Due to regimen-related toxicities, the use of conventional allogeneic hematopoietic cell transplantation (HCT) has been restricted to younger and medically fit patients. This is unfortunate, as the median ages at diagnosis of patients with most hematologic malignancies, such as acute and chronic leukemias, lymphomas, multiple myeloma, or myelodysplastic syndromes, range from 65 to 70 years (Table 96.1).1 The curative potential of allogeneic HCT is the result of eradication of malignant cells by high-dose chemotherapy and total body irradiation (TBI), and of immune-mediated graft-versus-tumor (GvT) effects.2 3 The power of the GvT effects, which are mediated by lymphocytes, has led several groups of investigators to infuse donor lymphocytes (donor lymphocyte infusion, DLI) in patients who have relapsed with hematologic malignancies after allogeneic HCT.45 The induction of durable remissions by DLI demonstrated that the GvT effects were capable of eradicating some hematologic malignancies by themselves, even in the absence of chemotherapy. This prompted the introduction of reduced-intensity conditioning regimens6-8 or truly nonmyeloablative regimens for allogeneic HCT9-11 that are mainly based on GvT effects. The lower degrees of regimen-related toxicities associated with these procedures have allowed the extension of allogeneic HCT to patients previously deemed ineligible for high-dose conventional approaches due to age or comorbidities.9

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