title: Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia.
abstract: Adult patients with acute lymphoblastic leukemia (ALL) who are stratified into the standard-risk (SR) group due to the absence of adverse prognostic factors relapse in 40% to 55% of the cases. To identify complementary markers suitable for further treatment stratification in SR ALL, we evaluated the predictive value of minimal residual disease (MRD) and prospectively monitored MRD in 196 strictly defined SR ALL patients at up to 9 time points in the first year of treatment by quantitative polymerase chain reaction (PCR). Frequency of MRD positivity decreased from 88% during early induction to 13% at week 52. MRD was predictive for relapse at various follow-up time points. Combined MRD information from different time points allowed definition of 3 risk groups (P < .001): 10% of patients with a rapid MRD decline to lower than 10(-4) or below detection limit at day 11 and day 24 were classified as low risk and had a 3-year relapse rate (RR) of 0%. A subset of 23% with an MRD of 10(-4) or higher until week 16 formed the high-risk group, with a 3-year RR of 94% (95% confidence interval [CI] 83%-100%). The remaining patients whose RR was 47% (31%-63%) represented the intermediate-risk group. Thus, MRD quantification during treatment identified prognostic subgroups within the otherwise homogeneous SR ALL population who may benefit from individualized treatment.
authors.affiliation: Medical Clinic II, University of Kiel, Kiel, Germany. m.brueggemann@med2.uni-kiel.de
authors.forename: Monika
authors.initials: M
authors.lastname: Brüggemann
authors.forename: Thorsten
authors.initials: T
authors.lastname: Raff
authors.forename: Thomas
authors.initials: T
authors.lastname: Flohr
authors.forename: Nicola
authors.initials: N
authors.lastname: Gökbuget
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakao
authors.forename: Jo
authors.initials: J
authors.lastname: Droese
authors.forename: Silke
authors.initials: S
authors.lastname: Lüschen
authors.forename: Christiane
authors.initials: C
authors.lastname: Pott
authors.forename: Matthias
authors.initials: M
authors.lastname: Ritgen
authors.forename: Urban
authors.initials: U
authors.lastname: Scheuring
authors.forename: Heinz-August
authors.initials: HA
authors.lastname: Horst
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoelzer
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.forename: Michael
authors.initials: M
authors.lastname: Kneba
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D010865:Pilot Projects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality* / Q000628:therapy; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome