Accelerated hyperfractionated total-lymphoid irradiation, high-dose chemotherapy, and autologous bone marrow transplantation for refractory and relapsing patients with Hodgkin's disease.

Abstract

To evaluate the feasibility and therapeutic effect of accelerated hyperfractionated total-lymphoid irradiation (TLI), high-dose chemotherapy, and autologous bone marrow transplantation (AuBMT) in patients with relapsing or chemotherapy-resistant Hodgkin's disease (HD). Forty-seven patients with HD who either relapsed after chemotherapy (n = 19), or failed to respond (n = 28) to at least two regimens of combination chemotherapy were studied. No patient received prior radiation therapy (RT). Treatment started with reinduction with standard-dose chemotherapy, followed by involved-field irradiation (15 Gy) to areas of relapsed or persistent disease and TLI (20.04 Gy given in 1.67 Gy fractions three times per day for 4 days). Subsequently, patients received etoposide and high-dose cyclophosphamide, followed by infusion of unpurged autologous bone marrow. All surviving patients had a minimum follow-up duration of 1 year. The median follow-up duration for survivors was 40+ months, and the maximum follow-up duration was 80+ months. Of the 47 patients treated, eight (17%) died of toxicity during the peritransplant period. Twenty-nine of the remaining 39 assessable patients (74%) attained a complete response (CR), while 10 remained with residual disease and progressed early after AuBMT. Four of the CR patients (14%) relapsed and 25 patients remained alive and free of disease. The actuarial disease-free survival (DFS) rate for the entire group at 6.5 years was 50%. Patients who received the protocol for relapsing HD had a significantly better DFS rate (79%) compared with patients treated for continuous refractory disease (DFS, 33%; P < .03). Previously unirradiated patients with relapsing or chemotherapy-resistant HD who have exhausted conventional chemotherapy may still respond to an aggressive therapeutic approach consisting of accelerated hyperfractionated TLI, high-dose chemotherapy, and AuBMT rescue. This program offers a potential for long-term DFS to approximately one half of patients who would otherwise have a dismal prognosis with standard-dose salvage therapy.