The impact of donor and recipient age-related factors on long-tenn haematopoietic potential and telomere length following allogeneic haematopoietic progenitor cell transplant

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.