Autologous-allogeneic tandem stem cell transplantation in patients with multiple myeloma

The decrease in treatment-related mortality by using reduced intensity conditioning and the well-proven immunological effect of the graft to multiple myeloma cells has increased the interest in using allogeneic stem cell transplantation in patients with multiple myeloma. The concept of a cytoreductive autograft followed by a dose-reduced allogeneic stem cell transplantation appears to be the most promising approach. Preliminary reports of several groups observed a treatment-related mortality at 1 year ranged from 0-17%. The rate of acute graft-vs.-host disease (GvHD) grade II-IV ranged from 32-44% and of chronic GvHD from 28-64%. The overall response rates for all studies ranged from 68-83%, including a high rate of complete remissions of 52-83%. The overall survival at 2 or 3 years was between 62% and 78%, and the progression-free survival between 54% and 56%. Despite the high rate of complete remissions after autologous-allogeneic tandem transplantation observed in nearly all trials, the relapse rate is quite considerable and exceeded nearly 40% at 2 years. Therefore, the reduced allogeneic treatment approach in patients with multiple myeloma has still to be improved and further preclinical and clinical research is focused on two major issues: (i) to further reduce treatment-related mortality and (ii) to enhance the remission status after transplantation, via adoptive immunotherapy inducing molecular remission and enhancing the cure rate of this approach.