title: Clinical significance of residual disease during treatment in childhood acute myeloid leukaemia.
abstract: In children with acute myeloid leukaemia (AML), morphological and karyotypic studies cannot precisely assess response to treatment, and less than one-third of patients have genetic markers for molecular studies of residual disease. We determined the usefulness of a four-colour flow cytometric strategy developed in our laboratory to study residual disease. We first compared the immunophenotypes of AML cells obtained from 54 children at diagnosis with those of cells from 59 normal or regenerating bone marrow samples. Forty-six of the 54 AML cases (85.2%) had immunophenotypes that allowed detection of 0.1-0.01% residual leukaemic cells. Of 230 bone marrow samples obtained from those 46 patients during and off treatment, 61 (26.5%) had >/= 0.1% AML cells by flow cytometry. We found that core binding factor-associated AML had a significantly better early treatment response. Mean (+/- standard error) 2-year survival estimate was 33.1 +/- 19.1% for patients with >/= 0.1% AML cells by flow cytometry after induction therapy, but 72.1 +/- 11.5% for those with < 0.1% AML cells (P = 0.022); overt recurrence of AML within the subsequent 6 months was significantly more likely in the former group. The assay described here holds promise for guiding the choice of post-remission treatment options in children with AML.
authors.affiliation: Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Coustan-Smith
authors.forename: Raul C
authors.initials: RC
authors.lastname: Ribeiro
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Rubnitz
authors.forename: Bassem I
authors.initials: BI
authors.lastname: Razzouk
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.forename: Stanley
authors.initials: S
authors.lastname: Pounds
authors.forename: Martin
authors.initials: M
authors.lastname: Andreansky
authors.forename: Frederick G
authors.initials: FG
authors.lastname: Behm
authors.forename: Susana C
authors.initials: SC
authors.lastname: Raimondi
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Shurtleff
authors.forename: James R
authors.initials: JR
authors.lastname: Downing
authors.forename: Dario
authors.initials: D
authors.lastname: Campana
mesh_terms: D000208:Acute Disease; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D001854:Bone Marrow Cells / Q000473:pathology; D002469:Cell Separation / Q000379:methods; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D008297:Male; D018365:Neoplasm, Residual; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor