• Failure-free survival as measured by two-sided 0.05 level logrank test at completion of therapy and then every 6 months for 3 years [ Designated as safety issue: No ]
  
• Overall progression-free survival by two-sided 0.05 level logrank test 5 and 10 years following study completion [ Designated as safety issue: No ]
  

• Pulmonary function by forced vital capacity and DLCO at baseline and 5 years following study completion [ Designated as safety issue: No ]
  
• Second cancers [ Designated as safety issue: No ]
  
• Reproductive function by Reproductive Health Assessment questionnaire, semen analysis, follicle-stimulating hormone, and luteinizing hormone at baseline and 5 years following study completion [ Designated as safety issue: No ]
  
• Deaths from causes other than Hodgkin's disease [ Designated as safety issue: No ]
  
• Corr. new EBV detect. tech. in plasma and tumor tissue w/ cytotoxic T-cell response to EBV antigens and antigens from other viruses before study tx, at 1 wk, at 1 mo. after compl. of tx, & 1 year from study entry [ Designated as safety issue: Yes ]
  
• Corr. new EBV detect. tech. in plasma and tumor tiss. w/ impact of chemotherapy and/or radiotherapy on T-cell responses to EBV ags and ags from other viruses before study tx, at 1 wk, at 1 mo. after compl. of tx, & 1 year from study entry [ Designated as safety issue: No ]
  

OBJECTIVES:

• Compare the failure-free survival of patients with locally extensive or advanced Hodgkin's lymphoma treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) vs doxorubicin, vinblastine, vincristine, bleomycin, mechlorethamine, etoposide, and prednisone (Stanford V) with or without radiotherapy.
• Compare the overall survival and freedom from progression in these patients at 5 and 10 years after treatment with these regimens.
• Compare pulmonary function, incidence of second cancers, reproductive function, and deaths from causes other than Hodgkin's lymphoma in patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are stratified according to number of adverse risk factors (0-2 vs 3-7) and disease characteristics (locally extensive vs advanced). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive doxorubicin, bleomycin, vinblastine, and dacarbazine IV on days 1 and 15. Courses repeat every 28 days. Patients are restaged after 4 courses. Patients who are in complete remission receive 2 additional courses. Patients with a partial response or less are evaluated after 6 courses, and if there is an ongoing response, patients may receive 2 additional courses for a total of 8. If no ongoing response is observed, patients are removed from the study. All patients with massive mediastinal disease, regardless of stage, receive radiotherapy 2-3 weeks after completion of chemotherapy.
• Arm II: Patients receive Stanford V chemotherapy comprising doxorubicin and vinblastine IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; vincristine and bleomycin IV on day 1 of weeks 2, 4, 6, 8, 10, and 12; mechlorethamine IV on day 1 of weeks 1, 5, and 9 (if mechlorethamine is unavailable, may substitute with cyclophosphamide IV); etoposide IV on days 1 and 2 of weeks 3, 7, and 11; and oral prednisone every other day of weeks 1-9 followed by a taper. All patients with bulky disease receive radiotherapy 2-3 weeks after completion of chemotherapy.

Patients are followed every 2 months for 1 year, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 850 patients will be accrued for this study within 4.3 years.