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 c yclophosphamide (TBC), prior to autologous hematopoietic cell transplantati on in patients with multiple myeloma (MM) and to analyze factors associated with outcome. One hundred and twenty patients with MM received high-dose c hemotherapy with TBC followed by autologous bone marrow (n = 24) or periphe ral blood stem cell (PBSC) transplantation (n = 96). Fifty-four patients ha d chemosensitive disease and 66 had refractory disease at the time of trans plantation. The overall response rate was 81% and the complete remission (C R) rate was 26%. Patients with chemosensitive disease had a CR rate of 52% vs 5% for patients with refractory disease. Multivariable analysis determin ed disease status at transplant as the factor most likely associated with l ong survival. Estimated median survival was 48, 35 and 9 months for patient s with chemosensitive, primary refractory or disease in refractory relapse, respectively. Short interval from diagnosis to transplant among patients w ith primary refractory disease and younger age were also favorable prognost ic factors for survival. Patients with refractory disease pre-transplant wh o achieved remission criteria rapidly after treatment had a worse outcome t han the slow responders. Treatment-related mortality with the introduction of PBSC and better supportive care was 4.8%. In conclusion, TBC is an effec tive and relatively well-tolerated intensive conditioning regimen in patien ts with MM. A more favorable outcome was observed in patients with chemosen sitive disease and with early treatment for primary refractory disease. TBC merits further study in these subgroups and comparison with alternative re gimens in prospective studies is warranted.