[Prophylaxis of acute graft-versus-host disease after allogeneic bone marrow transplantation by mycophenolate mofetil in a murine model].
OBJECTIVE
To evaluate the effect of mycophenolate mofetile (MMF) on acute graft versus host disease (aGVHD) prophylaxis after allogeneic bone marrow transplantation (allo-BMT) in a murine model.


METHODS
Acute GVHD was induced in male BALB/c mice by total-body irradiation (TBI) followed by female allogeneic (C57BL/6J) bone marrow and spleen cells transplantation. Acute GVHD was assessed both physically and histologically. Severe aGVHD was developed in the recipients and the mean survival time (MST) of untreated BM recipients was 6 days. After allo-BMT, animals were divided into 6 groups. Group 1 was given MMF (30 mg.kg(-1).d(-1)), group 2 CsA (1.5 mg.kg(-1).d(-1)) and MTX (0.4 mg.kg(-1).d(-1)), group 3 MMF (30 mg.kg(-1).d(-1)) in combination with CsA and MTX, group 4 MMF (60 mg.kg(-1).d(-1)) in combination with CsA and MTX, group 5 MMF (10 mg.kg(-1).d(-1)) in combination with CsA and MTX, and group 6 no agents for aGVHD prophylaxis. The physical signs, MST, peripheral blood counts, and aGVHD histopathologic examination were observed in all recipients.


RESULTS
Animals in control group developed typical aGVHD and 100% of mortality, with a MST of 6 days. The MSTs of group 1 approximately 5 were significantly longer than that of control, being 3.4, 8.4, 9.0, 6.1 and 8.8 days longer, respectively (P < 0.05). The MSTs of groups 2 approximately 5 were longer than that of group 1 (P < 0.05), but there was no statistical significance between groups 3 approximately 5 and 2. There was no statistical difference in peripheral blood count among groups 1 approximately 5. Histopathological examination of skin, liver, and gastrointestinal tract showed typical signs of aGVHD. Animals received immunosuppressive agents (MMF, CsA, MTX) showed the less severe signs.


CONCLUSIONS
MMF markedly prolonged MST of allo-BMT recipients, delayed the onset of aGVHD signs. The prophylaxis effect of CsA + MTX with or without MMF was better than that of MMF alone, synergism between MMF of 10 or 30 mg.kg(-1).d(-1) and CsA + MTX was better than that of MMF of 60 mg.kg(-1).d(-1) and CsA + MTX.
Bone Marrow Transplantation Center, The First Affiliated Hospital, College of Medical Sciences, Zhejiang University, Hangzhou 310003, China.
He
H
Huang
Weiyan
W
Zheng
Maofang
M
Lin
Jianyun
J
Fu
Ronghua
R
Zhang
D000818:Animals; D016026:Bone Marrow Transplantation; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006086:Graft vs Host Disease / Q000473:pathology / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013997:Time Factors; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D008727:Methotrexate