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

Patients with multiple myeloma (MM) and chronic renal failure have generally been excluded from myeloablative therapy programs followed by hematopoietic stem cell support because of the potential increase in transplant-related morbidity and mortality. We here report our experience treating six MM patients with moderate to severe renal insufficiency, with autologous stem cell transplantation. One of these patients required chronic hemodialysis since the diagnosis of MM was made. Peripheral blood stem cell collection was performed with either cyclophosphamide 5.5-7 g/m2 + G-CSF, 5 microg/kg/day (patients 1-3, 5 and 6) or G-CSF, 15 microg/kg/day alone (patient No. 4). Four patients (Nos 1-4) received autotransplant as front-line therapy, while the last two patients were treated in relapse, which occurred following prior autologous stem cell transplantation in support of melphalan, 200 mg/m2 (No. 5) or maintainance therapy with alpha-interferon (No. 6). High-dose chemotherapy administered as preparation to transplant included busulfan 12 mg/kg + melphalan 80 mg/m2 (patients 1-3 and 6) or melphalan 80 mg/m2 alone (patients 4 and 5) in order to reduce mucosal damage. Following transplant, prompt and sustained recovery of hematopoiesis was documented in all the patients; 500 PMN/microI and 20000 platelets/microI were reached after a median of 13 and 14 days, respectively. None of the patients suffered from WHO grade 3-4 infectious complications. Transplant-related toxicity included grade 3-4 oral mucositis (patients 1, 4 and 5) and veno-occlusive disease (patient No. 3). Renal function either improved or remained stable throughout the transplant period. All the patients but one responded to therapy, three of them are progression free after 2, 15 and 26 months; two relapsed after 16 and 4 months and one died from cholangiocarcinoma 7 months after transplant, while still in remission. Although our experience is limited so far, these results appear promising and support the investigational use of myeloablative therapy in MM patients with chronic renal failure.
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PMID:Safety of autologous hematopoietic stem cell transplantation in patients with multiple myeloma and chronic renal failure. 1091 57

One of the most prominent features of plasma cell dyscrasias is the frequent occurrence of renal dysfunction. Renal insufficiency is a common finding with elevated serum creatinine in more than 50% of patients with multiple myeloma at the time of diagnosis. Renal failure is the second most common cause of death in myeloma surpassed only by infections. The reasons for renal failure are multifactorial and early accurate diagnosis of the renal alterations may significantly impact morbidity and survival. Renal failure may result from selective glomerular, tubular interstitial, or vascular pathology or from a combination of pathologic events. The disorders associated with plasma cell dyscrasias include those characterized by monoclonal light chain deposition, encompassing AL-amyloidosis, in addition to the less well-characterized entities, such as heavy chain deposition disease and heavy chain amyloidosis. Therefore, it is more accurate to refer to them as monoclonal immunoglobulin deposition diseases. Staining of renal biopsy specimens for kappa and lambda light chains using immunofluorescence techniques and more sophisticated advanced diagnostic techniques such as immunoelectron microscopy permit detailed characterization of the various renal pathologic manifestations. Renal biopsies can identify monoclonal immunoglobulin deposition, and nephrologists have an opportunity to detect an underlying plasma cell dyscrasia early in its clinical course before overt hematologic alterations become manifest and irreversible renal damage has occurred. The overall spectrum of clinical and pathologic manifestations of monoclonal immunoglobulin deposition renal diseases has expanded considerably in recent years. Recent developments in the research arena promise new therapeutic interventions aimed at avoiding or ameliorating renal damage and even promoting reversal of some of the pathologic alterations. Currently, the 5-year survival rate in myeloma is 29% in white patients and 30% in African-American patients, a rather modest improvement from 24% in the 1970s. Bone marrow ablation followed by transplantation is available as an alternative mode of therapy that may be extraordinarily helpful in a subset of patients with early myeloma.
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PMID:Renal manifestations of plasma cell dyscrasias: an appraisal from the patients' bedside to the research laboratory. 1091 89

Multiple myeloma (MM) is a plasma-cell disorder in which malignant plasma cells accumulate in the bone marrow and usually produce a monoclonal immunoglobulin. Usual presenting features of overt MM include recurrent osteolytic lesions, bacterial infections, anemia and renal insufficiency. MM is responsible for about 1 percent of all cancer-related deaths in Western countries. Its epidemiologic pattern remains obscure, and its cause unknown [1]. The presence of somatic mutations within the immunoglobulin genes of myeloma cells indicate that the putative myeloma-cell precursors have been stimulated by antigens within germinal centers and are either memory B cells or migrating plasmablasts. Myeloma cells proliferate slowly in the bone marrow and display a weak apoptotic index in vivo [2]. This suggest that some defects in the apoptotic process could be involved in this neoplasia. Interleukin-6 (IL-6) is known to be an essential survival factor of myeloma cells and to protect them from apoptosis induced by different stimuli (e.g. dexamethasone, CD95, serum starvation, gamma-irradiation). More recently, important works have been devoted to the biology of the soluble form of the IL-6R alpha i.e., sIL-6R alpha. These works give IL-6/sIL-6R alpha complex an important role in the biology of IL-6. The purpose of the current review is to emphasize the role of this complex in the pathogenesis of MM.
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PMID:The role of interleukin-6 and interleukin-6/interleukin-6 receptor-alpha complex in the pathogenesis of multiple myeloma. 1112 96

Primary plasma cell leukaemia (P-PCL) is a variant of multiple myeloma (MM) first diagnosed in the leukemic phase, with >2000/mm(3) circulating plasma cells (PCs) and plasmacytosis >20% of the white cell count. We investigated the clinical characteristics, therapy, immunophenotype and prognosis factors of 18 patients. Common features at diagnosis were asthenia (seven patients), renal insufficiency (ten patients), bone pain (seven patients), splenomegaly or hepatomegaly (five patients). Hypercalcemia was present at diagnosis in seven patients and was the most potent poor prognosis factor (P<0.05). Most patients (16 out of 18) were treated with an anthracyclin containing regiment; complete remission was attained in one patient and partial remission in 11 patients while six patients had no response. The median survival time from diagnosis was 7 months (2--12, 95% confidence interval), but response to treatment had favorable predictive value (P<0.05). The PCs were usually positive for mature B-cell markers (PCA-1, CD38). They expressed integrins which may increase their binding to endothelial cells and thus participate in PCL physiopathology by favoring plasmocyte extramedullary spread.
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PMID:Primary plasma cell leukaemia: a report of 18 cases. 1116 24

Collapsing focal segmental glomerulosclerosis (FSGS) is a distinct clinicopathologic entity seen most commonly in young African American patients who present with renal insufficiency and nephrotic syndrome. The only epidemiologic factor previously linked to collapsing FSGS is HIV infection. Here clinicopathologic findings are reported for a distinctive population of seven patients, who were older, Caucasian, and HIV negative and developed collapsing FSGS during active treatment of malignancy (multiple myeloma in six patients and metastatic breast carcinoma in one). Although oncologic treatment regimens included vincristine for four patients, doxorubicin for five patients, cisplatin for two patients, and total-body irradiation for one patient, the only agent common to all patients was pamidronate (Aredia). All patients had normal renal function before the administration of pamidronate. Patients began therapy with pamidronate at or below the recommended dose of 90 mg, intravenously, monthly, which was increased to 180 mg monthly in two patients and 360 mg monthly in three patients. Patients received pamidronate for 15 to 48 mo before presentation with renal insufficiency (mean serum creatinine, 3.6 mg/dl) and full nephrotic syndrome (mean 24-h urinary protein excretion, 12.4 g/d). Pamidronate, which is a member of the class of bisphosphonates, is widely used in the treatment of hypercalcemia of malignancy and osteolytic metastases. At the recommended dose of 90 mg, intravenously, monthly, renal toxicity is infrequent; however, higher doses have produced nephrotoxicity in animal models. The temporal association between pamidronate therapy and the development of renal insufficiency, the use of escalating doses that exceed recommended levels, and the distinctive pattern of glomerular and tubular injury strongly suggest a mechanism of drug-associated podocyte and tubular toxicity. These data provide the first association of collapsing FSGS with toxicity to a therapeutic agent.
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PMID:Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. 1137 39

