Suttorp Meinolf, Sembill Stephanie, Lensker Phyllis, Hildebrand Verena, Schirmer Elke, Karow Axel, Krumbholz Manuela, Rauh Manfred, Metzler Markus
Pediatric Hemato-Oncology, Medical Faculty, Technical University Dresden, Dresden, Germany.
Pediatric Oncology and Hematology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany.
Br J Haematol. 2025 May;206(5):1397-1405. doi: 10.1111/bjh.20047. Epub 2025 Mar 10.
Imatinib (IMA) therapy for paediatric chronic myeloid leukemia (pCML) requires age-dependent dose adjustments. Assessment of therapeutic drug monitoring (TDM) under 'real-world' conditions was performed. Collection of blood and TDM-relevant data, calculation of individual dosage exposure, measurement of plasma C (IMA, Nor-IMA) by HPLC/MS-MS and recording of adverse event (AE). Two hundred and forty-six specimens from 66 patients were analysed. Individual median IMA dosage exposure was 253 mg/m (range: 128-504). Children <13 years received a median of 43 mg/m more than older patients (p < 0.0001). Median C of IMA and Nor-IMA was 1017 ng/mL (range: 51-3976) and 269 ng/mL (range: 21-981), respectively, correlating significantly with the prescribed dose. At 5/246 visits, non-adherence was confirmed by very low IMA C in 3/66 patients, all ≥13 years old. Correlation of IMA C >1000 ng/mL with achieving OMR demonstrated in each 63% (N = 24/37, N = 27/43, respectively) patients at months 3 and 6. In the cohort with lower levels, only 23% and 50%, respectively, achieved these milestones. This difference was significant only at month 3. Of 66 patients, 30 reported 125 AEs with gastrointestinal and musculoskeletal as leading complaints. In 9.3% of AEs, the correlated IMA C was ≥3000 ng/mL. TDM is a simple and rapid additional tool for managing pCML under 'real-world conditions'.
伊马替尼（IMA）治疗儿童慢性粒细胞白血病（pCML）需要根据年龄调整剂量。我们在“真实世界”条件下进行了治疗药物监测（TDM）评估。采集血液和与TDM相关的数据，计算个体剂量暴露，通过HPLC/MS-MS测量血浆C（IMA、去甲基伊马替尼）并记录不良事件（AE）。对66例患者的246份样本进行了分析。个体IMA剂量暴露中位数为253mg/m²（范围：128 - 504）。13岁以下儿童比年长患者的IMA剂量中位数多43mg/m²（p < 0.0001）。IMA和去甲基伊马替尼的C中位数分别为1017ng/mL（范围：51 - 3976）和269ng/mL（范围：21 - 981），与规定剂量显著相关。在246次就诊中有5次，3/66例患者因IMA C极低被证实未遵医嘱服药，所有患者年龄均≥13岁。在第3个月和第6个月时，IMA C >1000ng/mL与达到主要分子反应（OMR）的相关性在每组患者中分别为63%（分别为N = 24/37，N = 27/43）。在C水平较低的队列中，分别只有23%和50%的患者达到这些里程碑。这种差异仅在第3个月时显著。66例患者中有30例报告了125次不良事件，主要症状为胃肠道和肌肉骨骼问题。在9.3%的不良事件中，相关的IMA C≥3000ng/mL。在“真实世界”条件下，TDM是管理pCML的一种简单快速的辅助工具。
