Low-dose total body irradiation-based regimens as a preparative regimen for allogeneic haematopoietic cell transplantation in acute myelogenous leukaemia

Abstract

Although much progress has been made in understanding the molecular basis of acute myeloid leukaemia (AML), this has not yet led to major improvements in the overall survival of patients. In particular, the treatment of elderly patients with AML remains one of the major challenges in haematology. Despite increases in complete remission rates, relapse remains a major obstacle and the major determinant of overall survival. Allogeneic stem cell transplantation (SCT) is the most efficient antileukaemic treatment for patients with AML, but eligibility for the treatment was confined for a long time to younger patients. More than 10 years ago, SCT protocols were initiated with reduced-intensity conditioning (RIC) rather than ablative chemoradiotherapy, with the intention of inducing a graft-versus-leukaemia effect also in elderly patients and patients with concomitant diseases. Operationally, all protocols below the conventional preparative regimens are referred to as RIC. Low-dose total body irradiation-based protocols result in minimal myelosuppression and are among the most popular. After extensive phase I and phase II studies, associated problems of graft rejection have been largely resolved and transplant-related mortality (TRM) evaluated in more than 3000 patients. TRM does not currently exceed 10-12% in related and 20% in unrelated SCT even in patients up to the age of 75 years, so that relapse after transplantation remains the major problem. A number of strategies for decreasing relapse rates has been developed. The most promising approach consists of monitoring CD34+ donor cell chimerism after transplantation. This has led to decreases in the relapse rate over the past few years. Randomized studies are now being initiated to define the role of SCT in the treatment of elderly patients with AML.