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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prognostic value of morphological classifications and clinical variables was compared between 31 elderly (> or = 65 years) and 43 young (< 65 years) patients with myeloma. Prognostic factors were divided into three groups: factors useful in elderly patients, e.g., calcium, albumin; factors useful in young patients, e.g., platelet, creatinine, light-chain type; and factors useful in both patients, e.g., clinical stage, hemoglobin, LDH, CRP, bone marrow plasma cell and plasmablast percentages, light- and electron-microscopic classifications. The 5-year survival rates of elderly patients with calcium < 12 and > or = 12 mg/dl were 66.2 and < 11.1%, respectively (p<0.01). Those of the young patients were 64.1 and 33.3%, respectively. The 5-year survival rates of elderly patients with platelets > or = 200 x 10(9)/l and < 100 x 10(9)/l were 59.7 and 50.0%, respectively. Those of the young patients were 68.9 and 33.3%, respectively (p<0.05). The 5-year survival rates of elderly patients with few and numerous electron-microscopic abnormalities were 90 and 0%, respectively (p<0.01), those of young patients were 92.9 and < 14.3%, respectively (p<0.01). These findings suggest that individual clinical variables may differ in prognostic importance in elderly and young patients.
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PMID:Prognostic value of morphological classifications and clinical variables in elderly and young patients with multiple myeloma. 1003 64

Survival for myeloma has improved from a median of 7 months in the 1950s to about 30 months today. Progress in chemotherapy has contributed a great deal to this improvement, although it may also, in part, reflect the improved treatment of infections, renal failure and hypercalcaemia as well as earlier diagnosis. For over 30 years, the gold standard of treatment has been oral melphalan and prednisolone, producing a clinical response in approximately 60% of patients and a median survival of around 36 months. Relapse is unfortunately inevitable in all but a handful and, for the majority, treatment can only hope to produce significant periods of remission with minimal treatment-related morbidity and mortality. Recently, improved results have been seen with the introduction of aggressive chemotherapy and bone-marrow transplantation. Marrow ablative therapies produce remissions in virtually all patients, with complete remissions in approximately 1/3. The best response is seen in those with a lower tumour burden, which will reduce the development of secondary resistance. Current treatment is moving towards an approach using sequential therapy. This involves induction chemotherapy with VAD or a similar regimen such as VAMP (vincristine, adriamycin and methylprednisolone), proceeding to high-dose therapy, often with some form of stem-cell rescue. This ensures minimal tumour burden prior to high-dose treatment as well as reducing graft infiltration, improving general performance status and allowing recovery of renal function. Relapse remains a problem, although the use of IFN may reduce this by prolonging the plateau phase. High-dose therapy should be given early, before prolonged use of alkylating agents induces stem-cell dysplasia, before significant complications arise from the myeloma, and before drug resistance is significant. Unfortunately, these treatments come at a price, in terms of increased treatment-related toxicity. There also remains uncertainty as to the extra benefits of high-dose treatment with marrow rescue over high-dose chemotherapy alone. We await the current MRC trial with interest. For a very few, there is the tantalising possibility of cure with allografting. For those in complete remission after first-line induction therapy, allogeneic bone-marrow transplantation offers the best hope of survival, but comes at a greatly increased risk of toxicity, and it is uncertain if it is superior to autografting for the majority of patients. It may soon be possible to identify those poor prognosis patients in whom an allogeneic transplant should be offered at an early stage. Candidate biochemical markers include serum beta 2 microglobulin, neopterin, IL-6, plasma cell labelling index, CRP or LDH and prognostic clinical features include IgD myeloma or stage III disease at presentation. Many patients will have primary refractory of relapsing disease in whom survival is short despite all current therapeutic modalities. They should therefore be considered for trials of newer agents, drug combinations and therapeutic interventions such as cytokine manipulation or gene therapy. The lack of effective, curative treatment options for patients with myeloma places great importance on effective palliation. While improving survival duration remains elusive in this condition, all possible efforts must be made to ensure quality of life is maximized.
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PMID:Treatment of myeloma. 1020 67

