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)

In this multicenter, nonrandomized, open-label clinical trial conducted from July 2003 to July 2004, recombinant urate oxidase (rasburicase) was administered to patients at risk for tumor lysis syndrome before or during the initiation of chemotherapy. Forty-five patients were enrolled, including 18 children (10 with acute lymphoblastic leukemia, 6 with high-grade lymphoma, and 2 with acute myeloid leukemia) and 27 adults (8 with acute lymphoblastic leukemia, 4 with high-grade lymphoma, 9 with multiple myeloma, and 6 with acute myeloid leukemia). The age ranged from 3 to 98 years, with a median age of 7 years in children and 59.3 years in adults. There were 14 males and 4 females in the pediatric group and 18 males and 9 females in the adult group. Rasburicase 0.2 mg/kg was administered intravenously once a day for 2-6 days, for a median of 3 days in children and of 4 days in adults. After 3 days of treatment, the median uric acid levels in the 18 children decreased from 10.5 mg/dl (range 8-18.6) to 0.5 mg/dl (range 0.0-1.7). Similarly, in the 27 adults, the median levels decreased from 10.8 mg/dl (range 8-24.4) to 0.5 mg/dl (range 0.0-1.6). No significant changes were observed in serum potassium, calcium, and phosphorus concentrations. None of the patients required dialysis for acute renal failure. Rasburicase was very well tolerated, with only 1 adult having grade 1 vomiting. We conclude that rasburicase is safe and highly effective for preventing the complications of tumor lysis syndrome in patients with hematologic malignancies.
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PMID:Recombinant urate oxidase (rasburicase) for the prevention and treatment of tumor lysis syndrome in patients with hematologic malignancies. 1642 47

Hypercalcemia associated with malignancies is reported in up to 20 to 30% of patients with cancer during the course of the disease, and points to a poor prognosis. Symptoms related to the central nervous system, as progressive mental impairment, stupor and coma, predominate. Alterations in kidney function (water-concentrating defect leading to polyuria) and gastrointestinal tract (anorexia, nausea, vomiting) corroborate to dehydration and a further increase in serum calcium. Cancer-induced hypercalcemia may be classified as: 1) local osteolytic hypercalcemia (LOH), due to marked increase in osteoclastic bone resorption in areas surrounding the malignant cells within the marrow space; 2) humoral hypercalcemia of malignancy, caused by the secretion of parathyroid hormone-related protein (PTHrP) by the malignant tumor; 3) ectopic hyperparathyroidism; 4) 1,25(OH)2 D-secreting tumors. Adequate control of hypercalcemia is necessary to give the patient time to respond to anti-cancer therapy. Volume expansion with saline will correct dehydration, improve glomerular filtration and increase urinary calcium excretion, which may be further stimulated by loop diuretics. Intravenous bisphosphonates are the most effective agents to control hypercalcemia, as they block osteoclastic osteolysis and also have antitumoral effects, decreasing bone metastases. New approaches to control the skeletal manifestations of malignancies are anti-PTHrP and anti-RANKL antibodies, osteoprotegerin, and also proteasome inhibitors in the case of multiple myeloma.
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PMID:[Hypercalcemia of malignancy: clinical features, diagnosis and treatment]. 1644 66

Total body irradiation (TBI) is an important part of bone marrow transplantation conditioning regimens. In TBI, dose escalation is difficult, because of associated normal organ toxicities. A method to deliver a more targeted dose of TBI preferentially to sites of greatest tumor burden is needed to reduce the dose to normal organs, reduce toxicities, and permit dose escalation. The purpose of this study was to evaluate, through a dosimetric analysis, the potential advantages and feasibility of selectively delivering targeted myeloablative doses of radiation to bone and marrow using a recently developed image-guided tomographic intensity-modulated radiation therapy delivery system (helical tomotherapy). Whole-body computed tomography datasets from 3 patients, age 5, 20, and 53 years, were used for treatment planning studies to evaluate 2 targeted TBI strategies: total marrow irradiation (TMI), in which the target region was defined as the skeletal bone, and total marrow and lymphoid irradiation (TMLI), in which the target regions were defined as bone, major lymph node chains, liver, spleen, and sanctuary sites, such as brain. Organ doses and dose distributions were compared with those in conventional TBI. A 1.7- to 7.5-fold reduction in median organ doses was observed with TMI and TMLI compared with conventional TBI. With this more targeted approach, a dose-volume histogram analysis predicted the potential to escalate the dose to bone (and containing marrow) up to 20 Gy, while maintaining doses to normal organs at lower levels than in conventional TBI to 12 Gy. Results were similar for the adult and pediatric patients, indicating that this form of targeted TBI will be applicable to most patients regardless of frame size. TMI to 10 Gy was delivered as part of a tandem transplant regimen to the 53-year-old patient with multiple myeloma. Clinical results confirmed the treatment planning predictions. After TMI, the patient experienced the expected blood count nadir, followed by successful engraftment. Grade 2 nausea and grade 1 emesis occurred only briefly on day 2 of TMI. Skin erythema, oral mucositis, esophagitis, and enteritis were not observed. This report demonstrates the feasibility and potential dosimetric advantages of selectively delivering myeloablative doses of radiation to bone and marrow using an image-guided tomographic intensity-modulated radiation therapy delivery system. Organ doses are substantially lower than those associated with standard TBI and predict the potential to significantly reduce associated toxicities and allow for dose escalation. The results also suggest that this form of targeted TBI may have potential advantages over other forms of targeted TBI, such as radioimmunotherapy or bone-seeking radionuclide therapy. Ongoing clinical trials will define the maximum TMI and TMLI doses achievable and define the potential advantages and limitations of this new approach for patients undergoing hematopoietic stem cell transplantation.
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PMID:Targeted total marrow irradiation using three-dimensional image-guided tomographic intensity-modulated radiation therapy: an alternative to standard total body irradiation. 1650

