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J Clin Oncol. 2015 Apr 10;33(11):1275-84. doi: 10.1200/JCO.2014.58.4631. Epub 2015 Jan 20.

Monitoring of minimal residual disease after allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia allows for the identification of impending relapse: results of the ALL-BFM-SCT 2003 trial.

Author information

1
Peter Bader, Hermann Kreyenberg, Emilia Salzmann-Manrique, Andre M. Willasch, and Thomas E. Klingebiel, University Hospital for Children and Adolescents, Frankfurt/Main; Arend von Stackelberg and Cornelia Eckert, Children's Hospital Charité, Berlin, Berlin; Roland Meisel, Heinrich-Heine-University, Düsseldorf; Daniel Stachel, University Hospital Erlangen, Erlangen; Martin Schrappe, Julia Alten, Andre Schrauder, Christian-Albrechts-University and Medical Center Schleswig-Holstein, Kiel; Ansgar Schulz, University Medical Center, Ulm; Peter Lang, University Children's Hospital, Tuebingen; Ingo Müller, University Medical Center Hamburg-Eppendorf, Hamburg; Michael H. Albert, University Children's Hospital, Munich, Germany; and Ulrike Poetschger and Christina Peters, St Anna Children's Hospital, Vienna, Austria. peter.bader@kgu.de.
2
Peter Bader, Hermann Kreyenberg, Emilia Salzmann-Manrique, Andre M. Willasch, and Thomas E. Klingebiel, University Hospital for Children and Adolescents, Frankfurt/Main; Arend von Stackelberg and Cornelia Eckert, Children's Hospital Charité, Berlin, Berlin; Roland Meisel, Heinrich-Heine-University, Düsseldorf; Daniel Stachel, University Hospital Erlangen, Erlangen; Martin Schrappe, Julia Alten, Andre Schrauder, Christian-Albrechts-University and Medical Center Schleswig-Holstein, Kiel; Ansgar Schulz, University Medical Center, Ulm; Peter Lang, University Children's Hospital, Tuebingen; Ingo Müller, University Medical Center Hamburg-Eppendorf, Hamburg; Michael H. Albert, University Children's Hospital, Munich, Germany; and Ulrike Poetschger and Christina Peters, St Anna Children's Hospital, Vienna, Austria.

Abstract

PURPOSE:

To elucidate the impact of minimal residual disease (MRD) after allogeneic transplantation, the Acute Lymphoblastic Leukemia Berlin-Frankfurt-Münster Stem Cell Transplantation Group (ALL-BFM-SCT) conducted a prospective clinical trial.

PATIENTS AND METHODS:

In the ALL-BFM-SCT 2003 trial, MRD was assessed in the bone marrow at days +30, +60, +90, +180, and +365 after transplantation in 113 patients with relapsed disease. Standardized quantification of MRD was performed according to the guidelines of the Euro-MRD Group.

RESULTS:

All patients showed a 3-year probability of event-free survival (pEFS) of 55%. The cumulative incidence rates of relapse and treatment-related mortality were 32% and 12%, respectively. The pEFS was 60% for patients who received their transplantations in second complete remission, 50% for patients in ≥ third complete remission, and 0% for patients not in remission (P = .015). At all time points, the level of MRD was inversely correlated with event-free survival (EFS; P < .004) and positively correlated with the cumulative incidence of relapse (P < .01). A multivariable Cox model was fitted for each time point, which showed that MRD ≥ 10(-4) leukemic cells was consistently correlated with inferior EFS (P < .003). The accuracy of MRD measurements in predicting relapse was investigated with time-dependent receiver operating curves at days +30, +60, +90, and +180. From day +60 onward, the discriminatory power of MRD detection to predict the probability of relapse after 1, 3, 6, and 9 months was more than 96%, more than 87%, more than 71%, and more than 61%, respectively.

CONCLUSION:

MRD after transplantation was a reliable marker for predicting impending relapses and could thus serve as the basis for pre-emptive therapy.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01423747.

PMID:
25605857
DOI:
10.1200/JCO.2014.58.4631
[Indexed for MEDLINE]

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