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Biomedical subjects

J M Bennett

Publications and source records attributed to J M Bennett.

At least 253 records · Page 14Linked to original sources
PubMed1982

Comparative trial of two teniposide-based combination chemotherapy regimens for the treatment of advanced malignant lymphomas.

One hundred and twenty-three patients with advanced measureable malignant lymphomas resistant to conventional chemotherapy were entered in a prospectively randomized trial of two teniposide (VM-26)-based combination chemotherapy regimens: V-PLAT (VM-26, cisplatin, and prednisone) and V-HEX (VM-26, hexamethylmelamine, and prednisone). Ninety-seven eligible and evaluable patients received protocol therapy. Sixteen percent of the patients had Hodgkin's disease, and 84% had non-Hodgkin's lymphoma. All patients were ambulatory (Eastern Cooperative Oncology Group Performance status 0, 1, or 2), 70% had stage IV disease, 59% had "B" symptoms, and all had failed either two or three previous chemotherapy regimens. Toxicity was mainly hematologic and significantly greater with V-PLAT. Objective tumor responses were seen in nine of 45 patients (20%) treated with V-PLAT (duration, 4-35 + weeks) and in four of 51 patients (8%) treated with V-HEX (duration, 10-65 + weeks). Among the 12 patients with histologically confirmed histiocytic lymphoma treated with V-PLAT, five (42%) experienced objective tumor responses, including two complete responses. Overall median survival was approximately 6 months, with no difference between treatment regimens. Limited antitumor activity of these combination regimens in patients with advanced malignant lymphomas has been demonstrated. However, the objective response rates were not higher than we have previously seen with either VM-26 (22%) or hexamethylmelamine (27%) given in maximum tolerable doses as single agents.

Adult↗
PubMed1982

Proposals for the classification of the myelodysplastic syndromes.

New diagnostic criteria for the diagnosis of the various myelodysplastic syndromes (MDS) are proposed, and a detailed description is given of the features that may help define MDS. Five MDS are described: (1) refractory anaemia (RA), (2) RA with ring sideroblasts, (3) RA with excess of blasts (RAEB), (4) chronic myelomonocytic leukaemia (CMML), and (5) RAEB 'in transformation'. One of the main distinguishing features of these conditions is the proportion of blast cells in the peripheral blood (PB) and/or bone marrow (BM). The morphological features of the blast cells that are of diagnostic importance have been redefined. In RA, with or without ringed sideroblasts, there are fewer than 1% of blasts in the PB and fewer than 5% in the BM; RAEB is defined as having between 5% and 20% of blasts in the BM and fewer than 5% in the PB; RAEB in transformation (a newly defined category) will be considered when any of the following features is present: (i) more than 5% of blasts in the PB, (ii) 20-30% in the BM, and (iii) the presence of Auer rods in granulocyte precursors in BM or PB. In accordance with these newly defined criteria, it is now proposed that over 30% of bone marrow blasts will suffice for the diagnosis of acute myeloid leukaemia (AML) in any of its forms (M1-M6). The proposed descriptions of the MDS should facilitate the interpretation of data emerging from cytogenetic and bone marrow culture studies and the search for features of possible prognostic significance. Recognition of the new category, RAEB in transformation, may throw light on the pathogenesis of AML.

Anemia, Aplastic↗
PubMed1982

Treatment of advanced Hodgkin's disease: 10-year experience in the Eastern Cooperative Oncology group.

Between 1972 and 1981, the Eastern Cooperative Oncology Group completed two major studies of advanced Hodgkin's disease. The first trial EST 2472, demonstrated that the five-drug combination of carmustine (BCNU), cyclophosphamide, vinblastine, procarbazine, and prednisone (BCVPP) is an effective alternative to mechlorethamine, vincristine, prednisone, and procarbazine (MOPP) chemotherapy. Although the complete remission (CR) rate for BCVPP (77%) was similar to that for MOPP (73%) in this randomized trial, the choice of induction chemotherapy significantly influenced CR duration. Patients achieving CR with BCVPP had a significantly greater disease-free survival than those who achieved CR with MOPP (65% vs 50%, respectively, at 5 years, P = 0.02). Overall survival is not different at this time between patients who received BCVPP and those who received MOPP. BCVPP produced significantly less gastrointestinal toxicity and neurotoxicity than MOPP. There was no influence on CR duration or survival with maintenance chemotherapy or BCG immunotherapy when compared to no further treatment. In the second trial, EST 1476, there was only a 58% CR rate with six cycles of low-dose bleomycin-MOPP induction chemotherapy. Complete responders and continuing partial responders were then randomized to receive either non-cross-resistant chemotherapy with doxorubicin, bleomycin, vinblastine, and DTIC (dacarbazine) (ABVD) or low-dose radiotherapy to all sites of pretreatment involvement except bone marrow. Fifty percent of the partial responses were converted to CR with either ABVD or radiotherapy consolidation. The overall CR rate at the end of consolidation was 68%. At the present time, there is no significant difference in disease-free or overall survival between ABVD and radiotherapy.

Adult↗
PubMed1982

Phase III study of intermittent carmustine (BCNU), cyclophosphamide, and prednisone versus intermittent melphalan and prednisone in myeloma.

