High-dose etoposide and melphalan, and autologous bone marrow transplantation for patients with advanced Hodgkin's disease: importance of disease status at transplant.
OBJECTIVE
To evaluate an intensive therapy regimen of high-dose etoposide and melphalan and autologous bone marrow transplantation (ABMT) in advanced Hodgkin's disease; and to determine possible prognostic factors that predict for long-term disease-free survival (DFS).


METHODS
Seventy-three patients with advanced Hodgkin's disease who had failed to achieve remission with front-line chemotherapy (n = 16) or who had relapsed (n = 57) were treated with high-dose etoposide 60 mg/kg and melphalan 160 mg/m2 and ABMT. Previous therapy included mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), or hybrid MOPP/ABV. All patients received pretransplant cytoreduction with conventional-dose salvage chemotherapy and 40 also received pretransplant extended-field radiation to areas of bulky nodal disease (> 5 cm).


RESULTS
Response to high-dose etoposide and melphalan was determined at 3 months post-ABMT. The complete response (CR) rate was 75% (95% confidence interval [CI], 64% to 84%), including 35 of 50 patients with measurable disease before ABMT (70%; 95% CI, 60% to 86%). There were three early deaths (septicemia) and four late deaths (three interstitial pneumonitis, one intracerebral hemorrhage). Actuarial DFS is 38.6% at 4 years. Multivariate regression analysis showed that disease status at the time of ABMT (no evidence of disease [NED], nonbulky residual disease [NBRD], or bulky disease) was the most important factor determining DFS: 68% of those transplanted with NED versus 26% for patients with NBRD and 0% for bulky disease (P = .0002, log-rank test). Relapse in a previous radiation field was the only other significant prognostic factor.


CONCLUSIONS
Etoposide and melphalan is an effective and well-tolerated intensive therapy regimen in advanced Hodgkin's disease. Patients in complete remission after conventional-dose salvage therapy transplanted with this regimen enjoy superior long-term DFS.
Crump
M
M
University of Toronto Autologous Bone Marrow Transplant Program, Canada.
Smith
A M
AM
Brandwein
J
J
Couture
F
F
Sherret
H
H
Sutton
D M
DM
Scott
J G
JG
McCrae
J
J
Murray
C
C
Pantalony
D
D
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D015996:Survival Rate
D005047:Etoposide; D008558:Melphalan