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Post-Transplant Events

B-cell reconstitution after allogeneic SCT impairs minimal residual disease monitoring in children with ALL

Bone Marrow Transplantation volume 42, pages 187–196 (2008)Cite this article

Abstract

Minimal residual disease (MRD) detection using quantification of clone-specific Ig or TCR rearrangements before and after transplantation in children with high-risk ALL is an important predictor of outcome. The method and guidelines for its interpretation are very precise to avoid both false-negative and -positive results. In a group of 21 patients following transplantation, we observed detectable MRD positivities in Ig/TCR-based real-time quantitative PCR (RQ-PCR) leading to no further progression of the disease (11 of 100 (11%) total samples). We hypothesized that these positivities were mostly the result of nonspecific amplification despite the application of strict internationally agreed-upon measures. We applied two non-self-specific Ig heavy chain assays and received a similar number of positivities (20 and 15%). Nonspecific products amplified in these RQ-PCR systems differed from specific products in length and sequence. Statistical analysis proved that there was an excellent correlation of this phenomenon with B-cell regeneration in BM as measured by flow cytometry and Ig light chain-κ excision circle quantification. We conclude that although Ig/TCR quantification is a reliable method for post transplant MRD detection, isolated positivities in Ig-based RQ-PCR systems at the time of intense B-cell regeneration must be viewed with caution to avoid the wrong indication of treatment.

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Acknowledgements

This work was supported by MSM0021620813, MZO 00064203, MZdNR8269-3/2005, MZdNR9531-3 and GAUK 7543/2007.

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  1. E Fronkova and K Muzikova: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Paediatric Haematology/Oncology, 2nd Medical School, Charles University and University Hospital Motol, Prague, Czech Republic

    E Fronkova, K Muzikova, E Mejstrikova, M Kovac, R Formankova, P Sedlacek, O Hrusak, J Stary & J Trka

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Correspondence to E Fronkova.

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Fronkova, E., Muzikova, K., Mejstrikova, E. et al. B-cell reconstitution after allogeneic SCT impairs minimal residual disease monitoring in children with ALL. Bone Marrow Transplant 42, 187–196 (2008). https://doi.org/10.1038/bmt.2008.122

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