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Manipulating the Immunologic Characteristics of Both Graft and Host to Improve Transplant Outcome
BACKGROUND: Several critical outcomes of allogeneic stem cell transplantation for hematologic malignancies such as engraftment, incidence of graft-vs-host disease (GVHD) and disease-free survival depend on a balance between residual host and infused donor T cells and on chemosensitivity of the underlying disorder. Manipulating cell compartments of the allograft does affect long-term outcome. METHODS: The authors review investigations on the effect of blood and marrow graft components, treatment regimens, and immunologic interventions on eventual transplant outcome, an approach termed "graft engineering." Results: Major advances in graft engineering over the last decade are presented as a series of related developments or levels that derive from the goals of reducing GVHD and minimal residual disease. CONCLUSIONS: Morbidity and mortality of GVHD have decreased markedly by methods of T-cell depletion but at the expense of recurrent disease. Cellular therapy and immunotherapy show promise in potentially eradicating residual disease posttransplant.
BACKGROUND: Several critical outcomes of allogeneic stem cell transplantation for hematologic malignancies such as engraftment, incidence of graft-vs-host disease (GVHD) and disease-free survival depend on a balance between residual host and infused donor T cells and on chemosensitivity of the underlying disorder. Manipulating cell compartments of the allograft does affect long-term outcome. METHODS: The authors review investigations on the effect of blood and marrow graft components, treatment regimens, and immunologic interventions on eventual transplant outcome, an approach termed "graft engineering." Results: Major advances in graft engineering over the last decade are presented as a series of related developments or levels that derive from the goals of reducing GVHD and minimal residual disease. CONCLUSIONS: Morbidity and mortality of GVHD have decreased markedly by methods of T-cell depletion but at the expense of recurrent disease. Cellular therapy and immunotherapy show promise in potentially eradicating residual disease posttransplant.