The impact of donor and recipient age-related factors on long-tenn haematopoietic potential and telomere length following allogeneic haematopoietic progenitor cell transplant
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Date
2012-03-12
Authors
Tompkins, Jeffrey
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Abstract
OBJECTNE: Advanced donor and recipient age-related factors negatively impact outcomes of
haematopoietic progenitor cell (HPC) transplant. Telomere shortening, which occurs due to rapid
HPC proliferation during the transplant process, is a potential mechanism for age-related
haematopoietic dysfunction due to the induction of HPC senescence. This study aims to
determine whether age-related factors impair long-term haematopoiesis (manifested by
decreased peripheral blood counts) following allogeneic HPC transplant and assess the potential
role oftelomeres. Significant age-related differences could help guide graft selection in cases
where both old and young HLA -identical grafts are available for transplant.
METHODS: The Manitoba Blood and Marrow Transplant database was reviewed to identify
allogeneic transplant patients with donors or recipients of young (<22) or old (>40) age. Ageand
sex-nonnalized peripheral blood counts and engraftment times were compared between
groups at one year post-transplant. Telomere length was assessed in subset of these patients
using real-time PCR and quantitative 3D fluorescent in situ hybridization.
RESULTS: Young donor and recipient age significantly correlate to improved erythroid and
megakaryocyte indices at one year post-transplant. Telomere length was inversely correlated
with donor age and was reduced after transplantation. Telomere length was not correlated to
erythroid and megakaryocyte indices in the late post-transplant period.
CONCLUSION: Reduced erythroid and megakaryocyte indices in the late, but not early, posttransplant
period may be due to age-related changes in HPCs. It is unlikely that telomere
dysfunction is the underlying cause of these changes. Multivariate analysis of a larger cohort is
warranted to confinn the findings.
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medicine