal dysfunction
program comprised of infusional chemotherapy (IC) with VAMP/C-VAMP
(vincristine, doxorubicin, and methylprednisolone with/without
cyclophosphamide) followed by autologous transplantation and interferon
maintenance. The median overall survival (OS) of 251 patients from the
start of IC was 4.2 yr with the RD group faring significantly poorer
(median 2.5 yr) than those with no renal dysfunction (NRD; median 4.6
yr; p = 0.0025). Mortality during the first 100 d of IC was
significantly higher in patients with RD (11/59; p = 0.01) compared to
patients with NRD. In patients consolidated with high-dose therapy, the
OS and event-free survival (EFS) were not significantly different
between the two groups. Cox analysis of the variables at presentation
failed to show RD as a factor influencing outcome, but it showed that
patients with beta-2-microglobulin (beta2M) > or = 3.7 (p < 0.0001), age
> or = 52.5 yr (p = 0.002), performance status (PS) > or = 2 (p = 0.005)
and patients with light-chain myeloma (p = 0.03) had a significantly
shorter OS, beta2M > or = 3.7, PS > or = 2, and light-chain myeloma were
predictive of shorter EFS. The study shows that with modern intensive
schedules of treatment, renal disease at presentation in isolation does
not compromise outcome.
19
UI - 11778972
AU - Gulbrandsen N; Wisloff F; Brinch L; Carlson K; Dahl IM; Gimsing P; Hippe
TI -
E; Hjorth M; Knudsen LM; Lamvik J; Lenhoff S; Lofvenberg E; Nesthus I;
Nielsen JL; Turesson I; Westin J; The Nordic Myeloma Study Group
Health-related quality of life in multiple myeloma patients receiving
high-dose chemotherapy with autologous blood stem-cell support.
SO - Med Oncol 2001;18(1):65-77
AD - Department of Hematology, Ulleval University Hospital, Oslo, Norway.
nina.gulbrandsen@ioks.uio.no
In a population-based study, the Nordic Myeloma Study Group found a
survival advantage for high-dose melphalan with autologous blood
stem-cell support compared to conventional chemotherapy in myeloma
patients under 60 yr of age (risk ratio: 1.62; confidence interval [CI]
1.22-2.15; p = 0.001). A study of health-related quality of life (HRQoL)
was integrated in the trial, using the EORTC QLQ-C30 questionnaire. Of
the 274 patients receiving intensive therapy 221 (81%) were compared to
113 (94%) of 120 patients receiving conventional melphalan-prednisone
treatment. Prior to treatment, there were no statistically significant
differences in any HRQoL score between the two groups. One month after
the start of induction chemotherapy, the patients on intensive treatment
had more sleep disturbance than the control patients. At 6 mo,
corresponding to a mean of 52 d after high-dose melphalan, the patients
on intensive treatment had moderately lower scores for global QoL and
role and social functioning and there was also a significantly higher
score for appetite loss. At 12 and 24 mo, the HRQoL was similar to that
of the control patients. At 36 mo, there was a trend toward less
fatigue, pain, nausea, and appetite loss in the intensive-treatment
group. Thus, the 18 mo of prolonged survival seem to be associated with
a good health-related quality of life. Despite the moderate HRQoL
reduction associated with the early intensive chemotherapy phase, this
treatment modality must be regarded as an important step forward in the
care of multiple myeloma.
20
UI - 11778973
AU - Morris TC; Ranaghan L; Morrison J; Northern Ireland Regional Haematology
TI -
Group
Phase II trial of clarithromycin and pamidronate therapy in myeloma.
SO - Med Oncol 2001;18(1):79-84
AD - Haematology Department, Belfast City Hospital Trust, Belfast, Northern
Ireland. curly.morris@bll.n-i.nhs.uk
A phase II study to further evaluate any possible antimyeloma activity
of clarithromycin was conducted following a report of possible clinical
efficacy. Twenty patients, 11 male and 9 female with a median age of 73
yr, received clarithromycin 500 mg twice daily with monthly intravenous
infusions of disodium pamidronate. None of the study patients received
concomitant cytotoxic or steroid therapy. Ten patients had relapsed
disease, five had refractory disease, four were previously untreated,
and one patient was unsuitable for cytotoxic therapy. The median number
of previous treatment modalities was 1.5. Serum M protein levels and
urinary M protein excretion were monitored along with other parameters
to assess response. Median duration of therapy was 16 wk and six
patients had dose escalation. A significant decrease in M protein
production occurred in one patient at wk 12 of therapy, which maximized
following dose escalation to a 47% decrease from baseline. Two patients
had incremental but unsustained M protein reductions. Serum/urine M
protein levels remained static in six patients and rose in the remaining
six evaluable patients. The M protein response rates in this study are
much lower than those previously reported and do not confirm efficacy.
