Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

14 patients with osteolytic bone disease due to breast cancer or myeloma, 7 of whom had hypercalcaemia, received oral treatment with (3-amino-1-hydroxypropylidene)-1, 1-bisphosphonate (A.P.D.). Serum-calcium dropped to low normal values in all 14 patients, accompanied by a decrease in urine calcium and hydroxyproline excretion-rate. The results show that A.P.D. may inhibit tumour-induced osteolysis.
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PMID:Inhibition of osteolytic bone lesions by (3-amino-1-hydroxypropylidene)-1, 1-bisphosphonate (A.P.D.). 8 43

Fifteen patients presenting with plasma cell leukemia (PCL) are reported in detail. The clinicopathologic features of PCL differ from typical myeloma and resemble those of acute leukemia: patients with PCL have less bone disease but a much higher incidence of organomegaly and tissue infiltration as well as diffuse marrow involvement and more pronounced pancytopenia. One of the reported patients developed meningeal plasma cell leukemia and is reported in detail. Cytomorphologic assessment of PCL cells showed nuclear immaturity and obvious nuclear/cytoplasmic asynchrony. Despite the use of cytotoxic agents known to be effective in myeloma, the prognosis in PCL is poor, and the median survival of the reported patients was only 2 mo.
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PMID:Plasma cell leukemia (PCL): A report on 15 patients. 68 31

Patients with asymptomatic or smoldering multiple myeloma should not be treated but should be observed closely for progression. For symptomatic myeloma, chemotherapy is indicated. Melphalan, the agent of choice, should be given with prednisone for 1 week of every 6 weeks, If melphalan brings no response, or response and then relapse, cyclophosphamide (Cytoxan) should be give intravenously every 4 weeks or orally every day. BCNU, CCNU, and doxorubicin (Adriamycin) have also shown activity in myeloma. Hypercalcemia occurs in one-third of patients and should be countered with hydration, corticosteroids, Neutra-Phos, or mithramycin. Long-term hemodialysis has achieved some success. The combination of sodium flouride and calcium carbonate produces new bone formation; it seems a useful adjunct in treatment for myelomatous bone disease. Radiation should be utilized only for severe, localized pain or for solitary lesions. Survival with multiple myeloma varies, mean durations being 2 to 3 years. Multivariate analysis indicates that serum creatinine and calcium levels are the most significant indicators regarding 2-year survival. We have found monoclonal proteinuria not significantly more frequent with renal insufficiency than with normal renal function, renal insufficiency not significantly more frequent with lambda than with kappa chains, and survival not significantly greater with IgG myeloma than with IgA.
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PMID:Management and prognosis of multiple myeloma. 79 81

Mechanical rib testing and geometric analysis were explored as means of evaluating metabolic bone disease. Seventy-nine male patients were examined postmortem. Displacement rate at the loading point and patient age were important variables for which results had to be corrected. Like long bones, ribs apparently undergo progressive circumendosteal resorption with advancing age but unlike long bones, they show no evidence of continued subperiosteal apposition. Effects of selected individual diseases and of all diseases grouped by major organ system were analyzed. Most produced no discernible modification of rib volume, geometry or bending strength as quantified by modulus of rupture. Exceptions were myeloma and arthritis, where the bony material was weakened without remodeling or loss in volume.
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PMID:Rib structure and bending strength: an autopsy study. 126 Apr 94

