PMID- 16797417
OWN - NLM
STAT- MEDLINE
DCOM- 20060822
LR  - 20131121
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 34
IP  - 7
DP  - 2006 Jul
TI  - Graft engineering using ex vivo methods to limit GVHD: fludarabine treatment 
      generates superior GVL effects in allogeneic BMT.
PG  - 895-904
AB  - OBJECTIVE: To compare the abilities of different ex vivo methods of treating 
      donor lymphocytes to inhibit graft-vs-host disease (GVHD) while preserving 
      graft-vs-leukemia (GVL) activity in murine models of allogeneic bone marrow 
      transplantation. METHODS: Donor/recipient pairs included MHC fully mismatched, 
      MHC haplomismatched, and MiHA mismatched strain combinations. T cell-depleted BM 
      (TCD-BM) was transplanted in combination with untreated, fludarabine-treated, 
      7.5-Gy gamma-irradiated, or psoralen/UVA (PUVA)-treated splenocytes. GVL activity 
      was studied by adding a lethal number of recipient-type lymphoma cells. 
      Posttransplant survival was determined, and GVHD and GVL activity were assessed 
      by clinical and pathological scoring. Hematopoietic chimerism and donor T-cell 
      expansion were analyzed by flow cytometry of peripheral blood samples at 30 and 
      60 days posttransplant. RESULTS: Allogeneic splenocytes treated with fludarabine, 
      7.5 Gy gamma-irradiation, or PUVA had significantly diminished GVHD activity, and 
      all treated donor T cells facilitated engraftment by low-dose TCD-BM. Allogeneic 
      splenocytes treated with fludarabine and, to a lesser extent, PUVA retained GVL 
      activity and contributed more to donor T-cell chimerism compared to 
      gamma-irradiated donor splenocytes. CONCLUSION: Among ex vivo methods of treating 
      donor T cells to limit their proliferative capacity, fludarabine exposure had the 
      greatest differential ability to inhibit the GVHD activity of allogeneic 
      lymphocytes, while preserving their GVL activity and ability to engraft 
      recipients. Thus, ex vivo treatment with fludarabine was superior to 
      gamma-irradiation or PUVA in separating GVL from GVHD activity in murine models 
      of allogeneic bone marrow transplantation.
FAU - Li, Jian-Ming
AU  - Li JM
AD  - Emory University, Winship Cancer Institute, Hematology/Oncology, Atlanta, Ga., 
      USA.
FAU - Giver, Cynthia R
AU  - Giver CR
FAU - Waller, Edmund K
AU  - Waller EK
LA  - eng
GR  - R01 CA-74364-03/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - FA2DM6879K (Vidarabine)
RN  - P2K93U8740 (fludarabine)
SB  - IM
MH  - Animals
MH  - *Bone Marrow Transplantation
MH  - Flow Cytometry
MH  - *Graft vs Leukemia Effect
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Spleen/immunology
MH  - Transplantation Conditioning
MH  - Transplantation, Homologous
MH  - Vidarabine/*analogs & derivatives/pharmacology/therapeutic use
EDAT- 2006/06/27 09:00
MHDA- 2006/08/23 09:00
CRDT- 2006/06/27 09:00
PHST- 2005/05/03 00:00 [received]
PHST- 2006/03/13 00:00 [revised]
PHST- 2006/03/13 00:00 [accepted]
PHST- 2006/06/27 09:00 [pubmed]
PHST- 2006/08/23 09:00 [medline]
PHST- 2006/06/27 09:00 [entrez]
AID - S0301-472X(06)00195-0 [pii]
AID - 10.1016/j.exphem.2006.03.008 [doi]
PST - ppublish
SO  - Exp Hematol. 2006 Jul;34(7):895-904. doi: 10.1016/j.exphem.2006.03.008.