Thiotepa, busulfan, cyclophosphamide (TBC) and autologous hematopoietic transplantation: an intensive regimen for the treatment of multiple myeloma.
The study was designed to evaluate the efficacy and safety of an intensive, tri-alkylator conditioning regimen, consisting of thiotepa, busulfan and cyclophosphamide (TBC), prior to autologous hematopoietic cell transplantation in patients with multiple myeloma (MM) and to analyze factors associated with outcome. One hundred and twenty patients with MM received high-dose chemotherapy with TBC followed by autologous bone marrow (n = 24) or peripheral blood stem cell (PBSC) transplantation (n = 96). Fifty-four patients had chemosensitive disease and 66 had refractory disease at the time of transplantation. The overall response rate was 81% and the complete remission (CR) rate was 26%. Patients with chemosensitive disease had a CR rate of 52% vs 5% for patients with refractory disease. Multivariable analysis determined disease status at transplant as the factor most likely associated with long survival. Estimated median survival was 48, 35 and 9 months for patients with chemosensitive, primary refractory or disease in refractory relapse, respectively. Short interval from diagnosis to transplant among patients with primary refractory disease and younger age were also favorable prognostic factors for survival. Patients with refractory disease pre-transplant who achieved remission criteria rapidly after treatment had a worse outcome than the slow responders. Treatment-related mortality with the introduction of PBSC and better supportive care was 4.8%. In conclusion, TBC is an effective and relatively well-tolerated intensive conditioning regimen in patients with MM. A more favorable outcome was observed in patients with chemosensitive disease and with early treatment for primary refractory disease. TBC merits further study in these subgroups and comparison with alternative regimens in prospective studies is warranted.
Shimoni
A
A
Department of Blood and Bone Marrow Transplantation, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Smith
T L
TL
Aleman
A
A
Weber
D
D
Dimopoulos
M
M
Anderlini
P
P
Andersson
B
B
Claxton
D
D
Ueno
N T
NT
Khouri
I
I
Donato
M
M
Korbling
M
M
Alexanian
R
R
Champlin
R
R
Giralt
S
S
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D002066:Busulfan / Q000008:administration & dosage / Q000633:toxicity; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods / Q000592:standards*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D012074:Remission Induction; D016019:Survival Analysis; D013852:Thiotepa / Q000008:administration & dosage / Q000633:toxicity; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods* / Q000592:standards; D014182:Transplantation, Autologous / Q000379:methods / Q000592:standards
D003520:Cyclophosphamide; D013852:Thiotepa; D002066:Busulfan