A prospective randomized trial in patients with previously untreated multiple myeloma was performed comparing carmustine (BCNU), cyclophosphamide, and prednisone (BCP) to melphalan (Alkeran) and prednisone (AP). Induction response rates, remission duration, and survival were similar with both regimens. Hematologic toxicity was greater with AP. Crossover studies in patients who relapsed did not illustrate any significant activity with either drug treatment program. Therefore, BCP can be utilized as initial therapy in myeloma because of comparable remission rates and less hematologic toxicity.

Aged↗
PubMed1981

Granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases.

Granulocytic sarcoma is an uncommon tumor composed of granulocytic precursor cells. Because it occurs in a variety of clinical settings and because the tumor cells are primitive it is frequently unrecognized during life. This presentation details the authors' experience with 61 biopsy-proven granulocytic sarcomas. The patient age range was from 2 to 81 years (mean 48 years). In eight patients the tumors were multiple. Most common sites of involvement were bone, periosteum, soft tissue, lymph node and skin. Twenty-two tumors occurred in 15 patients with no known disease, 26 occurred in 24 patients with a known myeloproliferative disorder, and 13 occurred in 11 patients with proven acute myeloid leukemia. Thirteen of the 15 patients with no known disease developed acute leukemia in from one to 49 months after the biopsy of their tumors (mean 10 months). Most tumors occurring in patients with a known myeloproliferative disorder were associated with blast crisis. The authors' cases displayed a morphologic range from well-differentiated to those tumors that displayed virtually no evidence of differentiation by conventional microscopy. It was therefore not surprising that most tumors were originally diagnosed as lymphoma. Chloro-acetate esterase (CAE) stains were performed on 56 tumors and 47 were studied with antilysozyme immunoperoxidase technique. Fifty-six of the 57 specimens studied by either technique were positive. Antilysozyme immunoperoxidase stains were particularly useful in confirming the diagnosis.

Acetates↗
PubMed1981

Treatment of metastatic breast cancer with aminoglutethimide.

Seventy-three women with metastatic breast cancer were treated with aminoglutethimide and dexamethasone. No complete responses occurred. Ten patients (16%) achieved partial responses (mean duration, 12 months). The proportions of patients responding by disease site were breast (50%), nodes (33%), skin (23%), bone (16%), lung (11%), and liver (7%). Response did not correlate with age, menopausal status, performance status, or cortisol suppression. Ninety percent of responders had had previous responses to hormonal manipulations. No responses occurred in estrogen receptor negative patients. An additional 20% of patients had disease stabilization of eight or more months (mean, 17 months). Severe bone pain was present in 47 patients and was relieved in 19. Side effects occurred in 75% but caused discontinuation of therapy in only four patients. Somnolence, nausea, rash, Cushings syndrome, and leukopenia were the most frequent side effects. Aminoglutethimide with dexamethasone is an effective hormonal treatment for metastatic breast cancer.

Aminoglutethimide↗
PubMed1981

The morphological classification of acute lymphoblastic leukaemia: concordance among observers and clinical correlations.

The degree of concordance in the morphological classification of ALL was assessed by the FAB group after two successive reviews of 200 and 100 slides respectively. As a result, a simple scoring system for types L1 and L2 is proposed based on the following four features: (1) nuclear cytoplasmic ratio, (2) presence, prominence and frequency of nucleoli, (3) regularity of nuclear membrane outline, and (4) cell size. By this method, the overall concordance by seven observers (agreement of 7:0 or 6:1 only) increased from 63% to 84%. A significant difference in the incidence of the ALL morphological types in children (less than or equal to 15 years) and adults (greater than 15 years) was found: 74% of L1 cases were children while 66% of L2 cases were adults (P less than 0.001). No significant differences were observed in the incidence of L3 in children and adults or between L1 and L2 according to the membrane phenotype of the blast cells. All L3 cases had B-cell characteristics. A better prognosis for L1 and a higher relapse rate for L2 has been found in several recent reports; The present study may facilitate the morphological analysis of ongoing clinical trials in ALL by improving the reproducibility of the FAB classification.

Acute Disease↗
PubMed1981

Eastern Cooperative Oncology Group study of the cytochemistry of adult acute myeloid leukemia by correlation of subtypes with response and survival.

A study of over 300 adult patients with acute myeloid leukemia has been completed by member institutions of the Eastern Cooperative Oncology Group. A complete remission rate of 51% was achieved. The FAB classification was used with an overall concordance of 61% between investigators and the repository center. Acute monocytic leukemia (M5) and acute erythroleukemia (M6) accounted for 12% of the cases accessioned and had the worst median survival with no patients surviving 2 years. The longest response duration occurred in hypergranular promyelocytic leukemia (M3).

Adult↗
PubMed1981

Nodular mixed lymphoma: results of a randomized trial failing to confirm prolonged disease-free survival with COPP chemotherapy.

Fifty-two patients with stage III or IV nodular mixed lymphocytic-histiocytic lymphoma (NM) were entered on a prospective randomized trial comparing cyclophosphamide-prednisone (CP) to either COPP (cyclophosphamide, vincristine, procarbazine, prednisone) or BCVP (BCNU, cyclophosphamide, vincristine, prednisone). The COPP regimen utilized in this Eastern Cooperative Oncology Group (ECOG) trial was similar to the four-drug regimen C-MOPP reported by the National Cancer Institute to achieve prolonged relapse-free survival in this histology. No significant differences in complete response rates, response duration, or overall survival were noted among the three regimens. A pattern of continuous late relapse was observed for all three chemotherapy programs. Although 11 of the 18 (61%) COPP patients achieved a complete response, only 3/11 (27%) remain disease-free with a median follow-up of over 3 yr. However, two of these three long-term complete responders have died with no clinical evidence of recurrent disease. The COPP patients received 84% of the calculated ideal doses of cyclophosphamide and 78% of the ideal dosage of procarbazine. Grade 3-4 hematologic toxicity was noted in 22% of the COPP group, 36% with BCVP, and 0% for the CP patients. We were unable to confirm the ability of COPP to achieve durable complete remissions in NM lymphoma. The cyclophosphamide-prednisone combination was equally effective when compared with COPP and BCVP, but produced minimal toxicity.

Adult↗
PubMed1980

Cyclophosphamide, cytosine arabinoside and methotrexate versus cytosine arabinoside and thioguanine for acute non-lymphocytic leukemia in adults.

One-hundred and fifty-one adults with acute non-lymphocytic leukemia (ANLL) were entered into an Eastern Cooperative Oncology Group protocol (EST-1473) comparing twice daily cytosine arabinoside and thioguanine (AT) with weekly cyclophosphamide, cytosine arabinoside, and methotrexate (CAM) for remission induction. Of 111 evaluable patients, 16 treated with CAM and 16 treated with AT entered complete remission (CR) on their initial therapy and 5 additional patients entered CR on crossover for a total of 37 or 33% of the evaluable patients. Of the 71 patients who survived three weeks or longer, the overall CR rate was 52%. Cytochemical studies were performed on 85% of the evaluable cases, Minor disagreements between morphologic subtypes of ANLL occurred in 50% of cases. There was no difference in response rates between the major subtypes of ANLL regardless of whether the investigator's diagnosis or the cytochemical reference laboratory diagnosis was used. The median survival of all evaluable patients was 4.9 weeks; those patients who responded with a CR had a median survival of 60 weeks, while those who did not have a median survival of less than 3 weeks. Age less than 60, ambulatory performance status, or fewer than 50% marrow blasts were also associated with a better response rate and longer survival. CAM had more severe mucositis and vomiting associated with it than did AT, but toxicities were otherwise comparble. Weekly CAM and AT appear to be equally effective regimens in the treatment of ANLL.

Adult↗
PubMed1980

Nodular mixed lymphocytic-histiocytic lymphoma (NM): response and survival. Eastern Cooperative Oncology Group.

Eighty patients with nodular mixed lymphocytic-histiocytic lymphoma (NM) entered on four different Eastern Cooperative Oncology Group chemotherapy studies were analyzed for response and survival. They were compared with 249 patients with nodular lymphocytic poorly differentiated lymphoma (NLPD), who were treated similarly. The response rates in NM were: CR 45%, PR 30%, NC-PD 25%. In NLPD the quality of response had little effect on survival (CR 91%, PR 90%, NC-PD 76%), whereas in NM the two year survivorship of 85% for CR dropped drastically to 33% for the partial responders (P less than 0.01). Ninety percent of the previously untreated NLPD, but only 59% of the comparable group of NM, survived 2 years. In 23 patients with NM in which the pattern was reported as both nodular and diffuse (ND-M), the 2-year survival of 35% was markedly inferior to a 66% 2-year survivorship observed in 57 patients with the pure nodular pattern (P less than 0.05). It appears that NM is a less favorable lymphoma type than NLPD. In NM achievement of a CR affects survival favorably; consequently, the use of aggressive chemotherapy regimens in an attempt to achieve high rates of CR are recommended. In NLPD, on the other hand, since survival curves of partial and complete responders are almost identical, suboptimal treatments may be justified.

Antineoplastic Agents↗
PubMed1980

Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group.

The prognostic effect of weight loss prior to chemotherapy was analyzed using data from 3,047 patients enrolled in 12 chemotherapy protocols of the Eastern Cooperative Oncology Group. The frequency of weight loss ranged from 31 percent for favorable non-Hodgkin's lymphoma to 87 percent in gastric cancer. Median survival was significantly shorter in nine protocols for the patients with weight loss compared to the patients with no weight loss. Chemotherapy response rates were lower in the patients with weight loss, but only in patients with breast cancer was this difference significant. Decreasing weight was correlated with decreasing performance status except for patients with pancreatic and gastric cancer. Within performance status categories, weight loss was associated with decreased median survival. The frequency of weight loss increased with increasing number of anatomic sites involved with metastases, but within categories of anatomic involvement, weight loss was associated with decreased median survival. These observations emphasize the prognostic effect of weight loss, especially in patients with a favorable performance status or a limited anatomic involvement with tumor.

Activities of Daily Living↗