培门冬酶致儿童急性淋巴细胞白血病脑静脉窦血栓的临床研究

Cerebral venous sinus thrombosis of childhood acute lymphoblastic leukemia caused by pegaspargase

目的 探讨培门冬酶(Pegaspargase, PEG-Asp)所致急性淋巴细胞白血病(Acute lymphoblastic leukemia, ALL)患儿脑静脉窦血栓(Cerebral venous sinus thrombosis, CVST)的临床特征、防治及预后。方法 回顾性分析2017年1月至2021年1月青岛市妇女儿童医院血液科收治的103例ALL患儿资料,统计其中应用PEG-Asp化疗后出现CVST的患儿例数,分析其临床资料,并复习相关文献。结果 103例ALL患儿中,3例应用PEG-Asp化疗后出现CVST,占2.91%。3例患儿均为男性,年龄3~5岁,其中2例发生于诱导化疗期间,1例发生于延迟强化化疗期间,临床表现为头痛、头晕、抽搐等,经头颅MRV检查确诊CVST(1例为横窦血栓,1例为上矢状窦血栓并继发双侧额叶出血性梗死,1例为横窦及乙状窦血栓),给予抗凝、镇静、止血等治疗,2例患儿血栓吸收,1例患儿后遗梗死后脑软化,并继发癫痫。3例患儿再次应用PEG-Asp均未再出现血栓事件,白血病呈持续缓解状态。结论 CVST可于ALL患儿不同化疗阶段时应用PEG-Asp后发生,主要表现为头痛、头晕、抽搐等,头颅MRV检查可确诊,经抗凝治疗后预后良好,但部分可继发出血,并可有神经系统后遗症。大部分患儿再次应用PEG-Asp是安全的,并且不影响白血病预后。

Objective To explore the clinical features, prevention, treatment and prognosis of cerebral venous sinus thrombosis(CVST) caused by pegaspargase in childhood acute lymphoblastic leukemia(ALL).Methods The data of 103 children with ALL admitted to Hematology Department of Qingdao Women and Children′s Hospital from January 2017 to January 2021 were retrospectively analyzed.Clinical data of the cases who got CVST caused by PEG-Asp chemotherapy were retrospectively analyzed, and related literatures were reviewed.Results Among 103 children with ALL,3 cases(2.91%) developed CVST after PEG-Asp chemotherapy.Three cases were all male, 3 to 5 years of age, of which 2 cases occurred in the induction phase, and 1 case occurred in the reinduction phase.The clinical manifestations included headache, dizziness and convulsions, and MRV examination confirmed it to be CVST(1 case of transverse sinus thrombosis, 1 case of superior sagittal sinus thrombosis with secondary bilateral frontal hemorrhagic infarction, 1 case of transverse sinus and sigmoid sinus thrombosis).After the treatment of anticoagulation, sedation and hemostasis, the thrombus of 2 cases were absorbed, and one case had cerebral softening after infarction, which provoked epilepsy.No thrombotic events occurred in the 3 children after PEG-Asp was applied again, and the leukemia was in continuous remission.Conclusion CVST can occur in children with ALL after different stages of chemotherapy with PEG-Asp, and the main manifestations are headache, dizziness, convulsions, etc.Cerebral MRV can confirm the diagnosis, and the prognosis is good after anti-coagulant treatment;however, some may have secondary hemorrhage, and there may be neurological sequelae.Reapplication of PEG-Asp is safe in most cases and the prognosis of leukemia won′t be affected.