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Acute Tumor Lysis Syndrome Secondary to Hydroxyurea in Acute Myeloid Leukemia

Pharmacy Clinical Practice Leader, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada

Hamad M Al-Omar, MD FRCPC

Hematology Fellow, University Health Network, University of Toronto

Dominick Amato, MD FRCPC

Consultant Hematologist, Mount Sinai Hospital, University of Toronto

David MC Sutton, MD FRCPC

Consultant Hematologist, University Health Network, University of Toronto

Reprints: Jack T Seki BSc Phm PharmD, Princess Margaret Hospital, University Health Network, University of Toronto, 610 University Ave., Rm. 3-301, Toronto, Ontario M5G 2M9, Canada, FAX 416/340-5410, E-mail Jack.seki{at}uhn.on.ca

OBJECTIVE: To report 2 cases of acute tumor lysis syndrome (ATLS) associated with hydroxyurea treatment.

CASE SUMMARY: A 79-year-old woman diagnosed with chronic lymphocytic leukemia presented with an acute blastic transformation. She was promptly hydrated, started on allopurinol, and treated with hydroxyurea. About 24 hours later, her biochemistry panel showed parameters consistent with ATLS when compared with pretreatment levels. The second case was a 76-year-old man newly diagnosed with acute myeloid leukemia presenting with high blast fraction. He was given appropriate hydration and allopurinol prophylaxis, and was started on high-dose hydroxyurea treatment. He became symptomatic after 12 hours and results of his blood work were consistent with ATLS.

DISCUSSION: ATLS is a well-known metabolic disturbance that occurs after cell destruction of rapidly growing tumors. In standard doses, hydroxyurea leads to cell death in the S phase and is not thought to cause significant cell lysis. However, in large doses, it possibly acts by a different mechanism and had a direct cytolytic effect associated with ATLS in our patients.

CONCLUSIONS: Although ATLS caused by hydroxyurea appears to be rare, patients at risk should be closely monitored for this complication. An objective causality assessment using the Naranjo probability scale revealed that the adverse drug reaction was probable between ATLS and hydroxyurea therapy in these 2 patients.

Key Words: acute renal failure, acute tumor lysis, hydroxyurea, leukemia

Published Online, March 25, 2003. www.theannals.com, DOI 10.1345/aph.1C188

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