This article contains the data related to diagnosis and treatment of multiple myeloma from several bone marrow transplantation centers. High-dose chemotherapy with stem cell transplantation is currently the best way of treatment in patients with multiple myeloma. The risk factors are chromosomal aberrations, high level of beta-2-microglobulin, CRP and LDH serum levels. The optimal source of stem cells is the blood because of financial and hematological reasons.
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PMID:[Multiple myeloma--new therapeutic perspectives]. 1049 86

A 67-year-old man was admitted because of thrombocytopenia in May 1998. His white blood cell count was 4,900/microliter with 3.5% blasts. Laboratory findings were as follows: hemoglobin level, 10.1 g/dl; platelet count, 1.8 x 10(4)/microliter; ALT, 56 IU/l; LDH, 3,570 IU/l; IgG, 653 mg/dl; IgA, 64 mg/dl; IgM, 49 mg/dl; IgD, 674 mg/dl. Serum immunoelectrophoresis confirmed IgD lambda M-component. Bone marrow aspiration showed 79.2% myeloma cells expressing a mostly plasmablastic morphology. No mature plasma cells were found in the bone marrow. The patient received a continuous drip infusion of 20 mg/body cytarabine (Ara-C) and 50 mg/body etoposide (VP-16) for 7 days. No plasmablastic myeloma cells were detected, but 2.1% mature plasma cells were found in his bone marrow on day 20. On day 18 his platelet count exceeded 10.8 x 10(4)/microliter, and the serum IgD level fell to 210 mg/dl. Therapy consisting of melphalan, methylprednisolone and vincristine was started from day 23. No IgD lambda M-component was detectable by serum immunoelectrophoresis seven months after the diagnosis of multiple myeloma. The patient has been in complete remission as of April 2000.
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PMID:[Complete remission of plasmablastic IgD lambda multiple myeloma induced by continuous infusion of low-dose cytarabine and etoposide]. 1092 52

A 52-year-old woman complained of lower back pain and gluteal pain in April 1997, and was found to have anemia, hypercalcemia and renal disorder. In September of the same year, she was diagnosed as having IgA-lambda myeloma (stage IIIA). VMMD-IFN therapy was started in November, 1997, and this resulted in improvement of the M-protein level, and relief of the pain in the lower back and gluteal region. A second course of VMMD-IFN therapy was also effective. In April 1998, however, the back pain worsened, and in July the patient suffered a fall and fractured her left femur. Upon readmission to our hospital, the level of M-protein was lower, and high fever, hypercalcemia, renal disorder, elevation of the LDH level, anemia and thrombocytopenia were observed. Bone marrow examination revealed 30% atypical large-sized CD19-, CD38+, CD56+ myeloma cells and chromosomal abnormalities. Although the symptoms were improved temporarily after a third course of VMMD therapy, disease aggravation occurred again, and extramedullary masses appeared on the head, face and pelvis. VAD therapy was performed without effect, and the patient died about 2 months after recurrence. This was a comparatively rare case of fulminant multiple myeloma occurring in the terminal stage.
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PMID:[Aggressive transformation and extramedullary tumor formation in IgA-lambda multiple myeloma]. 1102 Sep 90

