Refractory chronic immune thrombocytopenia (r-cITP) is one of the most challenging situations in chronic immune thrombocytopenia (cITP). Pediatric r-cITP is inconsistently defined in literature, contributing to the scarcity of data. Moreover, no evidence is available to guide the choice of treatment. We compared seven definitions of r-cITP including five pediatric definitions in 886 patients with cITP (median [min-max] follow-up 5.3 [1.0–29.3] years). The pediatric definitions identified overlapping groups of various sizes (4%–20%) but with similar characteristics (higher proportion of immunopathological manifestations [IM] and systemic lupus erythematosus [SLE]), suggesting that they adequately captured the population of interest. Based on the 79 patients with r-cITP (median follow-up 3.1 [0–18.2] years) according to the CEREVANCE definition (≥3 second-line treatments), we showed that r-cITP occurred at a rate of 1.15% new patients per year and did not plateau over time. In multivariate analysis, older age was associated with r-cITP. One patient (1%) experienced two grade five bleeding events after meeting r-cITP criteria and while not receiving second-line treatment. The cumulative incidence of continuous complete remission (CCR) at 2 years after r-cITP diagnosis was 9%. In this analysis, splenectomy was associated with a higher cumulative incidence of CCR (hazard ratio: 5.43, 95% confidence interval: 1.48–19.84, p = 7.8 × 10⁻⁴). In sum, children with cITP may be diagnosed with r-cITP at any time point of the follow-up and are at increased risk of IM and SLE. Second-line treatments seem to be effective for preventing grade 5 bleeding. Splenectomy may be considered to achieve CCR.

中文翻译：

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儿科难治性慢性免疫性血小板减少症：识别、患者特征和结果


难治性慢性免疫性血小板减少症（r-cITP）是慢性免疫性血小板减少症（cITP）中最具挑战性的情况之一。文献中对儿科 r-cITP 的定义不一致，导致数据稀缺。此外，没有证据可以指导治疗的选择。我们比较了 886 名 cITP 患者的 7 种 r-cITP 定义，包括 5 种儿科定义（中位 [最小-最大] 随访时间 5.3 [1.0–29.3] 年）。儿科定义确定了不同大小（4%–20%）但具有相似特征（免疫病理学表现 [IM] 和系统性红斑狼疮 [SLE] 比例较高）的重叠群体，表明它们充分捕获了感兴趣的人群。根据 CEREVANCE 定义（≥3 次二线治疗），基于 79 名 r-cITP 患者（中位随访 3.1 [0–18.2] 年），我们发现 r-cITP 的发生率为 1.15% 新每年都有患者，并且不会随着时间的推移而趋于稳定。在多变量分析中，年龄较大与 r-cITP 相关。一名患者 (1%) 在满足 r-cITP 标准后且未接受二线治疗时经历了两次五级出血事件。 r-cITP 诊断后 2 年，持续完全缓解 (CCR) 的累积发生率为 9%。在本分析中，脾切除术与较高的 CCR 累积发生率相关（风险比：5.43，95% 置信区间：1.48–19.84，p = 7.8 × 10 ⁻⁴ ）。总之，患有 cITP 的儿童可能在随访的任何时间点被诊断为 r-cITP，并且患 IM 和 SLE 的风险增加。二线治疗似乎可以有效预防 5 级出血。可以考虑脾切除术来实现 CCR。