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, corresponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying karyotypes 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), independently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Additional 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 targeted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients.

常规核型分析在成人 T 细胞急性淋巴细胞白血病 (T-ALL) 中的潜在预后价值仍然是一个悬而未决的问题。我们假设，基于细胞遗传学异常的数量和类型的改良细胞遗传学分类将允许识别高危成人 T-ALL 患者。在本研究中，由 ≥ 3 种细胞遗传学改变定义的复杂核型确定了预后不良的 T-ALL 患者。具有 ≥ 3 个异常的核型占所有可评估核型的 16 % (22/139)，对应于迄今为止鉴定的最大的 T-ALL 预后不良细胞遗传亚组。携带 ≥ 3 个细胞遗传学改变的核型的患者对治疗的反应明显较差，并且在无事件生存 (EFS) 方面的结果较差，总生存期 (OS) 和累积复发率 (CIR)，独立于其他基线特征和诱导末期微小残留病 (MRD) 水平。对携带≥3 细胞遗传学改变的患者进行的额外分子分析显示出独特的分子谱，有助于了解耐药性的潜在分子机制并评估新的靶向治疗。例如IL7R 定向）对成人 T-ALL 患者的结果有潜在影响。