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Chimerism analysis for clinicians: a review of the literature and worldwide practices

Abstract

This review highlights literature pertinent to chimerism analysis in the context of hematopoietic cell transplantation (HCT). We also conducted a survey of testing practices of program members of CIBMTR worldwide. Questions included testing methods, time points, specimen type, cell lineage tested and testing indications. Recent literature suggests that detection of low level mixed chimerism has a clinical utility in predicting relapse. There is also increasing recognition of HLA loss relapse to potentially guide rescue decisions in cases of relapse. These developments coincide with wider access to high sensitivity next generation sequencing (NGS) in clinical laboratories. Our survey revealed a heterogeneity in practices as well as in findings and conclusions of published studies. Although the most commonly used method is STR, studies support more sensitive methods such as NGS, especially for predicting relapse. There is no conclusive evidence to support testing chimerism in BM over PB, particularly when using a high sensitivity testing method. Periodic monitoring of chimerism especially in diagnoses with a high risk of relapse is advantageous. Lineage specific chimerism is more sensitive than whole blood in predicting impending relapse. Further studies that critically assess how to utilize chimerism testing results will inform evidence based clinical management decisions.

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Fig. 1: Time points and cell subsets tested by chimerism analysis, survey responses.
Fig. 2: Accuracy, sensitivity, and current utilization of top three survey-reported chimerism analysis methods.

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Acknowledgements

We appreciate the support of the CIBMTR through distributing the survey to their program director members. The CIBMTR is supported primarily by Public Health Service grant/cooperative agreement U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID).

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MA conceived the idea; MA and AGB analyzed the survey results. MA and AGB searched and analyzed the literature and wrote the paper.

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Correspondence to Medhat Askar.

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MA has received compensation as a member of the scientific advisory board for CareDx, Inc. AGB declares no potential competing interests.

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Blouin, A.G., Askar, M. Chimerism analysis for clinicians: a review of the literature and worldwide practices. Bone Marrow Transplant 57, 347–359 (2022). https://doi.org/10.1038/s41409-022-01579-9

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