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)

Multiple myeloma (MM) is a plasma cell malignancy characterized by infiltration of bone marrow, bone destruction, infiltration of soft tissues with plasma cells, and suppression of normal hematopoiesis. The production of monoclonal immunoglobulins with or without light chains is a major feature of the disease. Full spectrum of plasma cell dyscrasias include monoclonal gammapathy of undetermined significance, smouldering myeloma, indolent multiple myeloma, and fully developed, symptomatic multiple myeloma. The usual presenting features of MM include bone pain, weakness, fatigue, fever and infection. Neurologic symptoms are less common but one must not forget that MM may present with a neurologic disease. Careful neurologic history and examination are mandatory in patients with MM. Neurologic symptoms may be a direct manifestation of MM or may be due to the immune effect of monoclonal proteins directed against different neural structures. Finally, metabolic consequences (uremia, hypercalcemia, hyperviscosity) of MM may produce a broad spectrum of different neurologic symptoms including headache, blurring of vision, drowsiness, precoma, coma, vertigo, ataxia, hemiparesis and epileptiform seizures. The most common location of bone changes in MM is the thoracic spine, where it causes osteolytic changes with consequent compressive fractures. The most disastrous sequel is paraplegia. Multiple vertebral involvement with the evidence of osteolytic changes in other bones is usual, but solitary vertebral myeloma may occur. Myeloma usually involves the bone of the vertebral body and then spreads into the extradural space. However, patients with solitary extradural myeloma have been reported. Skull myeloma is frequently asymptomatic. It may grow externally or, rarely, there is intracranial expansion. Involvement of the cranial nerves is not rare, with II, V, VI, VII and VIII cranial nerves being most often affected. Isolated intracerebral plasmacytomas are extremely rare. Diagnostic approach includes plain X-rays of the skeleton, which was found to be the method of choice for demonstration of osteolytic changes, whereas magnetic resonance with gadolinium enhancement most reliably displays the degree of vertebral involvement and demonstrates any associated soft tissue mass. Current treatment of osteolytic changes in multiple myeloma include chemotherapy, radiotherapy in combination with dexamethasone, monthly infusions of bisphosphonates, surgical decompression, and kyphoplasty. Therapeutic approach is dictated by the presenting symptoms. In case of pain as the predominant symptom, treatment with chemotherapy and radiotherapy may be appropriate. Compressive symptoms are relieved with dexamethasone followed by radiotherapy and chemotherapy. Surgical decompression is used in patients with vertebral collapse and vertebral instability. Kyphoplasty is a new method used in the treatment of osteolytic changes of vertebral bodies. A viscous cement is injected into the cavity by a balloon-like inflatable bone tampon. It has been successfully employed to improve the quality of life, to reduce pain, and to increase overall functioning in patients with vertebral compression fractures by restoring most of the original height of the vertebral body. Bisphosphonates reduce pain associated with osteolytic changes in multiple myeloma, but also significantly reduce skeletal events (pathologic fracture, spinal cord compression, surgery or irradiation of bone) via unknown mechanism. It seems that bisphosphonates, by inhibiting bone resorption, alter the microenvironment in which the MM cells grow.
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PMID:[Neurologic sequelae of bone changes in multiple myeloma and its therapy]. 1263 Mar 41

Osteolytic bone destruction, caused by the aberrant production and activation of osteoclasts, results in significant morbidity for patients with multiple myeloma (MM). Pamidronate [(3-amino-1-hydroxypropylidene)-1,1-bis-phosphonate] inhibits osteoclastic activity and reduces bone resorption. A potency of zoledronic acid (2-[imidazol-1-yl]-1-hydroxyethylidene-1,1-bisphosphonic acid, a new third generation bisphosphonate, as inhibitor of resorption was 850-fold greater than pamidronate, as was shown in preclinical models of bone resorption. Randomized, double-blind study was conducted to compare the efficacy and safety of zoledronic acid and pamidronate for treating myeloma bone disease. Since March 1999 the efficacy and safety of pamidronate and zoledronic acid is evaluated in MM patients all receiving anti-myeloma chemotherapy acc. to VMCP/VBAP alternating regimen. Nine patients with stage III myeloma and osteolytic lesions (3 female, 6 male, median age 57 years, range 52-67, with monoclonal protein: IgG-7, IgA-2) were randomly assigned (1:1:1 ratio) 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. All patients have received 500 mg of calcium supplements and 500 IU of vit.D, orally, once daily, for the duration of administration of study medication. In extension phase of the study (June 2000-April 2002) patients did not received bisphosphonates. In 7 patients 18 cycles of assessed treatment was administered to each of them and one patient received 16 cycles. One patient died after receiving of 12 pamidronate therapy cycles at 11 month of the trial duration (and at 49 month since MM diagnosis and anti-tumour treatment). The patient's death occurred during the progression of plasma cell proliferation due to acute left ventricle cardiac failure. During the 12-month-period of bisphosphonate treatment skeletal related events (SRE) and progression of osteolysis occurred with the same frequency in 3 treatment groups. One patient experienced spinal cord compression and received radiation to bone and 2 patients experienced vertebral fracture. Time from study entry to the first SRE was 304 days in pamidronate and 366 and 392 days in 4 and 8 mg zoledronic acid group, respectively. The skeletal morbidity rate was identical in all treatment groups. Single hypocalcemic events occurred in 2 patients, mild hypertransaminasemia was observed in 3, worsening of renal function parameters in 2 patients (transient in one of them). Muscular pain and fever up to 39 degrees C (transient and self-limiting "flu-like" symptoms) occurred in 6 patients after several or some dozens of hours from study drug administration. Adverse events were similar in nature and frequency with zoledronic acid and pamidronate and were experienced by a similar proportion of patients in each treatment group. Median time of patient's observation duration after completing of administered treatment with zoledronic acid and pamidronate amounts to 20 months. At present actual median survival time of analysed patients since MM diagnosis is 42 months, since the beginning of treatment with pamidronate and zoledronic acid--33 months, and since completing treatment--20 months and is similar in 3 treatment groups. As was shown in our single center study in MM patients the safety and efficacy of pamidronate 90 mg and zoledronic acid 4 mg and 8 mg in monthly i.v. infusion are comparable. Thus the recommended dosage of zoledronic acid is 4 mg administered as a 15 minute i.v. infusion at intervals of 3 to 4 weeks.
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PMID:Comparative evaluation of safety and efficacy of pamidronate and zoledronic acid in multiple myeloma patients (single center experience). 1266 77

We report two cases of spinal cord compression by AL amyloid deposits in the setting of multiple myeloma. The first patient, a 57 year old man, had a surgical procedure late in his course, when his neurological status worsened despite medical treatment. The second patient, a 61 year old man, had surgical treatment as soon as vertebral body collapse and epiduritis were diagnosed and spinal amyloidosis revealed a non secretory myeloma. Neurological recovery was significant in both cases and neither developed manifestations of systemic amyloidosis 4 years later.
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PMID:Localized epidural and bone amyloidosis, rare cause of paraplegia in multiple myeloma. 1276 43

Multiple myeloma is characterized by bone destruction mediated by osteoclastic bone resorption. Skeletal complications of myeloma, including bone pain, fractures, spinal cord compression and hypercalcemia, result in significant morbidity. Gallium nitrate was shown in a small, randomized trial to attenuate the rate of bone loss in patients with myeloma treated with chemotherapy. In a retrospective analysis, we found that patients with advanced multiple myeloma treated with chemotherapy plus gallium nitrate had markedly prolonged median survival compared with similar patients treated with chemotherapy alone (87+ months v 48 months, respectively). These data suggest that gallium nitrate may have a positive, indirect benefit on survival in myeloma by decreasing the rate of bone resorption. Further evaluation of gallium nitrate to attenuate progression of disease in patients with multiple myeloma is warranted.
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PMID:Gallium nitrate in multiple myeloma: prolonged survival in a cohort of patients with advanced-stage disease. 1277 56

