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    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2015 Jan 20. pii: JCO.2014.58.4631. doi: 10.1200/JCO.2014.58.4631
    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 P1,  Kreyenberg H2,  von Stackelberg A3,  Eckert C4,  Salzmann-Manrique E5,  Meisel R6,  Poetschger U7,  Stachel D8,  Schrappe M9,  Alten J10,  Schrauder A11,  Schulz A12,  Lang P13,  Müller I14,  Albert MH15,  Willasch AM16,  Klingebiel TE17,  Peters C18
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    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.


    © 2015 by American Society of Clinical Oncology.

    Publikations ID: 25605857
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