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)

Aclacinomycin A (ACM-A), an anthracycline analog, was given to 17 patients with solid tumors and to one patient with multiple myeloma, in a phase I clinical trial. A single dose of 60-120 mg/m2 was given every 3 weeks. Dose-limiting toxicity was myelosuppression, especially thrombocytopenia. Granulocytopenia was variable and did not always recover by Day 21 in time for the next ACM-A treatment. Other toxic effects were nausea, vomiting, urticaria, and elevation of hepatic enzymes. Alopecia was not a side effect, even in patients receiving multiple courses of ACM-A. Nine patients were monitored with 24-hour continuous ECG recordings (Holter) on 19 ACM-A treatment days. The incidence of premature atrial and ventricular beats was significantly increased following ACM-A administration. In addition, one patient developed episodes of high-degree atrioventricular block and complete heart block after each of four ACM-A doses, necessitating the insertion of a pacemaker. No antitumor responses were seen in the ten patients who had measurable disease and who had received two or more courses of ACM-A. The recommended doses for solid tumor phase II studies are 100 mg/m2 as a single dose every 4 weeks for patients with high performance status and minimal prior chemotherapy and 60 mg/m2 every 4 weeks for all other patients. Until the acute cardiac effects of ACM-A are further understood, we recommend that all patients receiving ACM-A be monitored by ECG recordings.
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PMID:Phase I trial of aclacinomycin A. 695 61

Acute myelogenous leukaemia (AML) following cytotoxic chemotherapy has been reported increasingly. Five new cases are presented including the first described following treatment for immune thrombocytopaenia. A review of the literature has revealed 226 case reports of treatment-linked AML with sufficient detail to permit further study. Of the total of 231 patients, 76 (33 per cent) followed Hodgkin's disease, 59 (25.5 per cent) multiple myeloma, 22 (9.5 per cent) non-Hodgkin's lymphoma, 32 (14 per cent) other solid tumours and 42 (18 per cent) non-malignant diseases. The time interval from the start of chemotherapy to the diagnosis of AML was similar in all disease groups whether the patients had received radiotherapy or not. Differences emerged when the duration of exposure to chemotherapy was analysed in the individual disease groups; exposure was shorter in those patients treated for Hodgkin's disease and solid tumours than with the others suggesting that the pattern of administration of chemotherapy may be important. The effects of radiotherapy in addition to chemotherapy could not be defined precisely, but the study highlights the particular risk that appears to arise from alkylating agents, and the need to define optimal methods of administration of chemotherapy with minimal risk of inducing leukaemia.
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PMID:Acute myelogenous leukaemia following cytotoxic therapy: five cases and a review. 695 25

A total of 151 patients with myeloma who had relapsed with or were resistant to melphalan and/or cyclophosphamide (Cytoxan) with prednisone received vincristine, carmustine (BCNU), doxorubicin (Adriamycin), and prednisone (VBAP) at 21-day intervals; 39 patients (25%) responded. Of the 123 patients with relapsing myeloma, 37 (30%) responded. Only two (7%) of the 28 patients with resistant myeloma responded. The regimen was well-tolerated in patients who had not had prior extensive irradiation. Thrombocytopenia was the most frequent form of toxicity. Survival was significantly longer in those patients responding to VBAP (median, 78 weeks) than in those not responding (median, 33 weeks) (P = 0.002). VBAP is a safe, effective regimen for patients with myeloma who relapse with alkylating agents.
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PMID:Vincristine, BCNU, doxorubicin, and prednisone (VBAP) combination in the treatment of relapsing or resistant multiple myeloma: a Southwest Oncology Group study. 704 34

Sixty-five patients with multiple myeloma resistant to melphalan were randomized to receive cyclophosphamide, doxorubicin (Adriamycin), and prednisone (CAP) (30 patients) or carmustine (BCNU), doxorubicin, and prednisone (BAP) (35 patients). Objective responses occurred in two patients in the CAP group and in seven in the BAP group. Indirect responses were noted in seven additional patients in the CAP group and in six additional patients in the BAP group. Toxic effects consisted mainly of leukopenia and thrombocytopenia. Median survival did not differ between the two treatment groups (CAP, 8.4 months; BAP, 7.7). Objective responders had a longer survival than nonresponders (14.5 vs 7.7 months).
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PMID:Multiple myeloma resistant to melphalan: treatment with doxorubicin, cyclophosphamide, carmustine (BCNU), and prednisone. 706 34

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

The clinical, laboratory and pathologic findings were studied in 62 consecutively autopsied patients with multiple myeloma between 1954 and 1975. All patients were 40 years of age or older. Bone pain was the initial symptom in 2/3 of patients. Anemia (81%), thrombocytopenia (29%), azotemia (41%), hypercalcemia (46%) and hyperuricemia (52%), were common laboratory findings at diagnosis. Ninety-seven percent had a monoclonal protein in serum or urine. Extensive plasma cell replacement of marrow was invariably seen at autopsy although in 15% of patients no abnormality was found on skeletal survey. Extraskeletal spread (67%) was due to direct extension to paraosseous tissue resulting from cortical destruction and to distant organ involvement mainly of splenic red pulp and hepatic sinusoids. The patients were susceptible to bacterial infection, mainly gram-negative, of the lung (56%), urinary tract (35%), and blood (24%). Fungal infection was less frequent and usually consisted of superficial candidal overgrowth of gastrointestinal tract ulcerations (18%). Amyloidosis (10%) was perivascular and associated with light chain proteinuria. Renal failure as a cause of death (21%) was secondary only to infection (52%). Severity of histologic findings in the kidney at autopsy had little correlation to initial BUN concentration. The median survival was 11.5 months with alkylating agent therapy (responders, 29 months; non-responders, 6 months), and 6 months with urethan. Initial azotemia (greater than 80 mg/dl) and hypercalcemia (greater than 12 mg/dl) were important prognostic indicators (median survival, less than 1 month and 3 months, respectively). A good response to alkylating agent therapy, initial BUN less than 40 mg/dl and serum calcium less than 12 mg/dl were favorable to prognostic indicators.
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PMID:Multiple myeloma: a clinicopathologic study of 62 consecutively autopsied cases. 743 54

