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Therapy of Hodgkin lymphoma (HL) is designed to prolong survival and minimize toxicity. A total of 124 patients with newly diagnosed HL and adverse prognostic factors were prospectively studied between July, 1999 and August, 2005. Patients with early unfavorable and advanced disease were eligible for the study. Patients were assigned to therapy based on international prognostic score (IPS). Those with IPS ≥ 3 received three cycles of escalated BEACOPP (EB). All others received two cycles of standard BEACOPP (SB). Subsequent therapy was prospectively assigned according to early interim GA67 or positron emission tomography (PET)/computerized tomography (CT). Four cycles of EB or SB were administered following a positive or negative scan, respectively. Complete remission rate, 10-year progression free (PFS), and overall survival (OS) were 97, 87, and 88%, respectively, at a median follow-up of 89 months (5–144). PFS and OS were similar in both groups. Fertility status was assessed in 38 females aged <40 years; 94% of females younger than 40 years preserved their cyclic ovarian function. Nineteen conceived during follow-up for 30 pregnancies, delivering 24 babies. Deliveries were reported up to 7 years from diagnosis. Predictive value of negative interim Ga67 or PET/CT was 87 and 93%, respectively. Six cycles of tailored BEACOPP, for patients with adverse prognostic factors, provide encouraging long-term PFS and OS, and fertility is preserved in most females.