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Minimal residual disease

Quantitative chimerism in CD3-negative mononuclear cells predicts prognosis in acute myeloid leukemia patients after hematopoietic stem cell transplantation

Leukemia volume 34, pages 1342–1353 (2020)Cite this article

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Abstract

Relapse is a major complication of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (SCT). The objective of our study was to evaluate chimerism monitoring on the CD3-negative mononuclear cells by RQ-PCR to predict relapse of patients allografted for AML and to compare its performance with WT1 quantification. A cohort of 100 patients undergoing allogenic SCT for AML was retrospectively analyzed in a single institution. Patients without complete chimerism, defined as less than 0.01% of recipient’s DNA in CD3-negative cells, had a significantly higher risk of relapse and a lower overall survival (p < 0.001). An increase in the percentage of recipient DNA in CD3-negative cells was associated with an increased risk of relapse (p < 0.001) but not with overall survival. Comparable performances between monitoring of CD3-negative cell chimerism and WT1 expression to predict relapse was observed up to more than 90 days before hematological relapse, with sensitivity of 82% and 78%, respectively, and specificity of 100% for both approaches. Quantitative specific chimerism of the CD3-negative mononuclear fraction, enriched in blastic cells, is a new and powerful tool for monitoring measurable residual disease and could be used for AML patients without available molecular markers.

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Acknowledgements

This work was realized in the context of (i) the LabEX IGO program supported by the National Research Agency via the investment of the future program ANR-11-LABX-0016-01 and of (ii) the SIRIC ILIAD program supported by the French National Cancer Institute national (INCa), the Ministry of Health and the Institute for Health and Medical Research (Inserm) (contract INCa-DGOS-Inserm_12558). The authors would like to thank the patients who participated in this study, and the technicians who participated in biological collection and experimental procedures.

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  1. These authors contributed equally: Anne Bouvier, Jérémie Riou

Authors and Affiliations

  1. CHU Angers, Laboratoire d’Hématologie, Angers, France

    Anne Bouvier, Damien Luque Paz, Laurane Cottin, Bénédicte Ribourtout, Annaëlle Beucher, Valérie Ugo & Odile Blanchet

  2. Fédération Hospitalo-Universitaire ‘Grand Ouest Against Leukemia’ (FHU GOAL), Angers, France

    Anne Bouvier, Sylvain Thépot, Sylvie François, Aline Schmidt, Corentin Orvain, Marie-Hélène Estienne, Alban Villate, Damien Luque Paz, Laurane Cottin, Bénédicte Ribourtout, Annaëlle Beucher, Norbert Ifrah, Valérie Ugo, Mathilde Hunault-Berger & Odile Blanchet

  3. CRCINA, INSERM, Université de Nantes, Université d’Angers, Angers, France

    Anne Bouvier, Sylvain Thépot, Aline Schmidt, Corentin Orvain, Damien Luque Paz, Yves Delneste, Norbert Ifrah, Valérie Ugo, Mathilde Hunault-Berger & Odile Blanchet

  4. MINT, UMR INSERM 1066, CNRS 6021, Université d’Angers, Angers, France

    Jérémie Riou

  5. Université d’Angers, UFR Santé, Angers, France

    Jérémie Riou, Sylvain Thépot, Aline Schmidt, Corentin Orvain, Damien Luque Paz, Laurane Cottin, Norbert Ifrah, Valérie Ugo, Mathilde Hunault-Berger & Odile Blanchet

  6. CHU Angers, Service des Maladies du sang, Angers, France

    Sylvain Thépot, Aurélien Sutra Del Galy, Sylvie François, Aline Schmidt, Corentin Orvain, Norbert Ifrah & Mathilde Hunault-Berger

  7. CHU Tours, Service d’Hématologie biologique, Tours, France

    Marie-Hélène Estienne

  8. CHU Tours, Service d’Hématologie et thérapie cellulaire, Tours, France

    Alban Villate

  9. CHU Angers, Laboratoire d’Immunologie et Allergologie, Angers, France

    Yves Delneste

  10. CHU Angers, Centre de Ressources Biologiques, BB-0033-00038, Angers, France

    Odile Blanchet

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Bouvier, A., Riou, J., Thépot, S. et al. Quantitative chimerism in CD3-negative mononuclear cells predicts prognosis in acute myeloid leukemia patients after hematopoietic stem cell transplantation. Leukemia 34, 1342–1353 (2020). https://doi.org/10.1038/s41375-019-0624-4

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