Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
Clinical Research Center, National Hospital Organization Nagoya Medical Center, Aichi, Japan.
Pediatr Blood Cancer. 2022 Aug;69(8):e29699. doi: 10.1002/pbc.29699. Epub 2022 Apr 11.
The feasibility of tyrosine kinase inhibitor (TKI) discontinuation in pediatric chronic myeloid leukemia (CML) remains to be fully elucidated.
TKI was prospectively discontinued in patients who were diagnosed with CML at <20 years of age, treated with TKI for ≥3 years, and sustained molecular response 4.0 (MR4.0) for ≥2 years. Molecular relapse was defined as a single loss of major molecular response (MMR) (BCR-ABL1 >0.1%). Relapsed patients resumed the same TKI therapy administered before discontinuation.
Twenty-two patients with chronic-phase CML were enrolled, and the median ages at diagnosis and at TKI discontinuation were 9 (range: 1-14) years and 16 (5-26) years, respectively. The median follow-up time after TKI discontinuation was 37 months (range: 24-41 months). The median duration of TKI treatment before discontinuation was 100 (42-178) months, and that of MR4.0 was 53.5 (25-148) months. The treatment-free remission (TFR) rate at 12 months was 50.0% (90% confidence interval: 31.7%-65.8%). Eleven patients experienced loss of MMR within 4 months after TKI discontinuation and resumed TKI as originally prescribed. No progression was observed, and all 11 patients regained MR4.0 after TKI resumption. No patient had a withdrawal syndrome. The quality-of-life analysis suggested that successful TFR may improve academic performance in some patients. In patients who discontinued TKI therapy before puberty, the possibility of improvement in growth velocity upon TKI discontinuation was observed.
TKI could be discontinued safely in patients with pediatric CML showing a sustained deep MR.
酪氨酸激酶抑制剂（TKI）在儿科慢性髓性白血病（CML）中的停药可行性仍有待充分阐明。
对诊断为<20 岁、接受 TKI 治疗≥3 年且持续分子学反应 4.0（MR4.0）≥2 年的 CML 患者，前瞻性地停用 TKI。分子学复发定义为单一主要分子学反应（MMR）丢失（BCR-ABL1>0.1%）。复发患者恢复停药前使用的相同 TKI 治疗。
共纳入 22 例慢性期 CML 患者，诊断时和 TKI 停药时的中位年龄分别为 9（范围：1-14）岁和 16（范围：5-26）岁，TKI 停药后中位随访时间为 37 个月（范围：24-41 个月）。TKI 停药前的中位治疗时间为 100（42-178）个月，MR4.0 的中位时间为 53.5（25-148）个月。停药后 12 个月的无治疗缓解（TFR）率为 50.0%（90%置信区间：31.7%-65.8%）。11 例患者在 TKI 停药后 4 个月内出现 MMR 丢失，并恢复原 TKI 治疗。未观察到进展，所有 11 例患者在恢复 TKI 治疗后均获得 MR4.0。无患者出现停药综合征。生活质量分析表明，成功的 TFR 可能改善某些患者的学业成绩。在青春期前停用 TKI 治疗的患者中，观察到停药后生长速度改善的可能性。
在持续深度分子学缓解的儿科 CML 患者中，安全地停用 TKI 是可行的。
