Reduced-intensity transplantation for lymphoma

Non-myeloablative stem cell transplantation was clinically introduced nearly a decade ago to circumvent the need for intensive preparative transplant regimens and instead rely on graft-versus-malignancy effects to eradicate disease. The general concept is to provide a sufficiently immunosuppressive and moderately myelosuppressive treatment regimen to allow donor and host hematopoietic coexistence, or chimerism. Because not all regimens are truly "non-myeloablative," a more appropriate term is reduced-intensity transplantation (RIT), which is used throughout this review. The most popular regimens incorporate a purine analog (such as fludarabine) and an alkylating agent (such as cyclophosphamide or melphalan), with or without low-dose total body irradiation. The addition of T-cell-depleting monoclonal antibodies, such as alemtuzumab, appears to reduce the incidence of acute graft-versus-host disease. For non-Hodgkin's lymphomas, the precise role of RIT continues to be defined. There are many questions regarding the optimal population and the timing of the modality. There is ample support that graft-versus-lymphoma (GVL) is a true phenomenon, but the specific contribution of GVL to outcomes after RIT is still in question, and some subtypes appear more susceptible to GVL than others. Clearly, the procurement of an uncontaminated graft plays a role. Supportive care remains a critical component of management because the reduced-intensity regimens do not completely abrogate the risk of serious infection and many do not appear to decrease the incidence of chronic graft-versus-host disease. Thus, transplant-related morbidity and mortality and graft-versus-host disease remain major obstacles, and future efforts should focus on minimizing risks and more clearly identifying patient-specific and disease-specific predictors of outcome.