Hematology and Clinical Immunology Unit, Department of Medicine, University of Padua, Padua, Italy.
Venetian Institute of Molecular Medicine, Padua, Italy.
Br J Cancer. 2019 Jul;121(2):150-156. doi: 10.1038/s41416-019-0502-x. Epub 2019 Jun 18.
Complex karyotype (CK) is a heterogeneous category with a negative impact in chronic lymphocytic leukaemia (CLL). Our group has recently reported that CK patients with major structural abnormalities (i.e. CK2) are characterised by a worse prognosis, as compared to other lesions within CK(CK1).
We performed a multicentre retrospective study to test whether the combination of CK subtypes with IGHV status could be a relevant prognostic and predictive tool.
Among 522 patients 13% harboured CK2, 41% CK1 and/or U-IGHV (U-CK1) and 46% M-IGHV without any CK subtypes (M-noCK). After a median follow-up of 5.8 years, CK2 patients had the shortest TTFT (5-year TTFT 31%, 39 and 81%, p < 0.0001) and OS (5-year OS 67%, 85 and 93%, p < 0.0001) as compared to U-CK1 or M-noCK cases, regardless of TP53 abnormalities. CK2 patients also had the worst outcome after chemoimmunotherapy. In fact, the median TTNT after FCR or BR was 1.86 and 4.79 years for CK2 and U-CK1, but not reached for M-noCK patients (p < 0.0005).
We herein suggest that the combined assessment of the IGHV mutational status and CK subtypes refines the prognostication of CLL, allowing to identify M-IGHV patients without any CK subtypes who are characterised by an indolent disease and excellent outcome after chemoimmunotherapy.
复杂核型（CK）是一种具有异质性的类别，对慢性淋巴细胞白血病（CLL）有负面影响。我们的团队最近报告称，与 CK（CK1）中的其他病变相比，具有主要结构异常（即 CK2）的 CK 患者预后更差。
我们进行了一项多中心回顾性研究，以检验 CK 亚型与 IGHV 状态的组合是否可以作为相关的预后和预测工具。
在 522 名患者中，13%的患者存在 CK2，41%的患者存在 CK1 和/或 U-IGHV（U-CK1），46%的患者存在 M-IGHV 且无任何 CK 亚型（M-noCK）。在中位随访 5.8 年后，与 U-CK1 或 M-noCK 病例相比，CK2 患者的 TTFT（5 年 TTFT 为 31%、39%和 81%，p<0.0001）和 OS（5 年 OS 为 67%、85%和 93%，p<0.0001）最短，无论是否存在 TP53 异常。CK2 患者在化疗免疫治疗后也有最差的结果。事实上，FCR 或 BR 后 CK2 和 U-CK1 的 TTNT 中位数分别为 1.86 年和 4.79 年，但 M-noCK 患者未达到（p<0.0005）。
我们在此建议，IGHV 突变状态和 CK 亚型的联合评估可细化 CLL 的预后，有助于识别 M-IGHV 患者且无任何 CK 亚型，这些患者具有惰性疾病，且在化疗免疫治疗后有极好的结果。
