chapter  17
14 Pages

Conditioning regimens and T-cell depletion

Allogeneic stem cell transplantation (SCT) remains the only curative therapeutic option in patients with CML. Using myeloablative conditioning regimens, long-term disease-free survival rates of up to 70% can be achieved in young patients who are fortunate enough to have an HLA-identical sibling donor. Until recently, it was believed that a myeloablative conditioning regimen played a critical role in the success of allografting – first by securing stem cell engraftment and secondly by eradicating malignant host haematopoiesis. However, such regimens are associated with substantial immediate and long-term toxicity, which, in addition to prejudicing transplant outcome in ‘good-risk’ patients, precludes their extension to older patients or those with significant comorbidities. The increased realization of the importance of a graft-versus-leukaemia (GVL) effect in CML has led to the proposal that it may be possible to improve the outcome of allografting by reducing the intensity of the conditioning regimen with the aim of harnessing a GVL effect as the main antileukaemic strategy. Preliminary results using such nonmyeloablative clinical protocols confirm that sustained engraftment of allogeneic stem cells can be achieved with a marked reduction in the

immediate toxicity of transplantation. The extent to which this radically different transplant strategy allows the delivery of a sustained antileukaemic effect is unclear at present, but it is likely that this approach will make an important contribution to allogeneic SCT in the future.