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) CD81 T cells eradicates an Epstein-Barr virus–driven lymphoblastoid tumor without causing xenogeneic GVHD. In the clinic, however, cord blood CD81 T-cell reconstitution is significantly delayed, and the observation of such a robust antileukemia effect mediated by cord blood CD81 T cells has not been reported. We describe an observation of very early T-cell expansion in 4 high-risk pediatric leukemia patients receiving third-party, pooled granulocytes after T cell–replete CB transplantation (CBT). The T-cell expansion was transient but robust, including expansion of CD81 T cells, in contrast to the delayed CD81 T-cell expansion ordinarily observed after T cell–replete CBT. The CD81 T cells were polyclonal, rapidly switched to memory phenotype, and had the ability to mediate cytotoxicity. This phenomenon is reproducible, and each patient remains in long-term remission without GVHD. The results suggest that fetal-derived CB CD81 T cells can be exploited to generate robust antileukemia effects without GVHD.
Mendeley helps you to discover research relevant for your work.
CITATION STYLE
Hiwarkar, P., Adams, S., Gilmour, K., Nataraj, R., Bonney, D., Poulton, K., & Wynn, R. (2020). Cord blood CD81 T-cell expansion following granulocyte transfusions eradicates refractory leukemia. Blood Advances, 4(17), 4165–4174. https://doi.org/10.1182/bloodadvances.2020001737