Peptide receptor radionuclide therapy (PRRT) may induce long-term toxicity to the bone marrow (BM). The aim of this study was to analyze persistent hematologic dysfunction (PHD) after PRRT with ¹⁷⁷Lu-DOTATATE in patients with gastroenteropancreatic neuroendocrine tumors (GEP NETs). Methods: The incidence and course of PHD were analyzed in 274 GEP NET patients from a group of 367 patients with somatostatin receptor–positive tumors. PHD was defined as diagnosis of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasm (MPN), MDS/MPN, or otherwise unexplained cytopenia (for >6 mo). Using data from The Netherlands Cancer Registry, the expected number of hematopoietic neoplasms (MDS, AML, MPN, and MDS/MPN) was calculated and adjusted for sex, age, and follow-up period. The following risk factors were assessed: sex, age over 70 y, bone metastasis, prior chemotherapy, prior external-beam radiotherapy, uptake on the [¹¹¹In-DTPA⁰]octreotide scan, tumor load, grade 3–4 hematologic toxicity during treatment, estimated absorbed BM dose, elevated plasma chromogranin A level, baseline blood counts, and renal function. Results: Eleven (4%) of the 274 patients had PHD after treatment with ¹⁷⁷Lu-DOTATATE: 8 patients (2.9%) developed a hematopoietic neoplasm (4 MDS, 1 AML, 1 MPN, and 2 MDS/MPN) and 3 patients (1.1%) developed BM failure characterized by cytopenia and BM aplasia. The median latency period at diagnosis (or first suspicion of a PHD) was 41 mo (range, 15–84 mo). The expected number of hematopoietic neoplasms based on The Netherlands Cancer Registry data was 3.0, resulting in a relative risk of 2.7 (95% confidence interval, 0.7–10.0). No risk factors for PHD could be identified for the GEP NET patients, not even bone metastasis or estimated BM dose. Seven patients with PHD developed anemia in combination with a rise in mean corpuscular volume. Conclusion: The prevalence of PHD after PRRT with ¹⁷⁷Lu-DOTATATE was 4% in our patient population. The median time at which PHD developed was 41 mo after the first PRRT cycle. The relative risk for developing a hematopoietic neoplasm was 2.7. No risk factors were found for the development of PHD in GEP NET patients.

肽受体放射性核素治疗（PRRT）可能对骨髓（BM）产生长期毒性。这项研究的目的是分析胃肠道胰腺神经内分泌肿瘤（GEP NETs）患者接受¹⁷⁷ Lu-DOTATATE进行PRRT后的持续血液学功能障碍（PHD ）。方法：分析了367名生长抑素受体阳性肿瘤患者中的274名GEP NET患者的PHD发生率和病程。PHD被定义为诊断为骨髓增生异常综合症（MDS），急性髓性白血病（AML），骨髓增生性肿瘤（MPN），MDS / MPN或其他原因不明的血细胞减少（> 6 mo）。使用荷兰癌症登记处的数据，计算出预期的造血肿瘤数量（MDS，AML，MPN和MDS / MPN），并针对性别，年龄和随访时间进行了调整。评估了以下风险因素：性别，70岁以上的年龄，骨转移，化疗之前，体外放射疗法之前，[ ¹¹¹ In-DTPA ⁰上的摄取奥曲肽扫描，肿瘤负荷，治疗期间3-4级血液学毒性，估计的BM吸收剂量，血浆嗜铬粒蛋白A水平升高，基线血球计数和肾功能。结果： 274名患者中有11名（4％）在接受治疗后有PHD，其中^177名Lu-DOTATATE：8例患者（2.9％）发展为造血系统肿瘤（4 MDS，1 AML，1 MPN和2 MDS / MPN），3例患者（1.1％）发展为以血细胞减少和BM发育不全为特征的BM衰竭。诊断时的中位潜伏期（或首次怀疑是PHD）为41 mo（范围15-84 mo）。根据荷兰癌症登记处的数据，预期的造血肿瘤数量为3.0，相对危险度为2.7（95％置信区间0.7-10.0）。对于GEP NET患者，没有发现PHD的危险因素，甚至没有骨转移或估计的BM剂量。七名PHD患者发生贫血并伴有平均红细胞体积增加。结论： PRRT后PHD患病率为¹⁷⁷Lu-DOTATATE在我们的患者中占4％。在第一个PRRT周期后，PHD发生的中位时间为41 mo。发生造血肿瘤的相对风险为2.7。在GEP NET患者中未发现PHD发展的危险因素。