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One hundred ninety patients who had advanced active Hodgkin's disease, lymphosarcoma, or reticulum cell sarcoma were treated with a combination of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) given in a cyclical fashion every month. Complete remission was produced in 91 of 138 (66%) patients with Hodgkin's disease and in 39 of 52 (75%) patients with non-Hodgkin's lymphoma (lymphosarcoma and reticulum cell sarcoma). The response rate was higher in patients who completed six cycles of therapy compared to those who completed only three to five cycles: 77% vs. 45%, respectively, in Hodgkin's disease, and 85% vs. 46%, respectively, in non-Hodgkin's lymphoma. The median duration of remission was longer for Hodgkin's disease patients who completed six cycles (30 months vs. 10 months). The median duration of complete remission of non-Hodgkin's lymphoma was 14 months. The response to treatment correlated positively with survival. The median survival time start of COPP treatment for patients with Hodgkin's disease was 7 months for nonresponders, 14 months for those who attained partial remission, and more than 48 months for those who attained complete remission. For patients with non-Hodgkin's lymphoma, the median survival time from start of COPP treatment was 24 months for nonresponders and those who had partial remission, and more than 32 months for those who attained complete remission. Of complete remission responders with Hodgkin's disease, 70% are still alive 84 months after diagnosis, and 63% of the patients witn non-Hodgkin's lymphoma are still alive 48 months after diagnosis.

1. The comparison between mean structural chromosomal aberration rates after immunosuppressive therapy and the rate of induction of malignant tumours after application of the same cytostatic substances to animals revealed a far-reaching parallelism: Highest mean aberration rates after therapy with procarbazine (Natulan) and cyclophosphamide (Endoxan) - fewer aberrations after mannitol mustard (Degranol) and no definite induction of chromosomal aberrations after azathioprine (Imurel) (8). 2. The possibility of the induction of chromosomal aberrations in lymphocytes of the peripheral blood after injection of gold 198 into the knee-joint, could be confirmed (9). 3. The mean chromosomal aberration rates before and after infusiontherapy with phenylbutazone (Butazolidin; 300 mg + 600 mg/die during 9 days) showed no significant difference (10).

Twenty-eight patients with oat cell carcinoma of the lung were treated with cyclophosphamide, vincristine, procarbazine, and prednisone with and without irradiation. Median survival was significantly increased in this treatment group (10 months) as compared to a retrospective radiation alone series (5 months). Intensive chemotherapy with this four-drug regimen represents an initial step in effective management of this disorder.

These diseases of the lymphoreticular system with neoplastic alteration of the involved tissues represent different entities and show marked variability in their clinical manifestations, pathologic behavior, prognosis, and response to treatment. New diagnostic, histopathologic, and therapeutic concepts in the past decade have led to significant advances in the care and management of these patients, particularly those with Hodgkin's disease.

A case of human fetal renal maldevelopment following the administration of nitrogen mustard, vincristine, procarbazine, and prednisone in early pregnancy for therapy of Hodgkin's disease is reported. While these agents have been shown to be teratogenic in animal experiments, adverse fetal effects following their use during early human pregnancy have not been described. In spite of this previous experience, it has generally been recommended that these agents be withheld during the first trimester of pregnancy because of their presumed teratogenic potential. This case would seem to reinforce this recommendation.

Eighty-seven previously untreated patients with pathologic Stage IA, II (A or B), or IIIA Hodgkin's disease were randomized over a 48-month period to receive either megavoltage extended field radiotherapy alone or megavoltage radiotherapy limited to involved lymph node sites (including at least an upper mantle field) followed by combination chemotherapy with nitrogen mustard, vincristine, prednisone, and procarbazine (MOPP). Four patients (4.6%) failed to achieve remission with initial radiotherapy. Seventy-two evaluable patients have currently completed therapy. Ten of 41 patients achieving remission with radiation alone have relapsed, compared to only 1 of 31 receiving radiation plus chemotherapy. Seven patients have died, 3 of whom failed to achieve remission with initial radiotherapy. The other 4 had Stage IIIA disease treated with radiation alone. Severe myelosuppression occurred infrequently during chemotherapy, and neither serious infections nor second neoplasms have observed. Although these preliminary results are encouraging, longer followup is required to determine the ultimate effects of combined modality therapy on survival and long-term complications.

