Adverse prognostic impact of complex karyotype (¿3 cytogenetic alterations) in adult T-cell acute lymphoblastic leukemia (T-ALL)

Abstract

The potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of >3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study. Karyotypes with >3 abnormalities accounted for 16 % (22/139) of all evaluable karyotypes, corre-sponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying kar-yotypes with >3 cytogenetic alterations showed a significantly inferior response to therapy, and a poor outcome in terms of event-free survival (EFS), overall survival (OS) and cumulative incidence of relapse (CIR), inde-pendently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Addi-tional molecular analyses of patients carrying >3 cytogenetic alterations showed a unique molecular profile that could contribute to understand the underlying molecular mechanisms of resistance and to evaluate novel tar-geted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients.