Reduced-intensity conditioning regimens for hematologic malignancies: what have we learned over the last 10 years?

Reduced-intensity conditioning (RIC) regimens have been investigated for more than 10 years as an alternative to traditional myeloablative conditioning regimens. RIC regimens are being commonly used in older patients as well as in disorders in which traditional myeloablative conditioning regimens are associated with high rates of non-relapse mortality. Hodgkin disease, myeloma, and low-grade lymphoid malignancies have been the diseases most impacted by RIC regimens. RIC regimens have also been shown to be safe and effective in older patients as well as patients with co-morbidities, although patients with chemorefractory disease still have high relapse rates and poor outcomes. Patients with chemosensitive disease have outcomes similar to those obtained with conventional ablative therapies, and thus comparative trials are warranted. RIC regimens are associated with lower rates of severe toxicity and non-relapse mortality; however, infections, graft-versus-host disease, and relapse of primary disease remain the most common obstacles to a successful outcome. The impact on survival and the relative benefits of RIC allografting compared with traditional conditioning regimens or alternative therapy remain to be defined. Incorporating targeted therapies as part of the conditioning regimens or as maintenance therapies is currently being explored to reduce relapse rates without increasing toxicity.