Journal of Clinical Oncology, Vol 9, 1871-1879, Copyright © 1991 by American Society of Clinical Oncology
Intensive chemotherapy with cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation for relapsed Hodgkin's disease [published erratum appears in J Clin Oncol 1992 Jan;10(1):170]
DE Reece, MJ Barnett, JM Connors, RN Fairey, JW Fay, JP Greer, GP Herzig, RH Herzig, HG Klingemann and CF LeMaistre
Leukemia/Bone Marrow Transplantation Program of British Columbia, British Columbia Cancer Agency, Vancouver General Hospital, Canada.
Fifty-six consecutive patients with advanced Hodgkin's disease considered
incurable with further conventional chemotherapy were entered into a
protocol that included high-dose cyclophosphamide (7.2 g/m2), carmustine
(BCNU; 0.6 g/m2), and etoposide (VP16-213; 2.4 g/m2) (CBV) followed by
autologous bone marrow transplantation (BMT). Prior combination
chemotherapy had failed in all the patients, and all but five had been
previously treated with both mechlorethamine, vincristine, procarbazine,
and prednisone (MOPP) and doxorubicin, bleomycin, and vinblastine with or
without dacarbazine (ABV[D]). Thirty- four eligible patients received
short-course conventional chemotherapy and/or involved-field radiotherapy
before CBV. However, formal restaging was not performed after these
conventional therapies; ie, the therapies were not used to select
responding patients for transplantation, and all who received such therapy
subsequently received CBV and autologous marrow grafts. Forty-four patients
(80%; 95% confidence interval [CI], 69% to 91%) achieved a complete
response after CBV and BMT. Performance status at protocol entry and the
use of conventional cytoreduction therapy before CBV correlated with
response. Median follow-up is now 3.5 years (range, 2.5 to 5.0 years).
Kaplan- Meier estimates for overall and event-free survival 5 years after
transplant are 53% (95% CI, 37% to 67%) and 47% (95% CI, 33% to 60%),
respectively. In a univariate analysis, patients with a normal performance
status and those without constitutional ("B") symptoms at protocol entry
had an improved overall and event-free survival. In a multivariate
analysis, only a normal performance status remained significant. Disease
progression occurred in 17 patients at an actuarial rate of 39% (95% CI;
26% to 56%) and occurred at previous sites of active disease in all but one
patient; our analysis did not identify prognostic factors for progression.
Toxic deaths, caused by either neutropenic sepsis or interstitial
pneumonitis (IP), occurred in 12 patients (21%; 95% CI, 10% to 32%). CBV
with autologous marrow support can produce durable remissions in a
substantial number of patients with Hodgkin's disease considered incurable
with conventional measures. Regimen refinements may even further improve
the therapeutic index of BMT in this malignancy.
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