autologous blood and marrow transplantation - Blog Science ...

604 Chapter 11: Minitransplants
Table 1. Marrow grafts from MHC-identical littermates after single-dose TBI (delivered
at 7 cGy/min) without postgrafting immunosuppression 1819
Total body irradiation No. dogs % of dogs with % of dogs surviving with
dose (cGy) transplanted stable allografts autologous marrow recovery
450, myeloablative +
supralethal 39 41 36
600 23 52 17
700 5 60 0
800 5 80 0
920, immunosuppressive 21 95 0
tested by Bjerke et al. with an anti-CD3 antibody for second transplants after
rejection of the first graft. 22
Dogs given CSP had stable engraftment in all cases,
which was significantly better than that seen in controls not given CSP (P=0.01).
However, the high-dose prednisone was completely ineffective, and none of the
dogs studied had sustained allogeneic engraftment. Next, the TBI dose was
lowered to the sublethal range of 200 cGy and, in this setting, the use of
posttransplant CSP alone failed to achieve engraftment (Table 2). By 4 weeks, all
four dogs studied had rejected their allografts but all survived with autologous
hematopoietic recovery. 23
To see if engraftment could be improved by using
combinations of drugs, the antimetabolite methotrexate (MTX) was added to CSP,
since previous data showed synergism of these two agents for prevention of GVHD
in both dogs and human patients. Of six dogs studied, three became stable mixed
chimeras and three rejected their grafts, although the rejections occurred much later
than seen in dogs given CSP alone. A novel immunosuppressive drug, mycophenolate
mofetil, was also tested in this model. MMF blocked the de novo purine
Table 2. Engraftment of MHC-identical littermate marrow using a sublethal dose of 200
cGy TBI (delivered at 7 cGy/min) before and immunosuppressive drugs for GVHD preven­
tion after transplant 23
(and unpublished data)
Immunosuppression
after transplant
No. dogs with stable grafts/
no. dogs studied
Duration of mixed
chimerism (weeks)
CSP* 0/4 4, 4, 4, 4
MTXt/CSP* 3/6 2, 7, 11, >8§, >134, >134
MMFt/CSP* 10/11 12, >49, >55, >56, (57, >62,
>63, >73, >104, >130, >130
*Cyclosporine 15 mg/kg b.i.d. p.o. days -1 to 35; ^methotrexate OA mg/kg i.v. days 1, 3,
6, 11; fmycophenolate mofetil 10 mg/kg/b.i.d. s.c. days 0-27; ^euthanized because of
papillomatosis.