Multiple myeloma is a disease in which angiogenesis is postulated to be a target for therapy. Based on this hypothesis, we conducted a phase II trial of ZD6474 (Zactima; a VEGFR inhibitor) 100 mg p.o. daily in patients with relapsed multiple myeloma. The primary efficacy endpoint was objective response as assessed by reduction in M protein. There were 18 patients with a mean age of 64 years. One patient was ineligible and one was not evaluable. Overall, ZD6474 was well tolerated and pharmacokinetic testing demonstrated that adequate drug levels were achieved. The most common drug-related adverse events were nausea, vomiting, fatigue, rash, pruritus, headache, diarrhea, dizziness, and sensory neuropathy, all of which were Grade I-II in severity. There were no drug-related serious adverse events. Laboratory adverse events were infrequent: one patient had Grade III anemia, and there were no Grade III changes in biochemistry. No significant QTc interval changes were seen. There were no responses in M protein levels. In conclusion, ZD6474 was well tolerated at a dose of 100 mg per day and achieved plasma levels predicted to inhibit VEGF signaling. However, this was not reflected in clinical benefit since none of the patients had a reduction in M protein.
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PMID:A phase II study of ZD6474 (Zactima, a selective inhibitor of VEGFR and EGFR tyrosine kinase in patients with relapsed multiple myeloma--NCIC CTG IND.145. 1679 11

A 60-year-old female patient with a therapy-resistant Bence-Jones (BJ) lambda-type multiple myeloma was treated with bortezomib. She had been treated with tandem autologous stem cell transplantations and achieved complete remission before her disease relapsed. Sixteen hours after the first administration of bortezomib, an episode of fever, slight consciousness disturbance and vomiting occurred, which was accompanied by a remarkable elevation of LDH (3608 IU/l). Serum levels of creatinine, uric acid, and AST were also transiently elevated. Serum interleukin-6 level was also increased after the administration of bortezomib. The symptoms disappeared rapidly within 48 hours. Bortezomib at a 25%-reduced dose was administered again along with dexamethasone 26 days later, which caused a moderate increase in LDH levels, but no other symptoms. Further treatment caused no increase in LDH. The treatment was very effective and eradicated both urinary BJ protein and bone marrow myeloma cells after 8 sessions of bortezomib administration. These findings suggest that a bortezomib-induced rapid reduction in tumor burden led to tumor lysis syndrome, for which caution is needed when treating myeloma patients with this very effective agent.
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PMID:[Bortezomib-induced tumor lysis syndrome with a remarkable elevation of LDH in a case of relapsed and therapy-resistant multiple myeloma]. 1698 18

Bone disease is an important feature of multiple myeloma, and hypercalcaemia is a frequent complication of this disease. We examined the association between serum calcium and quality of life (QOL) scores of 686 multiple myeloma patients at the time of diagnosis. Data from two Nordic studies using the EORTC QLQ-C30 questionnaire were analysed by means of linear regression analysis and a curve fitting program. Serum calcium was independently related to appetite loss, nausea/vomiting and physical functioning (P < 0.001) and to cognitive functioning (P = 0.001), i.e. scores reflecting symptoms that are well known in non-malignant hypercalcaemia. In addition, we found a highly significant independent relationship between serum calcium and the scores for fatigue and pain (P < 0.001). Serum calcium appeared to be as strong a predictor for fatigue as the concentration of haemoglobin. A cubic model (y = a + bx3) fitted the data slightly better than the simple linear model (y = a + bx) and suggested worsening QOL scores at levels of serum calcium above 2.5-3.0 mmol/L. Hypercalcaemia in patients with multiple myeloma seems to be associated with the same symptoms as in non-malignant hypercalcaemia. In addition, an increased level of serum calcium may aggravate the pain and fatigue caused by the skeletal disease itself.
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PMID:Serum calcium is an independent predictor of quality of life in multiple myeloma. 1703 19

