High-dose cyclophosphamide, carmustine, and etoposide with autologous transplantation in Hodgkin's disease: a prognostic model for treatment outcomes.
OBJECTIVE
To identify clinical factors predictive of treatment outcome after high-dose chemotherapy (HDC) for Hodgkin's disease and to develop a prognostic model for progression-free and overall survival.


METHODS
102 patients with relapsed or refractory Hodgkin's disease were treated with high-dose cyclophosphamide, carmustine, and etoposide and autologous marrow and/or peripheral blood progenitor cell support. Median follow-up of survivors is 4.1 years (1.8-7.5 years). Factors potentially important for treatment outcome were examined in univariate analysis, and Cox regression with forward selection was performed. A prognostic model was developed.


RESULTS
Poorer progression-free and overall survival were associated with nodular sclerosis histology, abnormal performance status, progressive disease at HDC, more than one extranodal site of disease, and shorter time from initial diagnosis to HDC. These factors and the presence of B symptoms at relapse also predicted for decreased overall survival. Progressive disease immediately prior to HDC, more than one extranodal disease site, and abnormal performance status retained significance for both progression-free and overall survival in multivariate analysis. Progression-free and overall survival are 42% (95% confidence interval, CI, 34 to 53) and 65% (95% CI 54 to 73) at three years. A model based on number of risk factors present divides patients into low, intermediate, and high risk groups with three-year actuarial survival of 82%, 56%, and 19% respectively. Treatment outcome for patients treated with HDC at first chemotherapy relapse was not significantly different from that of the group overall (p > 0.3).


CONCLUSIONS
Asymptomatic patients with Hodgkin's disease involving at most one extranodal site whose disease is controlled by conventional dose chemotherapy or radiation therapy at the time of HDC have good outcomes after this therapy. Presence of increasing numbers of risk factors are associated with poorer outcomes. Results of HDC compare favorably to those of standard dose salvage therapy. These data can be used to estimate likely outcomes in patients undergoing HDC for Hodgkin's disease, to identify potential candidates for innovative therapies, and to evaluate strategies for the optimal use of HDC in Hodgkin's disease.
Wheeler
C
C
Division of Hematology Beth Israel Hospital, Boston, MA 02214, USA.
Eickhoff
C
C
Elias
A
A
Ibrahim
J
J
Ayash
L
L
McCauley
M
M
Mauch
P
P
Schwartz
G
G
Eder
J P
JP
Mazanet
R
R
Ferrara
J
J
Rimm
I J
IJ
Guinan
E
E
Bierer
B
B
Gilliland
G
G
Churchill
W H
WH
Ault
K
K
Parsons
S
S
Antman
K
K
Schnipper
L
L
Tepler
I
I
Gaynes
L
L
Frei
E
E
Kadin
M
M
Antin
J
J
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
D005047:Etoposide; D003520:Cyclophosphamide; D002330:Carmustine