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Rasburicase for the Management of Tumor Lysis Syndrome in Neonates

Oncology Pharmacy Resident, University of Maryland, Baltimore, MD

Mark T Holdsworth, PharmD BCOP

Associate Professor of Pharmacy and Pediatrics, College of Pharmacy, University of New Mexico

Craig Wong, MD MPH

Assistant Professor of Pediatrics, Division of Pediatric Nephrology, Department of Pediatrics, University of New Mexico, Albuquerque, NM

Jeffery D Hanrahan, MD JD

Assistant Professor of Pediatrics, Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of New Mexico

Stuart S Winter, MD

Associate Professor of Pediatrics, Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of New Mexico

Reprints: Dr. Holdsworth, College of Pharmacy, MSC09 5360, 1 University of New Mexico, Albuquerque, NM 87131-0001, fax 505/272-6749, mholdsworth{at}salud.unm.edu

OBJECTIVE: 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.

CASE SUMMARY: 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.

DISCUSSION: 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.

CONCLUSIONS: 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.

Key Words: acute lymphoblastic leukemia, allopurinol, neuroblastoma, rasburicase, tumor lysis syndrome

Published Online, July 25, 2006. www.theannals.com, DOI 10.1345/aph.1G670