A major potential problem of autologous transplantation in the treatment of advanced malignancy is the infusion of tumor cells. A multi-institutional study of purified CD34-selected peripheral blood progenitor cell (PBPC) transplantation was conducted in 37 patients with advanced multiple myeloma receiving myeloablative chemotherapy. Fourteen days after intermediate-dose cyclophosphamide, prednisone, and granulocyte colony-stimulating factor (G-CSF), a median of 3 (range, 2 to 5) 10-L leukaphereses yielded 9.8 x 10(8)/kg (range, 3.7 to 28.3) mononuclear cells. The adsorbed (column-bound) fraction contained 5.9 x 10(6) cells/kg (range, 1.6 to 25.5) with 4.65 x 10(6) CD34 cells/kg (range, 1.2 to 23.3). Using Poisson distribution analysis of positive polymerase chain reactions with patient-specific complementarity-determining region 1 (CDR1) and CDR3 Ig-gene primers, tumor was detected in leukapheresis products from 8 to 14 unselected patients and ranged from 1.13 x 10(4) to 2.14 x 10(6) malignant cells/kg. After CD34 selection, residual tumor was detected in only three patients' products. Overall, a greater than 2.7- to 4.5-log reduction in contaminating multiple myeloma cells was achieved. CD34 PBPCs were infused 1 day after busulfan (14 mg/kg) and cyclophosphamide (120 mg/kg), and granulocyte-macrophage colony-stimulating factor was used until hematologic recovery. The median time to both neutrophil and platelet recovery was 12 days (range, 11 to 16 days and 9 to 52 days, respectively). The median number of erythrocyte and platelet transfusions was 7 (range, 2 to 37) and 3 (range, 0 to 85), respectively. Patients receiving fewer than 2 x 10(6) CD34 cells/kg had significantly prolonged neutropenia, thrombocytopenia, and an increased red blood cell and platelet transfusion requirement. Thus, CD34 selection of PBPCs markedly reduces tumor contamination in multiple myeloma and provides effective hematopoietic support for patients receiving myeloablative therapy.
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PMID:Transplantation of CD34+ peripheral blood progenitor cells after high-dose chemotherapy for patients with advanced multiple myeloma. 754 Aug 88

67 patients with relapsed or resistant multiple myeloma were randomized to receive either VAD (vincristine, doxorubicin, dexamethasone) or MOD (mitozantrone, vincristine, dexamethasone). 12/30 (40%) patients receiving VAD and 15/37 (41%) patients receiving MOD achieved plateaux. The median duration of plateaux was significantly longer on VAD (15 months) than on MOD (8 months). No significant difference in overall survival was seen between the two treatment arms. The only toxicity which was severe in more than 5% of treatment cycles on either treatment arm was myelosuppression. No toxicity was significantly more severe on MOD than VAD. However, hair loss was significantly more severe on VAD than MOD. The frequencies of thrombocytopenia, haematuria and cutaneous toxicity were significantly greater on VAD than on MOD. Raised serum direct bilirubin levels were seen significantly more often on MOD than VAD. MOD and VAD have similar efficacy in relapsed/resistant multiple myeloma. MOD is the less toxic of the two regimens.
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PMID:A randomized study of MOD versus VAD in the treatment of relapsed and resistant multiple myeloma. 754 39

In patients with advanced multiple myeloma (MM) there is an excess of production of interleukin-6 (IL-6) in vivo, and elevated serum levels are associated with plasmablastic proliferative activity and short survival. These data prompted us to perform a clinical trial with a murine anti-IL-6 monoclonal antibody (MoAb) to neutralize the excess of this putatively deleterious factor in these patients. Ten MM patients with extramedullary involvement frequently were treated with anti-IL-6 MoAb. The MoAb was administered intravenously to 9 patients; 1 patient with malignant pleural effusion received intrapleural therapy. Of the 3 patients who succumbed to progressive MM after less than 1 week of treatment (including the only 1 treated locally), 2 with evaluable data exhibited marked inhibition of plasmablastic proliferation. Among the 7 patients remaining more homogeneous receiving the anti-IL-6 MoAb for more than 1 week, 3 had objective antiproliferative effect marked by a significant reduction of the myeloma cell labelling index within the bone marrow. One of these 3 patients achieved a 30% regression of tumor mass. However, none of the patients studied achieved remission or improved outcome as judged by standard clinical criteria. Of major interest, objective antiproliferative effects were associated with complete inhibition of C-reactive protein (CRP) synthesis and low daily IL-6 production in vivo. On the other hand, the lack of effect in 4 patients was associated with a higher IL-6 production and inability of the MoAb to neutralize it. Anti-IL-6 was also associated with resolution of low-grade fever in all the patients and with worsening thrombocytopenia and mild neutropenia. The generation of human antibodies to Fc fragment of the murine anti-IL-6 MoAb observed in 1 patient was associated with dramatic progression. These data show that anti-IL-6 MoAb can suppress the proliferation of myeloma cells and underscore the biologic role of IL-6 for myeloma growth in vivo. Furthermore, suppression of CRP and worsening of neutropenia/thrombocytopenia both indicate that IL-6 is critically involved in acute-phase responses and granulopoiesis/thrombopoiesis.
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PMID:Biologic effects of anti-interleukin-6 murine monoclonal antibody in advanced multiple myeloma. 760 99


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