A group of 8 patients with malignant lymphomas received chlorambucil as the sole medication. It was observed that although an individual susceptibility to this drug exists, an increasingly serious lesion of the germinal epithelium develops with an increase in the accumulated dose of the drug. The germinal cell line disappears, only Sertoli cells remain, and a moderate peritubular fibrosis develops. There was neither morphological evidence of injury to the interstitial cells nor of the vascular apparatus at microscopical level. The degree of injury was found to be dose dependent; the minimum total dose necessary for azoospermia was 400 mg. Recovery from azoospermia could not be observed, as most of the patients continued treatment with other drugs at a later period; recovery from oligospermia did occur if the drug was suspended prior to the threshold dose mentioned. From the data presented, it can be seen that there is a probability of azoospermia developing after ingestion of determined amounts of chlorambucil. Since this condition is probably permanent, due to the extent of the germinal injury, it has to be taken into consideration when such treatment is indicated in patients at reproductive age.

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.

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