Salvage chemotherapy with mini-BEAM for relapsed or refractory non-Hodgkin's lymphoma prior to autologous bone marrow transplantation.
BACKGROUND
The role of intensive chemotherapy with autologous blood and marrow transplantation (ABMT) for patients with relapsed or refractory intermediate grade non-Hodgkin's lymphoma has recently been established. However, conventional dose salvage chemotherapy is frequently used to determine chemotherapy sensitivity and reduce tumor bulk prior to intensive therapy. Different salvage regimens have been proposed but none appears significantly superior. The purpose of this study was to determine the efficacy of mini-BEAM salvage chemotherapy in patients referred for AMBT and to define prognostic factors of response.


METHODS
One hundred four patients referred for consideration of AMBT after failure of primary anthracycline-based chemotherapy received BCNU 60 mg/m2 day 1, etoposide 75 mg/m2 day 2-5, ara-C 100 mg/m2 q12 h day 2-5, melphalan 30 mg/m2 day 6 (mini-BEAM) until maximum tumor reduction. Median age was 52 (range 18-65), 57% had failed to achieve a complete response (CR) to doxorubicin-based chemotherapy at diagnosis and only 13% had a previous CR lasting > 12 months. Seventy-six received mini-BEAM as first salvage chemotherapy.


RESULTS
The overall response rate (RR) was 37% (95% confidence interval (CI) 28-46%) with 12 patients achieving CR and 25 achieving PR. The response rate among patients treated as first salvage was 43% compared to 20% for patients who had failed to respond to a previous salvage regimen. Only 15% of patients who failed to respond to mini-BEAM responded to another conventional dose salvage regimen. Thirty-eight of 104 patients ultimately demonstrated sufficient response to proceed to ABMT. Actuarial survival at four years is 22% for all 104 patients, and 36% for those who went on to AMBT. For those who were not transplanted, four-year survival was 18%. B symptoms and tumor burden at relapse were significant predictors of response to mini-BEAM in multivariate analysis, and identified a poor prognosis group of patients unlikely to be cured by the approach.


CONCLUSIONS
Mini-BEAM does not appear to be a superior salvage regimen in this high-risk group of relapsed or refractory NHL patients for whom ABMT was the ultimate treatment intention. Only one-third of patients referred for ABMT ultimately proceed to transplant; alternative treatment strategies should be developed for those with a low likelihood of cure by this approach.
Girouard
C
C
University of Toronto Autologous Blood and Marrow Transplant Program, University of Toronto, Ontario, Canada.
Dufresne
J
J
Imrie
K
K
Stewart
A K
AK
Brandwein
J
J
Prince
H M
HM
Pantolony
D
D
Keating
A
A
Crump
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D012008:Recurrence; D016879:Salvage Therapy; D016896:Treatment Outcome
D003561:Cytarabine; D005047:Etoposide; D008558:Melphalan; D002330:Carmustine