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Minimal Residual Disease

Preemptive alloimmune intervention in high-risk pediatric acute lymphoblastic leukemia patients guided by minimal residual disease level before stem cell transplantation

Leukemia volume 24, pages 1462–1469 (2010)Cite this article

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Abstract

Relapse of pediatric acute lymphoblastic leukemia (ALL) remains the main cause of treatment failure after allogeneic stem cell transplantation (alloSCT). A high level of minimal residual disease (MRD) before alloSCT has been shown to predict these relapses. Patients at risk might benefit from a preemptive alloimmune intervention. In this first prospective, MRD-guided intervention study, 48 patients were stratified according to pre-SCT MRD level. Eighteen children with MRD level ⩾1 × 10−4 were eligible for intervention, consisting of early cyclosporine A tapering followed by consecutive, incremental donor lymphocyte infusions (n=1–4). The intervention was associated with graft versus host disease ⩾grade II in only 23% of patients. Event-free survival in the intervention group was 19%. However, in contrast with the usual early recurrence of leukemia, relapses were delayed up to 3 years after SCT. In addition, several relapses presented at unusual extramedullary sites suggesting that the immune intervention may have altered the pattern of leukemia recurrence. In 8 out of 11 evaluable patients, relapse was preceded by MRD recurrence (median 9 weeks, range 0–30). We conclude that in children with high-risk ALL, immunotherapy-based regimens after SCT are feasible and may need to be further intensified to achieve total eradication of residual leukemic cells.

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Acknowledgements

We thank Professor Dr M Tilanus for the analysis of chimerism, Dr CE van der Schoot and C Homburg for MRD analysis of selected samples and Monique ten Dam, Remy van der Hulst, Ada Struyk, Els Jol-van der Zijde, Maaike de Bie and Patricia Hoogeveen for technical assistance. We also acknowledge the support of the staff of the DCOG laboratory in The Hague, The Netherlands, for sample handling and analysis. This research was supported by Grant UL 2001-2515 from the Dutch Cancer Society (KWF, Amsterdam).

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Authors and Affiliations

  1. Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands

    A C Lankester, J M Vossen, R M Egeler, M J D van Tol & M W Schilham

  2. Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands

    M B Bierings, B Versluys & T Révész

  3. Dutch Childhood Oncology Group, The Hague, The Netherlands

    E R van Wering

  4. Department of Immunology, Erasmus MC, Rotterdam, The Netherlands

    A J M Wijkhuijs, J J M van Dongen & V H J van der Velden

  5. Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands

    R A de Weger

  6. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

    J T Wijnen

  7. Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands

    H Putter

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  1. A C Lankester
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Lankester, A., Bierings, M., van Wering, E. et al. Preemptive alloimmune intervention in high-risk pediatric acute lymphoblastic leukemia patients guided by minimal residual disease level before stem cell transplantation. Leukemia 24, 1462–1469 (2010). https://doi.org/10.1038/leu.2010.133

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