Karol Seth E, Yang Wenjian, Smith Colton, Cheng Cheng, Stewart Clinton F, Baker Sharyn D, Sandlund John T, Rubnitz Jeffrey E, Bishop Michael W, Pappo Alberto S, Jeha Sima, Pui Ching-Hon, Relling Mary V
Comprehensive Cancer Center, St. Jude Children's Research Hospital, Memphis, Tennessee.
Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Cancer. 2017 Sep 15;123(18):3602-3608. doi: 10.1002/cncr.30762. Epub 2017 May 11.
Palmar-plantar erythrodysesthesia syndrome (PPES) is an uncommon side effect of high-dose cytarabine or methotrexate. Prior case reports of PPES have been limited, and the predisposing factors for the development of PPES remain unknown.
A review of databases identified 22 patients (1.3%) who developed 39 episodes of PPES among 1720 patients after treatment with high-dose cytarabine or methotrexate.
Symptoms lasted a mean of 6.4 days. Hands and feet were both involved in 68% of the initial episodes. Parenteral opioids were required for pain control by 27% of the patients. In comparison with the 1698 children treated with similar therapy, the children who developed PPES were older (mean age at diagnosis, 14.3 vs 7.7 years; P = 7.5 × 10 ). The frequency of PPES was less common in patients receiving methotrexate alone (7 of 946 or 0.7%) versus cytarabine (7 of 205 or 3.4%; P = .005) but was not different for those receiving both high-dose methotrexate and cytarabine (8 of 569 or 1.4%; P = .32). Prolonged infusions of methotrexate were associated with less frequent PPES in comparison with rapid infusions (P = 1.5 × 10 ), as was the co-administration of dexamethasone with cytarabine (P = 2.5 × 10 ). Self-described race and sex were not associated with PPES. In a multivariate analysis, older age and high-dose cytarabine administration without dexamethasone remained associated with PPES (P = 1.1 × 10 and P = .038, respectively). A genome-wide association study did not identify any associations with PPES meeting the genome-wide significance threshold, but top variants were enriched for skin expression quantitative trait loci, including rs11764092 in AUTS2 (P = 6.45 × 10 ).
These data provide new insight into the incidence of PPES as well as its risk factors. Cancer 2017;123:3602-8. © 2017 American Cancer Society.
手足红斑感觉异常综合征（PPES）是大剂量阿糖胞苷或甲氨蝶呤罕见的副作用。既往关于PPES的病例报告有限，PPES发生的易感因素仍不清楚。
对数据库进行回顾，在1720例接受大剂量阿糖胞苷或甲氨蝶呤治疗的患者中，确定了22例（1.3%）发生39次PPES发作的患者。
症状平均持续6.4天。68%的首发发作中手和脚均受累。27%的患者需要胃肠外给予阿片类药物来控制疼痛。与1698例接受类似治疗的儿童相比，发生PPES的儿童年龄更大（诊断时的平均年龄，14.3岁对7.7岁；P = 7.5×10）。单独接受甲氨蝶呤治疗的患者中PPES的发生率较低（946例中有7例，即0.7%），而接受阿糖胞苷治疗的患者中PPES的发生率为205例中有7例（3.4%；P = 0.005），但接受大剂量甲氨蝶呤和阿糖胞苷联合治疗的患者中PPES的发生率无差异（569例中有8例，即1.4%；P = 0.32）。与快速输注相比，延长甲氨蝶呤输注时间与PPES发生率较低相关（P = 1.5×10），地塞米松与阿糖胞苷联合使用时也是如此（P = 2.5×10）。自述的种族和性别与PPES无关。在多变量分析中，年龄较大以及在无地塞米松的情况下给予大剂量阿糖胞苷仍与PPES相关（分别为P = 1.1×10和P = 0.038）。一项全基因组关联研究未发现任何与PPES相关且达到全基因组显著性阈值的关联，但顶级变异在皮肤表达数量性状位点中富集，包括AUTS2中的rs11764092（P = 6.45×10）。
这些数据为PPES的发生率及其危险因素提供了新的见解。《癌症》2017年；123：3602 - 8。©2017美国癌症协会。
