Treatment of children with Hodgkin's disease – Results of the German Pediatric Oncology Group

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Abstract
Six hundred sixty-seven children under age 16 were enrolled in 4 consecutive studies in West Germany between 1978 and 1990. These trials were mainly designed to reduce the long-term sequelae of high dose extended-field irradiation as well as the late effects of chemotherapy, in the context of combined modality treatment for all stages. Treatment concepts and results of studies HD-82, HD-85 and HD-87 are presented here. Patients with stages IA/B and IIA were treated with 2 cycles of OPPA (HD-82, n=100) or OPA without procarbazine (HD-85, n=53; HD-87, n=104), followed by involved field irradiation (IFI) using 35 Gy (HD-82, HD-85) or 30 Gy (HD-87). Kaplan-Meier estimates (KME) for event-free survival (survival) at 4.5 years are 99% (100%) in HD-82, 85% (98%) in HD-85 and 88% (100%) in HD-87. Thus, 2 × OPPA is a highly effective chemotherapy eradicating occult microfoci in the non-irradiated adjacent fields, whereas 2 × OPA is less efficacious. Reduction of the radiation dose to 30 Gy (IFI) within the combined modality concept does not affect treatment out come. About 30% of the boys treated with 2 × OPPA, but none of the girls and none of the boys treated without procar bazine (PC) showed elevated FSH-levels indicating gonadal dysfunction. No secondary leukemias and preleukemias were observed. Patients with the advanced stages IIIB and IVA/B (plus some patients with IIE B and IIIEA/B) were treated with 6 cycles of chemotherapy: 2 × OPPA plus 4 × COPP in HD-82 and HD-87; 2 × OPA plus 4 × COMP (without PC, M = methotrexate) in HD-85, followed by IFI using 25 Gy (HD-82, HD-85) or 20 Gy (HD-87). Radiation doses to involved lungs and liver were 12–15 Gy. KME for event-free survival (survival) at 4.5 years were 88% (90%) in HD-82 (n=54% (100%) in HD-85 (n=24) and 91% (95%) in HD-87 (n=58). 1 patient in HD-82 suffered MDS 6 years after beginning of therapy and died after ABMT. About 60% of the boys treated with 2 OPPA plus 4 COPP, but none of the girls (without pelvic irradiation) and none of the tested boys treated with 2 OPA plus 4 COMP showed gonadal dysfunction after puberty. It can be concluded that 2 × OPPA plus 4 × COPP combined with 25 or 20 Gy IFI is a highly effective treatment for advanced stages of HD, but causes testicular dysfunction in a considerable part of the boys. Thus, PC should be replaced by a drug which is as effective but does not impair testicular function. Event-free survival rates with OPA/COMP were disappointing. Identical conclusions can be drawn from the results with OPPA/COPP and OPA/COMP in the intermediate risk group (stages IIB and IIIA).