C. William Aungst

Myeloid Leukemia in Hodgkin's Disease: Chromosomal Abnormalities

Abstract Three cases of myeloid leukemia (acute myeloblastic leukemia, chronic myelocytic leukemia, erythroleukemia) were observed among a population of patients with Hodgkins disease. Chromosome ...

Complications of BCG Vaccination in Neoplastic Disease

More than 300 patients with neoplastic disease (most with lymphoma or leukemia) were given one or more BCG vaccinations. In the great majority of cases, these were well tolerated. The complications we observed were of three types: (A) persistent BCG infection that could disseminate widely, (B) activation of old, dormant acid-fast infection, and (C) hypersensitivity reactions. The latter were related to the frequency of administration and dose of organisms. It is important to recognize that BCG organisms may not be completely destroyed by patients with impaired immunologic defenses, and that their inoculation may create a source of disseminated acid-fast infection at a later time. In our limited experience, treatment with isoniazid for 2 to 3 months has resulted in cure of BCG infection. Hypersensitivity reactions may constitute a more serious problem than such infections.

Response to bcg vaccination and survival in advanced Hodgkin's disease

Thirty‐two patients with advanced Hodgkins disease (predominantly Stage IV), who had negative skin test responses to second strength PPD, were vaccinated with BCG during a period of quiescent or mildly active disease. Of 8 whose tuberculin responses were not converted, 7 died of Hodgkins disease within a year. In contrast, only one of the 24 patients who developed positive tuberculin skin tests died within this time period, and the median survival of the converted group, currently 30 months, is still increasing. This difference is significant (p <.001) and indicates that BCG vaccination can provide valuable prognostic information in advanced Hodgkins disease. It is suggested that cellular immune mechanisms may constitute the principal determinant of “host resistance” in Hodgkins disease.

Corticosteroid therapy for lymphomas and chronic lymphocytic leukemia

Corticosteroids were administered to 137 patients with lymphoma or chronic lymphocytic leukemia for a total of 188 courses. Although no complete responses were seen, two thirds of the patients with chronic lymphocytic leukemia, lymphosarcoma and Hodgkins disease and one third of reticulum‐cell sarcoma patients obtained objective benefit. Good responses were noted in 44% of patients with chronic lymphocytic leukemia, 42% of those with lymphosarcoma, 28% with Hodgkins disease and 18% of reticulum‐cell sarcoma patients. The responses included definite tumor shrinkage in all disease categories. Responsiveness was well maintained during successive treatments. Corticosteroid therapy was particularly useful in the presence of hematologic depression that precluded the use of other chemotherapeutic agents. Brevity of unmaintained remissions (median 3 months) and a significant rise in the incidence of fungal infections found at autopsy were definite disadvantages.

Delay in Progression of Malignant Lymphoma after BCG Vaccination

Abstract To determine the effect of BCG vaccination on the course of malignant lymphoma in remission, 50 patients with Stage IA or IIA, were randomly assigned in 1965–67 to serve as controls or to receive BCG vaccination. These patients had been staged and treated by technics associated with a 74 per cent relapse rate. Among the controls, 77 per cent relapsed within a follow-up period of six to eight years, with a mean time to the first new lesion of 10.6 months. Among the vaccinated patients, 61 per cent relapsed, with a mean time to the first new lesion of 25.9 months. The differences in relapse patterns were statistically significant, and could not be accounted for by differences in host, tumor or treatment characteristics. Clinical and immunologic data were consistent with the hypothesis that these differences were due to effects of BCG, operating over a period averaging about 2 1/2 years. (N Engl J Med 291:1226–1230, 1974)

Comparison of intensive versus moderate chemotherapy of lymphocytic lymphomas. A progress report

In an Eastern Cooperative Oncology Group trial, Cytoxan‐prednisone (CP) Induction was compared to BCNU‐prednisone (BP) in 273 patients with lymphocytic lymphoma. Response rates were comparable, with 21% achieving complete response and 40%, partial response. Patients with a nodular pattern responded better. Maintenance phase comparing cyclic intensive therapy (BCVP) with intermittent chlorambucil revealed the superiority of BCVP as demonstrated by improvement of the quality of response and somewhat longer remissions. The value of the Rappaport classification in the evaluation of lymphoma chemotherapy results is discussed. It is suggested that NHL be separated into “favorable” and “unfavorable” groups, based on the presence or absence of nodularity and treatment schedules devised accordingly.

IMMUNOTHERAPY OF CHRONIC MYELOCYTIC LEUKEMIA: EFFECTS OF DIFFERENT VACCINATION SCHEDULES*

In a clinical trial of immunotherapy in chronic myelocytic leukemia, 62 patients received repeated intradermal injections of BCG‐cultured cell mixtures, while 16 were vaccinated with BCG alone. The lymphoblastoid cell lines used for vaccination were established from blood of patients with advanced myeloid leukemia and were reactive with “specific” primate antisera against myeloid leukemic cells. Both sensitization to target cell antigens and substantial general increases in delayed hypersensitivity responses were recorded among immunized patients. Major immunologic complications (hypersensitivity and “autoimmune” phenomena) were observed in 10 patients. These complications were attributable to the BCG content of vaccines, and their incidence correlated with intensity of immunologic stimulation.

Lymphosarcoma. A comparison of extended to conservative chemotherapy

Sixty‐three patients with Stage III and IV lymphocytic lymphoma were randomized for induction treatment between a single course of nitrogen mustard and a 14‐day course of prednisone (conservative therapy) or sequential rotation of BCNU, nitrogen mustard and cytoxan with intermittent vincristine and prednisone for 6 months (extended therapy). Maintenance therapy by an oral alkylating agent (cytoxan or chlorambucil) with or without prednisone was given. Complete remission occurred in 75% of the conservative and 77% of the extended therapy group. The median duration of remission was similar, and greater than 27 months in both groups, and there was no difference in survival. At 1 year 80% of patients with no prior chemotherapy were in remission vs. 47% of patients with prior chemotherapy (p < .01). No significant advantage for extended chemotherapy was found. The addition of vincristine was not helpful in induction and prednisone during maintenance did not improve the duration of remission or survival.

Chemotherapy of the terminal phase of chronic myelocytic leukemia with combinations of colchicine derivatives and purine analogs

Abstract Forty-six patients in the terminal phase of chronic myelocytic leukemia were treated with combinations of desacetylmethylcolchicine or trimethylcolchicinic acid and 6-mercaptopurine or 6-thioguanine. The drugs were taken by mouth, in dosages intended to avoid severe granulocytopenia. The combinations were generally well tolerated and platelet and granulocyte counts were usually above life-threatening levels, permitting 57% of the patients to be treated principally as out-patients. Complete hematologic and clinical response was achieved in six patients (13%) and partial response was obtained in 18 (39%). There were no karyotypic remissions. Median survival for the 24 responders was 8 months, while that for the 22 patients who had no response or only minor improvement was 4 months. Survival was as good among patients with partial remission as among those with complete response.

An Immunologic Test for Prognosis in Advanced Hodgkin's Disease.

Excerpt Prognosis in Hodgkins disease is notoriously difficult. Some patients die rapidly despite early and aggressive therapy, while others with various combinations of unfavorable prognostic sig...