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Assessing quantitative chimerism longitudinally: technical considerations, clinical applications and routine feasibility

Abstract

In this review, we describe the current laboratory approach to quantitative chimerism testing based on short tandem repeats (STRs), focusing on a longitudinal analysis. The latter is based on relative changes appearing in the course of sequential samples, and as such exploits the ultimate potential of this intrinsically semiquantitative platform. Such an analysis is more informative than single static values, less likely to be confused with platform artifacts, and is individualized to the particular patient. It is particularly useful with non-myeloablative conditioning, where mixed chimerism is common. Importantly, longitudinal monitoring is a routinely feasible laboratory option because multiplex STR-polymerase chain reaction kits are available commercially, and modern software can be used to perform computation, reliability testing and longitudinal tracking in a rapid, easy to use format. The ChimerTrack application, a shareware, user friendly program developed for this purpose, produces a report that automatically summarizes and illustrates the quantitative temporal course of the patient's chimeric status. Such a longitudinal perspective enhances the value of quantitative chimerism monitoring for decisions regarding immunomodulatory post transplant therapy. This information also provides unique insights into the biological dynamics of engraftment underlying the fluctuations in the temporal course of a patient's chimeric status.

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Acknowledgements

We thank Roman Goz for his work on the time series analysis for forecasting, Moshe Israeli for help with the early phases of platform accuracy evaluation, Ronit Narinski and Hagit Or for technical assistance and Peggy Kristt for critical review of the paper. This work was partially supported by a grant from the Hirsh and Gania Wassermann Grant Fund for Intramural Research, Tel Aviv University.

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Kristt, D., Stein, J., Yaniv, I. et al. Assessing quantitative chimerism longitudinally: technical considerations, clinical applications and routine feasibility. Bone Marrow Transplant 39, 255–268 (2007). https://doi.org/10.1038/sj.bmt.1705576

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