Secondary cytogenetic aberrations in childhood Philadelphia chromosome positive acute lymphoblastic leukemia are nonrandom and may be associated with outcome

Heerema, N.A., Harbott, J., Galimberti, S., Camitta, B.M., Gaynon, P.S., Janka-Schaub, G., Kamps, W., Basso, G., Pui, C.H., Schrappe, M., Auclerc, M.F., Carroll, A.J., Conter, V., Harrison, C.J., Pullen, J., Raimondi, S.C., Richards, S., Riehm, H., Sather, H.N., Shuster, J.J., Silverman, L.B., Valsecchi, M.G. and Arico, M. (2004) Secondary cytogenetic aberrations in childhood Philadelphia chromosome positive acute lymphoblastic leukemia are nonrandom and may be associated with outcome. Leukemia, 18 (4), 693-702. (doi:10.1038/sj.leu.2403324).

Abstract

Additional chromosomal aberrations occur frequently in Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) of childhood. The treatment outcome of these patients is heterogeneous. This study assessed whether such clinical heterogeneity could be partially explained by the presence and characteristics of additional chromosomal abnormalities. Cytogenetic descriptions were available for 249 of 326 children with Ph+ ALL, diagnosed and treated by 10 different study groups/large single institutions from 1986 to 1996. Secondary aberrations were present in 61% of the cases. Chromosomes 9, 22, 7, 14, and 8 were most frequently abnormal. Most (93%) karyotypes were unbalanced. Three main cytogenetic subgroups were identified: no secondary aberrations, gain of a second Ph and/or >50 chromosomes, or loss of chromosome 7, 7p, and/or 9p, while other secondary aberrations were grouped as combinations of gain and loss or others. Of the three main cytogenetic subgroups, the loss group had the worst event-free survival (P=0.124) and disease-free survival (P=0.013). However, statistical significance was not maintained when adjusted for other prognostic factors and treatment. Karyotypic analysis is valuable in subsets of patients identified by molecular screening, to assess the role of additional chromosomal abnormalities and their correlation with clinical heterogeneity, with possible therapeutic implications.

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