A booster shot to cure hemoglobinopathies

Abstract

In utero transplantation has been successful in selected congenital immunodeficiencies. However, therapeutic levels of engraftment needed for hemoglobin (Hb) disorders have not been achieved.1 In this issue of Blood, Peranteau et al demonstrate a strategy to achieving tolerance induction for later therapeutic transplantation.2 After establishing immunologic tolerance in mouse models of Hb disorders, the investigators injected a "booster" dose of histocompatibility complex-mismatched donor marrow in the tolerant sickle or thalassemia (Thal) post utero recipients after a nonmyeloablative dose of total body irradiation. The booster dose was sufficient to eliminate the phenotypic expression of the underlying Hb disorder by virtue of an enrichment of donor red blood cells (RBCs) in the recipients' blood, resulting in mixed chimerism, which if stable, has been curative after conventional allografting (see figure).