培门冬酶治疗儿童急性淋巴细胞白血病药物活性与相关不良反应观察研究

Pegaspargase in the treatment of pediatric acute lymphoblastic leukemia and asparaginase activity assay

目的观察培门冬酶(pegaspargase,Oncaspar)在儿童急性淋巴细胞白血病(ALL)治疗中的药物活性水平与不良反应。方法选取我院确诊为ALL的住院患儿21例,给予以培门冬酶为主的VDLP方案进行定期强化治疗。其中高危型(HR-ALL)患儿全程使用2次培门冬酶,标危型(SR-ALL)患儿使用1次培门冬酶。采用标准试剂盒(Abcam)和酶标法检测化疗前和化疗后d7、d15和d21各时间节点时的血清左旋门冬酰胺酶(L-asp)活性及其变化。观察与记录培门冬酶相关不良反应发生率及其严重程度。对比观察接受1次和2次培门冬酶治疗患儿血清L-asp活性及其不良反应。结果接受治疗患儿血清L-asp活性均在治疗d7时达到峰值,两组患儿治疗后各时间节点的L-asp活性均达到有效抗肿瘤水平,且血清L-asp活性组间比较差异无统计学意义。所有患儿均未发生血栓形成和胰腺炎等严重不良反应或化疗相关死亡,但2次组患儿APTT延长和骨髓抑制程度高于1次组(P<0.05)。结论儿童ALL患者的VDLP方案中,加用1次和2次培门冬酶治疗患者血清L-asp活性组间比较差异并不显著,且均可达到抗肿瘤的有效活性水平,但加用2次培门冬酶的不良反应较为显著。

Objective To observe the asparaginase （L-asp） activity level and related adverse reactions following treatment with pegaspargase （PEG-asp） in pediatric acute lymphoblastic leukemia （ALL）, and provide reference for the clinical therapeutic method of PEG-asp. Methods Toatal of 21 patients with ALL were assigned to receive PEG-asp containing VDLP regimen for intensification phases of treatment. The L-asp activity before PEG-asp chemotherapy and at d7, dl 5, d21 after chemotherapy measured by standard kits （Abcam） and ELISA were compared. Adverse reactions rate and order of severity related to PEG-asp were observed and recorded. The L-asparaginase （L-asp） activity and untoward effects in the course of treatment were compared statistically. Results The L-asp activity was crested at d7 after PEG-asp. The L-asp activity achieved effective antitumor levels at each time point after the treatment, and the serum L-asp activity levels had no significant difference. None of the serious adverse reactions like thrombogenesis, pancreatitis or chemotherapy related death occurred in those patients. But the twice treatment group showed more severity than once group in APTT extension and myelosuppression （P〈0.05）. Conclusion Serum L-asp activity can achieve the effective antitumor levels in VDLP regimen.