National Cancer Institute®
Last Modified: February 1, 2002
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. firstname.lastname@example.org
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.
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. email@example.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.
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.
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.
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
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. firstname.lastname@example.org
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.
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. email@example.com
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.
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. firstname.lastname@example.org
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.
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.
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.
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.
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.
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-
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.
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. email@example.com
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.
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. firstname.lastname@example.org
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.
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.
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. email@example.com
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.
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.
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.
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.
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.
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.
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. firstname.lastname@example.org
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.
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.
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. email@example.com
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.
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. firstname.lastname@example.org
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.
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.
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.
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.
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. email@example.com
Potential antitumor effects of bisphosphonates are discussed, and trial results of zoledronic acid, a bisphosphonate that recently received FDA approval