1. ¹Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D1-100, P.O. Box 19024, Seattle, WA 98109-1024, USA
2. ²University of Liège, B-4000 Liège, Belgium
3. ³University of Washington, Seattle, WA 98109, USA

Correspondence: Rainer Storb, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D1-100, P.O. Box 19024, Seattle, WA 98109-1024, USA. Fax: +1 206 667 6124. E-mail: rstorb@fhcrc.org

Received 10 August 2005; Revised 21 September 2005; Accepted 21 September 2005.

Abstract

Allogeneic hematopoietic cell transplantation (HCT) after myeloablative conditioning regimens has been an effective treatment for many patients with hematologic malignancies or inherited blood disorders. Unfortunately, such regimens have been associated with significant toxicity, limiting their use to otherwise healthy, relatively young patients. In an attempt to extend treatment by allogeneic HCT to older patients and those with comorbid conditions, several groups of investigators have developed reduced-intensity or truly nonmyeloablative conditioning regimens, lacking such toxicity. Analogous to conventional regimens, reduced-intensity regimens both eliminated host-versus-graft (rejection) reactions and produced major anti-tumor effects. In contrast, nonmyeloablative regimens have relied on optimizing both pre-and posttransplant immunosuppression to overcome host-versus-graft reactions, while anti-tumor responses have depended mainly on immune-mediated graft-versus-tumor effects. In this review, we define reduced-intensity and truly nonmyeloablative regimens, describe the preclinical development and clinical application of a very low intensity nonmyeloablative regimen, and review results with reduced-intensity regimens in patients with hematologic malignancies or inherited blood disorders.