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Acute lymphoblastic leukemia

Monitoring minimal residual disease in children with high-risk relapses of acute lymphoblastic leukemia: prognostic relevance of early and late assessment

Leukemia volume 29, pages 1648–1655 (2015)Cite this article

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Abstract

The prognosis for children with high-risk relapsed acute lymphoblastic leukemia (ALL) is poor. Here, we assessed the prognostic importance of response during induction and consolidation treatment prior to hematopoietic stem cell transplantation (HSCT) aiming to evaluate the best time to assess minimal residual disease (MRD) for intervention strategies and in future trials in high-risk ALL relapse patients. Included patients (n=125) were treated uniformly according to the ALL-REZ BFM (Berlin-Frankfurt-Münster) 2002 relapse trial (median follow-up time=4.8 years). Patients with MRD ⩾10−3 after induction treatment (76/119, 64%) or immediately preceding HSCT (19/71, 27%) had a significantly worse probability of disease-free survival 10 years after relapse treatment begin, with 26% (±6%) or 23% (±7%), respectively, compared with 58% (±8%) or 48% (±7%) for patients with MRD <10−3. Conventional intensive consolidation treatment reduced MRD to <10−3 before HSCT in 63% of patients, whereas MRD remained high or increased in the rest of this patient group. Our data support that MRD after induction treatment can be used to quantify the activity of different induction treatment strategies in phase II trials. MRD persistence at ⩾10−3 before HSCT reflects a disease highly resistant to conventional intensive chemotherapy and requiring prospective controlled investigation of new treatment strategies and drugs.

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Acknowledgements

The authors heartily thank all patients, their families and treating physicians who participated in this study. We thank our molecular genetics laboratory technicians for their excellent work, PD Dr Richard Ratei and his laboratory for immunophenotyping and Andrea Kretschmann in the ALL-REZ BFM trial center for reliable comprehensive data management. We thank the Deutsche Kinderkrebsstiftung for financing the ALL-REZ BFM 2002 clinical trial and MRD studies in Germany, the Pediatric Oncology Competence Network for collaboration on frontline MRD studies (supported by the German Federal Ministry of Education and Research), the Deutsche José Carreras Leukämie-Stiftung e.V. for supporting the international principal investigator, and the GACR Centre of Excellence (#P302/12/G101) and MH CZ – DRO, University Hospital Motol (Prague, #00064203) for supporting the study in the Czech Republic.

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Authors and Affiliations

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

    C Eckert, N Hagedorn, K Astrahantseff, K Seeger, G Henze & A von Stackelberg

  2. Department of Pediatric Hematology and Oncology, Charles University, 2nd Medical School and University Hospital Motol, Prague, Czech Republic

    L Sramkova

  3. CLIP - Childhood Leukemia Investigation Prague, Prague, Czech Republic

    L Sramkova

  4. St Anna Children's Research Institute and Children’s Hospital, Medical University of Vienna, Vienna, Austria

    G Mann, R Panzer-Grümayer & C Peters

  5. Department of Pediatric Oncology, University Children's Hospital, Zurich, Switzerland

    J-P Bourquin

  6. Hospital for Children and Adolescents, Goethe-University Hospital Frankfurt, Frankfurt, Germany

    T Klingebiel

  7. Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich Heine University, Duesseldorf, Germany

    A Borkhardt

  8. Department of Pediatrics, University of Schleswig-Holstein, Kiel, Germany

    G Cario & J Alten

  9. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    G Escherich

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Correspondence to C Eckert.

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Eckert, C., Hagedorn, N., Sramkova, L. et al. Monitoring minimal residual disease in children with high-risk relapses of acute lymphoblastic leukemia: prognostic relevance of early and late assessment. Leukemia 29, 1648–1655 (2015). https://doi.org/10.1038/leu.2015.59

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