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)

Fludarabine phosphate is the 2-fluoro, 5'-monophosphate derivative of vidarabine (ara-A) with the advantages of resistance to deamination by adenosine deaminase (ADA) and improved solubility. The mechanism of cytotoxic action of the compound appears to involve metabolic conversion to the active triphosphate. Fludarabine phosphate has substantial activity against lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL) and low-grade non-Hodgkin's lymphoma (NHL). Its single-agent activity in CLL appears at least comparable to those of other conventional combination regimens. Its activity in Hodgkin's disease, mycosis fungoides, and macroglobulinemia, although suggestive, needs to be further defined and clinical trials are warranted in hairy cell leukemia, prolymphocytic leukemia, and previously untreated myeloma. The compound does not appear active against most common solid tumors. Early clinical trials indicated significant myelosuppression and the potential for severe neurotoxicity. Toxicity on the currently used low-dose schedules includes transient and reversible myelosuppression, nausea and vomiting, diarrhea, somnolence/fatigue, and elevations of liver enzymes and/or serum creatinine. Possible pulmonary toxicity has been suggested in several patients. The currently used low-doses of fludarabine phosphate, even with repeated administration, are well tolerated and appear safe with a negligible risk for severe neurotoxicity. Based on its single-agent activity and tolerability, the Food and Drug Administration recently granted group C designation of the drug for the treatment of patients with refractory CLL outside the clinical trials setting. The use of fludarabine phosphate in combination regimens and its impact on the natural history of the lymphoid malignancies is yet to be determined. Fludarabine phosphate may well occupy a pivotal role in the management of CLL and low-grade NHL.
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PMID:Fludarabine phosphate: a synthetic purine antimetabolite with significant activity against lymphoid malignancies. 170 43

Multiple myeloma of IgG kappa type was diagnosed in a 42-year-old man with bone pains, dyspnoea on exertion and increasing drowsiness. Six chemotherapy cycles extending over 14 weeks and consisting of 15 mg/m2 melphalan intravenously on day 1 and 60 mg/m2 prednisolone orally on days 1-4 produced a partial remission. As the HLA-identical sister of the patient was willing to donate bone marrow, an allogeneic marrow transplantation was planned. After 7 days' conditioning treatment (hyperfractionated whole-body irradiation with 12 Gy, chemotherapy with 70 mg/m2 melphalan and 60 mg/kg cyclophosphamide), 4.2 x 10(8) nucleated cells of donor marrow were infused per kg recipient body-weight through a central venous catheter. Despite prophylaxis with short-course methotrexate and cyclosporin, an acute graft-versus-host reaction of grade II-III occurred on day 26, though it settled almost completely after treatment with daily 2 mg/kg prednisone and monoclonal interleukin-2 receptor antibodies (B-B10, daily 10 mg). On day 100 after the marrow transplantation, marrow puncture showed the picture of complete remission with normal regeneration of haemopoietic cells. Allogeneic marrow transplantation may therefore be considered as a new and promising mode of treatment for younger patients with multiple myelomas.
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PMID:[Therapy of multiple myeloma by allogeneic bone marrow transplantation]. 190 93

Two patients with multiple myeloma who appeared to be producing ammonia are reported. Both patients showed hyperammonemia and amino acid disturbances, such as a low Fischer ratio. One patient had Bence Jones protein (lambda) type myeloma and became comatose, but the hyperammonemia and disturbance of consciousness were improved by chemotherapy for the myeloma. The other patient had IgA kappa type myeloma and somnolence and died of malignant pleurisy despite intensive chemotherapy. Autopsy showed widespread multiple myeloma and an almost normal liver. Ammonia levels in the supernatant of cultured myeloma cells from the patient's pleural effusion increased almost linearly from the time of cell seeding. These observations showed that ammonia was produced at a high level by these human myeloma cells. We also found that one of the common myeloma cell lines, RPMI 8226, could produce ammonia as well.
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PMID:Hyperammonemia in multiple myeloma. 212 62

A 63-year-old man was admitted to our hospital with tremor and somnolence, followed soon by coma. Anemia and retinal bleeding were observed. The blood smear exhibited rouleaux formation and leukoerythroblastosis. A bone marrow aspiration resulted in dry tap. The biopsy specimens revealed remarkable infiltration of myeloma cells with fibrosis. The M-component of IgG-lambda type and hyper-ammonemia were detected in the serum. Liver and renal functions, however, were within normal range. His consciousness recovered after plasmapheresis. Two courses of VMCP (vincristine, melphalan, carboquone and prednisolone) did not affect the paraproteinemia. Five courses of VAD (vincristine, adriamycin and dexamethasone) could lower the level of IgG. He died of pneumonia. The plasma of some patients with multiple myeloma may contain unidentified factors which increase the plasma ammonia.
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PMID:[Coma, hyperviscosity syndrome, hyperammonemia and myelofibrosis in a patient with IgG, lambda type multiple myeloma]. 250 73

Although several studies have shown that interferon does not readily cross the blood-brain barrier, recent reports have described central nervous system effects in patients receiving interferon. At our institution, we encountered three patients who had symptoms of toxicity of the central nervous system (somnolence, confusion, and gait difficulties) in association with electroencephalographic abnormalities while receiving alpha 2-interferon therapy for multiple myeloma. The electroencephalogram showed diffuse slow-wave abnormalities in two of the patients and generalized sharp-wave discharges in the third patient. Because the use of interferon is increasing, physicians should be aware of the central nervous system complications and the electroencephalographic changes that can be associated with such therapy.
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PMID:Electroencephalographic abnormalities in interferon encephalopathy: a preliminary report. 650 66

Malignant tumors are often complicated by hypercalcemia (malignancy associated hypercalcemia: MAHC) which causes various clinical symptoms. Hypercalcemia may occasionally lead to death. Unfortunately, many physicians caring for patients with malignant diseases are not aware of this danger. Hypercalcemia is seen in about 15% of patients with solid tumors. This condition is more frequent in some malignant proliferative hematological diseases. In patients with multiple myeloma, the incidence of hypercalcemia is about 20%. The rate of complication by hypercalcemia is as high as 80% in patients with adult T cell leukemia. The symptoms of hypercalcemia include anorexia, easy fatigability, nausea, and vomiting. These symptoms are often mistaken for adverse effects of anticancer drugs or as signs of aggravation of malignant disease. If abnormal thirst and polydipsia are noted in patients with malignant disease, a diagnosis of MAHC should always be considered because these two symptoms are highly characteristic of hypercalcemia. Caution should be exercised when CNS symptoms such as unstable emotions or somnolence are noted. These symptoms in patients with MAHC may lead to death, if untreated. The corrected serum calcium level should always be monitored in patients with malignant disease, so that a possible diagnosis of MAHC may not be overlooked when these symptoms appear. MAHC is caused by the bone resorption stimulating factor (BRSF), which is produced and secreted by the tumor cells. BRSF may act systemically to cause increased bone resorption, resulting in hypercalcemia. MAHC occurring in this manner is called the 'humoral hypercalcemia of malignancy (HHM)'. BRSF produced by multiple myeloma or bone metastasis enhances bone resorption through local osteolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Hypercalcemia in malignancy]. 796 19

Progressive day-time sleepiness developed in a 73-year-old man for 3 years known to have kappa-light-chain myeloma, treated with radio- and chemotherapy. His powers of concentration and intellectual performance were diminished. Neither clinical nor biochemically was there any indication of abnormal water and electrolyte metabolism or hyperviscosity syndrome. The neurological examination was unremarkable. His wife's observation of nocturnal breathing pauses suggested sleep-related abnormal breathing. Polysomnography showed severe central sleep apnoea: an apnoea index of 60/h and blood oxygen saturations as low as 78%. On biphasic positive airway pressure (BIPAP) ventilation by nasal mask at night the apnoea index fell to 6/h and the symptoms improved. During a break in treatment the day-time sleepiness again increased and regressed once again with BIPAP ventilation. There is a 1-5% prevalence of sleep-related impaired breathing among adults. This condition should thus be considered in the differential diagnosis of characteristic day-time sleepiness.
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PMID:[Central sleep apnea syndrome as a cause of impaired wakefulness in multiple myeloma]. 828 78

