Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
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

Among 750 previously untreated patients with multiple myeloma, 27 (4%) presented with plasma cell leukaemia. All but one patient had high tumour mass and, when compared with comparable patients without leukaemia, more frequent extraosseous involvement, thrombocytopenia, high serum lactate dehydrogenase and hypodiploid plasma cells. Most patients also had complex cytogenetic abnormalities. Treatment with standard melphalan-prednisone was ineffective, with a median survival of 2 months, but more intensive chemotherapy induced responses in approximately one-half of the patients, with a median survival of 20 months. Primary plasma cell leukaemia usually results from the proliferation and extramedullary expansion of immature plasma cells and requires prompt and intensive chemotherapy.
 ...
PMID:Primary plasma cell leukaemia. 781

A 35-year-old male presented with chronic myelomonocytic leukemia (CMMoL) after 6.5 years of alkylating agent therapy for IgG-kappa type multiple myeloma. The total dose of melphalan was 0.648 g. CMMoL was stable with weekly injection of alpha-interferon for one year. Thereafter, monocytosis and thrombocytopenia aggravated, and the patient died of disseminating intravascular coagulation. Prolonged drug therapy can induce CMMoL, as well as other myelodysplastic syndromes.
 ...
PMID:Chronic myelomonocytic leukemia following prolonged alkylating agent therapy for multiple myeloma. 789 29

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.
 ...
PMID:Phase II study of carboplatin (CBDCA) in refractory multiple myeloma. A Southwest Oncology Group study. 796 Jun 7

A 55-year-old woman, who had systemic amyloidosis associated with multiple myeloma, had sudden development of hematomas of her lip and upper eye lid. There was no evidence of deterioration of multiple myeloma, thrombocytopenia nor deficiency of coagulation factors. Biopsy specimen showed the deposit of amyloid substance in the dermis and perivascular region. The bleeding tendency in this patient with myeloma was likely due to the deposit of amyloid substance in the vascular wall; improvement was achieved with administration of hemostatic agents.
 ...
PMID:Bleeding tendency caused by the deposit of amyloid substance in the perivascular region. 801 92

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.
 ...
PMID:Combination chemotherapy with MCNU, vindesine, melphalan, and prednisolone (MCNU-VMP therapy) in induction therapy for multiple myeloma. Japan Myeloma Study Group. 801 4

Autologous blood stem cell transplants (ABSCT) are increasingly used for the treatment of haematological malignancies. The use of hemopoietic growth factors, in conjunction with stem cell mobilization by chemotherapeutic agents, has permitted successful harvests requiring only a few leukaphereses; cells mobilized in this manner contain a relatively large number of committed precursors of all lineages, as well as early progenitor cells capable of maintaining long-term haemopoiesis. Haematological recovery after ABSCT is rapid, thereby significantly shortening the period of post-chemotherapy neutropenia and thrombocytopenia. Furthermore, blood-derived grafts may contain fewer malignant cells than the bone marrow cells. The preliminary results have been so encouraging that it is envisaged that in myeloma, Hodgkin's disease and non-Hodgkin lymphomas, ABSCT may eventually replace autologous marrow transplantation.
 ...
PMID:Autologous blood stem cell transplantation in hematological malignancies. 802 21

A 67-year-old male was admitted to our hospital because of anemia, thrombocytopenia, and renal failure. On admission he showed splenomegaly and elevated serum LDH level. Bone marrow showed hypercellularity with massive infiltration of lymphoblastoid cells. He was diagnosed as having multiple myeloma (BJ-kappa, stage IIIB). He transiently responded to intensive chemotherapy (VAD, MP, IFN alpha) but relapsed with multiple subcutaneous tumors and pericardial effusion. This is a rare case that the myeloma cell invasion to pericardial space was diagnosed before his death. The level of interleukin 6 (IL-6) in pericardial effusion was 16382 pg/ml, and the myeloma cells obtained from the pericardial effusion responded to IL-6, which suggested that high level of IL-6 closely related to the proliferation of myeloma cells in this case.
 ...
PMID:[Aggressive myeloma with subcutaneous tumor and pericardial involvement]. 815 51

At a median time of 20 months following high dose melphalan for myeloma, 29 patients relapsed and were treated with induction chemotherapy to maximum response followed by a second course of high dose melphalan. The majority (90%) of patients received 200 mg m-2 with an autologous bone marrow transplant. Sixteen (55%) patients achieved complete remission and 11 (38%) a partial response. The median duration of remission was 17 (4-42) months. The median survival has not been reached, with 50% of patients alive at 58+ months after presentation. The period of neutropenia was similar during both first and second high dose procedures, but the duration of thrombocytopenia was longer in patients receiving melphalan for a second time (median 22 (16-56) days and 41 (18-69) days respectively). There was one treatment-related death due to thrombocytopenic haemorrhage. Repeated administration of high dose melphalan is a feasible approach for patients with relapsed myeloma.
 ...
PMID:Repeat administration of high dose melphalan in relapsed myeloma. 821 14

Twenty-four patients with a variety of malignant diseases (13 lymphoma, 4 myeloma, 1 ALL, 6 solid tumours) were treated with the alkylating agents busulphan and melphalan as a preparative regimen for autologous BMT. Thirteen males and 11 females, aged 27-53 years (median 39.5 years) received oral busulphan 1 mg/kg q6 h on days -6 to -3, followed by i.v. melphalan 140 mg/m2 on day -2 and infusion of cryopreserved haemopoietic cells on day 0. The major toxicity seen was gastrointestinal with nausea, vomiting and diarrhoea in 17 patients and severe mucositis in 22. There was no evidence of cardiotoxicity, nephrotoxicity, haemorrhagic cystitis or clinical signs of hepatic veno-occlusive disease. Twenty-three patients engrafted with the median duration of neutropenia (< 0.05 x 10(9)/l) 10 days (range 5-63 days) and thrombocytopenia (< 50 x 10(9)/l) 43 days (range 5-350 days). Three patients died of transplant-related complications. Of 15 evaluable patients with active disease at BMT, 9 responded and 6 were refractory. Sixteen evaluable patients were in CR after BMT. Seven relapsed, 1 died in remission and 8 remain in CR 12-46 months (median 29 months) later. Of the group of 13 lymphomas, overall and relapse-free actuarial survival at 36 months was 64% and 58%, respectively, while for the entire group of 24 patients these values were 39% and 34%. Busulphan and melphalan is a safe and inexpensive conditioning regimen for autologous BMT with acceptable toxicity and substantial antitumour activity particularly against lymphomas.
 ...
PMID:Busulphan and melphalan prior to autologous bone marrow transplantation. 827 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>