High-dose therapy and autologous bone marrow transplantation for relapsed/refractory Hodgkin's disease: the impact of involved field radiotherapy on patterns of failure and survival

Purpose: To assess the efficacy and toxicity of involved field (IF) radiotherapy in conjunction with high-dose therapy (HDT) and autologous bone marrow transplantation (ABMT) in relapsed or refractory Hodgkin's disease (HD). Methods and Materials: Between 1987 and 1994, 100 consecutive patients with relapsed or refractory HD were treated with high-dose carmustine, etoposide, and cyclophosphamide or fractionated total-body irradiation, high-dose etoposide, and cyclophosphamide before ABMT. In addition, 24 patients received IF radiotherapy as planned cytoreductive (n = 18) or consolidative (n = 6) therapy immediately before or following ABMT. Results: With a median follow-up of 40 months (range: 18-88 months), 3-year actuarial rates of freedom from relapse (FFR), survival (S), and event-free survival (EFS) were 66%, 64%, and 57%, respectively. Thirty-three patients (33%) relapsed at a median of 8 months after ABMT. Only 2 of 33 relapses (6%) occurred beyond 18 months. By multivariate analyses, factors associated with recurrence were pleural disease (p = 0.02), multiple pulmonary nodules (p 0.03), and a poor response to cytoreductive therapy (p = 0.001). A median IF radiotherapy dose of 30 Gy (range: 12.5-45 Gy) was given to 67 sites in the 24 patients. Local failure occurred within four irradiated sites (6%) in two patients (8%). In patients with relapse Stage I-III disease (n = 62), the use of IF radiotherapy was associated with an improved 3-year FFR (100% vs. 67%, p = 0.04) and a trend toward improved S (85 vs. 60%, p = 0.16). Among patients not previously irradiated (n = 39), IF radiotherapy was associated with an improved FFR (85 vs. 57%, p = 0.07) and S (93 vs. 55%, p = 0.02). Crude rates of treatment-related Grade 5 complications (including late events and second malignancies) were similar with or without IF radiotherapy (17 vs. 14%). Conclusions: In conjunction with high-dose therapy and autologous bone marrow transplantation, IF radiotherapy is well tolerated, effectively controls local and regional disease, and may improve survival in selected patients with relapsed or refractory Hodgkin's disease