D. L. Morton

LDH and melanoma

The histories of 121 Stage II melanoma patients were reviewed to determine the value of monitoring serum LDH in postoperative follow‐up examinations. Charts of 58 Stage III patients who had autopsies at UCLA also were reviewed to define the relationship between an elevated LDH and liver metastases. The sensitivity and specificity of LDH as an indicator of disease recurrence were 72.1% and 97.0%, respectively. As an indicator of liver metastases, LDH had a sensitivity and specificity of 95.1% and 82.8% in the Stage II patient group and 86.5% and 57.1% in the Stage III autopsied group. An elevated LDH was the first indication of recurrent disease in 11/88 (12.5%) Stage II patients and was almost as frequent an indicator of recurrent disease as pulmonary metastases found on chest x‐ray. Mean survival following elevation of LDH was 5.9 months whether or not liver metastases were present. Monitoring of serum LDH can provide useful information in the postoperative follow‐up of patients with melanoma.

GRANULOMATOUS HEPATITIS: A COMPLICATION OF B.C.G. IMMUNOTHERAPY

Abstract Granulomatous hepatitis developed in three P.P.D.-negative patients who received intralesional injections of B.C.G. It is suggested that the method of administration and/or sensitivity to tubercular antigens may play a role in the development of this complication.

Present status of BCG immunotherapy of malignant melanoma

SummaryBCG systemic adjuvant immunotherapy may be effective for improving both the recurrence and survival rates in patients with regional metastases from malignant melanoma. Clinical trials show that many of the principles derived from the study of animal tumor systems are applicable to human cancer in that immunotherapy is most effective for a small residual number of tumor cells. BCG treatment fulfills many of the ideal criteria for adjuvant treatment following surgery when disease burden is lowest. It is relatively nontoxic; it is effective for disseminated melanoma; it has systemic activity in the adjuvant treatment of subclinical metastases. However, until clinical trials are complete, BCG adjuvant therapy must be considered investigational.

Regional lymph node metastases and the level of invasion of primary melanoma.

One hundred and nineteen patients with primary malignant melanoma had their primary lesion classified according to Clarks level of invasion by Clark and the Division of Surgical Pathology at UCLA. Thirty patients had superficial melanoma (Level II) and did not undergo regional lymph node dissection (RLND). All other patients (Levels III, IV, and V) underwent regional lymph node dissection. Thirty‐two percent of patients with Level III melanoma, 67% of patients with Level IV melanoma, and 66% of patients with Level V melanoma had metastases to the regional lymph nodes. These studies suggest that the level of invasion, or the thickness of the primary melanoma, is helpful for predicting regional lymph node metastases.

Humoral immune response to melanoma-associated membrane antigen and fetal brain antigen demonstrated by indirect membrane immunofluorescence. I

SummaryA melanoma-associated membrane antigen and a fetal brain antigen were identified on the surface of a human melanoma cell line by indirect membrane immunofluorescence techniques. The target melanoma cells were grown in gamma globulin-depleted human serum. Sera from melanoma patients were used as the source of antimelanoma antibodies. To remove alloantibodies, the allogeneic sera were preabsorbed with cultured lymphoblastoid cells derived from the peripheral lymphocytes of the donor of the target cell line. To further define the antigen responsible for antibody activity, sequential absorption tests were performed with fetal brain cells, cultured sarcomas, and breast carcinomas. Some antibody activity was removed by fetal brain tissues. Further absorption with fetal brain or the cultured sarcoma or breast carcinoma did not remove additional activity. However, antibody activity was completely removed by either cultured or biopsy-derived melanoma cells. A serum autochthonous to the target cell line was also tested. The antibody titer of the serum was completely removed by absorption with either autochthonous biopsied tumor or an allogeneic melanoma cell line, but not with the normal tissues. Thus it appeared that sera from melanoma patients contained antibody to both a melanoma-associated membrane antigen and a fetal brain antigen.

Studies of lymphocyte stimulation to tumor-associated antigen - II. Comparison of extracts from fresh human tumors with tissue culture cell lines

SummaryExtracts of both fresh tumor and tissue culture cells propagated from these tumors were compared in a lymphocyte stimulation assay. Tissue culture lines were grown in media containing 20% fetal calf serum (FCS) and in serum-free chemically defined medium. Melanoma-associated antigens were extracted by means of 3 M KCl. Melanoma-associated antigens from two tissue culture cell lines stimulated 3H-thymidine (3H-Tdr) incorporation in lymphocytes from 7 of 17 melanoma patients, whereas no stimulation was noted in response to extracts of isologous fresh surgical specimens. The antigen solubilized from tissue culture cells demonstrated tumor-associated specificity. Stimulated 3H-Tdr incorporation was noted in lymphocytes from 17 of 38 melanoma patients, 2 of 18 patients with other cancers, and 3 of 18 normal subjects. Extracts from both FCS-grown-and chemically defined medium-grown cells were stimulatory. Fetal calf serum was detected in extracts of FCS-grown cells by complement fixation, but was not present in stimulatory concentrations. IgG antibody was detected by immunodiffusion in the nonstimulatory extract of fresh tumor, but was not detected in the stimulatory tissue culture extracts or extracts of normal tissues from the same patient.

Immunologic and Clinical Responses to Active Immunotherapy of Malignant Melanoma

During the past seven years, evidence of the importance of the immune system in malignant melanoma has accumulated from numerous sources. Morton and Malmgren’s initial description of tumor-associated antigens in human malignant melanomas using immunofluorescent techniques (11) was soon confirmed and extended by a number of independent investigators using a variety of immunologic techniques (8,10,14,16). The evidence to date implies that malignant melanomas contain tumor-specific antigens, which elicit the production of circulating humoral antibodies and cytotoxic lymphocytes in patients with melanoma.

Chemoimmunotherapy of stage III breast carcinoma with BCG and a live allogeneic tumor cell vaccine

SummaryTen women with metastatic breast carcinoma were treated with CMF, BCG, and a live TCV in a phase I study to determine whether viable allogeneic tumor cells can safely be given to women receiving adjuvant chemotherapy. Side effects of fatigue, nausea, vomiting, alopecia, and myelosuppression were attributable to chemotherapy. Side effects of BCG therapy were malaise, fever, and pruritis at the injection site, as previously described. Four patients developed hepatitis B due to viral contamination of the human agamma serum in which the tumor cells were grown. This complication has now been eliminated by omitting human sera, and hence the possibility of hepatitis B virus, from tumor cell growth media. No local tumor growth was observed in any patient. Results of this study show that live TCV is safe for patients receiving chemotherapy, and could be tested in combination with BCG and chemotherapy for control of micrometastases from breast cancer following mastectomy.