Heterogeneous prognostic impact of derivative chromosome 9 deletions in chronic myelogenous leukemia

Kreil, S., Pfirrmann, M., Haferlach, C., Waghorn, K., Chase, A., Hehlmann, R., Reiter, A., Hochhaus, A. and Cross, N.C. (2007) Heterogeneous prognostic impact of derivative chromosome 9 deletions in chronic myelogenous leukemia. Blood, 110 (4), 1283-1290. (doi:10.1182/blood-2007-02-074252).

Abstract

Derivative chromosome 9 deletions are seen in 10% to 15% of patients with chronic myelogenous leukemia and have been associated with a poor prognosis; however, no studies have been performed in the context of a randomized clinical trial. We developed a DNA-based deletion screen and investigated 339 chronic phase patients treated with interferon-alpha as first-line therapy in 3 controlled German studies with a median observation time of 7 years. Deletions were detected in pretreatment DNA of 59 of 339 (17%) patients. Of these, 21 spanned the ABL/BCR junction and 38 were centromeric (n = 20) or telomeric (n = 18) of the breakpoint. There was no significant difference in overall survival between deleted and nondeleted patients. Patients with breakpoint-spanning deletions had poorer survival compared with patients without deletions (4.7 versus 7.8 years; P = .003), but this was not significant when censored at allogeneic stem cell transplantation (n = 129) or imatinib (n = 62) treatment in the first chronic phase (P = .078). Unexpectedly, deletions that did not span the breakpoint were associated with improved survival compared with cases without deletions (P = .001). Multiple Cox regression analysis indicated that deletion status (P = .007), age (P = .018), and spleen enlargement (P < .001) were significant independent indicators of survival and confirmed that only deletions spanning the ABL/BCR breakpoint were associated with an adverse prognosis (P = .039).

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Contributors

Author: A. Chase

Author: N.C. Cross

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