Multiple studies have attempted to recognize the best markers of disease activity and outcome in myeloma (MM). Our objective was to identify the best variables that can reflect MM disease status. Design and methods: The data obtained from all the following tests were included in the analysis: serum levels of the 2 growth factors known to be crucial for MM growth (i.e. IL-6, and sIL-6R), routine peripheral blood data (Hb%, serum calcium, albumin, CRP, B2m, LDH) and bone marrow plasma cell (BMPC)%, as well as the age and sex of patients. The study was conducted on 21 cases of MM under chemotherapy (aged 48-74 years; M/F = 13/8) and 12 matched normal individuals. The patients were categorized into 2 groups according to their clinical status: Group#1 (n = 16; cases in plateau/stable phase), and Group#2 (n = 5; advanced/refractory cases). Results: Student t-test confirms that serum IL-6 and sIL-6R are the most statistically different variables upon comparing cases in plateau phase (Group#1) with those of advanced disease (Group#2). Stepwise discriminant analysis of data has resulted in a function that is composed of the 2 most salient variables (i.e. serum IL-6, sIL-6R). The proposed function was highly significant (p = 0.0000) with Wilk's Lambda = 0.02538. The diagnostic capability of the proposed function was very high (percent of grouped cases that were classified correctly= 100&percnt;). Conclusion: measurement of serum IL-6 and sIL-6R gives the best prediction of disease activity in patients with MM.
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PMID:Malignancy: Identification of Predictors of Disease Status and Progression in Patients with Myeloma (MM). 1139

Adjunctive anti-bone resorption therapy has become an important part of multiple myeloma (MM) treatment. Currently, no definite evidence exists that this therapy increases survival. We examined a cohort of 13 of 167 patients (8%) treated with the M-2 protocol who received adjuvant gallium nitrate (GN) treatment for osteolysis, and then compared the outcome of these patients to all individuals treated with the M-2 regimen. The stage at diagnosis was IA in two patients, IIIA in 10 patients and IIIB in one. Median age at diagnosis was 51 years (range 35-73). Median (range) of entry data were: paraprotein level: 6000mg/dl (3058-8675); beta2M: 2.7mg/l, (1.2-9.6); LDH: 166U/l (142-237); hemoglobin: 10.2 g/dl (8.3-12.6); albumin: 3.7 g/dl (2.5-5.0); calcium: 10.0 mg/dl (8.3-14.5); creatinine: 1.2 mg/dl (0.7-2.7). Median survival in these patients was 87+ months from time of diagnosis compared with 48 months for all other patients treated on the M-2 protocol. We identified a subgroup of patients with remarkably prolonged survival who had received M-2 chemotherapy and GN. Survival in this group markedly exceeds expectations for patients with advanced stage disease and poor prognostic features. The administration of GN may have a positive impact on survival either by decreasing skeletal complications or through a direct action of GN on the complex cytokine network involved in the proliferation of the malignant myeloma cell.
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PMID:Extended survival in advanced-stage multiple myeloma patients treated with gallium nitrate. 1200 65

We report the results of a dose-intense chemotherapy regimen designed to rapidly induce remissions in patients with advanced multiple myeloma (MM). Patients received VAD for 3-6 cycles depending on response kinetics. This was followed by three sequential cycles of cyclophosphamide (CTX) at 3 g/m2 every 15 days with G-CSF support. 71% of these patients had stage IIIa, 23% had renal failure. The median age was 58, median beta-2 microglobulin 4.6 and median albumin was 3.5, indicating poor prognosis. Of 35 patients, 66% achieved a complete response (CR) (SWOG). Six patients (18%) had a partial response. Fifty percent of the patients with renal failure recovered their kidney function. High-dose CTX contributed to tumor-mass reduction particularly in patients presenting with high-tumor burden. Tumor-mass reduction following three pulses of dexamethasone (4 days each) is significantly higher than with one pulse (p < 0.005). While high beta-2 microglobulin and LDH levels (p < 0.05) were associated with poor outcome, patients who responded faster to chemotherapy had a longer survival (p = 0.005). We conclude that this regimen is safe and effective. A rapid response may be useful in selecting patients who may benefit from further high dose chemotherapy and stem cell support.
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PMID:Impact of early response to sequential high-dose chemotherapy on outcome of patients with advanced myeloma and poor prognostic features. 1200 66

According to the widely accepted myeloma staging system, the bulk of paraprotein is the main determinant of disease stage. However, myelomatous plasma cells differ considerably in their ability to synthesize and secrete monoclonal paraprotein. We determined plasma cell secreting potential (PCSP) as the amount of M-component, divided by the percentage of marrow plasmacytic infiltration, in 240 patients with myeloma, and correlated our results with chain isotype, plasma cell morphology, severity of bone disease, well-recognized prognostic factors, such as serum LDH, CRP, albumin and beta2-microglobulin, treatment response and overall survival. PCSP was higher in IgG than in other myeloma types, and was an almost constant parameter for each individual patient, in 134/166 cases. A > 10% decrease of PCSP in 26 patients was associated with disease aggressiveness and treatment failure. Patients with MGUS had significantly higher PCSP than those with myeloma of the same chain type. Higher PCSP was associated with stage I, absence of Bence-Jones proteinuria and indolent forms of disease with lower proliferating cell nuclear antigen (PCNA) positivity, serum LDH, alpha2-globulins, CRP and beta2-microglobulin and higher albumin levels. Conversely, patients with immature/plasmablastic morphology and those with severe bone disease had lower PCSP. Good responders to treatment had significantly higher PCSP than moderate and poor responders and PCSP was strongly correlated with overall survival in IgG and IgA myeloma. In conclusion, PCSP reflects the maturation status of myelomatous cells and therefore can be used as a prognostic factor, since patients with high secreting potential represent a lower malignancy group, in comparison to those with a low secreting potential.
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PMID:Determination of plasma cell secreting potential as an index of maturity of myelomatous cells and a strong prognostic factor. 1240 Jun 3

Multiple Myeloma (MM) is a malignant disease of terminally differentiated B cells. It most likely originates in a B cell which has traversed the germinal center and has been exposed there extensively to antigens based on the high number of somatic mutations in the complementarity determining regions. The cell of origin is either a plasmablast, or more likely, a memory B-cell. Typically MM goes through different phases from indolent (MGUS, smoldering myeloma) to overt myeloma and then to a fulminant phase, characterized by extramedullary manifestations, high LDH, immature morphology and increased proliferation rate. In the indolent phase, the disease already has acquired major cytogenetic abnormalities as demonstrated by FISH and DNA flow cytometry. It has a gene pattern very similar to myeloma cells on gene array analysis. In the early stages of overt MM, the myeloma cells are completely dependent upon the micro-environment for their growth and survival. The interaction between myeloma cells and micro-environment causes bone disease, genetic instability and more importantly, drug-resistance, which is caused by upregulation of anti-apoptotic factors, resistance to apoptosis induced by FAS and TRAIL activation, and by cell adhesion-induced growth arrest. In this phase of the disease, MM is susceptible to chemotherapy, if delivered with adequate intensity. In the fulminant phase of MM, myeloma cells have acquired sufficient genetic alternations to become completely independent of the micro-environment which allows them to grow at extramedullary sites. Because of the many DNA breaks necessary for immature B cells to become mature plasma cells, B cells already have inherent genetic instability. DNA breaks are necessary for VDJ recombinations, somatic mutations and isotype switching and it is therefore not surprising that genetic alternations frequently occur at the Ig heavy chain site at 14q32, which is abnormal in three quarters of myeloma patients. Some of the translocations with 14q32 involve terminal fragments of chromosomes and can not be diagnosed with standard cytogenetics. Cytogenetic abnormalities are found in 30-35% of newly diagnosed patients and require sufficient proliferation of MM cells to find enough analyzable mitoses. The cytogenetic abnormalities are typically complex, involving > or = 3 chromosomes in 80% of patients. Almost all chromosomes can be involved in deletions, additions or translocations of genetic material. Our group has repeatedly stressed the prognostic significance of chromosome 13 deletion by conventional cytogenetics. The role of chromosome 13 deletion by FISH. is less clear. In addition to chromosome 13 deletion, the presence of a hypodiploid or hypotetraploid karyotye also carries a poor prognosis. Frequently, deletions of chromosome 13 and hypodiploidy go hand in hand. It remains unclear what specific gene confers the poor prognosis to patients with deletion 13. The issues of bone disease, drug resistance and cytogenetics will be addressed in detail during this presentation.
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PMID:New insights into role of microenvironment in multiple myeloma. 1243 Aug 76


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