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

Abstract

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-α 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).