Zulfikar Bulent, Koc Basak, Ozdemir Nihal
Department of Pediatric Hematology and Oncology, Cerrahpasa Medical Faculty and Oncology Institute, Istanbul University, Istanbul, Turkey.
J Pediatr Hematol Oncol. 2019 Aug;41(6):e355-e358. doi: 10.1097/MPH.0000000000001391.
The development of inhibitors against factors VIII/IX is the most serious complication in hemophilia. The best treatment strategy for inhibitor eradication is immune tolerance induction (ITI). The aim of this study was to evaluate patients treated with low-dose ITI at a single center with limited resources.
In total, 29 (8.05%) of 360 hemophilia A patients exhibited inhibitors. The data from hemophilia patients with inhibitors undergoing ITI between 1999 and 2017 were collected and analyzed.
Seventeen ITIs administered to 15 hemophilia A patients with inhibitors were analyzed, and the data from 13 ITIs conducted in 12 patients were evaluated. The median age at ITI onset was 10 years (range: 1.25 to 52 y). The maximum inhibitor titer before ITI was 30 Bethesda Units (BU) (range: 4.48 to 135), and the median inhibitor titer was 1.25 BU (range: 0 to 5.6) at the onset of ITI. The median time interval between the inhibitor development and ITI onset was 60 months (range: 7 to 264 mo). The median inhibitor titer during ITI was 3.4 BU (range: 0 to 158.7). At the end of the treatment, 4 of the 12 patients (33.3%) exhibited a complete response, 4 (33.3%) had partial responses (with continuing ITI), and 4 (33.3%) exhibited ITI failure.
Treatment of hemophilia patients with inhibitors is challenging, and ITI is the best treatment method; however, a high-dose daily ITI regimen cannot be given to every patient in every country due to its high cost. Our results show that low-dose ITI may be a choice for selected patients with inhibitors.
针对凝血因子VIII/IX的抑制剂的出现是血友病最严重的并发症。根除抑制剂的最佳治疗策略是免疫耐受诱导（ITI）。本研究的目的是评估在资源有限的单一中心接受低剂量ITI治疗的患者。
360例甲型血友病患者中，共有29例（8.05%）出现抑制剂。收集并分析了1999年至2017年间接受ITI治疗的血友病抑制剂患者的数据。
分析了对15例患有抑制剂的甲型血友病患者进行的17次ITI治疗，并评估了12例患者进行的13次ITI治疗的数据。ITI开始时的中位年龄为10岁（范围：1.25至52岁）。ITI前的最大抑制剂滴度为30贝塞斯达单位（BU）（范围：4.48至135），ITI开始时的中位抑制剂滴度为1.25 BU（范围：0至5.6）。抑制剂出现与ITI开始之间的中位时间间隔为60个月（范围：7至264个月）。ITI期间的中位抑制剂滴度为3.4 BU（范围：0至158.7）。治疗结束时，12例患者中有患者中有4例（33.3%）表现出完全缓解，4例（33.3%）有部分缓解（继续进行ITI），4例（33.3%）表现出ITI失败。
治疗患有抑制剂的血友病患者具有挑战性，ITI是最佳治疗方法；然而，由于成本高昂，并非每个国家的每个患者都能采用高剂量每日ITI方案。我们的结果表明，低剂量ITI可能是某些患有抑制剂的患者的一种选择。