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.
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PMID:Multiple myeloma: an old disease with new hope for the future. 1157 92

Several plasma cells morphological changes have been described in monoclonal gammopathies, including intracytoplasmic crystals. We report one case of indolent kappa-chain multiple myeloma with renal insufficiency, featuring plasma cells with Auer-rod-like intracytoplasmic inclusions. The relationship between such aberrations and those found in multiple-myeloma-associated adult Fanconi syndrome is discussed. The significance of intracellular storage and crystallisation of immunoglobulin within plasma cells remains partially unknown.
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PMID:Is there any significance for intracellular crystals in plasma cells from patients with monoclonal gammopathies? 1172

Not all patients who fulfill the minimal criteria for the diagnosis of multiple myeloma should be treated. If a patient is younger than 70 years, autologous peripheral blood stem cell transplantation should be seriously considered. Major challenges for stem cell transplantation are: 1) the inability to eradicate multiple myeloma from the patient, and 2) removal of myeloma cells and their precursors from the reinfused stem cells. Allogeneic transplantation cannot be recommended at present because of the excessive mortality. Nonmyeloablative approaches are promising. There is no evidence that combinations of alkylating agents are superior to melphalan and prednisone. The use of thalidomide and intermittently administered prednisone for maintenance is being explored. New agents include the immunomodulatory drugs, inhibitors of the ubiquitin proteasone pathway such as PS-341, antiangiogenesis drugs including 2-methoxy-estradiol, and farnesyl transferase inhibitors. Management of skeletal complications, hypercalcemia, anemia, infection, spinal cord compression, and renal insufficiency is discussed.
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PMID:Current therapy of multiple myeloma. 1192 76

Hemorrhagic tendency is frequent in uremic patients and is often associated with prolonged bleeding time and decreased platelet functions in vitro. Similarly, in multiple myeloma, platelet functions are affected, mainly by the inhibitory effect of paraprotein. We have studied patients with renal insufficiency and multiple myeloma to investigate the possible relation of oxidative stress to platelet functions, adhesion and aggregation activity. We observed diminished platelet aggregation response to collagen, ADP and thrombin receptor-activating peptide (TRAP) in both groups of patients as compared with normals. The adhesion of platelets to fibrin dimers was also diminished. Malondialdehyde concentration as a criterion of oxidative stress was significantly enhanced in both groups of patients together with increased concentrations of vitamins A and E. It seems to be possible that oxidative stress contributes to modification of adhesion proteins and fibrinogen and, thus, augments the observed inhibitory influence of vitamin E on platelet aggregation and adhesion. In conclusion, the concerted influence of both malondialdehyde and vitamins A and E can contribute to diminished platelet functions in renal insufficiency and augment the inhibitory influence of paraprotein on platelet functions in multiple myeloma.
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PMID:Oxidative stress and platelet function in multiple myeloma and renal insufficiency: clinical relations of different tests. 1203 20

We analysed CD56 expression in 70 patients with multiple myeloma (MM) to determine its clinicopathological and prognostic significance. Fifty-five (79%) patients were CD56+. CD56- patients (n = 15) had higher beta2 microglobulin levels and a higher incidence of extramedullary disease, Bence Jones protein, renal insufficiency and thrombocytopenia than CD56+ patients. Their myelomas more frequently had a plasmablastic morphology. Overall survival was significantly lower in CD56- than CD56+ patients (22 vs 63 months, P = 0.0002). We conclude that CD56- MM is a discrete entity associated with more aggressive disease. The higher incidence of plasmablastic cases suggested that CD56- MM may develop from a less mature plasma cell than CD56+ MM.
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PMID:Clinicopathological and prognostic characteristics of CD56-negative multiple myeloma. 1206 Jan 25


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