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

Hiwarkar, Prashant; Adams, Stuart; Gilmour, Kimberly; Nataraj, Ramya; Bonney, Denise; Poulton, Kay; Wynn, Robert; (2020) Cord blood CD8⁺ T-cell expansion following granulocyte transfusions eradicates refractory leukemia. Blood Advances , 4 (17) pp. 4165-4174. 10.1182/bloodadvances.2020001737. Green open access

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Abstract

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.

Type: Article
Title: Cord blood CD8⁺ T-cell expansion following granulocyte transfusions eradicates refractory leukemia
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1182/bloodadvances.2020001737
Publisher version: https://doi.org/10.1182/bloodadvances.2020001737
Language: English
Additional information: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: ADULTS, BONE-MARROW, CHILDREN, DOMINANCE, FETAL, Hematology, Life Sciences & Biomedicine, LYMPHOCYTES, REPERTOIRE, Science & Technology, TRANSPLANTATION
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10187232
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