title: Sequential monitoring of minimal residual disease in acute lymphoblastic leukemia: 7-year experience in a pediatric hematology/oncology unit.
abstract: We evaluated minimal residual disease (MRD) in 91 children with acute lymphoblastic leukemia (ALL) by PCR amplification of clonal rearrangements, immunoglobulin (IgH; VDJ rearrangement, CDR3 region) and T-cell receptor (TCRdelta). Sequential monitoring of MRD was performed at different time points during and after chemotherapy and was correlated to patient outcome. In total, 792 bone marrow samples were assessed for MRD at the end of induction, and during and after treatment completion. MRD positivity at the end of induction was detected in 12% of patients and was associated with high incidence of relapse, 54.55% (p = 0.0002), at 5 years. On the other hand, 88% of patients were MRD-negative at the end of induction and the relapse rate at 5 years was very low, 5%. The frequency of MRD decreased to 16% in the first 6 months of chemotherapy; however, the incidence of relapse in MRD-positive patients remained high, 42.8%. After treatment completion (24-36 months from diagnosis), 32% patients were MRD-positive and the relapse rate was 36.5% (p = 0.0009). Our results indicated that monitoring of MRD constituted an essential prognostic marker, and detection of MRD particularly at the end of induction and after treatment completion was strongly predictive for patient outcome.
authors.affiliation: Hematology/Oncology Unit, First Department of Pediatrics, University of Athens, Aghia Sophia Children's Hospital, Thivon & Levadias, 11527, Goudi-Athens, Greece. katharinakats@hotmail.com
authors.forename: Katerina
authors.initials: K
authors.lastname: Katsibardi
authors.forename: Maria A
authors.initials: MA
authors.lastname: Moschovi
authors.forename: Maria
authors.initials: M
authors.lastname: Braoudaki
authors.forename: Stefanos I
authors.initials: SI
authors.lastname: Papadhimitriou
authors.forename: Chrissa
authors.initials: C
authors.lastname: Papathanasiou
authors.forename: Fotini
authors.initials: F
authors.lastname: Tzortzatou-Stathopoulou
mesh_terms: D001853:Bone Marrow; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate; D013997:Time Factors
chemical_list: D004273:DNA, Neoplasm