We studied bone biopsies from 26 patients with myelomatosis with apparently normal skeletal metabolism. Quantitative histomorphometric measurements suggested that skeletal disease was progressive despite normocalcaemia and normal urinary excretion rates of calcium and hydroxyproline. When biopsies were divided according to the involvement of marrow by plasma cells, bone resorption--as judged by the eroded surface--increased significantly the greater plasma cell burden. Osteoclasts were frequent with moderate tumour burdens, but there was no further increase in the number of osteoclasts when plasma cell infiltration increased by more than 50% of bone marrow. Contrary to expectation, the numbers of osteoblasts and bone formation rates were increased with bone biopsies with moderate tumour burden, but were markedly lower when plasma cell infiltration occupied more than 50% of bone marrow, due to a decreased functional capacity of osteoblasts. We conclude that skeletal bone disease in myeloma is commonly progressive despite apparently stable bone disease as judged by biochemical measurements. The major mechanism of bone loss in myelomatosis is increased osteoclastic resorption but decreased bone formation contributes to bone loss with heavy plasma cell burdens. Urinary excretion of calcium and hydroxyproline provide insensitive indices of bone resorption in myelomatosis.
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PMID:Abnormal bone remodelling in patients with myelomatosis and normal biochemical indices of bone resorption. 146 62

From 1984 to 1990 the authors reviewed the radiologic-clinical charts of 237 patients affected with multiple myeloma (MM). The series included 127 males and 110 females (mean age: 66 years) who had been classified according to Durie and Salmon clinical criteria. All the patients underwent X-rays of the skeleton, as recommended in international literature; moreover, 148 subjects underwent whole-body bone scintigraphy, and 130 bone marrow scintigraphy. A selected group of cases (18 male/female patients) were submitted to bone densitometry employing both quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA). The results follow: 1) in the first stage of the disease, a high number of patients (29.5%) exhibits no skeletal abnormalities on X-rays; the most common lesion locations include the spine (49%), skull (35%), pelvis (34%), ribs (33%), humeri (22%), femora (13%) and mandible (10%); 2) the most frequent pattern is osteolysis, as a characteristic "punched-out" multiple lesion; the second most frequent lesion is osteopenia (43%), especially in the spine; pathologic fractures are common (54%) in the ribs, vertebral bodies, limbs; typical associations of features and sites are seen on X-ray images, which sometime make diagnosis easier; 3) whole-body scintigraphy, revealing aspecific uptake only in the presence of pathological fractures, is not recommended in the first staging of the disease, but is considered as a valuable technique in the follow-up, when the patients become symptomatic; 4) bone marrow scintigraphy, especially in the "marrow expansion" pattern, might be considered as an attempt made by the body to recover the central space which was destroyed by myelomatous involvement. The prognostic value of this technique is still to be assessed; 5) bone densitometry, by confirming the grade of osteopenia, reveals that osteoporosis is a peculiar pattern of bone disease in MM, which is not related to age only; 6) conventional radiography of the skeleton is the method of choice in the diagnosis of lytic areas of MM, and remains, as yet, irreplaceable. The other diagnostic techniques--i.e., CT and MRI--can be used to evaluate the extent of bone and soft tissue involvement, in the cases with questionable diagnosis, and to assess the degree of marrow involvement.
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PMID:[Bone disease in multiple myeloma. A study of 237 cases]. 163 29

Progressive bone disease in multiple myeloma frequently leads to osteolysis, bone resorption, pathologic fractures, vertebral compression, and hypercalcemia. We conducted a double-blind study in 173 newly diagnosed multiple myeloma patients of etidronate disodium (EHDP), a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity. The patients were randomly assigned to receive oral EHDP 5 mg/kg/d or placebo until death or discontinuation due to intolerance or refusal. The extent of vertebral deformity was measured by a vertebral index as well as height. The frequency of pathologic fractures, hypercalcemia, and bone pain was regularly assessed, as well as size and number of osteolytic lesions. All patients received melphalan and prednisone daily for 4 days every 4 weeks as the primary chemotherapy for their disease. Although the repeated measures analysis showed a significant height loss, there was no difference between treatment arms (P = .98). There was no significant difference in bone pain, episodes of hypercalcemia, or development of pathologic fractures. Patients on EHDP showed less deterioration in their vertebral index, but this difference only approached statistical significance (P = .07). We conclude that EHDP therapy used in this dosage schedule does not have a clinically significant impact in multiple myeloma.
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PMID:Effect of daily etidronate on the osteolysis of multiple myeloma. 171 35

