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Sixty previously untreated patients with high grade non-Hodgkin's lymphomas stages II-IV received cyclophosphamide 750 mg m2 i.v., doxorubicin 50 mg m2 i.v., and vincristine 2 mg i.v. on day 1, prednisolone 100 mg p.o. on days 1-5 and etoposide 100 mg m2 i.v. on days 3-5 (CHOP-VP16). After four courses an involved field irradiation with a total dose of 25 Gy was employed and followed by two additional courses of CHOP-VP16. The overall response rate was 93%, with 49 patients (82%) achieving a complete remission (CR). Seven patients had a partial response and four patients showed no response. During a median follow-up period of 55 months, 22 of the 49 patients with CR relapsed, seven of them achieving a second complete remission with the same drug regimen. A maintained complete remission of up to 68 months was seen in 55% of all patients initially achieving CR. The median survival is 43 months. Mean side-effects of this drug regimen were alopecia (89%), nausea/vomiting (76%) and leukopenia (61%). No therapy-related deaths were seen. The results of this study demonstrate that this combined modality treatment produces high complete remission rates and that more than half of these patients achieve long-term disease-free survival.