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High-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213)
with or without cisplatin (CBV +/- P) and autologous transplantation for
patients with Hodgkin's disease who fail to enter a complete remission
after combination chemotherapy
DE Reece, MJ Barnett, JD Shepherd, DE Hogge, RJ Klasa, SH Nantel, HJ Sutherland, HG Klingemann, RN Fairey and NJ Voss
Leukemia/Bone Marrow Transplantation Program of British Columbia, Division
of Hematology, Vancouver Hospital, Canada.
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.
Volume 86,
Issue 2,
pp. 451-456,
07/15/1995
Copyright © 1995 by The American Society of Hematology
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