Bone metastases secondary to myeloma, are characterized by severe bone pain, pathological fractures, hypercalcaemia and hypercalciuria. Histological and biochemical investigations have shown a wide spectrum of abnormalities in bone turnover in patients with multiple myeloma. The increased osteoclast activity caused by various osteoclast activating factors secreted by myeloma cells, is responsible for the diffuse localized osteolytic lesions. These lesions are responsible for the symptoms and respond poorly to standard chemotherapy, justifying the use of a bone-sparing agent. Clodronate is a potent inhibitor of osteoclast activity and does not impair bone mineralization. Several studies have shown that clodronate can normalize serum calcium in hypercalcaemic patients with metastatic bone disease, and a similar response is seen in multiple myeloma. In a long-term (18 months) placebo-controlled study we have shown that clodronate, given orally at a daily dose of 1.6g, can decrease both the incidence of pathological fractures and the activity of osteoclasts, as judged by measurements in iliac crest biopsy. These results, along with those from two other studies, are promising and suggest that clodronate may inhibit the progression of osteolytic lesions in multiple myeloma.
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PMID:The use of clodronate in multiple myeloma. 183 98

We compared the presentation features of three series of patients with multiple myeloma diagnosed between 1960 and 1971 (Kyle R, Mayo Clin Proc, 1975, 50, 29, n = 869), 1972 and 1986 (Clinica Medica, University of Pavia, n = 345) and 1987 and 1990 (Cooperative Group for Study and Treatment of Multiple Myeloma, n = 341). In the most recently diagnosed patients, the percentage of those who had symptoms related to multiple myeloma (i.e. any of bone pain, systemic symptoms, disturbances related to hypercalcemia, neurological involvement and hyperviscosity) was reduced (90 vs. 86 vs. 66%) (P less than 0.001), while the percentage of asymptomatic patients diagnosed by chance was increased (not reported, and 14 vs. 34%). In the most recent series, a lower percentage of spontaneous bone pain (68 vs. 60 vs. 37%, P less than 0.001) paralleled a lower incidence of advanced bone disease (osteolyses and pathological fractures, 60 vs. 64 vs. 34%), and renal failure (serum creatinine greater than 1.2 mg/dl) was also less common (56 vs. 44 vs. 33%, P less than 0.01), at least partially due to a decreased incidence of both hypercalcemia (30 vs. 20 vs. 18%, P less than 0.001) and of hyperuricemia (serum uric acid greater than 7 mg/dl, 47 vs. 32 vs. 26%, P less than 0.01). Systemic symptoms (weakness, infections, fever or weight loss) were reported more seldom by recently diagnosed patients, due to a decreased frequency of anaemia (haemoglobin less than 12 g/dl), leukopenia and thrombocytopenia, as well as of the systemic effects of bone pain and of renal insufficiency. These data indicate that multiple myeloma is diagnosed earlier now than in the past, and this must be taken into account when comparing survival data in treated series.
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PMID:Changing clinical presentation of multiple myeloma. 183 56

Eleven patients with advanced multiple myeloma refractory to standard doses of alkylating agents and salvage therapy with vincristine, adriamycin and dexamethasone (VAD) were treated with high dose cyclophosphamide, BCNU and VP-16 (CBV) with autologous blood stem cell support. Seven patients had marked marrow plasmacytosis (greater than 30%) and four had extensive pelvic bone disease precluding autologous marrow harvest. Four patients responded with a median remission duration of 7 months. Recovery of granulocytes and platelets occurred promptly in 10 evaluable patients with complete hematologic recovery. Autologous blood stem cells can provide safe and effective support for high dose CBV treatment of myeloma patients with extensive marrow plasmacytosis. The short remissions call for better cytoreductive regimens with consideration for earlier use when the myeloma may be more responsive to therapy.
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PMID:High dose cyclophosphamide, BCNU and VP-16 with autologous blood stem cell support for refractory multiple myeloma. 197 Sep 39


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