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Biomedical subjects

R Alexanian

Publications and source records attributed to R Alexanian.

At least 145 records · Page 8Linked to original sources
PubMed1981

Chemoimmunotherapy for multiple myeloma.

The effect of chemoimmunotherapy consolidation treatment using alternating courses of alkylating agents and BCG was studied in 105 responding patients with multiple myeloma. The survival time of these patients was similar to that of responding patients treated on previous maintenance programs, indicating no apparent value from BCG for myeloma. The duration of unmaintained remission was longest in those with low numbers of residual plasma cells, and relapse usually developed within one year in patients with persistent serum myeloma peaks. Disease recontrol was achieved in 50% of relapsing patients whose median survival from retreatment was 20 months. Patient follow-up without chemotherapy until relapse was justified mainly for those responding patients with disappearance of myeloma proteins.

Adult↗
PubMed1981

The growth fraction of human myeloma cells.

Greater reductions of tumor load in patients with multiple myeloma may result from therapeutic strategies that are based on a better knowledge of growth kinetics. We have previously shown that the labeling index of myeloma cells remains unchanged when tumor mass is reduced and that the cells of relapsing patients have differnt biologic properties than the cells present before melphalan-prednisone therapy. This study investigated the growth fraction (GF) of myeloma cells at various disease stages using continuous i.v. infusions of tritiated thymidine. We studied 17 patients on 22 occasions (4 untreated, 2 unresponsive, 6 in remission, and 10 in relapse). All untreated an unresponsive patients and 5 of 6 patients in remission had a GF of less than 4%. GF was defined in these studies as the maximum percentage of labeled plasma cells exposed continuously to tritiated thymidine. Relapsing patients, with the most rapid tumor doubling times, had GF ranging from 14% to 83%. The plasma cell transit time through the proliferative compartment for all of the relapsing patients ranged from 6.6 to 11.9 days and the calculated intrinsic cell loss ranged from 50% to 86%. These findings support our model for the growth kinetics of multiple myeloma that assumes that the entire tumor mass issues from a small proportion of proliferating cells and that the growth kinetics of myeloma cells in relapsing patterns differ from those in untreated and unresponsive patients. Therapeutic trials with cycle-active agents need further investigation in selected relapsing patients who are likely to have a high growth fraction.

Female↗
PubMed1980

Leukocyte interferon-induced tumor regression in human metastatic breast cancer, multiple myeloma, and malignant lymphoma.

Thirty-eight patients with advanced breast cancer, multiple myeloma, and malignant lymphoma were treated with partially purified (about 0.1%) leukocyte interferon. Patients were treated with a remission-induction schedule of 3 million to 9 million antiviral units daily intramuscularly for 4 to 26 weeks. Responding patients were maintained on a schedule of 3 million U three times weekly. Tumor regression was observed in seven of 17 patients with breast cancer. Six of 10 patients with multiple myeloma responded with a decrease of at least 50% in serum myeloma protein levels or Bence Jones protein excretion. Six of the 11 lymphoma patients achieved tumor regression. Complete remissions occurred in two patients. Of the 19 responding patients, five remain on study for 52 to 63 weeks. Toxicity included low-grade fever, fatigue, anorexia, and partial alopecia. Myelosuppression (lowest median leukocyte count, 2500/mm3; granulocytes, 1300/mm3) occurred in most patients. On the basis of this pilot study, we conclude that leukocyte interferon can induce tumor regression in patients with advanced cancer.

Adult↗
PubMed1980

Localized and indolent myeloma.

Criteria were defined for recognizing 29 patients with a localized plasmacytoma of bone and 20 patients with an indolent variety of multiple myeloma in order to justify long-term follow-up without chemotherapy. All patients with indolent myeloma were asymptomatic from their low tumor mass disease, had a hemoglobin greater than 10 g/dl, and showed no more than 3 lytic bone lesions. The presence of more than 200 mg/day of Bence Jones protein was usually followed by disease progression within 2 yr. Serial assessments of myeloma protein level provided a useful index of changing tumor load and the need for chemotherapy. In patients with localized disease, radiotherapy usually reduced myeloma proteins markedly with subsequent disease control for many years, even though small serum peaks persisted. Chemotherapy for multiple myeloma was not required for a median of 8 yr in patients presenting with localized disease and of 3 yr in those with indolent myeloma. The additional survival from the start of drug treatment was similar to that of comparable patients treated promptly for overt multiple myeloma. The delay of chemotherapy until evidence of tumor progression did not affect the long-term outcome of patients with localized or indolent myeloma.

Diagnosis, Differential↗
PubMed1979

Solid tumors in multiple myeloma.

