Use of a consortium to provide continuity in physician training: the OU-COM experience.
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Clinical Clerkship↗
Biomedical subjects
W Costello
Publications and source records attributed to W Costello.
The distribution of human C4 DNA variants in relation to major histocompatibility complex alleles and extended haplotypes.
A C4 DNA polymorphism that can subdivide C4 allotypes and major histocompatibility complex-linked complement gene cluster allele combinations (complotypes) that are not distinguishable by standard electrophoretic means was used to assess further the distribution and linkage association of C4 variants. Segregation of the DNA polymorphism in family studies allowed assignment of particular variants to particular major histocompatibility complex haplotypes. These studies revealed that some complotypes were exclusively correlated with a particular C4 DNA variant, whereas others were not and could be subdivided according to which particular C4 DNA variant was observed. When complotypes that could be subdivided at the DNA level were considered in relation to flanking major histocompatibility complex markers, it was apparent that complotypes associated with major histocompatibility complex "extended haplotypes" had an exclusive correlation with a particular C4 DNA variant. This finding supports the hypothesis that "extended haplotypes" are unique associations of major histocompatibility complex allele combinations and are genetically similar, stably inherited units.
Alleles↗
BCVPP chemotherapy for advanced Hodgkin's disease: evidence for greater duration of complete remission, greater survival, and less toxicity than with a MOPP regimen. Results of the Eastern Cooperative Oncology Group study.
Two chemotherapy regimens for treatment of patients with advanced Hodgkin's disease, BCVPP (carmustine, cyclophosphamide, vinblastine, procarbazine, and prednisone) and MOPP (mechlorethamine hydrochloride, vincristine, procarbazine, and prednisone), were compared in a randomized prospective study. Two hundred ninety-three patients were evaluable in the induction phase of this study. The complete remission rate with BCVPP was 76% (112/147) and with MOPP, 73% (106/146) (p = 0.51). The duration of complete remissions for previously untreated patients given BCVPP was significantly longer than that for previously untreated patients given MOPP (p = 0.02). Although hematologic toxicities were similar, BCVPP caused less gastrointestinal (p = 0.0001) and neurologic toxicity (p = 0.01) than MOPP. Previously untreated patients achieving complete remission with BCVPP survived significantly longer than those receiving MOPP (p = 0.03). As primary induction chemotherapy for advanced Hodgkin's disease, BCVPP is an effective alternative to MOPP, having equal or greater therapeutic benefit with less toxicity.
Adult↗
Cloning of human prealbumin complementary DNA. Localization of the gene to chromosome 18 and detection of a variant prealbumin allele in a family with familial amyloid polyneuropathy.
Prealbumin, a 55,000 Mr protein, is a normal constituent of human serum. In patients with familial amyloid polyneuropathy (FAP), an autosomal dominant disease, variant prealbumin molecules are found in association with systemic amyloid deposits. One variant prealbumin has a methionine for valine substitution at amino acid 30 and has been implicated in the pathogenesis of type 1 FAP. A prealbumin-specific complementary DNA clone has been isolated from an adult human liver library and used in Southern blot hybridization experiments to identify a unique NsiI restriction endonuclease site in the variant allele carried by type 1 FAP patients with the methionine for valine substitution. The complementary DNA clone has been used to analyse a panel of human-mouse and human--hamster somatic cell hybrid DNAs and localize the prealbumin gene to chromosome 18.
Alleles↗
Monitoring and evaluating new programs.
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Evaluation Studies as Topic↗
Nodular histiocytic lymphoma: factors influencing prognosis and implications for aggressive chemotherapy.
Twenty-five patients with Stage III and IV nodular histiocytic lymphoma (NH), entered on three different Eastern Cooperative Oncology Group protocols from 1972-78, were analyzed for response and survival. A complete response (CR) rate of 44% was observed, with 40% partial responders (PR). Four of the 11 CRs are continuing in their original remission. Median survival for CRs was 52 months; for PRs it was 30 months. The six patients treated with cyclophosphamide-prednisone had a median survival of 18 months versus 51 months for the 19 patients treated with more aggressive combination chemotherapy programs. No significant difference in survival was noted between those patients with both nodular and diffuse histology and those with a pure nodular pattern. The median survival of the 25 NH patients was 47 months and is similar to a group of 101 patients with nodular mixed lymphoma (NM) entered on the same ECOG protocols during this time. This survival is intermediate between the nodular lymphocytic poorly differentiated subtype and diffuse histiocytic lymphoma. It suggests that patients with NH histologies be treated with aggressive combination chemotherapy programs designed to achieve complete remission and prolonged disease-free survival.
Antineoplastic Agents↗
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↗
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↗
Eastern Cooperative Oncology Group experience with the rappaport classification of non-Hodgkin's lymphomas.
