PDF(Pubmed)
Abstract：
Background and Objectives: Essential thrombocythemia (ET) is a myeloproliferative neoplasm that overproduces platelets and is associated with life-threatening thrombosis. Medical cytoreduction either with hydroxyurea (HU) or anagrelide (AG) is widely used, but drug intolerance or resistance are major concerns. Low-dose combination of HU and AG as an alternative strategy has been explored in various studies. It showed comparable response with acceptable toxicity in second-line settings for patients who experienced side effects from prior monotherapy. In this study, we evaluated the efficacy and safety of upfront combination for ET patients. Materials and Methods: From January 2018 to June 2022, a total of 241 ET patients with intermediate to high risk were enrolled. We identified 21 patients with initial drug combinations and compared treatment outcomes and adverse events (AEs) between combination and monotherapy groups. Results: The median age was 62 years old (range, 26-87) and median platelet count was 912 × 109/L (range, 520-1720). Overall treatment response did not exhibit significant differences between the groups, although there was a trend towards a lower response rate in patients treated with AG alone at 3 months post-treatment (AG + HU, 85.7% vs. AG alone, 75.4%, p = 0.068). AEs of any grade occurred in 52.3% of the combination group, 44.3% of the HU monotherapy group, and 43.4% of the AG single group, respectively. Of note was that the HU plus AG combination group suffered a lower incidence of grade 3-4 AEs compared to the other two groups, with statistical significance (p = 0.008 for HU monotherapy vs. combination therapy and p < 0.01 for AG monotherapy vs. combination therapy). Conclusions: Our findings demonstrated that the upfront low-dose combination approach showed feasible clinical outcomes with significantly lower severe AEs compared to conventional monotherapy. These results may offer valuable insights to clinicians for future prospective investigations.
摘要：
背景和目的：原发性血小板增多症（ET）是一种骨髓增殖性肿瘤，可过度产生血小板，并与危及生命的血栓形成有关。广泛使用羟基脲（HU）或阿那格雷（AG）进行医学细胞还原，但药物不耐受或耐药性是主要问题。在各种研究中已经探索了HU和AG的低剂量组合作为替代策略。对于先前单一疗法出现副作用的患者，在二线设置中表现出相当的反应和可接受的毒性。在这项研究中,我们评估了ET患者前期联合用药的疗效和安全性.材料与方法：2018年1月至2022年6月，共纳入中高危ET患者241例。我们确定了21例初始药物组合的患者，并比较了组合和单药治疗组的治疗结果和不良事件（AE）。结果：中位年龄为62岁（范围，26-87），中位血小板计数为912×109/L（范围，520-1720）。总体治疗反应没有表现出显著的组间差异，尽管在治疗后3个月，单独使用AG治疗的患者的缓解率有降低的趋势（AG+HU，85.7%vs.AG独自一人,75.4%,p=0.068)。任何级别的不良事件发生在组合组的52.3%，HU单药治疗组的44.3%，AG单组的43.4%，分别。值得注意的是，与其他两组相比，HU+AG组合组的3-4级AE发生率较低，具有统计学意义(HU单一疗法与HU单一疗法的p=0.008联合疗法和p<0.01的AG单一疗法与联合治疗)。结论：我们的发现表明，与常规单药治疗相比，前期低剂量联合治疗方法显示出可行的临床结果，严重AE显着降低。这些结果可能为临床医生未来的前瞻性研究提供有价值的见解。
