title: Molecular detection of minimal residual disease in adult and childhood acute lymphoblastic leukaemia reveals differences in treatment response.
abstract: Immunoglobulin heavy chain gene (IgH gene) rearrangements are found in the majority of patients with B lineage acute lymphoblastic leukaemia (ALL). Two hundred and three bone marrow samples from 54 patients (33 adults and 21 children) were analysed by PCR within specific time-points after diagnosis (ie 1, 2-3, 4-6 and 7-12 months) using FR1 and JH primers (fingerprinting with a sensitivity > or =1:5 x 10[3]). CDR3-derived allele specific oligoprimers (ASO to achieve a sensitivity between 1:10[4] and 1:10[5]) were applied to 12 children and 18 adults, while size of CDR3 region, oligoclonality and background problems prevented their application to the remaining patients. All patients were followed clinically for > or =24 months. Thirty adults and 16 children presented as newly diagnosed ALL, while the remaining eight patients were analysed in first or subsequent relapse. Patients destined to relapse showed a higher proportion of positive tests (> or =50%), particularly after 1 month, than in the remission group, irrespective of age. Among patients staying in remission, a decrease in MRD-positive tests occurred during the first 12 months in both age groups. However, the proportion of positive tests dropped below 15% at a later stage in adults (4-6 months) than in children (2-3 months). Among children, only patients destined to relapse were MRD positive beyond 1 month, with the exception of only one patient, still positive at 2-3 months in the remission group. The difference in MRD positivity between relapse and remission patients was statistically significant in children (P < 0.03) at any time of testing, but only at 4-6 months in adults (P < 0.01). These data suggest that resolution of MRD in ALL occurs more rapidly in children compared to adults, particularly within the first 6 months. Children and adults, studied in first or subsequent relapse, showed a higher proportion of positive tests during reinduction compared to newly diagnosed patients.
authors.affiliation: Department of Haematology, Royal Free Hospital and School of Medicine, London, UK.
authors.forename: L
authors.initials: L
authors.lastname: Foroni
authors.forename: L A
authors.initials: LA
authors.lastname: Coyle
authors.forename: M
authors.initials: M
authors.lastname: Papaioannou
authors.forename: J C
authors.initials: JC
authors.lastname: Yaxley
authors.forename: M F
authors.initials: MF
authors.lastname: Sinclair
authors.forename: J S
authors.initials: JS
authors.lastname: Chim
authors.forename: P
authors.initials: P
authors.lastname: Cannell
authors.forename: L M
authors.initials: LM
authors.lastname: Secker-Walker
authors.forename: A B
authors.initials: AB
authors.lastname: Mehta
authors.forename: H G
authors.initials: HG
authors.lastname: Prentice
authors.forename: A V
authors.initials: AV
authors.lastname: Hoffbrand
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002869:Chromosome Aberrations; D016172:DNA Fingerprinting; D017931:DNA Primers; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D012680:Sensitivity and Specificity; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D017931:DNA Primers; D007143:Immunoglobulin Heavy Chains