McNutt Deborah M, Holdsworth Mark T, Wong Craig, Hanrahan Jeffery D, Winter Stuart S
University of Maryland, Baltimore, USA.
Ann Pharmacother. 2006 Jul-Aug;40(7-8):1445-50. doi: 10.1345/aph.1G670.
To describe the management of tumor lysis syndrome (TLS) with rasburicase in 2 patients who presented with cancer within the first month of life and compare and contrast both cases with respect to their underlying renal physiology, management, and eventual outcome.
TLS developed in 2 neonates born at 38 weeks' gestational age; both were managed in part with rasburicase. One patient was a 21-day-old infant who received 2 days of induction chemotherapy for the treatment of congenital Stage IV-S neuroblastoma. With a single 0.2 mg/kg dose of rasburicase, the serum urate level normalized and the infant completed therapy without incident. The second patient was a 4-day-old neonate with congenital precursor-B cell acute lymphoblastic leukemia who presented with spontaneous TLS complicated by renal dysfunction. Despite several doses of intravenous rasburicase (2 doses of 0.1 mg/kg and 4 doses of 0.2 mg/kg), as well as aggressive supportive therapy, the infant died of complications arising from uncontrolled TLS.
Neonates may be at particular risk for TLS given their immature renal function and its predisposition toward metabolic derangements. While rasburicase has the potential to provide a rapid reversal of TLS in this patient population, when TLS is complicated by pre-existing acute renal failure, additional interventions and alternative anti-tumor strategies may be necessary for a successful outcome. When managing TLS in infancy, clinicians must consider the relative degree of renal immaturity and its predisposition toward metabolic derangements.
Rasburicase appears to be well tolerated and effective in lowering serum urate concentrations in the treatment of therapy-related TLS in neonates. However, in instances of spontaneous TLS complicated by the normally low glomerular filtration rate in the newborn infant, the use of rasburicase and other supportive care measures may still be inadequate, warranting further study.
描述在出生后第一个月内患癌症的2例患儿中使用拉布立酶治疗肿瘤溶解综合征(TLS)的情况,并比较和对比这两例患儿在基础肾脏生理学、治疗及最终结局方面的异同。
2例孕38周出生的新生儿发生了TLS;二者均部分接受了拉布立酶治疗。其中1例为21日龄婴儿,因治疗先天性IV-S期神经母细胞瘤接受了2天的诱导化疗。给予单次0.2 mg/kg剂量的拉布立酶后,血清尿酸水平恢复正常,该婴儿顺利完成治疗,未发生意外。第二例为4日龄新生儿,患有先天性前体B细胞急性淋巴细胞白血病,出现自发性TLS并伴有肾功能不全。尽管给予了多剂静脉注射拉布立酶(2剂0.1 mg/kg和4剂0.2 mg/kg)以及积极的支持治疗,但该婴儿仍死于TLS失控引起的并发症。
鉴于新生儿肾功能不成熟且易发生代谢紊乱,他们可能特别容易发生TLS。虽然拉布立酶有可能使该患者群体的TLS迅速逆转,但当TLS合并预先存在的急性肾衰竭时,可能需要采取额外的干预措施和替代抗肿瘤策略才能取得成功结局。在处理婴儿TLS时,临床医生必须考虑肾脏不成熟的相对程度及其易发生代谢紊乱的倾向。
在治疗新生儿与治疗相关的TLS时,拉布立酶似乎耐受性良好且能有效降低血清尿酸浓度。然而,在新生儿自发性TLS合并通常较低的肾小球滤过率的情况下,使用拉布立酶和其他支持性护理措施可能仍然不足,值得进一步研究。