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Blood, 1 February 2007, Vol. 109, No. 3, pp. 910-915.
Prepublished online as a Blood First Edition Paper on October 5, 2006; DOI 10.1182/blood-2006-07-037093.
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Submitted July 26, 2006
Accepted September 13, 2006
Molecular relapse in adult standard risk ALL patients detected by prospective MRD-monitoring during and after maintenance treatment - data from the GMALL 06/99 and 07/03 trials
Thorsten Raff*, Nicola Gokbuget, Silke Luschen, Regina Reutzel, Matthias Ritgen, Sebastian Irmer, Sebastian Bottcher, Heinz-August Horst, Michael Kneba, Dieter Hoelzer, and Monika Bruggemann
Division of Hematology and Oncology, University Schleswig-Holstein, Campus Kiel, Germany
Division of Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt/Main, Germany
* Corresponding author; email: t.raff{at}med2.uni-kiel.de.
Although levels of minimal residual disease (MRD) decrease below the detection limit in the majority of adult patients with standard risk acute lymphoblastic leukemia (ALL) after consolidation treatment, about 30% of these patients will ultimately relapse. To evaluate the power of MRD-monitoring as an indicator of impending relapse, we prospectively analysed postconsolidation samples of 105 patients enrolled in the German Multicenter ALL (GMALL) trial by realtime quantitative PCR of clonal immunegene rearrangements. All patients were in hematological remission, had completed first year polychemotherapy and were tested MRD-negative prior to study entry. 28 of 105 patients (27%) converted to MRD-positivity thereafter, 17/28 (61%) relapsed so far. Median time from molecular (MRD+) to clinical relapse was 9.5 months. In 15 of these patients MRD within the quantitative range of PCR was measured in hematologic remission, and 13 of these patients (89%) relapsed after a median interval of 4.1 months. Of the 77 continuously MRD-negative patients, only 5 (6%) have relapsed. We conclude that conversion to MRD positivity during early postconsolidation phase in adult standard risk ALL patients is highly predictive of subsequent hematologic relapse. As a result of the study, in the ongoing GMALL trial salvage treatment is intended to be started at the time of reoccurence of quantifiable MRD.
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