In addition, the recently postulated antimyeloma activity of pamidronate
may explain some of the M protein decreases.
21
UI - 11799861
AU - Kirazli T; Oner K; Ovul L; Bilgen C; Ogut F
TI -
Petrosal presigmoid approach to the petro-clival and anterior
cerebellopontine region (extended retrolabyrinthine, transtentorial
approach).
SO - Rev Laryngol Otol Rhinol (Bord) 2001;122(3):187-90
AD - University Medical Faculty, Department of ENT, Head and Neck Surgery,
Ege, Turkey.
Intradural tumours affecting the clivus may be divided into three
categories depending the area primarily involved by tumour. The second
area extends from the spheno-occipital synchondrosis to the level of the
jugular foramina. This area is best approached through the petrosal
approach and suited for patients with serviceable hearing on the side of
the lesion. 35 cases having skull base lesions were operated by the
Skull Base Surgery Group of Ege University Medical Faculty between
tumours affecting the petroclival and anterior cerebellopontine region,
the petrosal presigmoid approach was performed in 4 patients. As hearing
was absent in another 4 patients, the translabyrinthine route was
coupled a the petrosal craniotomy (transtemporal approach). The aim of
this article is to highlight the definitions, indications, hints and
pitfalls of the approach from the otoneurological point of view.
22
UI - 11790977
AU - Hussein MA; Juturi JV; Lieberman I
TI -
Multiple myeloma: present and future.
SO - Curr Opin Oncol 2002 Jan;14(1):31-5
AD - Myeloma Research Program, Cleveland Clinic Taussig Cancer Center,
Cleveland, Ohio 44195, USA. husseim@ccf.org
Multiple myeloma is a clonal B-cell tumor of slowly proliferating plasma
cells within the bone marrow. Among hematologic malignancies, it
constitutes 10% of the cancers and ranks as the second most frequently
occurring hematologic cancer in the United States, after non-Hodgkin
lymphoma. Interleukin-6 is an important cytokine in myeloma cell growth
and proliferation. Close cell-to-cell contact between myeloma cells and
the bone marrow stromal cells triggers a large amount of interleukin-6
production, which supports the growth of these cells, as well as
protecting them from apoptosis induced by dexamethasone and other
chemotherapeutic agents. Therapies modulating the tumor and its
microenvironment are being actively pursued with the goal of converting
multiple myeloma to a chronic disease with the patients maintaining a
normal lifestyle.
23
UI - 11587522
AU - Voss SD; Murphey MD; Hall FM
TI -
Solitary osteosclerotic plasmacytoma: association with demyelinating
polyneuropathy and amyloid deposition.
SO - Skeletal Radiol 2001 Sep;30(9):527-9
AD - Department of Radiology, Beth Israel Deaconess Medical Center, Boston,
MA 02215, USA.
A 51-year-old man presented with a 1-year history of polyneuropathy
necessitating the use of a wheelchair. Initial diagnosis was idiopathic
chronic inflammatory demyelinating polyneuropathy (CIDP) and associated
monoclonal gammopathy. Investigations for multiple myeloma, including
bone marrow aspiration and biopsy, were negative. What was initially
felt to be an incidental osteosclerotic focus noted on the radiographic
bone survey was eventually shown to be a solitary osteosclereotic
plasmacytoma with associated amyloid. This dramatically altered
treatment. This case emphasizes the importance of including
osteosclerotic plasmacytoma in the differential diagnosis of a focal
sclerotic bone lesion in the clinical setting of polyneuropathy. These
lesions are less likely to progress to multiple myeloma than lytic
plasma cell neoplasms, and the presence of polyneuropathy often results
in earlier diagnosis and treatment with enhanced prospect of cure. The
finding of amyloid deposition within the osteosclerotic lesion may be of
prognostic importance.
24
UI - 11828720
AU - Harada Y; Egi Y; Honda Y; Shirota T; Hayashi T
TI -
[Multiple myeloma with Sweet disease developing from monoclonal
gammopathy of undetermined significance and Sjogren syndrome]
SO - Rinsho Ketsueki 2001 Dec;42(12):1176-80
AD - Third Department of Internal Medicine, Tokyo Medical University.
A 57-year-old woman was diagnosed as having monoclonal IgG kappa
gammopathy of undetermined significance with Sjogren syndrome. Five
years later, she was admitted with an increased level of serum IgG and
diagnosed as having multiple myeloma. After admission, fever and painful
erythema developed. Combined chemotherapy with adrenal cortical steroid
diminished the skin lesions. Erythema recurred during treatment with
granulocyte colony-stimulating factor for neutropenia due to
chemotherapy. A biopsy specimen from the skin revealed dense
neutrophilic infiltration in the dermis, and a diagnosis of Sweet
disease was made.
25
UI - 11779429
AU - Jia P; Chen G; Huang X; Cai X; Yang J; Wang L; Zhou Y; Shen Y; Zhou L;
TI -
Yu Y; Chen S; Zhang X; Wang Z
Arsenic trioxide induces multiple myeloma cell apoptosis via disruption
of mitochondrial transmembrane potentials and activation of caspase-3.
SO - Chin Med J (Engl) 2001 Jan;114(1):19-24
AD - Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second
Medical University, Shanghai 200025, China.
OBJECTIVE: To investigate the response of multiple myeloma (MM) cells to
arsenic trioxide (As2O3) and their possible mechanisms. METHODS: Two
MM-derived cell lines RPMI8226 and U266 cells were used as in vitro
models. Cell apoptosis was assessed by morphology, flow cytometry, and
DNA gel electrophoresis. Mitochondrial transmembrane potentials (delta
psi m) were evaluated by measuring cellular Rhodamine 123 staining
intensity. Protein expression was analyzed using Western blot. RESULTS:
Zero point one to 0.5 mumol/L As2O3 inhibited cell proliferation and 2.0
mumol/L As2O3 induced cell apoptosis, while 1.0 mumol/L As2O3 inhibited
proliferation with a weak degree of apoptosis induction in RPMI8226 and
U266 cell lines. As2O3-induced apoptosis was accompanied by
mitochondrial transmembrane potentials (delta psi m) collapse and
caspase-3 activation in the presence of intact membrane. Glutathione
depleter buthionine sulfoximine enhanced, while disulfide bond-reducing
agent dithiothreitol partially antagonized As2O3-induced delta psi m
collapse and apoptosis in MM cells. All-trans retinoic acid (ATRA) could
also induce apoptosis in RPMI8226 cells, but it did not show any
cooperative effects with As2O3. CONCLUSION: As2O3 exerts
apoptosis-inducing and growth-inhibiting effects on MM cells, and
mitochondrium is a pivotal and common target of As2O3 for apoptosis
induction.
26
UI - 11789008
AU - Vytrasova M; Scudla V; Nekula J; Bucil J; Vavrdova V; Bacovsky J
TI -
[Magnetic resonance in examination of the spine in patients with
multiple myeloma]
SO - Vnitr Lek 2001 Oct;47(10):694-8
AD - III. interni klinika Lekarske fakulty UP a Fakultni nemocnice, Olomouc.
Multiple myeloma (MM) is a malignant disease of the haematopoietic
system characterized by the formation of osteolytic foci of the skeleton
with predilection of the thoracolumbar portion of the spine. The
submitted investigation evaluates the importance of examination of the
spine by magnetic resonance (MR), as compared with results of
conventional radiology (CR). The analyzed group of 75 patients with
multiple myeloma was assembled in the course of the previous four years.
