Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：血小板减少是NET患者肽受体放射性核素治疗（PRRT）过程中相对常见的剂量限制性毒性。虽然不常见，一些患者出现持续性血细胞减少症，最终出现治疗相关性髓系肿瘤（t-MN），预后不佳。随着PRRT的适应症不断扩大，研究PRRT期间/之后可能预测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患者的克隆造血（CH）和血细胞减少症的患病率。
方法：纳入转移性NET患者，计划接受4个周期的Luti-177。在PRRT之前，使用一组220个基因对CH进行了评估，目标深度≥1,000×。在PRRT期间和之后每3个月对患者进行随访。
结果：在37名患者中，中位年龄为68岁,51.4%为男性.以前的治疗暴露包括30%的烷化剂，铂剂在8%，外部辐射占13%。使用≥2％和45.9％的变异等位基因频率（VAF）截止值检测到35.1％的CH，VAF≥1％。最常见的突变是与年龄相关的基因（DNMT3A，TET2).CH与贫血或中性粒细胞减少无关；然而，这与基线时血小板计数较低以及PRRT期间/之后在血小板减少状态中花费的时间较多有关.由于PRRT后持续的血液学功能障碍，五名患者进行了骨髓活检（BMBs），其中，诊断包括3例意义不明的克隆性血细胞减少症(CCUS)和2例意义不明的特发性血细胞减少症(ICUS).
结论：CH存在于35.1%的NET患者中，并与PRRT期间的血小板减少风险相关。未来的长期随访研究将描述CH是否可能是PRRT后t-MN风险较高的预测因子。
方法：纳入转移性NET患者，计划接受4个周期的Luti-177。在PRRT之前，使用一组220个基因对CH进行了评估，目标深度≥1,000×。在PRRT期间和之后每3个月对患者进行随访。
结果：在37名患者中，中位年龄为68岁,51.4%为男性.以前的治疗暴露包括30%的烷化剂，铂剂在8%，外部辐射占13%。使用≥2％和45.9％的变异等位基因频率（VAF）截止值检测到35.1％的CH，VAF≥1％。最常见的突变是与年龄相关的基因（DNMT3A，TET2).CH与贫血或中性粒细胞减少无关；然而，这与基线时血小板计数较低以及PRRT期间/之后在血小板减少状态中花费的时间较多有关.由于PRRT后持续的血液学功能障碍，五名患者进行了骨髓活检（BMBs），其中，诊断包括3例意义不明的克隆性血细胞减少症(CCUS)和2例意义不明的特发性血细胞减少症(ICUS).
结论：CH存在于35.1%的NET患者中，并与PRRT期间的血小板减少风险相关。未来的长期随访研究将描述CH是否可能是PRRT后t-MN风险较高的预测因子。
