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Immune Recovery

Chimerism analysis in peripheral blood using indel quantitative real-time PCR is a useful tool to predict post-transplant relapse in acute leukemia

Bone Marrow Transplantation volume 50, pages 259–265 (2015)Cite this article

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Abstract

Detection of increasing mixed chimerism (IMC) using standard PCR correlates with relapse after allo-SCT for acute leukemias (ALs). Quantitative real-time PCR of insertion/deletion polymorphism (indel qrtPCR) is a much more sensitive method, which can be performed on peripheral blood. We studied the significance of low increases of recipient cells (0.1%) detected by indel qrtPCR in a cohort of 89 transplants. We did not observe relapse among the 32 patients with no IMC. Fifty-seven patients presented a first IMC, which was followed by four different scenarios: a decreasing MC (26 cases, no relapse), a stable MC (1 case, 1 relapse), a second IMC (24 cases, 15 relapse) or no control of chimerism (6 cases, 5 relapses). In multivariate analysis, detection of two successive IMCs was strongly associated with relapse (hazard ratio (HR): 9.4, 95% confidence interval (CI): 3.8–23; P<0.0001). Among the 57 patients who presented at least one IMC, 27 underwent immunomodulation (tapering of immunosuppression or donor lymphocyte injection), leading to a 1-year relapse rate of 15.7% vs 57.6% in the 30 other patients (P=0.0007). Altogether, these results indicate that chimerism analysis using indel qrtPCR in peripheral blood is a useful tool for detection of relapse in patients transplanted for AL.

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Acknowledgements

We thank Dr Martine Torres for her editorial assistance.

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Author notes

  1. D Bories and N Dhédin: These authors contributed equally to this work

Authors and Affiliations

  1. Hematology Department, Pitié-Salpêtrière Hospital, Paris, France

    N Jacque, S Nguyen, M Uzunov, A Garnier, V Leblond, J-P Vernant & N Dhédin

  2. Biostatistics Department, Pitié-Salpêtrière Hospital, Paris, France

    J-L Golmard

  3. Molecular Hematology Unit, Henri Mondor Hospital, Créteil, France

    D Bories

  4. Hematology Department, Adolescent Young Adult Unit, Saint Louis Hospital, Paris, France

    N Dhédin

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Correspondence to N Dhédin.

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Author contributions

NJ collected and analyzed the data and wrote the paper; SN, AG, MU, VL and JPV provided patients and samples and contributed in writing the manuscript; JLG performed statistical analysis; DB provided chimerism analysis, analyzed the data and contributed in writing the manuscript; ND provided patients and samples, analyzed the data and contributed in writing the manuscript.

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Jacque, N., Nguyen, S., Golmard, JL. et al. Chimerism analysis in peripheral blood using indel quantitative real-time PCR is a useful tool to predict post-transplant relapse in acute leukemia. Bone Marrow Transplant 50, 259–265 (2015). https://doi.org/10.1038/bmt.2014.254

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