title: Monitoring treatment response of childhood precursor B-cell acute lymphoblastic leukemia in the AIEOP-BFM-ALL 2000 protocol with multiparameter flow cytometry: predictive impact of early blast reduction on the remission status after induction.
abstract: Treatment response is a strong outcome predictor for childhood acute lymphoblastic leukemia (ALL). Here, we evaluated the predictive impact of flow cytometric blast quantification assays (absolute blast count, BC, and blast reduction rate, BRR) in peripheral blood (pB) and/or bone marrow (BM) at early time points of induction therapy (days 0, 8 and 15) on the remission status in the AIEOP-BFM-ALL 2000 protocol. At the single parameter level (905 patients), the strongest predictive parameter for the remission status as a dichotomous minimal residual disease (MRD) parameter (positive/negative) has been provided by the BC at day 15 in BM (cutoff: 17 blasts/microl; 50 vs 15%; odds ratio: 5.6; 95% confidence interval: 4.1-7.6, P<0.001), followed by the BRR at day 15 in BM and by the BC at day 8 in pB (odds ratios: 3.8 and 2.6, respectively). In the multiple regression analysis (440 patients), BC in pB (d0 and d8) and in BM (d15) as well as BRR at day 8 in pB provided significantly contributing variables with an overall correct prediction rate of 74.8%. These data show that the quantitative assessment of early response parameters, especially absolute BCs at day 15 in BM, has a predictive impact on the remission status after induction therapy.
authors.affiliation: Department of Hematology and Oncology, Robert-Roessle-Clinic at HELIOS Klinikum Berlin, Charité-Campus Buch, Germany. richard.ratei@helios-kliniken.de
authors.forename: R
authors.initials: R
authors.lastname: Ratei
authors.forename: G
authors.initials: G
authors.lastname: Basso
authors.forename: M
authors.initials: M
authors.lastname: Dworzak
authors.forename: G
authors.initials: G
authors.lastname: Gaipa
authors.forename: M
authors.initials: M
authors.lastname: Veltroni
authors.forename: P
authors.initials: P
authors.lastname: Rhein
authors.forename: A
authors.initials: A
authors.lastname: Biondi
authors.forename: M
authors.initials: M
authors.lastname: Schrappe
authors.forename: W-D
authors.initials: WD
authors.lastname: Ludwig
authors.forename: L
authors.initials: L
authors.lastname: Karawajew
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D019540:Area Under Curve; D001773:Blood Cells / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D016903:Drug Monitoring; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D016130:Immunophenotyping / Q000379:methods*; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual; D014411:Neoplastic Stem Cells / Q000473:pathology*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; D011379:Prognosis; D012372:ROC Curve; D012074:Remission Induction; D016896:Treatment Outcome