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)

The influence of renal insufficiency on melphalan-induced myelosuppression was examined during the initial 10 weeks of treatment in 295 patients with multiple myeloma. Patients were randomized to receive either oral melphalan (0.15 mg/kg/day for 7 days, followed by 0.05 mg/kg/day after recovery from the wbc count nadir) or iv melphalan (16 mg/m2 every 2 weeks for four doses, followed by a single dose every 4 weeks). All patients received a 6-week tapering course of prednisone. Patients with renal insufficiency (BUN greater than or equal to 30 mg/100 ml) had a significantly higher frequency of severe leukopenia (less than or equal to 1000 cells/mm3) following iv melphalan than did patients with normal renal function (50% vs 15%, respectively; P = 0.007). The latter effect resulted in an increased frequency of drug-related deaths secondary to infection. The frequency of severe thrombocytopenia (less than or equal to 25,000 cells/mm3) was also greater in patients with renal failure following iv melphalan therapy. Reduction of iv melphalan dose to 50% in patients with elevated BUN reduced the frequency of these complications to levels that were not significantly different from those observed in patients with normal renal function. The frequency of severe myelosuppression was independent of renal function in patients receiving oral melphalan. Possible explanations for these findings are discussed.
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PMID:Influence of renal failure on myelosuppressive effects of melphalan: Cancer and Leukemia Group B experience. 706 36

Five patients with multiple myeloma ending in acute leukemia are described. The preleukemic phase was characterized by anemia, leukopenia and/or thrombocytopenia. The incidence of acute leukemia in myeloma was calculated to be 6%. Melphalan therapy for more than two years increased the incidence to 14%. All patients who developed leukemia had received a total melphalan dose of at least 1 100 mg.
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PMID:Melphalan-related leukemia in multiple myeloma. 708 Aug 65

Eight patients had multiple xanthomatous plaques and subcutaneous nodules that had a predilection for the periorbital area, flexures, and trunk and that tended to ulcerate. Skin biopsy specimens showed a combination of xanthogranulomatous nodules with necrobiosis. All patients had an accompanying dysproteinemia, which was a monoclonal IgG paraprotein in six. Hyperlipidemia, low serum complement, and cryoglobulinemia were variable features. Five patients had leukopenia. Bone marrow examination showed myeloma in two patients, a lymphoproliferative process in one, and some atypical plasma cells in two. Cutaneous necrobiotic xanthogranuloma is a distinctive histologic pattern most frequently related to plasma cell dyscrasias, and it should be distinguished from normolipemic plane xanthoma and other necrobiotic granulomas.
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PMID:Necrobiotic xanthogranuloma with paraproteinemia. 745 93

In a group of 10 patients (six with acute lymphatic leukaemia, one patient with Ewing's sarcoma, one patient with lung cancer, one patient with a myeloma and one patient with Hodgkin's lymphogranuloma) treatment with leucocytic growth factors (Neupogen Hoffman La Roche) was started only after the onset of leukopenia. Even after this mode of administration of leucocytic growth factors septic conditions in leukopenic patients were more easily controlled and it was thus possible to complete chemotherapy with planned doses in the planned time interval. In five patients with acute lymphatic leukaemia the leucocytic growth factors participated in the achievement of remission, in patients with myeloma and lymphogranuloma they contributed to marked improvement of the general condition and reduction of the time spent in hospital.
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PMID:[Leukocyte growth factors in patients with neoplasms]. 769 71

Hepsulfam is a bisulfamic ester which is similar in structure to busulfan and is believed to act as a bifunctional alkylator inducing both DNA-DNA and DNA-protein crosslinks. Prior studies in patients with refractory solid tumors have identified the dose-limiting toxicity of hepsulfam to be cumulative myelosuppression resulting in prolonged leukopenia and thrombocytopenia. This phase I trial was designed to determine the maximally tolerated dose of hepsulfam administered intravenously in patients with refractory leukemias and other advanced hematologic malignancies. Hepsulfam was administered as a 30-min or 2-h intravenous infusion to 21 patients with advanced leukemia or multiple myeloma. All patients had been extensively treated and had progressive disease. Cycles were repeated every 5 weeks. Cohorts of patients were treated at 360, 480, 640, and 800 mg/m2. The dose-limiting toxicity of intravenous hepsulfam was severe encephalopathy. The single patient treated at 800 mg/m2 became comatose within 48 h and required 3 weeks for his mental status to return to baseline. There were, however, no irreversible neurological sequelae. Several patients treated at 640 mg/m2 had clinical evidence of toxic deliriums and slowing of alpha rhythm waves on electroencephalograms indicative of a gray-matter encephalopathy. When hepsulfam was infused over 30 min, patients complained of uncomfortable parasthesias, but when the drug was administered over 2 h, these acute symptoms were less common. Myelosuppression was observed in most patients. Among those patients who had some suppression of their leukemia, peripheral blood counts recovered to pretreatment levels after 3-5 weeks. Apart from CNS toxicity, non-hematologic toxicity was minimal. Pharmacokinetic studies demonstrated rapid clearance of hepsulfam so that the drug was not reliably detected in the plasma after 24 h. The recommended phase II dose of hepsulfam as a single 2-h intravenous infusion is 480 mg/m2, but this dose provided relatively little clinical benefit for patients with refractory leukemia. The dose-limiting toxicity is CNS toxicity with increasingly severe encephalopathy at doses > or = 640 mg/m2. It would be reasonable to investigate further dose escalation of hepsulfam in a divided dose schedule to minimize the peak concentrations which may be related to the encephalopathy. EEG monitoring is recommended for early detection of slowing of alpha rhythm waves. Hematopoietic stem cell support will probably be required at total doses exceeding 800 mg/m2.
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PMID:Encephalopathy is the dose-limiting toxicity of intravenous hepsulfam: results of a phase I trial in patients with advanced hematological malignancies. 778 Nov 39