A randomised prospective trial comparing "no immediate treatment" with single and multiple agent chemotherapy in 188 patients with inoperable carcinoma of the bronchus is reported. No immediate treatment proved a significantly better policy both for patients' survival and for quality of remaining life.

One hundred and ninety-seven patients with measurable metastatic cancer of the colon have been treated with one of four anticancer drugs which have had little prior trial in this disease. Objective tumor responses lasting a median of 9 weeks occurred with 0.5 g/m of streptozotocin given intravenously every week (10 percent), 130 mg/m of CCNU given orally every 6 weeks (10%), 1.0 mg/kg/day of 6-thioguanine given orally (8%), and 3 mg/kg/day of procarbazine given orally (3%). Performance status declined more rapidly with streptozotocin and 6-thioguanine and the median survival time was less (12 and 16 weeks respectively) than with procarbazine and CCNU (23 and 20 weeks respectively). This study suggests that procarbazine given in this way is ineffective but trials of streptozotocin or 6-thioguanine combined with other agents active against colon cancer should ensue as well as further exploration of the usefulness of other nitrosoureas.

A combination of mustine, vincristine (Oncovin), procarbazine, and prednisione (MOPP) and the same combination without prednisone (MOP) were compared in the treatment of stage IV Hodgkin's disease in a prospective randomized trial. The complete remission rates were 80% with MOPP and 44% with MOP; the difference was highly significant. Prednisone seems to be an important component of the MOPP combination in the management of stage IV Hodgkin's disease.

Twenty-two patients with MOPP-resistant stage IVB Hodgkin's disease were treated with a combination of bleomycin and CCNU. The response rate in 18 patients surviving at least 1 month was 72% with 11 partial and two complete responses. The mean duration of response and survival in partial responders were 12.2 and 17.5 months respectively. The two complete responses resulted in survivals of 20 and 36 + months. Bleomycin toxicity contributed to two deaths, one pulmonary and and one hypotensive. Severe CCNU toxicity occurred after three of 82 administrations but there were no CCNU-related deaths. The majority of patients in the study tolerated the regimen without serious toxicity. Although highly effective in the temporary control of advanced resistant Hodgkin's disease, the program will hopefully be improved by the addition of longer-acting agents.

Kaposi sarcoma is a rare disorder, usually controlled with conservative localized treatment. However, prognosis is serious for patients with aggressive cutaneous disease, and aminous for those with visceral involvement. Two cases of advanced Kaposi sarcoma are reviewed to illustrate a chemotherapeutic approach to patients with this disease. The first case represents a verified response of visceral Kaposi sarcoma to chemotherapy. The second provides an example of the control of aggressive dermatologic disease.

Bilateral Salmonella empyema was diagnosed in a 34-year old woman with active stage IV-B Hodgkin's disease and marked depression of immunologic function. Factors which might have predisposed to her infectious complication are discussed. The patient's dramatic response to treatment is stressed.

The effects of various regimens of melphalan combination chemotherapy were evaluated in 508 patients with multiple myeloma. No value was confirmed from the addition of procarbazine or vincristine sulfate to melphalan-prednisone combinations. Ninety-six patients who responded to treatment were allocated at random to one of three maintenance regimens, namely intermittent courses of carmustine with prednisone, continued courses of melphalan with prednisone, or no chemotherapy. There were no differences in the frequency of relapse, the remission duration, or the survival time among these maintenace groups. The frequencies of pneumonia and herpes zoster were higher in patients receiving continued chemotherapy. Continued melphalan-prednisone chemotherapy after the first year is of no major value to responding patients with multiple cyeloma. Attempts to reduce tumor mass maximally with a change in therapy are justified.

