autologous blood and marrow transplantation - Blog Science ...

608 Chapter 11: Minitransplants
transplant from a healthy MHC-identical littermate (unpublished data).
Pretransplant liver and marrow biopsies showed extensive hemosiderosis and
fibrosis and, in addition, there was extramedullary hepatic hematopoiesis. The
dog's hematocrit was 24% with an uncorrected reticulocyte count of 30%. Twenty-
one weeks after transplant, the hematocrit was 44% with a reticulocyte count of
1.2%, and the donor contribution among the dog's hematopoietic cells was approx­
imately 80%. These very preliminary findings support the concept that mixed
chimerism can be effective in correcting a nonmalignant hematologic disease.
CONCLUSIONS
We believe that the current intensive cytoreductive and toxic conditioning
regimens can be replaced by nonmyelotoxic immunosuppression. Allogeneic stem
cell grafts create their own space in the host's marrow through a GVH reaction and
do not require myeloablation through radiation or chemotherapy.
Immunosuppression has a twofold effect: it is directed first at host cells before HSC
transplant and next at both donor and host cells after transplant with the intent of
establishing mutual graft-host tolerance. The resultant effect is to have stable
mixed donor-host hematopoietic chimerism. Based on the results in the preclinical
model in the MHC-identical setting, clinical studies have been initiated in the
setting of both malignant and nonmalignant diseases. Early data in human patients
with malignancies have shown the feasibility of establishing mixed chimerism
using an outpatient transplant approach. Preliminary data from preclinical studies
in the MHC-nonidentical setting will allow extension of this application to patients
who do not have MHC-identical donors.
ACKNOWLEDGMENTS
This work was supported in part by grants CA15704, HL36444, and DK42716
from the National Institutes of Health, Department of Health and Human Services,
Bethesda, MD. Support was also received through a prize from the Josef Steiner
Krebsstiftung, Bern, Switzerland, awarded to R.S. B.S. and R.S. are also supported
by a grant from the Gabriella Rich Leukemia Foundation.
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