A 59-year-old-woman received related non-myeloablative allogeneic peripheral blood stem cell transplantation (PBSCT) subsequent to autologous PBSCT in our hospital five years after she was diagnosed as oligo-secretory myeloma. She was admitted to our hospital because of vomiting and grayish diarrhea 4 months after non-myeloablative allogeneic PBSCT (mini-alloPBSCT). Although her initial symptoms improved after admission, she gradually showed thrombocytopenia, anemia, and oliguria during the 2 weeks after admission. Our diagnosis was thrombotic thrombocytopenic purpura (TTP) and acute renal failure (ARF) secondary to mini-alloPBSCT. After cessation of cyclosporine administration, we began to treat her with plasma exchange (PE) and hemodialysis. During the three and a half months after we started PE, the TTP gradually improved. Although PE had been reported to be ineffective for TTP post bone marrow transplantation, we could finally discontinue PE. In contrast, since her anuria continued, she was managed with hemodialysis. One month after PE was started, her activity of von Willebrand factor-cleaving protease was 41% (normal range, >50%) and the ultrasonographic investigation of both kidneys was normal. She could be discharged after four and a half months hospitalization and lived well as an outpatient for a further two months. She died shortly after readmission from multiple organ failure without the relapse of TTP. The patient's clinical course would suggest that TTP post mini-alloPBSCT could be treated with PE in some cases, despite the development of dialysis-requiring severe ARF being a poor prognostic factor.
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PMID:A case report of thrombotic thrombocytopenic purpura and severe acute renal failure post non-myeloablative allogeneic peripheral blood stem cell transplantation treated with plasma exchange and hemodialysis. 1784 2

We report a fatal case of disseminated strongyloidiasis in a patient with multiple myeloma receiving chemrotherapy. A fifty-seven years old man presented with severe diarrhoea and vomiting, fever, weight loss and dysphagia,due to mouth ulcers. Despite broad-spectrum intravenous antibiotics, albendazole (anti protozoal) and supportive treatment, the patient died of Gram-negative sepsis.
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PMID:A fatal case of gram negative bacterial sepsis associated with disseminated strongyloidiasis in an immunocompromised patient. 1833 31

The novel immunomodulatory drugs lenalidomide and thalidomide and the novel proteasome inhibitor bortezomib can cause gastrointestinal side effects, including constipation, diarrhea, nausea, and vomiting, which can have a deleterious effect on quality of life and interfere with optimal therapy. The International Myeloma Foundation's Nurse Leadership Board developed this consensus statement for the management of gastrointestinal side effects associated with novel therapies to be used by healthcare providers in any medical setting. It includes grading criteria and general recommendations for assessing and managing the side effects. Although constipation, diarrhea, nausea, and vomiting are expected side effects associated with novel therapies for multiple myeloma, they are manageable with appropriate medical interventions.
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PMID:Gastrointestinal side effects associated with novel therapies in patients with multiple myeloma: consensus statement of the IMF Nurse Leadership Board. 1849 Feb 56

Three Asian patients with plasma cell myeloma stage IIIa with IgG predominant were selected for autologous hematopoietic cell transplantation (HSCT). Total marrow irradiation (TMI) tomotherapy planned with melphalan 140 mg/m2 as a preconditioning regimen of HSCT. Two image sets of computed tomography (CT) were scanned with 2.5 mm and 5 mm for the upper and lower part of the plan, respectively. The junction was determined and marked at 15 cm above knee on both thighs for upper and lower part of the plan. The clinical target volume (CTV) included the entire skeletal system. The planning target volume (PTV) was generated with with 0.8 cm for CTV(extremities) and with 0.5 cm margin for all other bones of CTV. A total dose of 800 cGy (200 cGy/fraction) was delivered to the PTV. Update to presentation, all of three patients post transplant without evidence of active disease were noted. During TMI treatment, one with grade 1 vomiting, two with grade 1 nausea, one with grade 1 mucositis, and three with grade 1 anorexia were noted. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0). The average for upper part versus lower part of PTV (Bone marrow) of CI and H-index were 1.5 and 1.4 versus 1.2 and 1.2, respectively. The dose reduction of TMI tomotherapy to various OARs of head, chest, and abdomen relative to TBI varied from 31% to 74%, 21% to 51%, and 46% to 63%, respectively. The maximum average value of registration for upper torso versus lower extremities in different translation directions were 5.1 mm versus 4.1 mm for pretreatment and 1.5 mm versus 0.7 mm for post-treatment, respectively. The average treatment time for the upper versus lower part in beam-on time, setup time, and MVCT registration time took roughly 49.9, 23.3, and 11.7 min versus 11.5, 10.0, and 7.3 min, respectively. The margin of PTV could be less than 1 cm under good fixation and close position confirmation with MVCT. Antiemetics should be prescribed in the whole course of TMI for emesis prevention. TMI technique replaced TBI technique with 8 Gy as conditioning regiment for multiple myeloma could be acceptable for the Asian and the outcomes were feasible for the Asian.
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PMID:Total marrow irradiation with helical tomotherapy for bone marrow transplantation of multiple myeloma: first experience in Asia. 1916 40


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