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Minimal Residual Disease

Very early/early relapses of acute lymphoblastic leukemia show unexpected changes of clonal markers and high heterogeneity in response to initial and relapse treatment

Leukemia volume 25, pages 1305–1313 (2011)Cite this article

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Abstract

Minimal residual disease (MRD) quantified after induction treatment of childhood acute lymphoblastic leukemia (ALL) predicts risk of relapse. It has been assumed that early relapses derive from a residual population of leukemic cells, which is still present after induction and that relapsed disease will consequently be more resistant to treatment. To test these hypotheses, we performed a prospective study on patients treated according to the frontline-trial ALL-BFM 2000, which used MRD response for risk-group stratification. Patients (n=45) showed a median time to relapse of 1.5 years. In 89% of patients at least one T-cell-receptor/immunoglobulin gene rearrangement chosen for initial MRD quantification remained stable; however, at least one of the preferred markers for MRD stratification at relapse was different to diagnosis in 50% of patients. A similar proportion of very early, early and late relapses appeared to gain a marker at relapse although backtracking-analysis revealed that in 77% of cases, the gained markers were present as small sub-clones at initial diagnosis. Comparing initial and relapse MRD response to induction, 38% of patients showed a similar, 38% a better and 25% a poorer response after relapse. These data demonstrate an unexpectedly high clonal heterogeneity among very early/early relapses and challenge some current assumptions about relapsed ALL.

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Acknowledgements

We are grateful to NW, NP, CH, SH and WK for their excellent technical assistance. We thank the study documentation officers for the data management of the ALL-BFM trial (Kiel, Germany) and the ALL-REZ BFM trial (Berlin, Germany). We are very thankful to RS for her detailed reading, comments and suggestions for our manuscript. This work was kindly supported by the Deutsche José Carreras Leukämie-Stiftung e.V, by the Kompetenznetz für Pädiatrische Onkologie (BMBF), by the Deutsche Kinderkrebsstiftung and by the Deutsche Krebshilfe, Germany.

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Authors and Affiliations

  1. Department of Pediatric Oncology/Hematology, Charité Universitätsmedizin Berlin, Berlin, Germany

    C Eckert, N Hagedorn, R Kirschner-Schwabe, Av Stackelberg & G Henze

  2. Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany

    T Flohr, R Koehler & C R Bartram

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

    A Moericke, M Stanulla, G Cario, M Schrappe & A Schrauder

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  1. C Eckert
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Correspondence to C Eckert.

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Eckert, C., Flohr, T., Koehler, R. et al. Very early/early relapses of acute lymphoblastic leukemia show unexpected changes of clonal markers and high heterogeneity in response to initial and relapse treatment. Leukemia 25, 1305–1313 (2011). https://doi.org/10.1038/leu.2011.89

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