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© 2002 American Society for Clinical Oncology
Tumor Lysis Syndrome After STI571 in Philadelphia Chromosome–Positive Acute Lymphoblastic LeukemiaRambam Medical Center, Haifa, Israel To the Editor:STI571 is a tyrosine kinase inhibitor recently shown to be effective in chronic myeloid leukemia (CML). It is a specific competitor of the adenosine triphosphate binding site of the BCR/ABL fusion protein, considered to be the hallmark of CML. It is also present in approximately 20% of adults with acute lymphoblastic leukemia and 2% with acute myeloid leukemia. However the intracellular mode of action of STI571 is not fully elucidated.1-3 CML patients in chronic phase, accelerated phase, or blast crisis may achieve a response to STI571 within 4 weeks of therapy.4 Reported here is a 74-year-old man diagnosed with Philadelphia chromosome–positive acute lymphoblastic leukemia (bcr/abl, e1a2, 190-kd transcript). He was treated with the standard chemotherapy protocol and achieved a complete remission, but he relapsed shortly after the first consolidation. He was retreated with etoposide and cytarabine, with some reduction in his blast count. He was admitted with chest discomfort and back pains. His WBC count was 3,500/µL and his platelet count was 20,000/µL. His peripheral-blood smear showed 63% blasts. He was enrolled onto a phase II study (Novartis Protocol CSTI 0114) with STI571. He had normal renal and hepatic function and was not exposed to any contrast media or other nephrotoxic medications. Four days later he presented with nausea and vomiting that had started after 2 days of therapy with STI571 600 mg/d. At that point—after only 2 days of therapy—the patient discontinued the STI571. He was dehydrated and afebrile, and his laboratory results were as listed in Table 1. His WBC count decreased from 41,000/µL to 700/µL.
A diagnosis of tumor lysis syndrome and acute renal failure was made. He was treated vigorously with fluid replacement, and continuous hemodialysis was initiated. On day 14 after STI571, his renal function returned to normal and the STI571 was resumed at a reduced dose. Reported here is an apparent episode of acute tumor lysis syndrome following 2 days of therapy with STI751. To the best of our knowledge, this has not been previously reported in detail. There is only a passing reference in a recent publication.5 We suggest that patients receiving STI571 be monitored closely for this possibility. Because termination of the drug may cause a rapid expansion of the Philadelphia chromosome–positive clone, resumption of therapy should be considered at a reduced dosage. REFERENCES
1.
Kilic T, Alberta JA, Zdunek PR, et al: Intracranial inhibition of platelet-derived growth factor-mediated glioblastoma cell growth by an orally active kinase inhibitor of the 2-phenylaminopyrimidine class. Cancer Res 60: 5143-5150, 2000
2.
Buchdunger E, Cioffi CL, Law N, et al: Able protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-Kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther 295: 139-145, 2000 3. Vigneri P, Wang JY: Induction of apoptosis in chronic myelogenous leukemia cells through nuclear entrapment of BCR-ABL tyrosine kinase. Nat Med 7: 228-234, 2001[CrossRef][Medline]
4.
Druker BJ, Talpaz M, Resta DJ, et al: Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344: 1031-1037, 2001
5.
Druker BJ, Sawyers CL, Kantarjian H, et al: Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 344: 1038-1042, 2001
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Copyright © 2002 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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