血小板减少症是 NET 患者肽受体放射性核素治疗 (PRRT) 期间相对常见的剂量限制性毒性。虽然不常见，但一些患者会出现持续性血细胞减少，并最终出现治疗相关的骨髓肿瘤 (t-MN)，其预后较差。随着 PRRT 的适应症不断扩大，研究可预测 PRRT 期间/之后血细胞减少的因素非常重要。我们前瞻性评估了接受 PRRT 的 NET 患者中克隆造血 (CH) 和血细胞减少的患病率。计划接受 4 个周期的 ute-177 治疗的转移性 NET 患者被纳入。在 PRRT 之前使用一组 220 个基因（目标深度≥1,000×）评估 CH。在 PRRT 期间以及此后每 3 个月对患者进行一次随访。在 37 名入组患者中，中位年龄为 68 岁，其中 51.4% 为男性。之前的治疗暴露包括 30% 的烷化剂、8% 的铂剂和 13% 的外部辐射。当变异等位基因频率 (VAF) 截止值≥2% 时，CH 检出率为 35.1%；当 VAF ≥1% 时，CH 检出率为 45.9%。最常见的突变是年龄相关基因（DNMT3A、TET2）。 CH 与贫血或中性粒细胞减少症无关；然而，它与基线时血小板计数较低以及 PRRT 期间/之后处于血小板减少状态的时间较长有关。 5 名患者因 PRRT 后持续血液功能障碍而进行了骨髓活检 (BMB)，其中 3 名患者诊断为意义未明的克隆性血细胞减少症 (CCUS)，2 名患者诊断为意义未明的特发性血细胞减少症 (ICUS)。CH 存在于35.1% 的患者患有 NET，并且与 PRRT 期间血小板减少的风险相关。未来的长期随访研究将阐明 CH 是否可能是 PRRT 后 t-MN 较高风险的预测因子。

Thrombocytopenia is a relatively common dose-limiting toxicity during peptide receptor radionuclide therapy (PRRT) in patients with NET. Although uncommon, some patients develop persistent cytopenia and eventually therapy-related myeloid neoplasm (t-MN), which has a dismal prognosis. As the indications for PRRT are expanding, it is important to investigate factors that may predict cytopenias during/after PRRT. We prospectively evaluated the prevalence of clonal hematopoiesis (CH) and cytopenia in patients with NET undergoing PRRT.Patients with metastatic NET with plan to receive four cycles of lutetium-177 were enrolled. CH was evaluated before PRRT using a panel of 220 genes with a targeted depth of ≥1,000×. Patients were followed during PRRT and every 3 months thereafter.Of 37 patients enrolled, the median age was 68 years and 51.4% were male. Previous treatment exposures included alkylating agents in 30%, platinum agents in 8%, and external radiation in 13%. CH was detected in 35.1% using a variant allele frequency (VAF) cutoff of ≥2% and 45.9% with a VAF of ≥1%. The most common mutations were in age-related genes (DNMT3A, TET2). CH was not associated with anemia or neutropenia; however, it was associated with lower platelet count at baseline and more time spent in a thrombocytopenic state during/after PRRT. Five patients had bone marrow biopsies (BMBs) because of sustained hematologic dysfunction post-PRRT, and of those, diagnoses included clonal cytopenia of undetermined significance (CCUS) in three and idiopathic cytopenia of undetermined significance (ICUS) in two.CH is present in 35.1% of patients with NET and is associated with thrombocytopenia risk during PRRT. Future studies with long-term follow-up will delineate whether CH might be a predictor for higher risk of t-MN after PRRT.