Bendamustine with total body irradiation conditioning yields tolerant T-cells while preserving T-cell-dependent graft-versus-leukemia

Jessica Stokes, Emely A. Hoffman, Megan S. Molina, Nicole Kummet, Richard J. Simpson, Yi Zeng, Emmanuel Katsanis

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Graft-versus-host disease (GvHD) remains a significant impediment to allogeneic hematopoietic cell transplantation (HCT) success, necessitating studies focused on alleviating GvHD, while preserving the graft-versus-leukemia (GvL) effect. Based on our previous studies showing bendamustine with total body irradiation (BEN-TBI) conditioning reduces GvHD compared to the current clinical standard of care cyclophosphamide (CY)-TBI in a murine MHC-mismatched bone marrow transplantation (BMT) model, this study aimed to evaluate the role and fate of donor T-cells following BEN-TBI conditioning. We demonstrate that BEN-TBI reduces GvHD compared to CY-TBI independently of T regulatory cells (Tregs). BEN-TBI conditioned mice have a smaller proportion and less activated donor T-cells, with lower CD47 expression, early post-transplant, but no sustained phenotypic differences in T-cells. In BEN-TBI conditioned mice, donor T-cells gain tolerance specific to host MHC antigens. Though these T-cells are tolerant to host antigens, we demonstrate that BEN-TBI preserves a T-cell-dependent GvL effect. These findings indicate that BEN-TBI conditioning reduces GvHD without compromising GvL, warranting its further investigation as a potentially safer and more efficacious clinical alternative to CY-TBI.

Original languageEnglish (US)
Article number1758011
JournalOncoImmunology
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2020

Keywords

  • BMT
  • GvHD
  • GvL
  • bendamustine
  • conditioning

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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