Treatment of pediatric hodgkin disease tailored to stage, mediastinal mass, and age an italian (aieop) multicenter study on 215 patients

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Abstract
Background. Attempting to optimize treatment results in pediatric Hodgkin disease while minimizing major side effects, at least in early-stage patients, in 1983 the Italian Association of Pediatric Hematology and Oncology (AIEOP) conceived a multicenter study tailored according to stage, bulky mediastinal mass, and age. Methods. Between December, 1983 and January, 1989, 215 evaluable patients (median age, 9.9 years, range, 1–15 years) received the AIEOP-MH 1983 Hodgkin disease protocol of low-dose radiation therapy (20–25 Gy), with three cycles of adriamycin, bleomycin, vinblastine, and imidazole carboxamide (ABVD) for children with early-stage and favorable disease, and with alternating cycles of an eight non-cross-resistant drug combination regimen (nitrogen mustard, vincristine, procarbazine, and prednisone [MOPP]/ABVD) for 6 months for those with bulky and unfavorable disease. Patients in advanced stages received four additional courses of MOPP/ABVD as maintenance therapy. Results. The overall survival and freedom from progression (FFP) probabilities at 7 years are 85.7% and 81.5% respectively. FFP probabilities at 7 years in Groups 1 (58 patients in Stages I and IIA with mass/thorax [M/T] < 0.33), 2 (56 patients in Stages IIA, IB, IIA with M/T > 0.33, IIB, and IIIA), and 3 (38 patients in Stages IIIB and IVA and B) were 94.8%, 81.4%, and 60.3%, respectively. Multivariate analysis showed B symptoms, M/T > 0.33, and stage to be significant, independent prognostic factors affecting survival and FFP curves. Conclusions. The encouraging results in early-stage disease indicate the validity of using less toxic treatment in this subgroup to maximize quality of life. Patients with bulky mediastinal disease tended to fare worse than those with M/T < 0.33 or without mediastinal involvement (FFP at 7 years: 69.4% versus 93.3%) and showed early local recurrence. In advanced stages, the eight-drug combination regimen (MOPP/ABVD) plus low-dose radiation therapy provided no major improvement in outcome; here, alternative chemotherapeutic regimens should be tested in a large, randomized, clinical trial to evaluate their efficacy and determine the frequency of delayed toxicity.