Prognostic impact of karyotypic findings in childhood acute lymphoblastic leukaemia: a Nordic series comparing two treatment periods

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Abstract
The prognostic impact of acquired chromosome abnormalities was evaluated in a population-based consecutive series of 768 children (< 15 years of age) with acute lymphoblastic leukaemia (ALL). The study cohort included all cases of cytogenetically abnormal childhood ALL diagnosed between 1986 and 1997 in the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden). The probability of event-free survival (pEFS) for the total cohort was 0·72 ± 0·02. When comparing the two treatment periods of July 1986 to December 1991 and January 1992 to December 1997, a better survival was seen for the latter time period (pEFS of 0·69 ± 0·02 vs. 0·76 ± 0·02, P = 0·05). Hypodiploidy with less than 45 chromosomes, t(9;22)(q34;q11) and 11q23 translocations were associated with a dismal outcome during the whole study period (pEFS of 0·57 ± 0·12, 0·41 ± 0·14 and 0·37 ± 0·10 respectively). The poor prognostic influence of 11q23 rearrangements seemed to be restricted to infants and older children (> 10 years), who differed significantly from children aged 1–10 years in this regard (P < 0·01). Patients with t(9;22)-positive ALL seemed to benefit from allogeneic bone marrow transplantation in first remission (P = 0·05). The pEFS for children with t(1;19)(q23;p13)-positive ALL was intermediate (0·63 ± 0·17), with a tendency to a better outcome for patients with the unbalanced variant der(19)t(1;19). Hyperdiploid ALL patients, subdivided into moderate hyperdiploidy (47–51 chromosomes), massive hyperdiploidy (52–60 chromosomes) and cases in the tri-/tetraploid range (> 60 chromosomes) had the best outcome in the last treatment period (pEFS of 0·81 ± 0·06, 0·80 ± 0·04 and 0·88 ± 0·07 respectively), unless t(1;19), t(8;14), t(9;22) or 11q23 translocations were present. In a multivariate analysis including white blood cell (WBC) count, immunophenotype, age, mediastinal mass, central nervous system involvement and leukaemia karyotype, only WBC and modal chromosome number were shown to be significant independent risk factors (P < 0·01).