Abstract
Much of the therapeutic benefit of allogeneic transplant is by a graft versus tumor effect. Further data shows that transplant engraftment is not dependant on myeloablation, instead relying on quantitative competition between donor and host cells. In the clinical setting, engraftment by competition alone is not feasible due to the need for large numbers of infused cells. Instead, low-level host irradiation has proven to be an effective engraftment strategy that is stem cell toxic but not myeloablative. The above observations served as the foundation for clinical trials utilizing allogeneic matched and haploidentical peripheral blood stem cell infusions with minimal conditioning in patients with refractory malignancies. Although engraftment was transient or not apparent, there were compelling responses in a heavily pretreated patient population that appear to result from the breaking of tumor immune tolerance by the host through the actions of IFNγ, invariant NK T cells, CD8 T cells, NK cells, or antigen presenting cells.
Highlights
Allogeneic marrow transplantation exerts much of its therapeutic effect through graft killing of tumor cells. This was established in studies of the effect of donor lymphocyte infusions on relapsed chronic myelocytic leukemia (CML) in marrow transplant patients [1]
Initial insights on the presence of graft versus leukemia came from the work of Thomas and colleagues [2, 3], showing that leukemic relapses were lower in allogeneic transplant patients who had acute and chronic graft-versus-host disease (GVHD) as compared to those who did not develop these complications
There were no responses with the solid tumor patients, and two patients who converted to total chimerism died, one of GVHD
Summary
Allogeneic marrow transplantation exerts much of its therapeutic effect through graft killing of tumor cells This was established in studies of the effect of donor lymphocyte infusions on relapsed chronic myelocytic leukemia (CML) in marrow transplant patients [1]. Initial insights on the presence of graft versus leukemia came from the work of Thomas and colleagues [2, 3], showing that leukemic relapses were lower in allogeneic transplant patients who had acute and chronic graft-versus-host disease (GVHD) as compared to those who did not develop these complications. The most direct evidence of a cellular immune attack against leukemic cells was provided by Kolb and colleagues [1] They demonstrated high rates of durable remissions in relapse CML with the simple infusion of donor lymphocytes. Cellular therapy in patients with a variety of marrow malignancies has been established and appears to be mediated by T lymphocytes other cell types might be involved
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