PMID- 27030315
OWN - NLM
STAT- MEDLINE
DCOM- 20170505
LR  - 20211204
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 174
IP  - 1
DP  - 2016 Jul
TI  - Post-transplant bendamustine reduces GvHD while preserving GvL in experimental 
      haploidentical bone marrow transplantation.
PG  - 102-16
LID - 10.1111/bjh.14034 [doi]
AB  - 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.
CI  - (c) 2016 John Wiley & Sons Ltd.
FAU - Stokes, Jessica
AU  - Stokes J
AD  - Department of Pediatrics, University of Arizona, Tucson, Arizona.
FAU - Hoffman, Emely A
AU  - Hoffman EA
AD  - Department of Pediatrics, University of Arizona, Tucson, Arizona.
FAU - Zeng, Yi
AU  - Zeng Y
AD  - Department of Pediatrics, University of Arizona, Tucson, Arizona.
AD  - University of Arizona Cancer Center, University of Arizona, Tucson, Arizona.
FAU - Larmonier, Nicolas
AU  - Larmonier N
AD  - Department of Pediatrics, University of Arizona, Tucson, Arizona.
AD  - Department of Immunobiology, University of Arizona, Tucson, Arizona.
AD  - University of Arizona Cancer Center, University of Arizona, Tucson, Arizona.
FAU - Katsanis, Emmanuel
AU  - Katsanis E
AD  - Department of Pediatrics, University of Arizona, Tucson, Arizona.
AD  - Department of Immunobiology, University of Arizona, Tucson, Arizona.
AD  - Department of Medicine, University of Arizona, Tucson, Arizona.
AD  - Department of Pathology, University of Arizona, Tucson, Arizona.
AD  - University of Arizona Cancer Center, University of Arizona, Tucson, Arizona.
LA  - eng
GR  - P30 CA023074/CA/NCI NIH HHS/United States
GR  - R01 CA104926/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20160331
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - 981Y8SX18M (Bendamustine Hydrochloride)
SB  - IM
MH  - Animals
MH  - Bendamustine Hydrochloride/*administration & dosage/pharmacology
MH  - Bone Marrow Transplantation/*methods
MH  - Cyclophosphamide/pharmacology
MH  - Graft vs Host Disease/drug therapy/*prevention & control
MH  - Graft vs Leukemia Effect/*drug effects
MH  - Histocompatibility/immunology
MH  - Immunosuppression Therapy
MH  - Mice
MH  - Transplantation, Homologous
PMC - PMC4917459
MID - NIHMS763085
OTO - NOTNLM
OT  - bendamustine
OT  - bone marrow transplantation
OT  - cyclophosphamide
OT  - graft-versus-host disease
OT  - graft-versus-leukaemia
COIS- The authors have declared that no conflict of interest exists.
EDAT- 2016/04/01 06:00
MHDA- 2017/05/06 06:00
PMCR- 2017/07/01
CRDT- 2016/04/01 06:00
PHST- 2015/11/30 00:00 [received]
PHST- 2016/01/06 00:00 [accepted]
PHST- 2016/04/01 06:00 [entrez]
PHST- 2016/04/01 06:00 [pubmed]
PHST- 2017/05/06 06:00 [medline]
PHST- 2017/07/01 00:00 [pmc-release]
AID - 10.1111/bjh.14034 [doi]
PST - ppublish
SO  - Br J Haematol. 2016 Jul;174(1):102-16. doi: 10.1111/bjh.14034. Epub 2016 Mar 31.