Cord blood maternal microchimerism following unrelated cord blood transplantation

Abstract

Cord blood transplantation (CBT) is associated with low risk of leukemia relapse. Mechanisms underlying antileukemia benefit of CBT are not well understood, however a previous study strongly but indirectly implicated cells from the mother of the cord blood (CB) donor. A fetus acquires a small number of maternal cells referred to as maternal microchimerism (MMc) and MMc is sometimes detectable in CB. From a series of 95 patients who underwent double or single CBT at our center, we obtained or generated HLA-genotyping of CB mothers in 68. We employed a technique of highly sensitive HLA-specific quantitative-PCR assays targeting polymorphisms unique to the CB mother to assay CB-MMc in patients post-CBT. After additional exclusion criteria, CB-MMc was evaluated at multiple timepoints in 36 patients (529 specimens). CB-MMc was present in seven (19.4%) patients in bone marrow, peripheral blood, innate and adaptive immune cell subsets, and was detected up to 1-year post-CBT. Statistical trends to lower relapse, mortality, and treatment failure were observed for patients with vs. without CB-MMc post-CBT. Our study provides proof-of-concept that maternal cells of the CB graft can be tracked in recipients post-CBT, and underscore the importance of further investigating CB-MMc in sustained remission from leukemia following CBT.

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Fig. 1: Maternal microchimerism of the cord blood donor (CB-MMc) in patients who received double or single CB transplantation (CBT).
Fig. 2: Dynamics of maternal microchimerism of the cord blood donor (CB-MMc) in the seven patients who had positive results post-CB transplantation (post-CBT).
Fig. 3: Probability (cumulative incidence) of relapse, overall mortality, and treatment failure post-cord blood transplantation (CBT), with a follow-up of up to 8+ years (2920+ days).

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Acknowledgements

This research was supported by the National Institutes of Health grant R01HL117737. The authors are grateful to the patients and families who consented to participate in the study.

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JLN conceived the study, SBK, and JLN designed the experiments. SBK, OS, EK, AMF, and EC performed the experiments. Resources for the study including samples from cord blood mothers and study subject recruitment was accomplished by JA. SBK, CD, FM, AS, KVB, LAT, JA, NCL, and JLN analyzed the data and/or provided helpful comments and critical review. SBK wrote the paper.

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Correspondence to Sami B. Kanaan.

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Conflict of interest

SBK and JLN are co-founders of Chimerocyte, Inc. that develops highly sensitive chimerism analysis technologies. Chimerocyte, Inc. had no role in funding this research project.

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Kanaan, S.B., Delaney, C., Milano, F. et al. Cord blood maternal microchimerism following unrelated cord blood transplantation. Bone Marrow Transplant (2020). https://doi.org/10.1038/s41409-020-01149-x

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