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.
Although levels of minimal residual disease (MRD) decrease below the detection limit in most 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 analyzed postconsolidation samples of 105 patients enrolled in the German Multicenter ALL (GMALL) trial by real-time quantitative polymerase chain reaction (PCR) of clonal immune gene rearrangements. All patients were in hematologic remission, had completed first-year polychemotherapy, and tested MRD negative prior to study entry. Twenty-eight of 105 patients (27%) converted to MRD positivity thereafter, and 17 of 28 (61%) relapsed so far. Median time from molecular (MRD-positive) 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 the early postconsolidation phase in adult standard-risk ALL patients is highly predictive of subsequent hematologic relapse. As a result of the study, as of spring 2006, salvage treatment in the ongoing GMALL trial is intended to be started at the time of recurrence of quantifiable MRD.
Raff
Thorsten
T
Second Medical Department, University Schleswig-Holstein, Campus Kiel, Germany. t.raff@med2.uni-kiel.de
Gökbuget
Nicola
N
Lüschen
Silke
S
Reutzel
Regina
R
Ritgen
Matthias
M
Irmer
Sebastian
S
Böttcher
Sebastian
S
Horst
Heinz-August
HA
Kneba
Michael
M
Hoelzer
Dieter
D
Brüggemann
Monika
M
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000188:drug therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000188:drug therapy; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016879:Salvage Therapy