The study of engraftment after hematopoietic stem cell transplantation: From the presence of mixed chimerism to the development of immunological tolerance.

Over the last three decades, allogeneic hematopoietic stem cell transplantation (HSCT) has become an important therapeutic tool that can cure life-threatening diseases affecting children and adults, including a variety of neoplastic and inborn genetic disorders of the hematopoietic system. Engraftment of donor-derived cells represents a crucial event in order to obtain a successful transplant; therefore, many techniques have been developed to monitor engraftment and eventually determine the presence of mixed chimerism (MC) after HSCT. PCR based on the amplification of short tandem repeats is currently the most common technique used to monitor chimerism, although the degree of achievable quantification can be increased by performing quantitative PCR. In hemoglobinopathies, different studies have showed that complete donor hematopoiesis is not essential for sustained engraftment and that the simultaneous presence of hematopoietic cells of both donor and recipient origin is not a rare event after HSCT. In the present study our data confirmed that the presence of MC in thalassemic patients negatively influence the outcome of HSCT early after HSCT, but not if it becomes persistent in the long follow-up. Different studies have shown that T regulatory type 1 (Tr1) cells, characterized by the coexpression of CD49b and LAG-3 and by their ability to secrete IL-10, have been associated with the presence and maintenance of persistent MC in beta-thalassemic patients after HSCT. In the present study we summarize the incidence of MC after HSCT in a single transplant center cohort of thalassemic patients, showing the role of regulatory T cells in promoting and maintaining immune tolerance in some of them.