Optimising the conditioning regimen for acute myeloid leukaemia

Abstract

The conditioning regimen administered prior to allogeneic transplantation for acute myeloid leukaemia (AML) must be sufficiently immunosuppressive to ensure engraftment, and contributes to the anti-leukaemic impact of the procedure. A broad spectrum of regimens have been studied, varying in their intensity, whether high-dose or reduced intensity, and in the agents used, containing total body irradiation (TBI) plus cyclophosphamide, fludarabine, busulfan and/or anti-thymocyte globulin. Over the past 2 decades, research has influenced the way conditioning regimens are applied. Newer research shows that targeted radiotherapy using an anti-CD45 antibody should be able to reduce toxicity, improve tumour cell kill and thereby improve results.

Figure 1

Relapse rates in two prospective randomized trials of allogeneic transplantation from matched siblings following a preparative regimen of cyclophosphamide plus 12 Gy or 15.75 Gy of TBI in AML (left panel) or CML (right panel).^, Permission requested by BW on 10/1/09

Figure 2

Kaplan-Meier curves of relapse-free survival comparing nonmyeloablative and myeloablative transplant results among patients with low comorbidities and lower-risk disease (A), low comorbidities and higher-risk disease (B), high comorbidities and lower-risk disease (C), and high comorbidities and higher-risk disease (D). Sorror, ML et al: J Clin Oncol 25(27), 2007: 4246-4254). Reprinted with permission. © 2008 American Society of Clincal Oncology. All rights reserved.

Figure 3

Estimates of the probability of overall survival, disease-free survival, transplant-related mortality, and relapse among patients treated at the maximum tolerated dose of 24 Gy of radiation delivered to the liver by 131-I-BC8, followed by FLU and 2 GY TBI. Permission requested by BW on 10/1/09

Figure 4

Fluorescent images of HEL xenograft-bearing athymic mice treated with either conventionally labeled anti-CD45 (A) or pretargeted anti-CD45. Images are shown of same camera intensity settings at 12 hours after injection. T indicates the tumor and B indicates the blood pool. The tumor to total body flourescence ratios are shown in panel C. Permission requested by BW on 10/1/09: Denied (10/7/09; re-requested)