melphalan and Myocardial-Infarction

The purpose of this study was to evaluate a new regimen for the treatment of multiple myeloma based on alternating 3-week cycles of chemotherapy and interferon (rIFN alpha 2). In this prospective phase II clinical trial the Eastern Cooperative Oncology Group evaluated a regimen consisting of 2 cycles of VBMCP (Vincristine 1.2 mg/M(2) IV d1, BCNU 20 mg/M(2) IV d1, Melphalan 8 mg/M(2) PO dl-4, Cyclophosphamide 400 mg/M2 IV d1, Prednisone 40 mg/M(2) PO d1-7) followed by alternating 3-week cycles of VBMCP and rIFN alpha2 5 Mu/M(2) SC 3x/week. Treatment was administered for 2 years. Fifty-eight patients with previously untreated multiple myeloma were entered. Objective response (OR) required 50% decrease in M-protein with correction of severe anemia and no progression of skeletal disease. Complete remission (CR) was defined by disappearance of M-protein and normalization of the bone marrow morphology. Life table analysis was utilized to express survival and response duration. Fifty-four patients were evaluable. Objective response was seen in 80% of patients including CR in 30% (16 patients). The median response duration is 35 months, 46 months for patients with CR. The median survival is 42 months for all patients. Five year survival is 42%. Although 78% of patients had neutrophil nadirs <1000 x 10(9)/L, the incidence of severe infection was only 9%. These data demonstrate that VBMCP + interferon is an effective new regimen combining chemotherapy with a biological response modifier for the treatment of multiple myeloma. The incidence of CR is high, and the response and survival durations appear to be 1 year longer than usually seen with standard chemotherapy. A current ECOG randomized trial compares VBMCP + interferon with VBMCP alone.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cyclophosphamide; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Immunologic Factors; Interferon alpha-2; Interferon-alpha; Life Tables; Male; Melphalan; Middle Aged; Multiple Myeloma; Myocardial Infarction; Neutropenia; Prednisone; Recombinant Proteins; Remission Induction; Survival Analysis; Thrombocytopenia; Treatment Outcome; Vincristine

A 63-year-old man, known to have Bechterev's disease was admitted because of weight gain and nocturnal sweating. He also had signs of heart failure with progressive exertional dyspnoea. Many months previously numerous bleedings had occurred in the skin, predominantly the face (periorbital and perioral), the inguinal region and the penis.. Extensive diagnostic test failed to find any evidence of tumor. The Rumpel-Leede tourniquet test was positive, while platelet functions was normal, suggesting vascular disease. The skin biopsy showed many perivascular amyloid deposits (AL). Immunochemical differentiation also demonstrated the same amyloid in rectal and hepatic biopsies. But there was AA amyloid in a hepatic artery. Immunophoresis indicated a biclonal gammopahty of unknown significance.. These findings indicated the diagnosis of primary AL amyloidosis associated with a gammopathy of unknown significance and a secondary AA amyloidosis in the presence of chronic Bechterev s disease. The clinical picture also showed cardiac complications, predominantly heart failure and numerous previous myocardial infarctions without S-T elevations. Echocardiography, which revealed marked thickening of the left ventricle with a restrictive filling pattern, suggested cardiac co-morbidity. The patient underwent chemotherapy with melphalan and prednisone but had a sudden cardiac death.. In a case of bleeding of unknown cause systemic amyloidosis should be considered in the differential diagnosis. A tendency towards bleeding, as in this patient, may be the first sign of amyloidosis, which ist often diagnosed quite late in the course of the disease.

Topics: Amyloidosis; Death, Sudden, Cardiac; Diagnosis, Differential; Fatal Outcome; Glucocorticoids; Heart Failure; Hemorrhagic Disorders; Humans; Male; Melphalan; Middle Aged; Myocardial Infarction; Paraproteinemias; Prednisone; Spondylitis, Ankylosing

Effort angina due to left main trunk (LMT) lesion was diagnosed in a 58-year-old man. Platelet count was markedly increased and essential thrombocythemia was also diagnosed. Because of LMT disease, coronary artery bypass grafting (CABG) was performed prior to medication for essential thrombocythemia. There were no complications during the operation or in the early postoperative period. Melphalan was administered postoperatively resulting in the decrease of platelet count. Postoperative coronary angiography demonstrated that both grafts were patent; however, immediately after coronary angiography, the patient suffered from a sudden onset of myocardial infarction and cerebral infarction. The therapeutic problems associated with hematological disorder in such patients are discussed in this report.

Topics: Angina Pectoris; Cerebral Infarction; Coronary Angiography; Coronary Artery Bypass; Humans; Male; Melphalan; Middle Aged; Myocardial Infarction; Platelet Count; Postoperative Complications; Thrombocytosis; Vascular Patency

Interferon alfa-2b (Intron A; Schering Plough) has been shown to be active in advanced previously treated multiple myeloma (MM). Recent in vitro evidence has suggested synergy between cytotoxic agents and interferon alfa-2b. This phase I-II protocol was initiated to study interferon alfa-2b in combination with melphalan and prednisone. Groups of five patients received interferon alfa-2b twice-weekly for two weeks at dose levels of 0.5, 1.0, 2.0, 5.0 and 10.0 X 10(6) IU/m2. During week 2, melphalan (9 mg/m2) and prednisone (40 mg/m2) were administered concurrently with interferon alfa-2b followed by a rest period during nadir myelosuppression, the cycles being repeated every 28 days. Thirty patients were entered of whom 21 were Stage III, 3 Stage II and 6 Stage I. Median nadir WBC/mm3 and platelets/mm3 at the various dose levels are given in the table. Serious adverse reactions while on study included myocardial infarction, renal failure and leukopenia-related sepsis. Early response information is available. Twenty-six patients are evaluable for response. Seven have had progressive disease and 19 (69%) a partial response, the median duration was 11+ months. Interferon alfa-2b does not appear to antagonize melphalan/prednisone effectiveness and may be additive or synergistic. Full evaluation of this combination will be undertaken in randomized controlled trials which are now underway.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Evaluation; Drug Synergism; Female; Humans; Interferon Type I; Leukopenia; Male; Melphalan; Middle Aged; Multiple Myeloma; Myocardial Infarction; Prednisone; Sepsis