Complete or mixed chimerism after HSC transplantation

When a myeloablative regimen is used, all recipient HSC are destroyed and only blood cells of donor origin are produced so that the patient will become a full donor chimera (complete chimerism). Nevertheless, there are circumstances under which recipient cells persist or reappear with time; this is referred to as mixed chimerism.

The occurrence of mixed chimerism

FULL VS MIXED

The most common reason is a relapse of the original malignancy. However, the presence of recipient cells in the blood is not always a sign of a recurring disease. When the patient has received a graft from which the donor T cells have been removed (T cell depletion), some of the recipient T cells that have survived the conditioning (T cells are more radio-resistant than cells of other hematological lineages) may expand together with the few residual donor cells in the graft so that the T cell compartment becomes of mixed origin (see figure).

This only happens when very few donor T cells are infused because otherwise, the donor T cells will simply dominate the cells of recipient origin by numbers or eradicate them through an allogeneic effect (click full chimerism to compare). Because T cells have a very long life span, recipient T cells may persist for more than 20 years in the patient. However, with time new T cells will be produced by the thymus and because all these (naive) T cells will be of donor origin the ratio recipient/donor cells will decrease.

Mixed chimerism after non-myeloablative regimen

The situation is quite different when a non-myeloablative regimen is used. Thereafter, the HSC of the recipient continue to produce blood cells so that all lineages remain of mixed origin. It is only with time that the allogeneic effect of the graft will start to destroy the recipient cells (normal HSC as well as residual leukemic cells). This desired effect can be accelerated by giving a DLI during the first months after transplant.