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Acute Leukemia

Correlation between microsatellite discrepancy scores and transplant outcome after haemopoietic SCT for pediatric ALL

Abstract

Microsatellite analyses show that self-reported ethnicity often correlates poorly with true genetic ancestry. As unknown ancestral differences could potentially have an impact on transplant outcome, we developed an average allele length discrepancy (AALD) score to assess allele length discrepancy between donor/recipient (D/R) using microsatellites analysed routinely in post-transplant chimeric assessment. This was then compared with outcome in a homogeneously treated cohort of pediatric patients undergoing high-resolution sibling or matched unrelated donor transplantation for acute lymphoblastic leukemia (ALL). AALD scores formed a numeric continuum ranging from 0 to 1.4 (median 0.76) for sibling pairs and 0.8–2.17 (median 1.6) for high-resolution matched unrelated donor (HR-MUD) pairs. There was a trend for worse OS with increasing AALD score, which reached statistical significance above a threshold of 1.7 for OS. Patients whose transplants had an AALD score of 1.8 had a risk of non-relapse mortality 4.9 times greater (P=0.025) and relapse risk three times greater (P=0.058) than those scoring <1.8. This approach will now be explored in a Centre International for Blood and Marrow Transplantation Research (CIBMTR) study of 750 D/R pairs across all disease groups; if confirmed, it has the potential to improve donor selection for patients with multiple prospective donors.

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Acknowledgements

We thank Dr Frances Seeney from the Statistics and Clinical Audit Department of the Clinical Directorate, NHS Blood and Transplant, for her interest and support with the statistical analysis. This work was supported by the NHS Blood and Transplant Authority and the Bristol Royal Hospital for Children.

Author Contributions

JH and CGS designed and performed this work and drafted the paper: JC, JM and MC provided clinical data and advice on the transplant pairs, SJG, AG, LK, SC and AP provided and collated laboratory analysis data for the study and WH performed statistical analysis. All authors contributed to writing the paper.

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Correspondence to J Harvey.

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Harvey, J., Green, A., Groves, S. et al. Correlation between microsatellite discrepancy scores and transplant outcome after haemopoietic SCT for pediatric ALL. Bone Marrow Transplant 50, 363–366 (2015). https://doi.org/10.1038/bmt.2014.282

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