autologous blood and marrow transplantation - Blog Science ...

Radford et al. 489
transplantation, perhaps through the use of growth factors or as a result of the
unique cytokine milieu that predominates posttransplant.
Our studies also show that the CD34-positive progenitors of approximately half
of MDS patients contain predominantly cells that do not show the MDS-associated
clonal chromosomal abnormality. Again, this does not prove that CD34-positive
progenitors are not part of the myelodysplastic process; the clonal karyotypic
abnormalities studied may be later acquisitions in the evolution of the myelodysplastic
process. Nevertheless, these abnormalities appear to be acquired or expressed
predominantly in the CD34-negative population in a substantial fraction of patients.
If the acquisition of these abnormalities is an integral part of the evolution to a
clinically relevant disorder of hematopoiesis, then it is conceivable that this
distinction could be exploited clinically in the prevention and treatment of MDS.
These results have therapeutic implications. Most importantly, they would
suggest that strategies intended to prevent the development of posttransplant MDS
should focus primarily on the pretransplant, conventional-dose therapy. Such
strategies might include limiting the extent or duration of pretransplant therapy,
avoidance of alkylating agents during the pretransplant period, or early marrow or
stem cell harvesting before administration of the bulk of conventional-dose
therapy. It is also possible that one could use molecular cytogenetic techniques,
such as FISH, to screen for common MDS-related clonal karyotypic abnormalities
pretransplant in high-risk populations such as heavily pretreated lymphoma
patients. In such high-risk situations, the finding that the CD34-positive progenitor
compartment is spared in many patients suggests that the use of CD34-selected
autografts might prevent or delay onset of posttransplant MDS by preventing
reinfusion of cells belonging to the dysplastic clone. In reality, such an approach is
unlikely to be curative or completely preventive, since such selection is not 100%
effective. Moreover, earliest cells affected by the transforming event may exist in
the CD34-positive compartment and may not have acquired the karyotypic
abnormalities that characterize more advanced subclones. Nevertheless, such an
approach might delay onset of MDS by removing the majority of cells belonging
to late-evolving, more aggressive subclones that have acquired the karyotypic
abnormalities characteristic of clinically manifest MDS.
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