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 myelo-suppressive 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.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/621784 |
| Date | 07 1900 |
| Creators | Stokes, Jessica, Hoffman, Emely A., Zeng, Yi, Larmonier, Nicolas, Katsanis, Emmanuel |
| Contributors | University of Arizona, Department of Pediatrics; University of Arizona; Tucson Arizona, Department of Pediatrics; University of Arizona; Tucson Arizona, Department of Pediatrics; University of Arizona; Tucson Arizona, Department of Pediatrics; University of Arizona; Tucson Arizona, Department of Pediatrics; University of Arizona; Tucson Arizona |
| Publisher | WILEY-BLACKWELL |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | Article |
| Rights | © 2016 John Wiley & Sons Ltd. |
| Relation | http://doi.wiley.com/10.1111/bjh.14034 |
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