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Biomedical subjects

R T Silver

Publications and source records attributed to R T Silver.

At least 109 records · Page 6Linked to original sources

A comparative trial of daunorubicin, cytosine arabinoside, and thioguanine, and a combination of the three agents for the treatment of acute myelocytic leukemia.

In this study 523 previously untreated patients with acute myelocytic leukemia were randomly allocated to induction therapy with daunorubicin 60 mg/M2 daily X 3, cytosine arabinoside and thioguanine 100 mg/M2 each every 12 hours until marrow hypoplasia was achieved, or a 5-day course of the three drugs with daunorubicin 100 mg/M2 given on dav 1 and cytosine arabinoside plus thioguanine each given at a dose of 100 mg/M2 every 12 hours for five days. All patients received cyclophosphamide 600 mg/M2 followed in 24 hours by hydroxyurea 500 mg/M2 every six hours for four doses monthly for maintenance therapy. Patients were randomized to receive one of three antimetabolite treatments beginning 24 hours after the last dose of hydroxyurea each month for seven days. One such treatment consisted of 6-mercaptopurine 100 mg/M2 daily, another group received 6-thioguanine at the same dose daily, and the third group received 50 mg/M2 of both antimetabolites daily. There were no significant differences in complete response rate, remission duration, or survival among the various treatment groups.

Adult↗

Comparison of methyl-CCNU and CCNU in patients with advanced forms of Hodgkin's disease, lymphosarcoma nad reticulum cell sarcoma.

In May 1972, the Cancer and Leukemia Group B initiated a randomized study comparing the effectiveness of CCNU and methyl-CCNU in patients with advanced malignant lymphomas, including Hodgkin's disease (HD), lymphosarcoma (LYS) and reticulum cell sarcoma (RCS). A single dose of 100 mg/m2 of CCNU or 150 mg/m2 of methyl-CCNU was given orally every 6 weeks. In patients with leukopenia or thrombocytopenia, due to prior treatment, this dose was reduced to 70 mg/m2 of CCNU and 100 gm/m2 of methyl-CCNU. Of 109 evaluable patients, 60 received CCNU and 49 received methyl-CCNU. Response rates (complete and partial) to CCNU and methyl-CCNU were respectively 42% (14/33) and 15% (3/20) in HD, 21% (3/14) and 21% (3/14) in LYS, 15% (2/13) and 27% (4/15) in RCS. Responses to methyl-CCNU, but not to CCNU, were seen only in patients who developed significant hematologic toxicity. Responses to both drugs were generally of short duration due to the advanced stage of the disease. Renal, hepatic or neurological toxicity was not observed. In conclusion, CCNU proved to be superior to methyl-CCNU for the treatment of advanced HD. CCNU was also observed to be of higher activity in Hodgkin's than in non-Hodgkin's lymphomas.

Clinical Trials as Topic↗

Factors associated with prolonged survival in chronic myeloid leukemia.

Four patients who demonstrated unusually prolonged survival with Philadelphia chromosome positive Ph' (+) chronic myeloid leukemia (CML) were analyzed for factors associated with survival. Survival duration from initial diagnosis ranged from 120 to 222 months, with a mean of 170 months. At diagnosis, age, symptoms, liver or spleen size, hematocrit, white blood cell count, absolute peripheral myeloblast plus promyelocyte count, and uric acid did not have unique prognostic significance. At diagnosis all four patients had normal or low-normal platelet counts, (range: 170,000 to 248,000/mm3). Thrombocytopenia occurred during treatment in three patients. None of the four patients, however, developed severe marrow hypoplasia or leukopenia during treatment for the chronic phase. Cytogenic studies performed from 103 to 156 months after diagnosis did not reveal a large subpopulation of marrow cells with a normal karyotype or cells with the XO genotype in the male patients. These observations suggest that prolonged survival in CML 1) is not contingent upon intensive treatment resulting in marrow hypoplasia, and 2) does not require the persistence of a clone of karyotypically-normal bone marrow cells or a clone of marrow cells in males which has lost the Y chromosome. A normal or low-normal platelet count at diagnosis may be a favorable prognostic indicator.

