Nonmyeloablative stem cell transplantation for lymphoma.

High-dose chemotherapy and allogeneic stem cell transplantation is a potentially curative therapy for younger patients with non-Hodgkin's lymphoma (NHL). The benefits of this therapy, however, are largely offset by the high rate of treatment-related mortality, exceeding 40% in many studies. Risks increase with comorbidities, advanced age, histocompatibility, and disease-related prognostic factors. Given the potential efficacy of graft-versus-malignancy effects against many lymphoid malignancies, we evaluated an alternative strategy utilizing less toxic, nonmyeloablative conditioning regimens to allow engraftment of donor cells, and then exploit the graft-versus-lymphoma (GVL) effects of allogeneic transplantation as the primary therapy. This strategy involved fludarabine-based preparative regimens +/- high-dose rituximab, graft-versus-host disease (GVHD) prophylaxis for 6 months, and donor lymphocyte infusion (DLI) only for progressive or nonresponding disease. Results from these trials confirm the full potential on nonmyeloablative transplantation for patients with NHL.