Eastern Cooperative Oncology Group experience in the clinical application of the Rappaport Classification on Non-Hodgkin's lymphomas (NHL) is reviewed in 670 cases studied since 1972. The diagnoses of institutional pathologists were reviewed by the Pathology Panel and Repository Center for Lymphoma Clinical Studies. Diagnostic agreement in regard to histologic pattern (nodular versus diffuse) was excellent (90%) but was less favorable when concurrence as to both pattern and cell type was assessed (82% in NLDP and 60% or less in other subtypes). Disagreement in regard to NHL diagnosis is related to the complexity of present nomenclature and to the lack of support of pathology activities within cooperative groups. It is suggested that patients entered into group NHL studies be randomized into favorable and unfavorable groups, primarily on the basis of histological pattern.
Humans↗
Survival of nodular versus diffuse pattern lymphocytic poorly differentiated lymphoma.
Response and survival were analyzed in 97 patients with NLPD (Nodular Lymphocytic Poorly Differentiated Lymphoma) and 77 with DLPD (Diffuse Lymphocytic Poorly Differentiated) treated by intensive versus moderate chemotherapy regimens. The complete and overall response rate in NLPD of 47% and 81% was significantly superior to 25% and 59% obtained in DLPD. The estimated two year survival of 83% in NLPD was also significantly superior to 47% two year survivorship of DLPD (p less than .001). The chemotherapy responsiveness had a significantly favorable effect on DLPD survivorship with two year survivals of 84% for CR, 58% for PR and 17% for PD. In NLPD the effect of chemotherapy responsiveness on survival was less striking (CR 91%, PR 85%, and PD 72% surviving two years). The data, in our opinion, confirm the rationale for the use of aggressive multiple agent chemotherapy regimens in DLPD where achievement of compelte response appears to be the single most important factor in improving survivorship. On the other hand NLPD, with excellent survival rates which appear to be only partially dependent on chemotherapy responsiveness might serve as an ideal model for moderate intensity or single agent chemotherapy trials.
Adult↗
Treatment of histiocytic and mixed lymphomas: a comparison of two, three and four drug chemotherapy.
The Eastern Cooperative Oncology Group has studied 187 patients with generalized progressive malignant lymphoma classified as having the histologic sub-types histiocytic or mixed. Histology review by the Pathology Panel for Lymphoma Clinical Trials demonstrated a 31% disparity with contributing institution's pathologists in regard to cell type, but good agreement with interpretation of nodular or diffuse nodal pattern. Patients were assigned at random to treatment with cyclophosphamide 1 g/m2 on day 1 and prednisone 100 mg/m2 daily for five days (CP); CP plus vincristine 1 mg/m2 on day 1 (CVP); or CVP plus BCNU 60 mg/m2 on day 1 (BCVP). Chemotherapy was given for nine, twenty-one day cycles. The observed complete remission rates were CP-21%, CVP 34%, BCVP 34%. Both CVP and BCVP had significantly more complete remissions than CP, but survival following CVP (118 weeks) was significantly longer than that following either BCVP (76 weeks) or CP (74 weeks). Histologic sub-type, lymph node pattern, response to chemotherapy, performance status and stage of disease were also found to influence survival.
Adult↗
Diffuse well-differentiated lymphocytic lymphoma (DLWD): response and survival.
34 patients with the diagnosis of diffuse well-differentiated lymphocytic lymphoma (DLWD), confirmed by a Pathology Panel, who were entered on a previously reported Eastern Cooperative Oncology Group study (EST 1472), were analyzed for response and survival. The response rates were as follows: CR 32%, PR 39%, NC or PD 29%. Survival analysis according to chemotherapy response revealed an estimated two-year survivorship of CR 89%, PR 65%, NC 69%, and PD 44%. Comparison with NLPD entered on the same study showed a two-year survival of 83% for NLPD and 67% for DLWD, indicating significantly poorer survival for DLWD as compared to NLPD (p less than .05). Median survival for DLWD from diagnosis was 39.0 + months. The presence of lymphocytosis over 4000/mm3 had little effect on response rates or survival. We conclude that DLWD is a less favorable lymphoma type than NLPD and should be treated with aggressive chemotherapy since achievement of CR seems to effect survival favorably.
Aged↗
Eastern Cooperative Oncology Group studies with DTIC (NSC-45388).
In four randomized controlled clinical trials with DTIC involving patiens with malignant melanoma, the Eastern Cooperative Oncology Group has seen a consistent objective response rate of 16%. A study of combinations of DTIC with two nitrosoureas indicated no additive effect. Survival and response were strongly correlated with sex, ambulatory status, and site of disease involvement. As secondary treatment DTIC was less effective, indicating only a 3% response rate. Survival benefit could be related to response. Among the ten largest contributors of patients, response rates varied from 3% to 40%. Similarly, while the overall response rate was not different for the combinations as compared to DTIC alone, the variation noted from study to study reflects the need for controlled randomized trials of chemotherapy for patients with malignant melanoma.
Adult↗