title: Major impact of an early bone marrow checkpoint (day 21) for minimal residual disease in flow cytometry in childhood acute lymphoblastic leukemia.
abstract: The early persistence of minimal residual disease (MRD) is considered a poor prognostic factor indicative of chemoresistance in acute lymphoblastic leukemia. In French children, chemosensitivity is assessed at day 21 post-induction by cytomorphology. Here, it was investigated whether a more precise evaluation could be obtained at this time point with multiparameter flow cytometry (MFC). This study enrolled 123 children with de novo acute lymphoblastic leukemia. MRD0 was investigated at day 21 in MFC with a combination of antibodies based on the immunophenotype of diagnosis. It was also evaluated at day 35 by immunoglobulin/T-cell receptor quantitative real-time polymerase chain reaction (MRD1). Three risk groups could be delineated based on MRD0. Patients with MFC/MRD0 levels >10-2(n = 25) were considered high risk, those with levels between 10-2and 10-4(n = 46) intermediate risk, and those <10-4(n = 50) low risk. Overall survival (p = 0.048) and event-free survival (EFS, p = 0.00017) were significantly different between these three groups. EFS of the 14 corticoresistant patients strongly depended on their MRD0 level (p = 0.004). Similarly, both EFS (p = 0.0004) and overall survival (p = 0.02) were significantly different in the 109 chemosensitive patients, according to MRD0 levels. MRD0 and MRD1 levels, compared with 112 patients, were consistent (-/- or +/+) in 57.2% of the cases. Both MRD0+/MRD1+ and MRD0+/MRD1- patients had a significantly worse EFS (p = 0.0001) than those with undetectable MRD at both MRD0 and MRD1. This study confirms the usefulness and superiority of an early point of MRD detection by MFC. In addition, MRD0 in MFC identifies a subgroup of patients with poorer prognosis (MRD0+/MRD1-). Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Hematology Biology, Nantes University Hospital, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Eveillard
authors.affiliation: Hematology Biology, Nantes University Hospital, France.
authors.forename: Nelly
authors.initials: N
authors.lastname: Robillard
authors.affiliation: Hematology Biology, Timone University Hospital, Marseilles, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Arnoux
authors.affiliation: Hematology Biology, Nantes University Hospital, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Garand
authors.affiliation: Oncopediatrics Department, Nantes University Hospital, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Rialland
authors.affiliation: Oncopediatrics Department, Nantes University Hospital, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Thomas
authors.affiliation: Oncopediatrics Department, Nantes University Hospital, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Strullu
authors.affiliation: Oncopediatrics Department, Timone University Hospital, Marseilles, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Michel
authors.affiliation: Hematology Biology, Nantes University Hospital, France.
authors.forename: Marie C
authors.initials: MC
authors.lastname: Béné
authors.affiliation: Hematology Biology, Timone University Hospital, Marseilles, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Fossat
authors.affiliation: Hematology Biology, Timone University Hospital, Marseilles, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Loosveld
mesh_terms: D000293:Adolescent; D001853:Bone Marrow / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D007223:Infant; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D055815:Young Adult
keywords: chemosensitivity; childhood acute lymphoblastic leukemia; flow cytometry; minimal residual disease; prognostic value