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for skeletal metastases is based on data from 16 randomized trials. Moreover, data from 20 prospective studies, 5 retrospective studies and 22 other articles were used. A total of 63 scientific articles are included, involving 8051 patients. The results were compared with those of a similar overview from 1996 including 13,054 patients. The conclusions reached can be summarized as follows: Irradiation of skeletal metastases is, with few exceptions, a palliative treatment. There is strong evidence that radiotherapy of skeletal metastases gives an overall (complete and partial pain relief) in more than 80% of patients. There is strong evidence that the duration of pain relief in at least 50% of patients lasts for > or = 6 months. There is convincing evidence that pain relief, in terms of degree and duration, does not depend on the fractionation schedules applied. Irrespective of the fractionation schedule used at irradiation, the number of later complications, such as spinal cord compression or pathological fractures, at the index fields are low. There are some data showing that the difference in cost between single and multifraction treatment is small. However, these data do not permit any firm conclusions to be drawn. Several reports indicate that early diagnosis and early therapy of spinal cord compression are the two most important predictors of a favourable clinical outcome after radiotherapy. However, no controlled studies have been undertaken. When the diagnosis of spinal cord compression is late, a favourable outcome might depend on the radio-responsiveness of the tumour. The documentation is weak and no conclusions can be drawn. There is some evidence that a small proportion of totally paralytic patients can regain walking function after radiotherapy. There is strong evidence that the radionuclides 89Sr and 153Sm are efficient when they are used as a systemic treatment of generalized bone pain due to metastasis from carcinomas of the prostate and breast. Overall bone pain relief occurs in about 60-80% of patients with a median response duration of 2-4 months. There is strong evidence that intravenous treatment with bisphosphonates in patients with myeloma and osteolytic bone metastasis due to carcinoma of the breast significantly decreases the number of skeleton-related events and bone pain.
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PMID:A systematic overview of radiation therapy effects in skeletal metastases. 1459 19

Patients with metastatic cancer and bone involvement are at chronic risk of skeletal complications, including bone pain, fractures, spinal cord compression and hypercalcaemia of malignancy. Therapies targeting the primary malignancy are often unable to prevent skeletal complications, which often require orthopaedic surgery, radiation therapy and analgesics. Intravenous bisphosphonates can reduce the risk of skeletal complications and the requirement for palliative radiation therapy. Since its broad regulatory approval, zoledronic acid (ZOMETA, Novartis Pharma AG/Novartis Pharmaceuticals Corporation) 4 mg by 15-minute intravenous infusion has become widely used to treat bone metastases from all solid tumours and is becoming the standard of care for advanced breast cancer and multiple myeloma. Additionally, cancer treatment-induced bone loss is an emerging problem in clinical oncology, and bisphosphonates -- particularly intravenous bisphosphonates -- may provide benefits even before bone lesions develop. Further investigations of bisphosphonates in these and other indications are ongoing.
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PMID:Bisphosphonate therapy in the oncology setting. 1466

The skeleton is the third most common site for cancer to spread to after the liver and lungs. Malignancies that can cause destruction of skeletal bones include multiple myeloma and metastatic disease of the breast, prostate, and lung. Bone metastases are problematic for patients with cancer because accelerated bone breakdown occurs with many associated complications. One or more of the following problems may occur: pain, hypercalcemia, pathologic fractures, myelosuppression, and spinal cord compression with subsequent progressive immobility. Quality of life is affected negatively, and associated feelings of fear, grief, anger, despair, anxiety, and depression can occur. Management of malignancies of the bone involves a multimodal approach. Therapies include analgesia, hormone therapy, chemotherapy, surgery, radiation therapy, and the use of bisphosphonates. Nurses can be instrumental in promoting positive outcomes for patients with bone metastases.
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PMID:Advances in the treatment of bone metastases. 1470 79

Patients with multiple myeloma often experience skeletal-related complications including pathological fractures, hypercalcemia, spinal cord compression, pain requiring surgery or radiotherapy. Myeloma bone disease is characterized by the presence of lytic lesions due to increased osteoclastic activity, which is not accompanied by a comparable increase in bone formation. Targeting osteoclastic bone resorption therefore represents an important approach to treating patients with myeloma-related bone disease. Bisphosphonates are potent inhibitors of osteoclast activity and function. Recent large, placebo-controlled clinical trials have shown the efficacy of bisphosphonates in reducing skeletal complications in multiple myeloma and suggest that these agents may also alter the overall course of the disease. In this review, we summarize the data covering the effect of different types of bisphosphonates on myeloma bone disease, their mode of action and the future implications of their use.
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PMID:Bisphosphonate treatment for multiple myeloma. 1498 68

