autologous blood and marrow transplantation - Blog Science ...

Sandmaier et al. 603
The resultant stable mixed donor-host hematopoietic chimerism is a manifestation
of mutual graft-host tolerance.
For assessment of mixed hematopoietic chimerism in the canine model, a
polymerase chain reaction (PCR)-based assay of polymorphic mini- or
microsatellite markers has been established. 16
This assay is informative in both sex-
matched and sex-mismatched transplant settings and can be employed on different
subsets of hematopoietic cells. Mixed chimerism is defined as the presence of 2.5
to 97.5% cells of donor or host origin, and these cut-offs are based on the
sensitivity of the assay.
MARROW TOXICITY OF TBI IN DOGS
In the absence of an HSC graft, a single dose of 400 cGy TBI delivered at 7
cGy/min is lethal despite intensive supportive care. Twenty-seven of 28 dogs died
from problems related to prolonged pancytopenia. 17
At a dose of 300 cGy TBI, 14
of 21 dogs died, whereas at 200 cGy, only one of 19 animals died, with the
remainder showing spontaneous hematopoietic recovery. When only 100 cGy is
given, none of the animals (0 of 12) died. At 200 cGy, the granulocyte counts
reached their nadirs at about 20 days after TBI, with a median value of 750/(L,
while the platelet nadirs were reached between 15 and 24 days, with a median value
of 7500/(L.
MHC-MATCHED MARROW GRAFTS: IMMUNOSUPPRESSIVE TBI DOSE
NEEDED FOR ENGRAFTMENT
The results of unmodified MHC-matched marrow allografts after TBI doses
from 450 to 920 cGy are shown in Table 1. While a dose of 920 cGy was
sufficiently immunosuppressive to result in 95% engraftment, a dose of 450 cGy
led to rejection in the majority of dogs which either had autologous hematopoietic
recovery (36%) or died of marrow aplasia (23%). 18,19
USE OF IMMUNOSUPPRESSIVE DRUG TREATMENT FOR INDUCTION
OF MIXED CHIMERISM AFTER LOW-DOSE TBI IN RECIPIENTS
OF MHC-MATCHED MARROW
At the myeloablative TBI dose of 450 cGy, two commonly used immunosuppressive
GVHD prevention drugs, CSP and prednisone, were tested for their ability
to promote engraftment. CSP was given at a dose of 15 mg/kg b.i.d. p.o. from day
-1 through day 35, and prednisone was administered at 12.5 mg/kg orally b.i.d. on
day -5 to 3 with subsequent taper through day 32. 20
The high dose of prednisone
2 1
was based on a regimen initially used by Kernan et al. along with ATG and later