Do different conditioning regimens really make a difference?

Over the past 15 years, the use of reduced-intensity/nonmyeloablative conditioning regimens before allogeneic hematopoietic stem cell transplantation has been increasing. Despite major disparities in the level of myeloablation, intensity of immunosuppression (including great diversity of in vivo T-cell depletion), and postgraft immunomodulation, the different approaches have contributed jointly to a modification of the stage of allogeneic stem cell transplantation: transplantation-related procedure mortality has been decreased dramatically, allowing allogeneic immunotherapy to be used in previously excluded populations, including elderly patients, young but clinically unsuitable patients, patients with lymphoid malignancies or solid tumors, and patients without an HLA-identical related or unrelated donor. Together, these diverse regimens have provided one of the biggest breakthroughs since the birth of allogeneic BM transplantation. However, consensus on how to reach the optimal goal of minimal transplantation-related mortality with maximum graft-versus-tumor effect is far from being reached, and further studies are needed to define optimal conditioning and immunomodulatory regimens that can be integrated to reach this goal. These developments, which will most likely vary according to different clinical situations, have to be compared continuously with advances achieved in traditional allogeneic transplantation and nontransplantation treatments. However, the lack of prospective comparative trials is and will continue to make this task challenging.