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Diagnostic value of highly-sensitive chimerism analysis after allogeneic stem cell transplantation

Bone Marrow Transplantation volume 53, pages 1457–1465 (2018)Cite this article

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Abstract

Conventional analysis of host chimerism (HC) frequently fails to detect relapse before its clinical manifestation in patients with hematological malignancies after allogeneic stem cell transplantation (allo-SCT). Quantitative PCR (qPCR)-based highly-sensitive chimerism analysis extends the detection limit of conventional (short tandem repeats-based) chimerism analysis from 1 to 0.01% host cells in whole blood. To date, the diagnostic value of highly-sensitive chimerism analysis is hardly defined. Here, we applied qPCR-based chimerism analysis to 901 blood samples of 71 out-patients with hematological malignancies after allo-SCT. Receiver operating characteristics (ROC) curves were calculated for absolute HC values and for the increments of HC before relapse. Using the best cut-offs, relapse was detected with sensitivities of 74 or 85% and specificities of 69 or 75%, respectively. Positive predictive values (PPVs) were only 12 or 18%, but the respective negative predictive values were 98 or 99%. Relapse was detected median 38 or 45 days prior to clinical diagnosis, respectively. Considering also durations of steadily increasing HC of more than 28 days improved PPVs to more than 28 or 59%, respectively. Overall, highly-sensitive chimerism analysis excludes relapses with high certainty and predicts relapses with high sensitivity and specificity more than a month prior to clinical diagnosis.

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Acknowledgements

This work was supported by the German Federal Ministry of Education and Research (reference number: 01EO1302). The funding agency had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Lea Sellmann was supported by the Hannover Biomedical Research School (HBRS). We thank all the physicians and nurses at the Hannover Medical School transplant unit and in the outpatient clinic for their dedicated work.

Author contributions

Conceived and designed the experiments: LS, LH, and IB. Performed the experiments: LS, KR, and IB. Analyzed the data: LS, IB, and LH. Collection of materials: LS, KR, and IB. Provision of MRD data: GG. Patient documentation: ED. Wrote the paper: LS, AG, EW, and LH.

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Authors and Affiliations

  1. Dept. of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany

    Lea Sellmann, Kim Rabe, Ivonne Bünting, Elke Dammann, Arnold Ganser, Michael Stadler, Eva M. Weissinger & Lothar Hambach

  2. Integrated Research and Treatment Center for Transplantation (IFB-Tx), Hannover, Germany

    Lea Sellmann & Kim Rabe

  3. Department Human Genetics, Hannover Medical School, Hannover, Germany

    Gudrun Göhring

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  1. Lea Sellmann
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Correspondence to Lothar Hambach.

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Sellmann, L., Rabe, K., Bünting, I. et al. Diagnostic value of highly-sensitive chimerism analysis after allogeneic stem cell transplantation. Bone Marrow Transplant 53, 1457–1465 (2018). https://doi.org/10.1038/s41409-018-0176-7

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