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

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-1(hi) 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.

• Authors: Jessica Stokes, Emely A Hoffman, Yi Zeng, Nicolas Larmonier, Emmanuel Katsanis
• Journal: British journal of haematology (Br J Haematol) Vol. 174 Issue 1 Pg. 102-16 (07 2016) ISSN: 1365-2141 [Electronic] England
• PMID: 27030315 (Publication Type: Journal Article)
• Copyright: © 2016 John Wiley & Sons Ltd.

Chemical References

• Cyclophosphamide
• Bendamustine Hydrochloride

Topics

• Animals
• Bendamustine Hydrochloride (administration & dosage, pharmacology)
• Bone Marrow Transplantation (methods)
• Cyclophosphamide (pharmacology)
• Graft vs Host Disease (drug therapy, prevention & control)
• Graft vs Leukemia Effect (drug effects)
• Histocompatibility (immunology)
• Immunosuppression Therapy
• Mice
• Transplantation, Homologous