Strategies for Success With Umbilical Cord Haematopoietic Stem Cell Transplantation in Children With Malignant and Non-Malignant Disease Indications.

Umbilical Cord blood is an intuitively attractive stem cell source, but its use has declined since it is associated with an increased procedure-related morbidity and transplant related mortality. Some of this reflects that cord blood transplants are more often HLA-mismatched compared to other unrelated donor transplants. The ability to transplant in such a setting, indeed without high rates of chronic Graft versus Host Disease (GVHD), constitutes an advantage compared to other unrelated donor cell sources and there are other advantages specifically associated with cord blood as a donor cell source.

Lifelong Immune Modulation Versus Hematopoietic Cell Therapy for Inborn Errors of Immunity.

Advances in diagnosis of inborn errors of immunity (IEI) and an understanding of the molecular and immunologic mechanisms of these disorders have led to both the development of new therapies and improved approaches to hematopoietic cell transplantation (HCT). For example, monoclonal antibodies (mAbs) and small molecules, such as Janus tyrosine kinase inhibitors, that can modulate immunologic pathways have been designed for or repurposed for management of IEI. A better understanding of molecular mechanisms of IEI has led to use of drugs typically considered "immunosuppressive" to modulate the immune response, such as mammalian target of rapamycin inhibitors in disorders of phosphoinositide 3-kinase gain of function.

Cord blood CD8+ T-cell expansion following granulocyte transfusions eradicates refractory leukemia.

The action of hematopoietic cell transplantation in controlling leukemia is principally mediated by donor T cells directed against residual recipient malignant cells. However, its utility is limited by graft-versus-host disease (GVHD), where alloreactivity is extended beyond leukemic and marrow cells. In a human/murine chimeric model, we previously showed that the preferential infiltration of cord blood (CB) CD8+ T cells eradicates an Epstein-Barr virus-driven lymphoblastoid tumor without causing xenogeneic GVHD.