Graft-versus-Leukemia (GVL) activity in childhood leukemias

Allogeneic hematopoietic stem cell transplantation (HSCT) today contributes significantly to the cure of children with high-risk leukemias. The contribution of cellular graft-versus-leukemia (GVL) reactions to the anti-leukemic effects of allogeneic transplantation in pediatric leukemias has not been clarified in detail. Evidence is mainly based on indirect associations of clinical signs of alloreactivity with maintenance of full donor chimerism and relapse-free survival. Therapeutic interventions aimed at deliberately enhancing alloreactive donor cells via early reduction of immunosuppression or administration of donor lymphocytes are limited by the occurrence of graft-versus-host-disease (GVHD). Therefore, an important goal in advancing the use of allogeneic HSCT as treatment for childhood leukemias is the development of therapeutic strategies that induce or augment GVL effects while avoiding GVHD. One potential strategy relies on genetic modification of the receptor specificity of T cells or NK cells to recognize leukemia-associated antigens. Current efforts further focus on an optimal in vivo functionality of therapeutic T cells, including homing to the leukemia microenvironment, persistence, and capacity for specific reactivation.