Adult↗

Guidelines for protocol studies in chronic lymphocytic leukemia.

The treatment of any malignant disease requires appropriate criteria for diagnosis of the disease, appropriate methods for study, and techniques for evaluating response to treatment. In the past five years, there have been a number of proposed guidelines for studies in chronic lymphocytic leukemia (CLL). These submitted guidelines represent a further re-evaluation of concepts in CLL, and are currently in use by Cancer and Leukemia Group B for protocol studies. It is clear that revisions will continue to be make as new knowledge accumulates. In the meantime, these are submitted for publication for use by other investigators.

Drug Therapy↗

Morbidity of staging laparotomy in Hodgkin's disease.

The morbidity of exploratory laparotomy and splenectomy in Hodgkin's disease was determined at three institutions--a university hospital, a major university affiliated hospital and a large community hospital. Of the 90 patients who underwent exploratory laparotomy, 33 (37%) sustained a major or minor complication within two weeks of surgery. Seventeen patients (19%) sustained a minor complication and 16 patients (18%) a major complication. There was no mortality. A higher complication rate occurred in patients more than 28 years of age (p = 0.01), and in patients with advanced clinical stage when age was controlled (p = 0.05). We suggest that prior to performing an exploratory laparotomy in a given patient, the necessity of the procedure be weighed against its potential hazards.

Adult↗

Splenectomy in chronic myeloid leukemia.

We review splenectomy in chronic myeloid leukemia, emphasizing recent studies that have evaluated early splenectomy during the chronic phase of the disease. Despite current interest in splenectomy in chronic myeloid leukemia, uncontrolled clinical trials to date suggest that the operation during the early phase neither delays the onset of blastic transformation nor prolongs survival. Immediate operative mortality of splenectomy during the chronic phase is low, generally less than 1%. The morbidity of the procedure, however, remains formidable due to infectious and thromboembolic complications. Splenectomy during chronic-phase chronic myeloid leukemia permits easier control of the disease in patients who are thrombocytopenic due to busulfan toxicity or sensitivity. Splenectomy during the chronic phase may also palliate those patients who suffer from acute splenic events or massive splenomegaly. Splenectomy in blast-phase disease should be considered a heroic measure providing little benefit to most patients.

Aged↗

Fever, rash, and muscle tenderness. A distinctive clinical presentation of disseminated candidiasis.

Five patients had fatal, disseminated candidiasis. At the onset of candidemia, a remarkably similar and distinctive triad of high fever, papular erythematous skin lesions, and diffuse severe muscle tenderness developed in each patient. This previously unreported clinical syndrome is sufficiently unique to justify a presumptive diagnosis of disseminated candidiasis and the use of empiric antifungal therapy pending culture and biopsy results.

Adult↗

A new combination chemotherapy for resistant Hodgkin disease.

A new four-drug combination chemotherapeutic regimen (BVDS) was used in the treatment of advanced Hodgkin disease resistant to MOPP (mechlorethamine hydrochloride, vincristine sulfate, procarbazine hydrochloride, and prednisone). The BVDS regimen, consisting of 12 cycles of bleomycin sulfate, vinblastine sulfate, doxorubicin hydrochloride (Adriamycin), and streptozocin (streptozotocin), was administered to ten patients. Responses were seen in five (50%) of these patients. Complete remissions occurred in three (30%). These results suggest that BVDS is an effective alternative regimen to MOPP, and may be of benefit not only to patients resistant to MOPP, but also to newly-diagnosed patients with advanced hodgkin disease when combined sequentially with MOPP.

Adolescent↗

High dose methotrexate with citrovorum factor in adult resistant lymphoma.