All patients were examined by conventional radiology and magnetic
resonance and the assembled results were mutually compared. On
examination by MR a pathological finding was recorded in 68/75 (91%)
patients, when using CR in 41/75 (55%) patients. Compression of the
vertebral bodies was assessed by means of magnetic resonance in 42/75
(56%) patients, when using CR in 37/75 (49%) patients. Secondary
stenosis of the spinal canal was detected by MR in 23/75 (30%),
extramedullary spread of myelomatous masses was found in 15/75 (20%)
patients whereby radiographic examination was negative in these
patients. Osteolytic foci in the area of the spine were recorded in
62/75 (83%) patients examined by MR, while by using CR only in 3/75
(4%). From the presented results ensues that nuclear magnetic resonance
is for evaluation of spinal lesions in MM much more sensitive than
conventional radiography, mainly due to the possibility of direct
visualization of soft tissue tumourous masses and evaluation of their
relationship to the spinal canal. The contribution of MR examination is
invaluable in particular in patients with obscure back pain and a
negative finding on radiographic examination of the skeleton where X-ray
examination does not explain adequately the patient's complaints, as
well as in patients with suspected compression of the spinal cord. In
some liminal situations it contributes to more accurate assessment of
the clinical stage and thus to selection of adequate treatment.
27
UI - 11813635
AU - Kinkor Z; Benkova K
TI -
[Metastases in peripheral lymph nodes as the first sign of anaplastic
skeletal plasmacytoma--2 case reports]
SO - Cesk Patol 2001 Nov;37(4):168-71
AD - Oddeleni patologie Fakultni nemocnice Na Bulovce, Praha.
The paper discusses two unusual cases of solitary skeletal plasmacytoma
and multiple myeloma presenting clinically as a metastatic disease in
cervical lymph nodes. The pathology report of lymph node plasmacytoma
initiated an extensive clinical search for eventual discovery of
skeletal disease in both patients. We are not aware of any report in the
literature dealing with this issue (Medline 1970-2000). The early
involvement of lymph nodes by plasmacytoma with the appearance of
undifferentiated neoplasm is challenging and poses great difficulties in
correct diagnosis; this is almost impossible from hematoxylin eosin
slides. The problem is that one has to think about the rare possibility
of metastasing plasmacytoma in differential diagnosis of anaplastic
tumors in lymph nodes. Immunohistochemistry and clinical records are
very helpful in making a final diagnosis.
28
UI - 11697621
AU - Saif MW; Greenberg BR
TI -
Multiple myeloma and hairy cell leukemia: a rare association or
coincidence?
SO - Leuk Lymphoma 2001 Sep-Oct;42(5):1043-8
AD - NCI, National Naval Medical Center, Bethesda, MD 20892, USA.
saifw@mail.nih.gov
Hairy cell leukemia (HCL) and multiple myeloma (MM) are well-defined
entities with distinctive clinical and pathological features. Although
most cases of HCL and MM fit their classic descriptions, more recent
studies have revealed that their clinical and morphological boundaries
may not only overlap but a transformation of HCL into MM could also
occur. We report another case of HCL followed by the development of MM
after 9 years. He also developed hemarthrosis of his right ankle at the
time of diagnosis of MM. PCR analysis of DNA extracted from the bone
marrow aspirate was negative for the presence of a monoclonally
rearranged immunoglobulin heavy chain gene. Immunophenoytping revealed
no evidence of HCL. There are several possible explanations for the
development of MM in HCL patients, such as the coexistence of separate
disease entities or different clinical and morphologic phases of a
single disease entity. An accurate diagnosis of HCL or MM is critical
because of differences in their treatment. Hemarthrosis in this patient
may also have been the first manifestation of MM, a feature of MM which
has rarely been reported.
29
UI - 11757219
AU - Bolek M; Sztuk S
TI -
[Ten years survival of solitary plasmocytoma: a case report]
SO - Pol Merkuriusz Lek 2001 Aug;11(62):160-1
AD - Klinika Onkologii Szpitala Uniwersyteckiego Collegium Medicum
Uniwersytetu Jagiellonskiego.
The authors describe 71 year-old man with solitary plasmocytoma of jaw.
Long-term survival was achieved by early diagnosis and combined
treatment with surgery and radiotherapy.
30
UI - 11426557
AU - Kanda Y; Ara C; Chizuka A; Yamamoto R; Hamaki T; Suguro M; Matsuyama T;
TI -
Takezako N; Miwa A; Tohma J; Shirakawa K; Yatomi T; Nakamura N; Hirai H;
Togawa A
Lack of correlation between clinical characteristics and serum soluble
Fas ligand levels in patients with multiple myeloma.
