Post-transplant bendamustine reduces GvHD while preserving GvL in experimental haploidentical bone marrow transplantation

Jessica Stokes, Emely A. Hoffman, Yi Zeng, Nicolas Larmonier, Emmanuel Katsanis

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Advances in haploidentical bone marrow transplantation (h-BMT) have drastically broadened the treatment options for patients requiring BMT. The possibility of significantly reducing the complications resulting from graft-versus-host disease (GvHD) with the administration of post-transplant cyclophosphamide (PT-CY) has substantially improved the efficacy and applicability of T cell-replete h-BMT. However, higher frequency of disease recurrence remains a major challenge in h-BMT with PT-CY. There is a critical need to identify novel strategies to prevent GvHD while sparing the graft-versus-leukaemia (GvL) effect in h-BMT. To this end, we evaluated the impact of bendamustine (BEN), given post-transplant, on GvHD and GvL using clinically relevant murine h-BMT models. We provide results indicating that post-transplant bendamustine (PT-BEN) alleviates GvHD, significantly improving survival, while preserving engraftment and GvL effects. We further document that PT-BEN can mitigate GvHD even in the absence of Treg. Our results also indicate that PT-BEN is less myelosuppressive than PT-CY, significantly increasing the number and proportion of CD11b+Gr-1hi cells, while decreasing lymphoid cells. In vitro we observed that BEN enhances the suppressive function of myeloid-derived suppressor cells (MDSCs) while impairing the proliferation of T- and B-cells. These results advocate for the consideration of PT-BEN as a new therapeutic platform for clinical implementation in h-BMT.

Original languageEnglish (US)
Pages (from-to)102-116
Number of pages15
JournalBritish Journal of Haematology
Volume174
Issue number1
DOIs
StatePublished - Jul 1 2016

Keywords

  • bendamustine
  • bone marrow transplantation
  • cyclophosphamide
  • graft-versus-host disease
  • graft-versus-leukaemia

ASJC Scopus subject areas

  • Hematology

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