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

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.

journal_name

Oncoimmunology

journal_title

Oncoimmunology

authors

Stokes J,Hoffman EA,Molina MS,Kummet N,Simpson RJ,Zeng Y,Katsanis E

doi

10.1080/2162402X.2020.1758011

subject

Has Abstract

pub_date

2020-04-30 00:00:00

pages

1758011

issue

1

eissn

2162-4011

issn

2162-402X

pii

1758011

journal_volume

9

pub_type

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