The frequency of solid tumors was evaluated in 628 consecutive patients with multiple myeloma who had been treated with various melphalan-prednisone combinations. Among those patients who lived at least 2 months, the incidence and diversity of second tumors were similar to those in normal persons of the same age and duration at risk. The diagnosis was usually made within 2 years after the start of chemotherapy for the myeloma. Long-term melphalan therapy did not seem to contribute to the pathogenesis of second solid tumors in patients with multiple myeloma.

Aged↗
PubMed1978

Unmaintained remissions in multiple myeloma.

Twenty-eight patients with multiple myeloma responding to prior melphalan-prednisone combinations, but without additional chemotherapy, were followed until relapse. Patients receiving no further treatment had a median survival time similar to that of those receiving indefinite courses of melphalan-prednisone or carmustine-prednisone. Prolonged periods of unmaintained remission occurred primarily in patients without extensive disease at the time of diagnosis or in whom the abnormal protein disappeared from the electrophoresis strip. The initial relapse after an unmaintained remission was controlled in 80% of patients with the resumption of melphalan-prednisone, but second remissions were usually less marked in degree and shorter in duration. Results supported the long-term evaluation without chemotherapy of selected patients with low numbers of plasma cells after treatment who were likely to experience long durations of disease stability and respond again to retreatment with melphalan-prednisone.

Cell Transformation, Neoplastic↗
PubMed1977

Tumor growth patterns in multiple myeloma.

Serial changes in tumor mass were evaluated in 61 patients with multiple myeloma who had received intermittent courses of melphalan-prednisone until death. The variations in the kinetics of tumor reduction and relapse could be explained by a mathematical model based on two cell populations, one sensitive to and one resistant to chemotherapy. For all responding patients, the median tumor halving-time was 1.3 months and the median doubling time was 2.9 months. The duration of a constant tumor mass during remission was brief in most patients. A larger fraction of resistant cells prior to therapy was associated with a slower tumor doubling-time during relapse. With a constant fractional reduction of sensitive cells and a tumor halving-time of one month or less, all cells sensitive to alkylating agents would be eliminated with 3 years of uninterrupted intermittent therapy.

Cell Division↗
PubMed1977

Combination therapy for multiple myeloma.

The effect of six different chemotherapy regimens were evaluated in 462 previously untreated patients with multiple myeloma. In comparison with other treatments, drug combinations that included vincristine and were given at 3-week intervals were associated with higher response rates and longer survival times. No gain was noted from the use of Adriamycin or from combinations of alkylating agents unless vincristine was given and the treatment intervals were short. Seventy-one responding patients were allocated at random to maintenance treatment with intermittent courses of either azathioprine--prednisone or a combination of melphalan--cyclophosphamide--carmustine (BCNU)--prednisone. The survival time was not prolonged with either maintenance treatment in comparison with that for responding patients continued on other therapies or on no therapy in previous studies. Attempts to reduce tumor was maximally with a change in the therapeutic modality, such as with immunotherapy or radiotherapy, remain to be evaluated.

Antineoplastic Agents↗
PubMed1977

Clinical evaluation of Asaley.

Asaley is an L-leucine derivative of sarcolysin which is more active against some rodent tumors. Studies in the USSR demonstrated activity in patients with ovarian and breast carcinoma, Hodgkin's disease, and multiple myeloma. This study in 73 evaluable patients indicated that an appropriate oral dose for patients with adequate bone marrow is 800 mg/M2/day X 4 days at 5-6 week intervals. The most common toxicities were myelosuppression, nausea, and vomiting. Antitumor activity was observed in 2 of 24 evaluable patients with melanoma, and stabilization of previously progressive disease was observed in patients with adenocarcinoma of the colon, multiple myeloma, lymphoma, breast carcinoma, and thyroid carcinoma. Responses were minimal and of short duration but most of the patients had received extensive prior therapy.

Adenocarcinoma↗
PubMed1977

Growth kinetics of plasma cell myeloma.

The plasma cell labeling index(ex) (LI) of 128 patients with multiple myeloma at various stages of disease was compared as a function of tumor mass load and length of treatment. No significant differences in LI were noted for patients with various degrees of tumor reduction. Patients observed during the first 3 months of treatment had significantly higher LI than did untreated patients and those studied after longer intervals. In vivo cell-cycle analysis of myeloma cells by the halving time of the grain-count method failed to establish the length of the cell cycle but defined the length of S+G2 phases as being longer than 60 hours. Similar studies conducted in vitro defined a shorter combined length of S+G2 phase. In 2 patients in whom continuous infusion with [3H] thymidine was performed, the generation time was established as 8 days. Both patients had similar initial LI (5.7 and 6.6) but different growth fractions (19 and 47%). The measured tumor mass doubling time was much longer than the calculated one, suggesting the presence of considerable intrinsic cell loss (83 and 47%). These observations were summarized by a hypothetical two-compartment model for the growth kinetics of multiple myeloma.

Bone Marrow↗
PubMed1977

Acute leukemia in multiple myeloma.

Of 476 patients with multiple myeloma treated during a 9-year period, 11 developed acute myelogenous leukemia or sideroblastic anemia. In all, the myeloma was in remission from chemotherapy with melphalan-prednisone combinations that had been continued for a median duration of 3 years. The incidence of acute leukemia or sideroblastic anemia was about 100 times higher than found in normal individuals of the same age. In all patients studied, major cytogenetic abnormalities were present, with hypodiploidy and evidence of chromosomal damage being noted most frequently. The frequency and nature of the chromosome changes were attributed to effects resulting from the prolonged drug therapy. These findings supported the long-term follow-up of selected patients with myeloma without any chemotherapy when marked degrees of remission followed the initial treatment courses.

Aged↗
PubMed1977

Blood volume in monoclonal gammopathy.

The plasma volume, red cell volume, or both were measured in 170 normal, anemic, or polycythemic subjects. For anemic subjects without a serum protein abnormality or splenomegaly, the relationship between hematocrit and red cell volume was linear and predictable. In patients with a serum monoclonal globulin on electrophoresis, the plasma voluem was significantly increased for the hematocrit in 30%, and the total blood volume was increased in 45%. The frequency of an elevated plasma volume was higher in patients with a markedly increased level of monoclonal protein. Reductions of abnormal proteins with chemotherapy were associated with declines in plasma volume. For a specific concentration, the serum viscosity was highest in patients with IgM proteins and lowest in patients with IgG globulins. Marked elevations in viscosity were noted only in sera with macroglobulinemia or with more than 5 g/dl of IgG or IgA globulins.

Anemia↗
PubMed1976

Erythrokinetics and androgens in bone marrow cancer.

Erythrokinetic studies were conducted in 60 patients with chronic anemia due to bone marrow involvement by cancer and other diseases. Fifty-seven percent had evidence of ineffective erythropoiesis contributing to the severity of their anemia. Enhanced bone marrow activity in the extremities was detected in 14% of patients. Maximal doses of several oral androgens were given to 31 patients for at least 3 months. Only 26% of the patients increased their red cell mass by at least 20%. All who benefitted had a minimum level of effective erythropoiesis and showed a decline in serum iron concentration at least 30 mug/100 ml after 1 month of treatment. Erythropoietin values were not helpful in identifying responding patients. These findings indicated the value of erythrokinetic studies in defining the bone marrow capacity of patients with cancer who are considered for androgen treatment trials.

Androgens↗
PubMed1976

Multiple myeloma in young persons.

Three young men were found to have multiple myeloma. Because their ages ranged from 17 to 22 years, the diagnosis was not considered initially, and then it was doubted until electrophoretic studies were completed. In none was the disease far advanced. These patients are the first well-documented group of young persons with multiple myeloma.

Adolescent↗
PubMed1975

Prognostic factors in multiple myeloma.

The effect of certain disease parameters on remission and survial time was evaluated in 482 patients with multiple myeloma treated with intermittent courses of melphalan-prednisone combinations. Increasing degrees of anemia, hypercalcemia, azotemia, and high serum myeloma protein levels were associated with progressive lifespan shortening. The short survival of patients with anemia and hypercalcemia was associated with short remissions in responding patients with these abnormalities. The extent of tumor mass was defined from specific laboratory parameters reported by Durie to be associated with large numbers of plasma cells. More advanced stages of myeloma were associated with higher frequencies and degrees of normal immunoglobulin depression. The response rate was not affected by the tumor mass grade, but increasing tumor mass was associated with a shorter lifespan. Greater degrees of tumor reduction were associated with longer remission and survival times. Patients in whom a marked tumor reduction was rapid had shorter survival and remission times than patients who responded more slowly.

Aged↗
PubMed1975

Monoclonal gammopathy in lymphoma.

Serum protein electrophoresis was performed in 68% of 1,682 consecutive patients with lymphoma. Of 400 patients with chronic lymphocytic leukemia and lymphocytic lymphoma, 2.3% had an IgG peak, a frequency significantly higher than that found in normal individuals of comparable age. IgM peaks occurred in 4.5% of patients with lymphomas characterized by diffuse histologic infiltration of lymph nodes. This frequency was about 100 times greater than predicted and indicated that most IgM peaks detected by electrophoresis are produced by lymphomas. Clinical responses to therapy were associated with reductions of tumor mass usually ranging from 10% to 50% of the pretreatment level. A much greater magnitude of tumor reduction is needed to improve remission duration for patients with chronic lymphocytic leukemia and lymphocytic lymphoma.

Adult↗