SO - Leuk Lymphoma 2001 Jan;40(3-4):351-6
AD - Department of Hematology, International Medical Center of Japan, Tokyo.
ycanda-tky@umin.ac.jp
Multiple myeloma is characterized by the accumulation of malignant
plasma cells in the bone marrow and rarely cured by chemotherapy.
Villunger et al. showed that the neoplastic plasma cells express Fas
ligand (FasL), which transmits a signal of apoptosis upon ligation to
Fas, and suggested that the FasL suppresses the T-cells activated
against malignant cells, resulting in escape from tumour immunity. We
examined serum soluble FasL (sFasL) levels in 35 multiple myeloma
patients to evaluate the correlation between sFasL levels and clinical
characteristics. The serum sFasL levels were not affected by the disease
status, serum monoclonal protein levels, or other prognostic factors. We
could not determine whether the expression of FasL is involved in the
poor clinical course of the disease.
31
UI - 11426560
AU - Lincz LF; Crooks RL; Way SL; Granter N; Spencer A
TI -
Tumour kinetics in multiple myeloma before, during, and after treatment.
SO - Leuk Lymphoma 2001 Jan;40(3-4):373-84
AD - Hunter Haematology Research Group, Mater Misericordiae Hospital, NSW,
Waratah, Australia. leukres@hunter-link.net.au
Tumour progression was monitored in seven multiple myeloma (MM) patients
undergoing a novel oral chemotherapy regimen (cyclophosphamide,
idarubicin and dexamethasone; CID) followed by early autologous stem
cell transplantation (ASCT). Allele-specific oligonucleotide PCR
(ASO-PCR) was used to semi-quantitate the number of tumour cells within
the peripheral blood (PB) and PB progenitor cell (PBPC) harvests and
compared with paraprotein levels and morphological bone marrow (BM)
assessments. Tumour cells were detected in the PB of all patients at
diagnosis, but decreased in response to CID therapy. All but two of the
22 PBPC collections contained MM cells, the levels of which were
statistically correlated with overall clinical response to therapy, but
not with individual BM or PB tumour loads prior to mobilisation. We also
found no correlation between the day of leucapheresis collection and the
number of contaminating MM cells, CD34+ cells or MM cells per CD34+
cell. Regardless of tumour contamination levels in the PBPC collections,
the majority of patients demonstrated post-ASCT clearing of circulating
MM cells. This study suggests that levels of circulating MM cells may be
the best indication of patient response to treatment and argues against
the theory of differential mobilisation of tumour cells and CD34+ cells
in response to cytokine treatment.
32
UI - 11426566
AU - Shek TW; Ma SK; Au WY
TI -
Nodal plasmacytoma with significant paraproteinaemia.
SO - Leuk Lymphoma 2001 Jan;40(3-4):425-8
AD - Department of Pathology, Queen Mary Hospital, Hong Kong.
We present a case of primary nodal plasmacytoma in an elderly Chinese
woman that was associated with significant paraproteinaemia and
paraproteinuria. Clinical and laboratory features of the patient
satisfied Durie's criteria for the diagnosis of multiple myeloma. The
present case was unusual in two aspects. Firstly, there was no evidence
of clonal plasma cell proliferation elsewhere in the body after
extensive radiological investigations, repeated bone marrow
examinations, and polymerase chain reaction for immunoglobulin gene
rearrangement study. Secondly, the clinical behaviour was indolent
despite the large amount of paraprotein production, and showed
satisfactory disease control with local radiotherapy. The differential
diagnoses of plasmacytosis in the lymph node are also discussed.
33
UI - 11806193
AU - Srinivasan C
TI -
Mistaken identity?
SO - Dent Update 2001 Nov;28(9):475
34
UI - 11823041
AU - Rasmussen T; Bjorkstrand B; Andersen H; Gaarsdal E; Johnsen HE
TI -
Efficacy and safety of CD34-selected and CD19-depleted autografting in
multiple myeloma patients: a pilot study.
SO - Exp Hematol 2002 Jan;30(1):82-8
AD - The Stem Cell Laboratory, Department of Haematology, Herlev Hospital,
University of Copenhagen, Herlev, Denmark.
