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Biomedical subjects

R Alexanian

Publications and source records attributed to R Alexanian.

At least 127 records · Page 7Linked to original sources
PubMed1985

Ten-year survival in multiple myeloma.

Of 305 consecutive patients with symptomatic multiple myeloma treated between 1965 and 1974, a total of 4% survived ten years. Virtually all were less than 65 years old, presented with low or intermediate stage disease, and responded well to chemotherapy. Prolonged unmaintained remissions, slow tumor growth, and recontrol of relapsing disease were common. Acute leukemia caused the death of two of six long-term survivors. Patients treated since 1974 lived longer than those seen previously, a finding attributed to better control of complications and more effective combination chemotherapy.

Aged↗
PubMed1984

Effective treatment of advanced multiple myeloma refractory to alkylating agents.

Twenty-nine patients with advanced refractory multiple myeloma were treated with intermittent high-dose dexamethasone in combination with four-day infusions of vincristine and doxorubicin. Rapid and marked tumor-mass reduction (greater than 75 per cent) was noted in 14 of 20 patients whose disease was resistant to alkylating agents and in 3 of 9 patients with additional resistance to doxorubicin--a result far superior to those in previous trials with similar patients. In responsive patients, remissions were of excellent quality, and survival was significantly longer than in unresponsive patients.

Alkylating Agents↗
PubMed1984

Chemotherapy for multiple myeloma.

The effects of eight different drug combinations were evaluated in 256 patients with multiple myeloma. The response rate and time to remission were superior from regimens that added both vincristine and Adriamycin (doxorubicin) to an alkylating agent-prednisone combination. There was no improvement in response rate or survival time from two alternating drug combinations evaluated in an attempt to achieve more marked tumor reductions and to delay the emergence of resistant subclones. The addition of levamisole during remission maintenance did not improve survival time. Results supported the utility of unmaintained remission follow-up in selected patients with marked reductions in myeloma cell mass.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Collaborative phase I-II study of recombinant DNA-produced leukocyte interferon (clone A) in metastatic breast cancer, malignant lymphoma, and multiple myeloma.

Fifty-two patients with advanced cancer received sequentially escalating doses of 3 to 50 million units of recombinant DNA-produced alpha interferon by daily intramuscular injection. There were 23 patients with metastatic breast cancer, 17 patients with nodular poorly differentiated lymphocytic lymphoma, and 12 patients with multiple myeloma. Complete and partial remissions were obtained in 35 percent of patients with nodular poorly differentiated lymphoma, whereas rare activity was found in breast cancer and multiple myeloma. Dose-limiting toxicity occurred in patients receiving 36 million units or more and consisted of fatigue/asthenia, weight loss, and elevation of transaminase levels, requiring frequent interruption, reduction in dose, or cessation of treatment. Hematologic toxicity was rarely a limiting factor, but myelosuppression was severe in some patients with multiple myeloma. All toxicities were reversible on discontinuation of treatment. Antibodies to recombinant leukocyte A interferon were seen infrequently but may adversely affect therapy.

Adult↗
PubMed1984

High-dose cytosine arabinoside in multiple myeloma.

In 14 patients with advanced refractory multiple myeloma, the effect of high-dose cytosine arabinoside (ara-C) administration was evaluated. There was one partial remission among 13 evaluable patients who received 2 g/m2 intravenously over 2 hr every 12 hr, for a total of 2-8 g/m2 per course, repeated every 3-4 weeks. Myelosuppression constituted the dose-limiting toxicity, causing two treatment-related deaths from infection and bleeding. Prior extensive therapy, a low percentage of cells in S phase and low levels of intracellular ara-CTP accumulation in the bone marrow could explain the resistance of myeloma to this treatment.

Aged↗
PubMed1984

Connective tissue disease manifested as multiple myeloma.

A diagnosis of Sjögren's syndrome or rheumatoid arthritis was made in five women in whom multiple myeloma was first suspected. All had mild symptoms of sicca or arthritis, positive tests for rheumatoid factor or antinuclear antibody, and markedly increased IgG immunoglobulins. A connective tissue disorder may produce the characteristic electrophoretic pattern of multiple myeloma.

Adult↗
PubMed1984

Addition of cisplatin and bleomycin to vincristine-carmustine-doxorubicin-prednisone (VBAP) combination in the treatment of relapsing or resistant multiple myeloma: a Southwest Oncology Group study.

Fifty-five patients with myeloma who had relapsed on or were resistant to melphalan and/or cyclophosphamide with prednisone received vincristine, carmustine, doxorubicin, and prednisone (VBAP) plus cisplatin and bleomycin at 21-day intervals. Eighteen (32.7%) patients responded. The response rate was 38.5% (15 responses among 39 patients) in relapsing patients. Three (18.8%) of 16 patients with resistant myeloma responded. Granulocytopenia was the most frequent toxic effect, and was severe in 12 (22%) patients. Severe thrombocytopenia occurred in seven (13%) patients and severe nausea and vomiting occurred in eight (15%). One patient with previously normal renal function developed renal failure on this regimen. The median survival (100 weeks) in those patients responding to treatment was significantly longer than that in patients not responding (25 weeks; P = 0.001). VBAP plus cisplatin and bleomycin was at least as effective as VBAP but had greater toxicity, expense, and inconvenience; it therefore is not preferable to VBAP.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Amyloidosis in multiple myeloma or without apparent cause.

Thirty-two patients with primary amyloidosis (AL) either due to multiple myeloma or without apparent cause were studied. The most common manifestations were carpal tunnel syndrome and nephrosis. Rectal biopsy specimens showed amyloid infiltrates in 65% (15 of 23) of the patients studied, but virtually all biopsies of normal skin were negative. lambda Light chains were present in 75% (21 of 28) of patients with a monoclonal gammopathy. The median survival time was 14 months after histologic diagnosis, following a median delay of seven months from the recognition of disease by a physician. An earlier diagnosis would have been possible in most of the patients if the initial findings of amyloidosis had been recognized and evaluated definitively. The prognosis remains poor, because effective therapy is not available.

Amyloidosis↗
PubMed1983

Anaplastic myeloma with massive extramedullary involvement. Report of two cases.

Two patients developed anaplastic myeloma associated with prominent extramedullary disease one and four years after the initial diagnosis of multiple myeloma. Most tumor cells in the extramedullary sites were primitive-appearing and anaplastic, although plasmacytoid differentiation was evident. One patient had concurrent bone marrow involvement by cytologically similar cells, while the other patient was in bone marrow remission when he developed clinically evident soft tissue infiltration. Immunoperoxidase staining showed similar cytoplasmic immunoglobulin in both the mature-appearing and anaplastic cells in both patients. Electron microscopy in both cases showed a morphologic spectrum between the mature-appearing and anaplastic cells. DNA flow cytometric studies following the onset of extramedullary disease revealed a tumor cell population with a high degree hyperdiploid abnormality and unusually high proliferative activity in both cases, consistent with the morphologic anaplasia. Anaplastic myeloma appears to represent a distinct, aggressive variant of multiple myeloma which may result from a transformation of well differentiated myeloma cells to poorly differentiated immunoblast-like cells.

Abdominal Neoplasms↗
PubMed1983

Marrow cytometry and prognosis in myeloma.

We have previously shown that flow cytometric analysis of acridine orange-stained bone marrow cells is useful for the objective enumeration and characterization of plasma cells from patients with myeloma, frequently exhibiting an abnormal DNA and an elevated RNA content. In this report on 77 previously untreated patients, we have investigated the biologic and prognostic implications of these quantitative tumor cell parameters. The degree of marrow involvement by tumor, both by microscopic and cytometric analysis, correlated with the clinically derived tumor mass stage. Examination of the product of relative tumor cell RNA content and marrow tumor infiltrate (as a measure of metabolic capacity for immunoglobulin production) in relationship to the myeloma protein concentration in the serum revealed differences in the efficiency of immunoglobulin production and/or catabolism. There was an inverse relationship between the degree of marrow tumor involvement and RNA index, suggesting a more aggressive behavior of myeloma in patients with a low tumor cell RNA content. Prognostically, high tumor cell RNA content identified patients with a high likelihood of response to both initial treatment (32 patients, P = 0.004) and salvage therapy (29 patients, P = 0.01). Favorable factors for survival were low clinical tumor mass stage (P = 0.07) and low marrow tumor infiltrate as determined morphologically (P = 0.04) and cytometrically (P = 0.004). Thus, the direct examination of marrow cellular DNA and RNA content permitted assessment of tumor burden and was useful in the prediction of response and survival.

Bone Marrow↗
PubMed1983

Prednisone pulse therapy for refractory myeloma.

The utility of vindesine and a frequent prednisone schedule was evaluated in 70 patients with refractory myeloma. No patient responded to vindesine alone, but about one-fourth achieved significant tumor reductions from intermittent high-dose prednisone, either alone or in combination with vindesine. Forty-seven percent responded when prednisone pulses were combined with vincristine and doxorubicin, providing the best results yet achieved in our patients with refractory myeloma. In responding patients, remissions were of excellent quality and survival was prolonged significantly. These results supported the utility of a more frequent corticosteroid schedule with increased doxorubicin dose in patients with advanced and resistant multiple myeloma.

Bone Marrow↗
PubMed1982

Nonsecretory multiple myeloma.

The clinical features and disease course of 29 consecutive multiple myeloma patients without monoclonal globulins are described. This variant accounted for 4.7% of all patients with this disease referred over a 17 year time span. Despite bone marrow plasmacytosis and multiple bone lesions in all, hemoglobin levels were less frequently depressed and immunoglobulin values more frequently preserved in comparison with typical myeloma patients. A low tumor mass was defined in 69%, in comparison with 24% of those with evidence of myeloma protein production. Such earlier disease contributed to the long median survival of 39 months in these patients, a duration about 1 year longer than that of typical patients.

Bone Marrow↗
PubMed1982

Recombinant leukocyte A interferon: pharmacokinetics, single-dose tolerance, and biologic effects in cancer patients.

Sixteen patients with advanced cancer were treated with recombinant-DNA-produced pure leukocyte A interferon (IFLrA) intramuscularly in doses ranging from 3 to 198 X 10(6) units. with interval periods of 72 to 96 hours between doses. At the two lowest doses of 3 and 9 million units, there was a cross-over evaluation between IFLrA and partially pure leukocyte interferon (IFN-C) produced from human cells. THe maximum observed serum concentration of IFLrA measured by enzyme immunoassay and bioassay increased with increasing doses. The mean serum concentrations of IFLrA and IFN-C were similar. Clinical effects produced by IFLrA and IFN-C were similar, including fever, chills, myalgias, headache fatigue, and reversible leukopenia and granulocytopenia. Eight patients had transient and mild numbness of the hands or feet, or both. Three patients developed low titers of antibody to IFLrA, Seven of 16 patients showed objective evidence of tumor regression during the study.

Adult↗
PubMed1982

Ploidy and proliferative characteristics in monoclonal gammopathies.

Measurements were performed in 143 patients with monoclonal gammopathy of the cellular substrate in the bone marrow, including analysis of DNA and RNA content and tritiated thymidine labeling index. Aneuploidy by DNA content was present in 80% of 115 patients with active multiple myeloma and in 4 of 9 patients with benign monoclonal gammopathy, but was absent in all 12 patients with myeloma in remission and in 7 individuals with Waldenström's macroglobulinemia. With regard to prognosis in multiple myeloma, a low pretreatment plasma cell labeling index of less than or equal to 1% heralded longer survival than that observed in patients with a labeling index less than 1%, independent of myeloma tumor burden and ploidy pattern, except for a subset of 17 patients with a low-degree hyperdiploid abnormality whose survival was not affected by the magnitude of the pretreatment labeling index. Thus, besides tumor burden, tumor proliferative activity and ploidy both appear to have additional prognostic importance for patients with multiple myeloma.

Cell Division↗
PubMed1982

Vincristine, BCNU, doxorubicin, and prednisone (VBAP) combination in the treatment of relapsing or resistant multiple myeloma: a Southwest Oncology Group study.

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.

Antineoplastic Agents↗
PubMed1982

Myeloma protein kinetics following chemotherapy.

The effects of chemotherapy were evaluated in 43 multiple myeloma patients with high monoclonal globulin levels in both serum and urine. In responding patients, Bence Jones protein excretion declined more rapidly and markedly than the serum myeloma protein. Bence Jones protein excretion was reduced by 50% within 2 mo in responders, remained unchanged in nonresponders, and declined with a slow halving time of 2-7 mo in patients with partial disease control. Three patients with clinical resistance to treatment showed atypical protein changes and progressively more Bence Jones protein excretion relative to their serum monoclonal component. Serial measurements of Bence Jones protein excretion provided an early and reliable index of tumor mass change in patients with multiple myeloma.

Alkylating Agents↗