A 69-year-old male presented with fever, ascites and leg edema in February, 1994. He had a pathological fracture of cervical supine in October. Pathological findings at operation showed plasmacytoma. Bone marrow aspiration showed 16.2% myeloma cells. So he was diagnosed as multiple myeloma presenting biclonal gammopathy of IgA-L and IgD-K. Ascites was massive and drainage of 2 to 4 liter per week was required. Ascites was supposed to be related to multiple myeloma, because the IL-6 level in the ascites was increased (2,440 pg/ml), although repeated cytologic studies were negative. After the operation, he developed hyperammonemic drowsiness. It was also suggested that hyperammonemia was associated with multiple myeloma. In addition to radiation therapy for the cervical lesion, MP therapy, Interferon-alpha, VAD therapy and intraperitoneal cyclophosphamide infusion were administered. But no improvement of ascites or hyperammonemia were noticed. Here we described a case of multiple myeloma with very notable clinical features.
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PMID:[Massive ascites as an initial sign, plasmacytoma of the cervical supine, and hyperammonemic consciousness disturbance in a patient with biclonal type multiple myeloma]. 884 7

In addition to immunomodulatory and cytokine-modulatory properties, thalidomide has antiangiogenic activity. It has been investigated in a number of cancers including multiple myeloma, myelodysplastic syndromes, gliomas, Kaposi's sarcoma, renal cell carcinoma, advanced breast cancer, and colon cancer. Its role has been best explored in myeloma, where, at daily doses of 100 to 800 mg, it is remarkably active, causing clinically meaningful responses in one-third of extensively pretreated patients and in over half of patients treated early in the course of the disease. It also acts synergistically with corticosteroids and chemotherapy in myeloma. Thalidomide produces improvement of cytopenias characteristic of myelodysplastic syndrome, resulting in the reduction or elimination of transfusion dependence in some patients. Responses have also been seen in one-third of patients with Kaposi's sarcoma, in a small proportion of patients with renal cell carcinoma and high grade glioma and, in combination with irinotecan, in some patients with colon cancer. Thalidomide is being investigated currently in a number of clinical trials for cancer. Drowsiness, constipation and fatigue are common adverse effects seen in 75% of patients. Symptoms of peripheral neuropathy and skin rash are seen in 30%. A minority of patients experience bradycardia and thrombotic phenomena. Despite the high frequency of adverse effects, those severe enough to necessitate cessation of therapy are seen in only 10 to 15% of patients. A therapeutic trial of thalidomide should be considered in all patients with myeloma who are unresponsive to or relapse after standard therapy. In other malignant diseases, the most appropriate way to use the drug is in the setting of well designed clinical trials. In the absence of access to such studies, thalidomide could be considered singly or in combination with standard therapy in patients with no meaningful therapeutic options.
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PMID:Thalidomide in cancer: potential uses and limitations. 1143 82

We conducted a clinical trial of thalidomide as initial therapy for asymptomatic smoldering (SMM) or indolent multiple myeloma (IMM). Sixteen patients were studied. Thalidomide was given orally at a dose of 200 mg/day for 2 weeks, and then increased as tolerated by 200 mg/day every 2 weeks to a maximum dose of 800 mg/day. Bone marrow microvessel density (MVD) and angiogenesis grading were estimated using CD34 immunostaining. Six patients had a confirmed response to therapy with at least 50% or greater reduction in serum and urine monoclonal (M) protein. When minor responses (25-49%) decrease in M protein concentration) were included, 11 of 16 patients (69%) responded to therapy. Major grade 3-4 toxicities included two patients with somnolence, and one patient each with syncope and neutropenia. Pre-treatment MVD was not a significant predictor of response to therapy, median MVD 4 and 12 in responders and non-responders respectively, P = 0.09. We conclude that thalidomide has significant activity in the treatment of newly diagnosed SMM/IMM. However, we do not recommend treatment with thalidomide at this stage since some patients with SMM/IMM can be stable for several months or years without any therapy. Additional randomized trials are needed to determine if thalidomide will delay progression to active multiple myeloma.
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PMID:Thalidomide for previously untreated indolent or smoldering multiple myeloma. 1148 May 71


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