Patients with
Hodgkin's disease (HD) who fail to enter a complete remission after an initial course of
combination chemotherapy are usually considered to have an induction failure (IF); this subset of patients has an extremely poor outcome with further conventional
therapy. Since 1985, we have entered 30 IF patients into protocols using conditioning with high-dose
cyclophosphamide,
carmustine (
BCNU), and
etoposide (VP16-213) with or without
cisplatin (CBV +/- P) followed by autologous
stem cell transplantation (ASCT) with bone marrow (19 patients), peripheral blood stem cells (PBSCs; 8 patients), or both (3 patients). All except 2 patients had previously received
chemotherapy regimens for HD that contained at least 7 drugs, and 9 had received prior
radiotherapy (RT). After documentation of IF, the majority of patients received some cytoreductive
therapy as specified by protocol (local RT in 9, two cycles of conventional
chemotherapy in 2, both modalities in 2, or high-dose
cyclophosphamide to enhance PBSC collection in 11) before CBV +/- P. Five treatment-related deaths occurred, all before day 150 posttransplant. Eleven patients have had progressive HD at a median of 6 months (range, 0.1 to 45 months) after ASCT. The actuarial progression-free survival (PFS) at a median follow-up of 3.6 years (range, 0.2 to 8.2 years) is 42% (95% confidence intervals, 21% to 61%). The statistical analysis identified only prior clinical
bleomycin lung toxicity as an adverse risk factor for PFS, mainly because of the increased nonrelapse mortality seen in these patients. CBV +/- P and ASCT can produce durable remission in a substantial proportion of IF HD patients who otherwise have a poor survival, and we believed ASCT approaches represent the best
therapy currently available for these patients. Additional measures are needed to reduce the primary problem of
disease progression despite high-dose
chemotherapy and
stem cell transplantation.