Can reduced-intensity allogeneic transplantation cure older adults with AML?

Development of nonablative and reduced-intensity conditioning regimens has enabled older or medically infirm patients with myeloid malignancies to be treated with allogeneic hematopoietic cell transplantation (HCT). These regimens rely largely on graft-versus-leukemia effects rather than high-dose therapy to eliminate malignant cells. Studies indicate that there is sustained engraftment with relatively low transplant-related mortality in the small number of patients who have been treated. This review summarizes the outcome in recent studies of patients with myeloid malignancies who received HCT following nonmyeloablative or reduced-intensity conditioning. Comparison of nonmyeloablative with myeloablative transplant shows that the myeloablative patients are about 10-15 years younger. Toxicity is a major problem in the elderly who have comorbid conditions, but otherwise the patient has a similar outcome, again emphasizing the graft-versus-leukemia effect. Comparison of patients receiving related or unrelated grafts following nonmyeloablative conditioning shows that the outcome in these patients is similar. These studies have demonstrated encouraging overall survival and nonrelapse mortalities with evidence for graft-versus-leukemia responses in elderly patients with hematologic malignancies. Relapse and progressive disease continued to be problems, particularly in patients with large tumor burdens at time of HCT. Elimination of tumor burden prior to transplant with immunotherapy such as with radiolabeled anti-CD45 antibody or vaccines may improve outcome further.