Tanimura Kazuki, Yamasaki Kai, Okuhiro Yuki, Hira Kota, Nitani Chika, Okada Keiko, Fujisaki Hiroyuki, Matsumoto Kana, Hara Junichi
Department of Pediatric Hematology and Oncology, Children's Medical Center, Osaka City General Hospital, Osaka, Japan.
Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyoto, Japan.
Case Rep Oncol. 2021 Feb 15;14(1):24-28. doi: 10.1159/000511071. eCollection 2021 Jan-Apr.
Ponatinib is a third-generation tyrosine kinase inhibitor (TKI) reported to show a higher efficacy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) than other TKIs. However, few studies describe ponatinib for pediatric Ph+ALL; therefore, the efficacy, safety, and optimal dosage have not been determined. Here, we report a 3-year-old girl with Ph+ALL treated by a ponatinib-containing regimen with therapeutic drug monitoring in the plasma and cerebrospinal fluid (CSF). In our case, a ponatinib-containing regimen was able to keep minimal residual disease negative, and the pharmacokinetics (PKs) of plasma ponatinib resembled that previously reported in adults. Penetration to the CSF was extremely limited. Thus, ponatinib was feasible and effective for a child with Ph+ALL, although the plasma concentration of ponatinib varied significantly throughout the treatment. The appropriate dosage should be confirmed in a prospective trial, including a detailed PK study.
波纳替尼是一种第三代酪氨酸激酶抑制剂（TKI），据报道，它对成人费城染色体阳性急性淋巴细胞白血病（Ph+ALL）的疗效高于其他TKI。然而，很少有研究描述波纳替尼用于儿童Ph+ALL的情况；因此，其疗效、安全性和最佳剂量尚未确定。在此，我们报告一名3岁的Ph+ALL女童，采用含波纳替尼的方案进行治疗，并对血浆和脑脊液（CSF）进行治疗药物监测。在我们的病例中，含波纳替尼的方案能够使微小残留病呈阴性，血浆波纳替尼的药代动力学（PKs）与先前在成人中报道的相似。药物穿透至脑脊液的能力极其有限。因此，波纳替尼对患有Ph+ALL的儿童是可行且有效的，尽管在整个治疗过程中波纳替尼的血浆浓度有显著变化。合适的剂量应在前瞻性试验中确定，包括详细的PK研究。