Treatment of advanced Hodgkin's disease by associating vincristine, adriblastine, prednisone and procarbazine is compared with other widely employed protocols. Most subjects in the series had already received one or more drugs and had relapsed. In spite of this, 60% were still in complete remission one year after the administration of 6 courses of the new association. An account is given of maintenance therapy in Hodgkin's disease once remission is obtained, and the problems thus raised are illustrated.

The treatment of 10 cases of Peyronie's disease with procarbazine, a cytotoxic drug, is presented. The results were disappointing.

Sifting the preceding factors, which may weigh for or against routine laparotomy and splenectomy as a staging procedure in Hodgkin's disease, we advocate that one be sure the diagnosis and histologic classification are confirmed by an experienced hematologic pathologist, that complete clinical studies for clinical staging with the exception of the lymphangiogram be performed, and that a laparotomy and splenectomy be performed in appropriate centers for clinical Stages I through III and unconfirmed Stage IV patients unless some contraindication is present. The subdiaphragmatic nodal areas should not be irradiated without evidence of the presence of disease in these areas. A minimum of 4,000 rads of supervoltage therapy should be delivered to the areas known to be involved with Hodgkin's disease plus the neighboring lymph node areas, using total nodal irradiation only on definite indication but not prophylactically.

Progress in the chemotherapy of Hodgkin's disease and experimental therapeutic, pharmacologic, and clinical studies of the antitumor antibiotic, adriamycin, are presented in this abstract. In patients with disseminated Hodgkin's disease, the combination chemotherapy program (MOPP) produces a significant increase in the complete remission rate. This has been increased to 90% by the addition of low dose bleomycin to the MOPP program. The continuation of MOPP treatment beyond 6 months and to a total of 24 months provides improved results in patients in remission as measured either from time of onset of complete remission or from end of treatment. Finally, the pattern of relapse in patients with Hodgkin's disease provides a rationale basis for the selective use of radiotherapy in patients in complete remission. Adriamycin has a broad spectrum of antitumor activity in man. Its mechanism of action involves intercalation with DNA and inhibition of DNA function. The selective effect against tumors is not understood but may relate to membrane transport. Adriamycin is a highly important new antitumor agent for the treatment, not only of hematologic malignancies, but for a variety of solid tumors as well.

A patient with Stage IV-A nodular sclerosing Hodgkin's disease is described who, at initial presentation, demonstrated an apparent large filling defect in the spleen by 99mTc-sulfur colloid scan. Following a 6-month course of MOPP therapy, the patient was clinically free of disease although the spleen scan remained unchanged. After laparotomy, the spleen was found to be entirely normal histologically.

By evaluating the results obtained in 50 patients the authors stated that VM-26 given in combination with Natulan and Prednisolone is a drug of value in the therapy of generalized Hodgkin's disease. It cause milder side effects than drugs previously used in combination therapy. Complete or partial remissions were obtained in 84% of patients treated. 75% of the therapy-resistant cases proved to be Hodgkin's sarcoma by the postmortem examination. Remission lasted longer in stage III than in stage IV and the previously untreated patients responded better than the treated one. Definite correlation could not be revealed between histologic type and duration of remission.

Despite androgens and intensive supportive care, satisfactory survival in severe aplastic anemia remains at 20% or less. Histocompatible bone marrow transplantation can restore normal hematopoiesis in approximately 40% of similarly severe individuals. Delay of transplantation for 3 wk after diagnosis allows time for proper evaluation and for many spontaneous recoveries. Further delay increases risks of fatal complications and decreases chances for successful transplantation while the incidence of spontaneous remission declines. When available, early histocompatible bone marrow transplantation may be the treatment of choice for severe aplastic anemia.

Surgery, high-energy radiotherapy and cyclic polychemotherapy are best indicated for the treatment of Hodgkin's disease and other forms of lymphoma. Overall evaluation will determine the most suitable management in each case. Clinical andpathological stage, the histological picture, the degree of vascular invasion and the immunological reactivity of the patient are the most important factors in such an evaluation. Close cooperation between the haematologist, histologist, radiologist, surgeon, radiotherapist, pharmacologist and immunologist will obviously be required.