Epidural spinal cord compression is a neurologic emergency requiring immediate attention. The therapy instituted depends on several factors, including the patient's condition at the time of presentation, the nature of the underlying malignancy, the extent of systemic disease burden, and patient prognosis. The most essential aspect of treatment is the establishment of the diagnosis. If one suspects malignant cord compression an emergency, magnetic resonance imaging of the entire spinal axis is indicated. If magnetic resonance imaging is unavailable, post-myelographic computed tomography is an alternative. However, treatment should not be delayed until imaging is performed, particularly if neurologic deficits are present. Pain should be adequately addressed and opioids administered if necessary. Steroids should be given. If significant neurologic deficits are present, a high-dose corticosteroid bolus, followed by standing doses, should be given. However, if pain is the predominant symptom, steroids can be withheld pending immediate imaging or lower doses can be given without a bolus. Neurosurgical consultation should be obtained, and surgery should be considered if the patient's condition permits. This is particularly true if spinal instability or significant kyphosis is present or compression is secondary to bony fragments. Other indications include patients with limited systemic disease burden in whom better survival is predicted and possibly those with radioresistant tumors. The type of surgery performed should be tailored to the distribution of disease within the spine and accessibility through anterior body cavities. Radiation therapy, an effective noninvasive treatment that can be delivered quickly and safely, is an appropriate option as well. This is particularly true in radio-responsive tumors, such as myeloma and lymphoma, in which surgery may be avoided entirely. Chemotherapy may play a role as adjuvant therapy in some tumors.
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PMID:Epidural Spinal Cord Compression. 1515 6

Bisphosphonate drugs are a group of pyrophosphate analogues which bind avidly to hydroxyapatite bone mineral surfaces and their major action is to inhibit osteoclast activity and thus bone resorption. In oncology, their role in metastatic bone disease is well established, but there is increasing interest in their potential role in preventing and treating cancer-induced bone loss and their possible anti-tumour effects. Metastatic bone disease is associated with a variety of skeletal complications, including pathologic fractures, bone pain, impaired mobility, spinal cord compression and hypercalcaemia. Intravenous bisphosphonates, particularly zoledronic acid, in conjunction with rehydration, are now established as the treatment of choice for hypercalcaemia. For treatment of bone pain, it has also been shown that bisphosphonates can be an effective supplementary approach to radiotherapy. In breast cancer and myeloma, bisphosphonates have now become part of standard therapy to treat and prevent skeletal-related events (SRE) and, until recently, treatment was largely with intravenous pamidronate or oral clodronate. However, large, randomised, multicentre trials using intravenous administration of the highly potent bisphosphonate zoledronic acid every 3-4 weeks have recently demonstrated a reduction of 20% in the risk of developing an SRE compared with pamidronate for patients with breast cancer. Moreover, these trials have demonstrated, for the first time, that a bisphosphonate significantly reduces the occurrence of skeletal events in hormone-refractory prostate cancer and in non-small cell lung cancer and a range of other solid tumours. Investigations into the potential of the relatively low potency bisphosphonate, clodronate, for the prevention of bone metastases in breast cancer have produced conflicting data. Further large, randomised studies with clodronate and zoledronic acid are planned and until the results are available it is not possible to identify a definite adjuvant role for bisphosphonates. Evidence is accumulating in vitro that bisphosphonates are also able to directly affect tumour cells, in addition to their effects on osteoclasts, with zoledronic acid being particularly potent. Over recent decades there has been a significant improvement in cure rates and survival times in certain cancers and the use of chemotherapy and hormone therapy has expanded greatly, leading to increasing numbers of long-term survivors who have received these treatments. Management of treatment-induced bone loss is therefore assuming a greater importance and bisphosphonates represent an attractive treatment option in such patients. Several placebo-controlled trials using oral clodronate, oral risedronate, intravenous pamidronate and intravenous zoledronic acid have all now demonstrated benefits in reducing the loss in bone mineral density.
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PMID:The role of bisphosphonates in breast and prostate cancers. 1516 99


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