OBJECTIVE: If multiple myeloma patients are to be cured after high-dose
treatment supported by autologous stem cell transplantation, grafts must
be purged of circulating myeloma cells. Myeloma cells are present in all
grafts and have been identified as CD38(++)CD45(-) plasma cells, plasma
blasts, and CD19(+) B cells. MATERIALS AND METHODS: In an attempt to
improve the purging strategy, we studied a two-step procedure consisting
of CD34(+) enrichment followed by CD19 depletion. This article describes
the evaluation of this sequential magnetic microbead selection after 18
procedures in 14 patients. RESULTS: The processed autografts contained a
median CD34 purity of 81% (range 21-99%) and a recovery of 47% (range
15-82%). Flow cytometric analysis documented the expected reduction of
CD34(-) B cells and plasma cells, in most cases to a level below the
sensitivity of flow cytometry. Real-time reverse transcriptase
polymerase chain reaction documented a CD19 mRNA relative reduction to
0.042 (range 0.01-0.21). Allele-specific oligonucleotide IgH primers
were designed for five patients. All products were positive for clonal
myeloma cells before processing, but only 1 of 5 was negative after the
procedure. The clinical outcome after reinfusion of the processed
autografts was evaluated by blood cell recovery and found to be within
the range expected from engraftment of unmanipulated autografts. One
patient who had delayed platelet recovery associated with
cytomegalovirus infection recovered after anti-cytomegalovirus
treatment. CONCLUSIONS: This pilot study documented engraftment after
reinfusion of CD34-selected and CD19-depleted autografts. However, one
patient suffered from unexpected prolonged thrombocytopenia. The
efficacy of the procedure was evaluated and reduction of myeloma cells
was indicated, with only one autograft free of clonal cells.
35
UI - 11587225
AU - Lincz LF; Yeh TX; Spencer A
TI -
TRAIL-induced eradication of primary tumour cells from multiple myeloma
patient bone marrows is not related to TRAIL receptor expression or
prior chemotherapy.
SO - Leukemia 2001 Oct;15(10):1650-7
AD - Hunter Haematology Research Group, Mater Misericordiae Hospital, NSW,
Australia.
TNF-related apoptosis-inducing ligand (TRAIL) shares significant
homology with CD95 (Fas) ligand and has the ability to induce apoptosis
in sensitive cells through a caspase-mediated pathway. We have evaluated
the activity of purified human recombinant soluble TRAIL (S-TRAIL,
comprising residues 114-281; Biomol, Plymouth Meeting, PA, USA) and a
leucine zipper construct of TRAIL (LZ-TRAIL; Immunex, Seattle WA, USA)
against myeloma cell lines NCI H929, U266, RPMI 8226, the FasL-sensitive
Jurkat T cell ALL line, the lymphoblastoid cell line MC/CAR and primary
tumour cells from 16 myeloma patients. Furthermore, we examined the
relationship between TRAIL-induced apoptosis and TRAIL receptor
expression utilising RT-PCR and flow cytometry. Two of three myeloma
cell lines and Jurkat were TRAIL sensitive whereas MC/CAR was relatively
resistant. Five of 16 (31%) primary tumours demonstrated > or =20%
reduction in myeloma cells following TRAIL incubation (20-59%). This did
not correlate with prior therapy. Four cell lines (two sensitive) and
five primary tumours (two sensitive) demonstrated mRNA expression of the
intra-cellular death domain containing TRAIL-R1. Variable expression of
the two decoy (TRAIL-R3 and R4) and soluble (osteoprotegerin) receptors
was seen and this did not correlate with TRAIL resistance. We conclude
that myeloma cell expression of death effector receptors for TRAIL is
insufficient to confer sensitivity to TRAIL-induced apoptosis but that
in a significant minority of patients, irrespective of prior therapy,
tumour cells are sensitive to TRAIL. The further investigation of TRAIL
as an adjunct to presently available therapies for myeloma is justified.
36
UI - 11757204
AU - Berenson JR
TI -
Advances in the biology and treatment of myeloma bone disease.
SO - Am J Health Syst Pharm 2001 Nov 15;58 Suppl 3():S16-20
AD - University of California-Los Angeles School of Medicine, Multiple
Myeloma and Bone Metastasis Programs, Division of Hematology/Oncology,
Cedars Sinai Medical Center, Bev. Mod. 1, Room 100, 8700 Beverly
Boulevard, Los Angeles, CA, USA. berensonj@cshs.org
Potential antitumor effects of bisphosphonates are discussed, and trial
results of zoledronic acid, a bisphosphonate that recently received FDA
approval
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