Seven adult patients with advanced lymphoma, resistant to vincristine, prednisone, alkylating agents and Adriamycin were treated with "high dose" methotrexate and citrovorum factor rescue. Therapy consisted of 4 to 6-hour infusions of methotrexate (5--100 mg/kg) every 1 to 2 weeks with citrovorum rescue initiates 2 to 12 hours after termination of the infusion. Objective responses were obtained in three patients but these were short lived. Mucosal and hematologic toxicity occurred when repeat courses of therapy were administered. The results suggest that high dose methotrexate may be effective therapy in lymphoma, particularlly if citrovorum factor rescue is used early and in adequate dosage.

Adolescent↗

Comparison of daily versus intermittent chlorambucil and prednisone therapy in the treatment of patients with chronic lymphocytic leukemia.

Ninety-six patients with stage III and stage IV chronic lymphocytic leukemia (CLL) were randomized into one of three treatment schedules. Prednisone was common to all three schedules and was given daily in an initial dosage of 0.8 mg/kg for the first 14 days, with successive halving of the daily dose on days 15 and 29 for a total 6-wk course. Prednisone was then given once a month at 0.8 mg/kg once a day for each of 7 consecutive days. Schedule I was prednisone plus chlorambucil (CLB) given as a once-a-month dose of 0.4-0.8 mg/kg; schedule II was both drugs, but the CLB was given as a daily dose of 0.08 mg/kg; schedule III was prednisone alone. Complete and partial remission (CR + PR) was 47% for schedule I, 38% for schedule II, and 11% for schedule III. Patients who responded (CR + PR) in each of the treatment schedules survived longer than the nonresponders. Complete remission was obtained in both CLB treatment schedules, but not with the prednisone alone regimen. Although overall survival was best in the intermittent CLB arm, there was no significant difference in survival time between the three treatment schedules. Toxicity was minimal in all three regimens. Augmentation of the intermittent monthly CLB, even to 1.5 and 2.0 mg/kg, was tolerated without undue marrow toxicity. About 22% of these patients either had diabetes mellitus at the time of entry on the study or manifested hyperglycemia during the course of treatment and observation.

Anemia↗

Value of biopsy in diagnosis of primary lymphosarcoma of marrow.

We report the clinical, hematologic, and survival characteristics of 12 patients with lymphosarcoma primarily involving the marrow but without substantial nodal disease. The importance of the biopsy in establishing this diagnosis is stressed, since in 7 of the 12 cases the diagnosis would not have been made had only a marrow aspiration been performed.

Biopsy, Needle↗

Peritoneoscopy in Hodgkin disease. Confirmation of results by laparotomy.

Peritoneoscopy was used to evaluate the liver in 35 previously untreated patients with Hodgkin disease. Four were found to have hepatic involvement. Of the 31 patients with normal peritoneoscopies, only one had liver disease demonstrated subsequently at confirmatory exploratory laparotomy. The diagnostic accuracy of peritoneoscopy was 93% for patients at high risk for hepatic disease and 97% for all patients studied. Morbidity from the procedure was minimal. There was no mortality. Peritoneoscopy is a highly accurate staging procedure that should be considered as an antecedent or as an alternative to laparotomy in patients with Hodgkin disease. Its accuracy and minimal morbidity should be considered in the critical selection process of determining which individuals should undergo laparotomy.

Biopsy, Needle↗

Mediastinal irradiation for chronic lymphocytic leukemia.

Thirty-one patients with chronic lymphocytic leukemia were treated with mediastinal radiation. In none of the patients was complete remission achieved; either partial remission or clinical improvement was achieved in 52 per cent, but the duration of response was short. The response rate was 77 per cent for the patients receiving a total radiation dose greater than 3,000 rads and 45 per cent for those receiving less than 3,000 rads. Severe life-threatening toxicity was noted in 11 patients and seven of these patients died; two patients died with progressive disease. Severe toxicity was manifested by one or more of the following: bone marrow aplasia, pancytopenia, gram-negative sepsis, generalized herpes zoster and severe esophagitis. Neither the total dose of radiation nor the dose per week correlated withe the severity of reaction or death.

Aged↗