Management of Relapsed and Refractory Hodgkin's Disease

Hodgkin's disease remains highly curable after relapse or even after an ineffective initial therapy. The likelihood of attaining a lasting second remission is particularly high for patients who failed to respond to a primary program of radiation therapy (RT) alone. The preferred treatment for these patients is with a doxorubicin-containing chemotherapy and additional RT (if feasible). The prospect for a "second cure" after failure to respond to initial chemotherapy is smaller and for most cases a program of high-dose therapy followed by stem-cell transplantation is required. Advances in using this modality over the last 15 years have resulted in a disease-free survival of approximately 40% with a follow-up that extends up to 10 years. Most important, a recent dramatic decrease in treatment-related mortality of high-dose therapy as well as a reduction in cost have been documented. Analysis of prognostic factors allows better selection of patients and a sounder choice of salvage options. Although it appears that further dose escalation of chemotherapy is limited by nonhematologic toxicity, the benefit from incorporation of RT into high-dose programs has only recently been recognized. Because of the availability of hematopoietic growth factors and easier mobilization and collection of peripheral blood stem cells, these have become the preferred source for hematopoietic support. The use of peripheral blood stem cells and growth factors was shown to correlate with more rapid recovery of granulocytes and platelets and a shorter hospitalization period. Still, many patients remain refractory to salvage despite intensive therapy. These patients can be identified by their response to re-induction chemotherapy before transplant and should be considered for alternative approaches such as allogeneic bone marrow transplantation, sequential bone marrow transplant, and other experimental programs. This article reviews standard-dose salvage as well as current development in high-dose therapy with particular attention to the role of RT.