Costa Alessandro, Pilo Federica, Pettinau Martina, Piras Eugenia, Targhetta Clara, Rojas Rodrigo, Deias Paola, Mulas Olga, Caocci Giovanni
Hematology, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Hematology and HSCT Unit, "A. Businco" Hospital, ARNAS, Brotzu, Cagliari, Italy.
Front Oncol. 2025 Apr 24;15:1563990. doi: 10.3389/fonc.2025.1563990. eCollection 2025.
Therapy-related myeloid neoplasms (t-MN) are aggressive hematologic malignancies with poor prognosis and high-risk clinical features. Recent advances have highlighted the role of molecular data in refining prognostic models. This study aims to analyze a monocentric cohort of t-MN patients, focusing on the clinical and prognostic impact of prior malignancies and their associated molecular landscape.
A retrospective analysis was conducted on 61 patients diagnosed with t-MN from an Oncology Hospital and referred to a hematology Unit. Diagnoses were based on established criteria for therapy-related myelodysplastic syndrome (t-MDS) and therapy-related acute myeloid leukemia (t-AML), with a history of prior exposure to cytotoxic therapy. Cytogenetic and molecular analyses supported the diagnoses. Risk stratification was performed using the revised International Prognostic Scoring System (IPSS-R) and molecular IPSS (IPSS-M) for t-MDS and the 2022 European LeukemiaNet (ELN) classification for t-AML.
Overall, 61 patients with t-MN were diagnosed: 38 (62.3%) with t-MDS, and 23 (37.7%) with t-AML. The median latency from primary cancer to t-MN diagnosis was 5.8 years (IQR: 2.6-12.5). Risk stratification identified 63.2% of t-MDS cases as IPSS-R very-low to intermediate risk, while 57.9% were reclassified as IPSS-M moderate-high to very high risk. Patients with prior hematologic cancer showed a greater tendency toward higher IPSS-R (=0.021) and IPSS-M (=0.015) risk compared to solid cancer. The IPSS-M, more accurately than R-IPSS, demonstrated predictive value for survival in both univariate and multivariate analyses and effectively predicted leukemic progression in t-MDS. -mutated cases were more prevalent in patients with prior hematologic cancer (=0.043) and associated with longer latency (8.2 years) compared to wild type (6.1 years, =0.044). Allogeneic transplantation proved beneficial, significantly improving survival outcomes in eligible t-MDS and t-AML patients.
t-MN exhibits distinct clinical and molecular profiles according to prior malignancy type. Intriguingly, our analysis reveals a distinct latency pattern in -mutated cases, suggesting unique leukemogenic dynamics. Moreover, IPSS-M proved highly accurate in predicting t-MDS survival. Integrating molecular data into prognostic models enhances risk stratification and informs therapeutic strategies, potentially improving outcomes for t-MN patients. Further studies are needed to validate these findings and refine tailored treatment approaches.
治疗相关髓系肿瘤（t-MN）是侵袭性血液系统恶性肿瘤，预后不良且具有高危临床特征。最近的进展突出了分子数据在完善预后模型中的作用。本研究旨在分析t-MN患者的单中心队列，重点关注既往恶性肿瘤及其相关分子格局的临床和预后影响。
对一家肿瘤医院诊断为t-MN并转诊至血液科的61例患者进行回顾性分析。诊断基于治疗相关骨髓增生异常综合征（t-MDS）和治疗相关急性髓系白血病（t-AML）的既定标准，患者有既往细胞毒性治疗史。细胞遗传学和分子分析支持诊断。使用修订的国际预后评分系统（IPSS-R）和分子IPSS（IPSS-M）对t-MDS进行风险分层，对t-AML采用2022年欧洲白血病网（ELN）分类。
总体而言，诊断出61例t-MN患者：38例（62.3%）为t-MDS，23例（37.7%）为t-AML。从原发性癌症到t-MN诊断的中位潜伏期为5.8年（四分位间距：2.6 - 12.5年）。风险分层显示，63.2%的t-MDS病例为IPSS-R极低至中度风险，而57.9%被重新分类为IPSS-M中度高至极高风险。与实体癌相比，既往有血液系统癌症的患者表现出更高的IPSS-R（=0.021）和IPSS-M（=0.015）风险倾向。在单变量和多变量分析中，IPSS-M比R-IPSS更准确地显示出对生存的预测价值，并有效预测了t-MDS中的白血病进展。 -突变病例在既往有血液系统癌症的患者中更为普遍（=0.043），与野生型相比潜伏期更长（8.2年）（6.1年，=0.044）。异基因移植被证明是有益的，显著改善了符合条件的t-MDS和t-AML患者的生存结果。
t-MN根据既往恶性肿瘤类型表现出不同的临床和分子特征。有趣的是，我们的分析揭示了 -突变病例中独特的潜伏期模式，提示独特的白血病发生动力学。此外，IPSS-M在预测t-MDS生存方面被证明高度准确。将分子数据整合到预后模型中可增强风险分层并为治疗策略提供信息，有可能改善t-MN患者的结局。需要进一步研究来验证这些发现并完善量身定制的治疗方法。
