Cornelius J. Cornell

A comparative study of a bcnu containing 4-drug program versus mopp versus 3-drug combinations in advanced Hodgkin's disease. A cooperative study by the cancer and leukemia group B

A prospective randomized trial by CALGB examined the relative value of four chemotherapy regimens in 537 patients with stage III B and IV Hodgkins disease. A new combination BOPP, derived by substitution of BCNU for nitrogen mustard in the MOPP regimen, was compared to MOPP and to two 3‐drug regimens, derived by removing the procarbazine in BOPP (BOP) or removing the alkylating agent (OPP). The 4‐drug programs gave significantly higher frequency of complete remissions (BOPP 67%, MOPP 63%) than the 3‐drug regimens (BOP 40%, OPP 42%), and significantly longer duration of remission and survival. BOPP had a therapeutic activity equal to MOPP, and was accompanied by less toxicity. After 6 cycles of induction chemotherapy, responding patients, both CR and PR, were continued on maintenance chemotherapy for 3 years. No significant difference in relapse rate was demonstrated following maintenance treatment with either vinblastine, chlorambucil, or chlorambucil plus monthly vincristine + prednisone doses. Nor could a reinforcement phase late in the maintenance program be shown to influence the relapse rate. The median survival for all patients entered on the 4‐drug programs was 5 years, while the median has not yet been reached at 6 years for those patients, who obtained CR.

Comparison of methyl-CCNU and CCNU in patients with advanced forms of Hodgkin's disease, lymphosarcoma and 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 Hodgkins 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 Hodgkins than in non‐Hodgkins lymphomas.

Successful donation and transplantation of multiple organs after fatal poisoning with brodifacoum, a long-acting anticoagulant rodenticide: case report.

BACKGROUND Successful organ donation has been reported after death from poisonings with cyanide, carbon monoxide, methanol, benzodiazepines, and tricyclic antidepressants. In this report, we describe a case of multiple organ donation from a previously healthy individual who died from poisoning with the long-acting anticoagulant rodenticide, brodifacoum. METHODS Case report and review of the literature. RESULTS All organs procured from the poisoned donor functioned adequately, and there were no hemorrhagic complications in any of the recipients. CONCLUSION This case demonstrates that brodifacoum poisoning is not an absolute contraindication to organ donation from brain-dead patients who have sustained a fatal ingestion.

Atherosclerosis and coronary bypass surgery in hereditary factor VII deficiency

A 66-year-old man with homozygous deficiency of factor VII (less activity than 4 percent of normal) had a minimal hemorrhagic tendency and severe coronary atherosclerosis, and underwent aortocoronary saphenous vein bypass surgery. Although plasma factor VII coagulant activity and cross-reacting material were markedly reduced, comparable amounts of factor VII antigen were detected in peripheral blood mononuclear cells of both the patient and of a normal subject by Western blotting techniques. Accelerated coagulation was observed following brief exposure of the patients phytohemagglutinin-stimulated peripheral blood mononuclear cells to low concentrations of ambient factor VII in vitro. Evidence indicates that factor VII plays a role in vivo in both hemostasis and atherogenesis and it might be assumed that factor VII deficiency would both predispose to excessive bleeding and forestall atherosclerosis. However, these observations suggest that factor VII-mediated thrombin generation may proceed by partitioning of small amounts of factor VII on tissue factor-expressing cells and that factor VII contained within monocytes may facilitate tissue factor-induced coagulation by these cells. These features may provide efficient coagulation activation despite a deficiency of the plasma coagulant protein. The current results may explain, at least in part, the minimal bleeding tendency, and also the occurrence of thrombosis and atherosclerosis in certain persons with factor VII deficiency.

Prohemostatic therapy: the rise and fall of aprotinin.

Aprotinin has been used clinically to enhance hemostasis for decades and was approved in the United States by the Food and Drug Administration in 1993 to reduce the transfusion requirement during coronary artery bypass surgery. Marketing of aprotinin ceased recently when observational studies and a randomized clinical trial reported increased cardiovascular toxicity in patients receiving this drug. The importance of prohemostatic therapy is reviewed in light of new information on long-term deleterious effects of blood transfusion, including increased risk of cardiovascular disease, malignancy, and infection possibly attributable to delivery of a load of red cell-derived redox-active iron. Weaknesses in design of clinical trials that failed to control adequately for such alternative mechanisms of toxicity complicate interpretation of risks versus benefits in clinical trials of aprotinin given to reduce transfusion requirement in the acute surgical setting. Properties and applications of aprotinin that may not have received sufficient attention in the decision to remove this drug from the therapeutic armamentarium are reviewed. Potential application of prohemostatic drugs, including aprotinin to special populations at risk for operative blood loss requiring transfusion, is illustrated by the description of nine patients with coagulopathies whose operative bleeding was managed effectively with aprotinin. This drug may remain safe and effective in patients at risk of bleeding with surgery. Beneficial effects of aprotinin seemingly unrelated to its prohemostatic properties, especially its apparent striking antineoplastic effects, warrant further study.

Thrombotic Thrombocytopenic Purpura: Failure of Plasma Infusion and Antiplatelet Agents

Excerpt To the editor: Byrnes and Khurana (1) have reported the successful treatment of patients with thrombotic thrombocytopenic purpura using plasma infusions. Different promising treatments have...

Heparin Therapy for Heat Stroke

Excerpt To the editor: The role of disseminated intravascular coagulation and the fibrinolytic mechanism in heat stroke has been controversial (1-3). We recently observed a 17-year-old male with he...