Xie Zhuoer, Al Ali Najla, Zhang Ling, Papenhausen Peter, Volpe Virginia Olivia, Chan Onyee, Kuykendall Andrew, Yun Seongseok, Walker Alison, Sweet Kendra, Lancet Jeffrey E, Padron Eric, Sallman David A, Komrokji Rami S
Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL.
Department of Pathology, Moffitt Cancer Center, Tampa, FL.
Blood Neoplasia. 2024 Dec 13;2(2):100062. doi: 10.1016/j.bneo.2024.100062. eCollection 2025 May.
Most myelodysplastic syndromes/neoplasms (MDS) risk stratification models dichotomize conventional cytogenetic abnormalities into present or absent, neglecting the prognostic impact of clone size (percentage of the total cells/metaphases harboring the chromosome abnormality). We investigated the prognostic value of clone size in 1001 patients with MDS using G-banding and fluorescence in situ hybridization. Clone size correlated with anemia severity and thrombocytosis in del(5q) cases, and with anemia and blast percentage in complex karyotypes. mutation prevalence was significantly elevated in patients with clone size of ≥25% compared with those with <25% (34.2% vs 3%; = .07). Complex karyotypes with clone size of ≥75% demonstrated superior response to hypomethylating agents (20.8% vs 10%; = .03). Crucially, clone size of ≥25% independently predicted overall survival and leukemia-free survival, regardless of revised International Prognostic Scoring System (IPSS) or molecular IPSS. Our findings establish clone size as a robust prognostic factor in MDS, warranting its integration into clinical practice and potential incorporation into risk stratification models.
大多数骨髓增生异常综合征/肿瘤（MDS）风险分层模型将传统细胞遗传学异常分为存在或不存在，而忽略了克隆大小（携带染色体异常的细胞/中期细胞总数的百分比）的预后影响。我们使用G显带和荧光原位杂交技术研究了1001例MDS患者中克隆大小的预后价值。在del(5q)病例中，克隆大小与贫血严重程度和血小板增多相关，在复杂核型中与贫血和原始细胞百分比相关。与克隆大小<25%的患者相比，克隆大小≥25%的患者突变发生率显著升高（34.2%对3%；P = 0.07）。克隆大小≥75%的复杂核型对去甲基化药物表现出更好的反应（20.8%对10%；P = 0.03）。至关重要的是，无论修订后的国际预后评分系统（IPSS）或分子IPSS如何，克隆大小≥25%独立预测总生存期和无白血病生存期。我们的研究结果确立了克隆大小作为MDS中一个可靠的预后因素，值得将其纳入临床实践并可能纳入风险分层模型。
