Department of Pediatrics, Dalhousie University and Isaak Walton Killam Health Centre, Halifax, NS, Canada.
Blood. 2009 Dec 10;114(25):5146-51. doi: 10.1182/blood-2009-07-231084.
Asparaginase (ASP) therapy is associated with depletion of antithrombin (AT) and fibrinogen (FG). Potential toxicities include central nervous system thrombosis (CNST) and hemorrhage. Historical practice at the Izaak Walton Killam Health Centre (IWK) involves measuring AT and FG levels after ASP administration and transfusing fresh-frozen plasma (FFP) or cryoprecipitate (CRY) to prevent thrombotic and hemorrhagic complications. To determine whether this reduced these complications in children with acute lymphoblastic leukemia (ALL), incidence, outcome, and clinical characteristics of ASP-related CNST in ALL patients at IWK were compared with a similar cohort from BC Children's Hospital (BCCH), where prophylaxis was not performed. Costs associated with preventative versus expectant management were estimated. From 1990 to 2005, 240 patients were treated at IWK and 479 at BCCH. Seven BCCH patients developed venous CNST (1.5%), compared with none at IWK. CNST occurred exclusively during induction. Six patients received anticoagulation and continued ASP. All 7 patients remain in remission. National Cancer Institute high-risk ALL predicted CNST risk (P = .02), whereas sex, age, race, and body mass index did not. Neither FFP nor CRY protected against CNST, suggesting prophylaxis is unwarranted for unselected ALL patients. However, prophylactic replacement for HR patients in induction may be cost-effective.
天冬酰胺酶(ASP)治疗与抗凝血酶(AT)和纤维蛋白原(FG)的消耗有关。潜在的毒性包括中枢神经系统血栓形成(CNST)和出血。艾萨克·沃尔顿·基尔曼健康中心(IWK)的历史实践包括在 ASP 给药后测量 AT 和 FG 水平,并输注新鲜冷冻血浆(FFP)或冷沉淀(CRY)以预防血栓形成和出血并发症。为了确定这是否降低了急性淋巴细胞白血病(ALL)儿童的这些并发症,比较了 IWK 中 ALL 患者与 BC 儿童医院(BCCH)中接受 ASP 治疗的类似患者的 ASP 相关 CNST 的发生率、结局和临床特征,BCCH 未进行预防。估计了预防与期待治疗相关的成本。从 1990 年到 2005 年,IWK 治疗了 240 名患者,BCCH 治疗了 479 名患者。BCCH 有 7 名患者发生静脉 CNST(1.5%),而 IWK 没有。CNST 仅发生在诱导期。6 名患者接受抗凝治疗并继续接受 ASP。所有 7 名患者均处于缓解期。国家癌症研究所高危 ALL 预测 CNST 风险(P =.02),而性别、年龄、种族和体重指数则没有。FFP 和 CRY 均不能预防 CNST,表明未选择 ALL 患者进行预防是合理的。然而,在诱导期对高危患者进行预防性替代可能具有成本效益。