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Monitoring minimal residual/relapsing disease after allogeneic haematopoietic stem cell transplantation in adult patients with acute lymphoblastic leukaemia

Bone Marrow Transplantation volume 55, pages 1410–1420 (2020)Cite this article

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Abstract

Relapse after allogeneic haematopoietic stem cell transplantation (SCT) is a major cause of death in patients with acute lymphoblastic leukaemia (ALL). Here, we retrospectively analysed the contributions of lineage-sorted donor cell chimerism (sDCC) and quantitative PCR (qPCR) targeting disease-specific genetic rearrangements to detect minimal residual/relapsing disease (MRD) and predict impending relapse in 94 adult ALL patients after SCT. With a median follow-up of surviving patients (n = 61) of 3.3 years, qPCR and/or sDCC measurements turned positive in 38 patients (40%). Of these, 22 patients relapsed and 16 remained in complete remission. At 3 years, qPCR and/or sDCC positive patients showed an increased incidence of relapse (50% vs. 4%, p < 0.0001), decreased relapse-free survival (RFS, 40% vs. 85%, p < 0.0001), and decreased overall survival (OS, 47% vs. 87%, p 0.004). Both, qPCR and sDCC pre-detected 11 of 21 relapses occurring within the first two years after SCT and, overall, complemented for each other method in four of the relapsing and four of the non-relapsing cases. Patients receiving pre-emptive MRD-driven interventions (n = 11) or not (n = 10) showed comparable median times until relapse, RFS, and OS. In our single centre cohort, qPCR and sDCC were similarly effective and complementary helpful to indicate haematological relapse of ALL after SCT.

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Fig. 1: Summary of follow-up.
Fig. 2: Overall outcome after allogeneic SCT.
Fig. 3: CIR after qPCR and/or sDCC positivity.
Fig. 4: Individual follow-up of qPCR and/or sDCC positive patients.

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Acknowledgements

The authors thank the nursing staff and the physicians of all participating institutions as well as the technicians of the MRD laboratories for excellent patient care and high quality diagnostic analyses.

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Authors and Affiliations

  1. Department of Medicine A/Haematology and Oncology, University of Muenster, Muenster, Germany

    Klaus Wethmar, Svenja Matern, Eva Eßeling, Linus Angenendt, Patrick Stelmach, Simon Call, Jörn C. Albring, Jan-Henrik Mikesch, Christian Reicherts, Christoph Groth, Christoph Schliemann, Wolfgang E. Berdel, Georg Lenz & Matthias Stelljes

  2. Department of Haematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany

    Heike Pfeifer

  3. Department of Haematology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Monika Brüggemann

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Contributions

KW, SM, EE, and MS treated patients, designed the research study, collected and analysed the data, and wrote the paper. HP and MB contributed diagnostic data and critically revised the manuscript. LA, PS, SC, JA, JM, CR, CG, CS, WB, and GL treated patients, collected data, and critically revised the manuscript.

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Correspondence to Matthias Stelljes.

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Wethmar, K., Matern, S., Eßeling, E. et al. Monitoring minimal residual/relapsing disease after allogeneic haematopoietic stem cell transplantation in adult patients with acute lymphoblastic leukaemia. Bone Marrow Transplant 55, 1410–1420 (2020). https://doi.org/10.1038/s41409-020-0801-0

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