One hundred and seven patients with carcinoma of the lung underwent immunologic testing, and 62 of these patients were randomized to an immunotherapy protocol comparing the effects of Pasteur strain BCG, either alone or combined with allogeneic tumor cells, to the effects of no immunotherapy. Patients with residual disease left at the time of surgery or with metastatic disease at the time of diagnosis showed no increase in survival as a result of this form of immunotherapy. An insufficient number of patients with less advanced disease, in whom we would expect the most beneficial effect, have been entered in this study. In general, we were unable to document substantial effects of immunotherapy on the immunologic parameters tested. Only in recall antigen skin testing was there a statistically significant increase in reactivity in the immunotherapy groups. Tests of general immune status appeared to have a predictive value in monitoring lung cancer patients. Anergic patients had a poorer prognosis than did patients who demonstrated skin test reactivity. Patients with normal percentages of lymphocytes (T cells) forming rosettes with sheep erythrocytes at 29 degrees C were generally normal in other tests of immune competence. In serial studies of rosette formation, all patients who developed recurrent disease had a pattern of depressed or falling rosette values, and these abnormalities occurred an average of 3.1 months prior to clinical detection of recurrence. Patients with large-cell anaplastic carcinoma were found to have a significantly higher incidence of depressed rosette levels than the other histologic types. Both large and small-cell anaplastic patients had significantly depressed lymphocyte proliferation by mitogens and allogeneic cells. Although lung cancer patients have been described as immunologically depressed, they are capable of recognizing tumor-associated antigens. When tested in leukocyte migration inhibition assays with tumor-associated antigens, the majority of the patients in our study were found to be reactive. The use of a 3 M KCl extract of pleural effusion cells from a patient with pulmonary adenocarcinoma has given good reactivity and specificity in lung cancer patients of all histologic types. In addition, these patients have been shown to respond in a mixed lymphocyte/tumor interaction to tumor-associated antigens (Dean, 1976b).

Seven patients with multiple myeloma who developed a second neoplasm are presented. There were four patients with acute leukemia and three patients with non-hematologic neoplasms. The patients with acute leukemia were among the longest survivors (median duration ≈ 72 months) and the response to anti-leukemic therapy in these patients was generally poor. Of the three patients with non-hematologic neoplasms, one patient was observed with simultaneous renal cell carcinoma and the other two patients developed adenocarcinoma of the colon and lung subsequently. In addition, two patients with mammary carcinoma who subsequently developed multiple myeloma were included. Literature was reviewed and the possibility that multiple myeloma itself might be a risk factor for the development of other malignancies was discussed.

Twenty-four patients with non-Hodgkin's lymphoma and CNS involvement are presented. There were 7 cases with diffuse histiocytic lymphoma (HL), 9 with diffuse poorly differentiated lymphocytic lymphoma (PDLL-D), of whom 6 patients were in leukemic conversion, 5 patients with nodular poorly differentiated lymphocytic lymphoma (PDLL-N), and 3 cases with undifferentiated lymphoma (UL). CNS complications were noted only in Stage IV lymphoma; the prognosis was generally poor. Histiocytic lymphoma was associated with widespread parenchymatous infiltration, whereas PDLL was usually associated with leptomeningeal seeding. The clinical course and the neuropathologic findings are discussed.Cancer 36:225-231, 1975.

Cytogenic and immunologic studies were performed on 20 members of a family who had an increased susceptibility to carcinomas of the colon, uterus and of lymphoproliferative malignancy. Chromosomal abnormalities such as small G and/or long submetacentric marker chromosome and other aberrations were observ.ed in members who had cancer as well as some asymptomatic siblings. In addition, impairment of T cell function was noted in many of the members suggesting that defective cell-mediated immunity, which also may be genetically determined, played an important role in the expression of this disease. Cancer 3 9 : 1 2 29-1 23 6, 19 7 7. ITH T H E RECOGNITION OF INCREASED FRE-W quency of malignancy in patients with immune deficiency, attention has been directed to the study of immunologic functions in family members and patients with various familial car-cinomas and lymphoproliferative disorders. It has been shown recently that subclinical immune defects were present in healthy relatives of patients with familial gastric cancer, non-Hodgkin's lymphoma, '' and chronic lymphocy

The incidence and frequency of CNS relapses in long term surviving adults, age eighteen and over, covering the period 1967-1972, were presented. Four of 20 patients with ANLL and 12 of 24 patients with ALL were demonstrated to have CNS leukemia during the course of their illness. The onset of neurologic manifestation in three of four ANLL patients with CNS leukemia w a s observed within three months of the diagnosis, whereas it was delayed to 6-12 months interval in eight of 12 ALL patients. CNS relapses, a major determinant for CNS prophylactic and maintenance therapy, were observed in 75% of the patients with ALL and none in ANLL patients who were treated with I.T. chemotherapy and cranial radiation of 2000 R. Therefore, our observation suggests that CNS prophylactic and maintenance therapy should be of value in adults with ALL as in children; whereas, in ANLL, further observation is warranted before any definite therapy can be advocated.cac~r 40:1304-1306, 1977. ITH THE INCREASED RECOGNITION OF CEN-tral nervous system (CNS) involvement in children with acute lymphoblastic leukemia (ALL) and the subsequent introduction of CNS prophylactic and maintenance therapy, the overall survival in childhood acute leukemia has improved tremendously. In the past few years, our observationse and others"" have also shown an increase in CNS complications in adults with acute leukemia. However, the applicability of CNS prophylactic and maintenance therapy is still unsettled. This paper reports our follow-up observations on adult long-term survivors with acute leukemia, which show that the increased frequency of CNS relapses, a major determinant for CNS maintenance therapy, was seen only in ALL and not in ANLL patients, once adequately treated. were evaluated. Patients with acute stem cell and undifferentiated leukemia were included under acute lymphoblastic leukemia (ALL), and all granulocytic leukemia and its subtypes were included under acute non-lymphocytic leukemia (ANLL). All patients who presented initially as lymphoma with subsequent leukemic conversion (lymphosarcoma cell leukemia) were considered to be a lymphoma from inception and have been recently reported7 and were excluded from this study. MATERIALS AND METHODS AllSeventy-six ANLL and thirty-seven ALL patients were seen at Walter Reed General Hospital during that period. Excluding all ALL patients who were on CNS prophylaxis, there were 20 patients with ANLL and 24 ALL patients who survived over 12 months to four years. Among the long survivors, four ANLL and 12 ALL patients were demonstrated to have CNS leukemia by the following criteria: 1) the presence at lumbar puncture of ten or more mononuclear and/or blast cells/mmain the absence of positive bacteriologic and fungal cultures or of gross blood contamination and/or 2) the presence of leukemic infiltration of the brain and/or the leptomeninges at autopsy.The diagnosis of acute leukemia was made by examinations of the peripheral blood and bone marrow aspirates including bone marrow biopsies and cytochemical st...