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

Bader P, Kreyenberg H, Von Stackelberg A, Eckert C, Salzmann-Manrique E, Meisel R, Poetschger U, Stachel D, Schrappe M, Alten J, Schrauder A, Schulz A, Lang P, Mueller I, Albert MH, Willasch AM, Klingebiel TE, Peters C (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Journal of Clinical Oncology American Society of Clinical Oncology

Publisher: American Society of Clinical Oncology: JCO

Book Volume: 33

Pages Range: 1275-84

Journal Issue: 11

DOI: 10.1200/JCO.2014.58.4631

Abstract

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

Authors with CRIS profile

Klaus Daniel Stachel Medizinische Fakultät

Involved external institutions

Universitätsklinikum Frankfurt am Main (KGU) DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Heinrich-Heine-Universität Düsseldorf DE Germany (DE) St. Anna Kinderkrebsforschung AT Austria (AT) Christian-Albrechts-Universität zu Kiel DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE) Universitätsklinikum Münster DE Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE)

How to cite

APA:

Bader, P., Kreyenberg, H., Von Stackelberg, A., Eckert, C., Salzmann-Manrique, E., Meisel, R.,... Peters, C. (2015). 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. Journal of Clinical Oncology, 33(11), 1275-84. https://doi.org/10.1200/JCO.2014.58.4631

MLA:

Bader, Peter, et al. "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." Journal of Clinical Oncology 33.11 (2015): 1275-84.

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