Nineteen patients with multiple myeloma resistant to standard alkylating agent therapy or to the VAD regimen received carboplatin at a planned daily dose of 100 mg/M2 on four successive days. Two patients erroneously received a four-fold higher drug dose resulting in bone marrow aplasia and death without antitumor effect in one patient with post-mortem examination. No anti-tumor effect was observed among 15 patients evaluable for response (two lacked follow-up examination of tumor markers). Major toxicities were hematologic and included grade > or = III, leukopenia in 9, thrombocytopenia in 6 and anemia in 3 of the 17 evaluable patients. Their median survival was 9 months. These results indicate that carboplatin is inactive in refractory multiple myeloma.
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PMID:Phase II study of carboplatin (CBDCA) in refractory multiple myeloma. A Southwest Oncology Group study. 796 Jun 7

A kappa light-chain myeloma was diagnosed as the underlying disease in a 52-year-old woman with acute oliguric renal failure. The patient was erroneously treated with high-dose intravenous melphalan (60 mg/m2). Because of this overdose treatment with granulocyte colony-stimulating factor was initiated, but pronounced absolute leukopenia (white blood cell count < 0.5 x 10(9)/l) developed and lasted for 13 days. Following melphalan treatment a continuous increase in urine volume was accompanied by a decrease of serum creatinine and blood urea nitrogen. Within 10 days after the administration of melphalan the patient no longer required hemodialysis. We conclude that high-dose chemotherapy in combination with hematopoietic growth factors should be considered in individual cases with newly diagnosed light-chain nephropathy.
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PMID:High-dose intravenous melphalan in a patient with multiple myeloma and oliguric renal failure. 798 81

From January 1988 until December 1990, 99 previously untreated patients with multiple myeloma (MM) were enrolled in a randomized prospective study comparing two combination chemotherapies with and without MCNU as induction therapy for MM; 49 patients with vindesine, melphalan and prednisolone (VMP therapy) versus 50 patients with MCNU, vindesine, melphalan and prednisolone (MCNU-VMP therapy). Seventy-two evaluable patients (34 patients in the VMP group, 38 in the MCNU-VMP group) were analyzed. The response rate was slightly higher with MCNU-VMP than with VMP (81.6% vs. 64.7%). In 43 responders (21 patients in the VMP group and 22 in the MCNU-VMP group) who were treated with the same regimen as the induction therapy to maintain remission, the remission duration was significantly longer in patients treated with MCNU-VMP than in those treated with VMP (median > 10.1 vs. 8.0 months, P = 0.018), particularly in patients with PS 3-4. The remission duration in the MCNU-VMP group was also slightly longer in the patients with stage III disease and who were older than 65 years. The median survival time showed no significant difference between the VMP group (20.3 months) and the MCNU-VMP group (> 15 months). Leukopenia, thrombocytopenia and nausea/vomiting were found to be somewhat severe in the MCNU-VMP group. In summary, MCNU-VMP therapy is effective as induction therapy for MM.
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PMID:Combination chemotherapy with MCNU, vindesine, melphalan, and prednisolone (MCNU-VMP therapy) in induction therapy for multiple myeloma. Japan Myeloma Study Group. 801 4

A 52-year-old man was admitted to our hospital because of oliguric renal failure. The patient was well until four weeks earlier, when he developed nausea and anorexia. The urea nitrogen was 179 mg/dl, creatinine 29.2 mg/dl, uric acid 19.0 mg/dl and potassium 8.6 mEq/1. Hemodialysis was started immediately after admission. Bone marrow aspiration showed atypical plasma cell infiltration consistent with multiple myeloma. The immunoelectrophoresis revealed urinary lambda -type Bence Jones protein and serum IgD- lambda -type M protein. The findings of renal biopsy study were consistent with myeloma kidney. On the fourth hospital day, administration of prednisolone 40 mg and melphalan 2 mg was started. The patient also underwent double filtration plasma-pheresis (DFPP). Serum IgD level was decreased from 950 to 113 mg/dl. After a course of chemotherapy, however, he developed severe leukopenia and was complicated with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. This complication was successfully treated with imipenem/cilastation and vancomycin combined with granulocyte colony stimulating factor (G-CSF). The patient was discharged and returned to work on maintenance hemodialysis. Fifteen months after the presentation, he manifested progressive peripheral nerve disturbances. Three months later, the patient died--not from renal failure, but from ventricular arrhythmia. The application of maintenance dialysis therapy to myelomatosis has until now been questioned. The present case, however, suggests that aggressive treatment consisting of chronic dialysis therapy as well as chemotherapy and plasma exchange should be administered even in patients with established renal failure.
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PMID:[Maintenance hemodialysis in IgD- lambda -type multiple myeloma associated with severe renal failure]. 813 51

In the submitted study the authors summarize experience with the treatment of resistant forms of multiple myeloma by a combination of Mitoxantrone, Vincristine and Prednisone (NOP regime). The above treatment produced an objective therapeutic response in 33% of the patients, in 50% a partial response, in 17% it failed. The median of survival in the whole group was 10.5 months. Substantially poorer therapeutic results were recorded in patients with primary resistance to the initial chemotherapy (objective response only in one of 6 patients) than in the group with secondary resistance which developed during a relapse of the disease (objective response in 3 of 6 patients). With the exception of marked leukopenia and neutropenia treatment by the NOP regime was very well tolerated. The NOP regime is an expedient approach which extends practical possibilities, in particular ambulatory treatment of refractory forms of multiple myeloma.
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PMID:[Treatment of resistant forms of multiple myeloma using a combination of mitoxantrone, vincristine and prednisone (the NOP regimen)]. 821 24


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