Korean Journal of Clinical Pharmacy (한국임상약학회지)

Korean College Of Clinical Pharmacy (한국임상약학회)
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Analysis of L-asparaginase Related Adverse Reaction

L-asparaginase 약물 유해 반응 보고 분석

  • Ko, Kyung Mi (Department of basic/clinical pharmacology, The Catholic University) ;
  • La, Hyen O (College of Pharmacy, The Catholic University of Korea)
  • 고경미 (가톨릭 대학교 기초임상약리학 교실) ;
  • 나현오 (가톨릭 대학교 약학대학)
  • Received : 2017.05.18
  • Accepted : 2017.06.27
  • Published : 2017.09.30
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Abstract

Background: L-asparaginase (L-ASP) is a critical agent for the treatment of acute lymphoblastic leukemia and lymphoma, which is associated with serious toxicities including hypersensitivity, pancreatitis and thrombosis. Methods: To evaluate the toxicity of L-ASP in real clinical settings, we included the patients with L-ASP adverse drug reactions (ADRs) reported in a regional pharmacovigilance center of Seoul St. Mary's hospital from January 2014 to December 2015. Results: A total of 83 cases of L-ASP related ADRs were reported in 54 patients. Of these 83 cases, 65 cases (78.3%, 65/83) were spontaneously reported and 18 cases (21.7%, 18/83) were detected by further medical records review. Of the patients with ADRs, pediatric patients accounted for 83.3% of the cases (45/54) and median age was 9 years. The most common clinical manifestations of ADRs were hematology manifestations (31.3%, 26/83), followed by hepatobiliary manifestations (18.1%, 15/83). Thirty-four serious ADRs were reported in 19 patients. The sserious ADR group showed significantly longer hospitalization and higher rate of discontinuation of L-ASP than the non-serious ADR group (p = 0.005, 0.03). The most common clinical manifestations of serious ADRs were hepatobiliary manifestations (41.2%, 14/34). In total, 8 cases (9.6%, 8/83) of unlabeled ADRs were identified. They were serious ADRs. Conclusion: We identified unlabeled serious ADRs of L-ASP. Also, correlations were observed between serious ADRs and length of hospitalization, discontinuation rate respectively. Further investigations and developed spontaneous ADR reporting systems are needed to evaluate these correlations.

Keywords

References

  1. Whitecar JP, Bodey GP, Harris JE, et al. L-asparaginase. The New Eng J Med 1970;282(13):732-4. https://doi.org/10.1056/NEJM197003262821307
  2. Clarkson B, Krakoff I, Burchenal J, et al. Clinical results of treatment with E. coli L-asparaginase in adults with leukemia, lymphoma, and solid tumors. Cancer 1970;25(2): 279-305. https://doi.org/10.1002/1097-0142(197002)25:2<279::AID-CNCR2820250205>3.0.CO;2-7
  3. Wang B, Relling MV, Storm MC, et al. Evaluation of immunologic crossreaction of antiasparaginase antibodies in acute lymphoblastic leukemia (ALL) and lymphoma patients. Leukemia 2003;17(8):1583-8. https://doi.org/10.1038/sj.leu.2403011
  4. Lanvers-Kaminsky C. Asparaginase pharmacology: challenges still to be faced. Cancer Chemother Pharmacol 2017;79(3):439-450. https://doi.org/10.1007/s00280-016-3236-y
  5. Land VJ, Sutow WW, Fernbach DJ, et al. Toxicity of L-asparginase in children with advanced leukemia. Cancer 1972;30(2):339-47. https://doi.org/10.1002/1097-0142(197208)30:2<339::AID-CNCR2820300206>3.0.CO;2-P
  6. Raetz E, Salzer W. Tolerability and efficacy of L-asparaginase therapy in pediatric patients with acute lymphoblastic leukemia. J Pediatr Hematol Oncol 2010;32(7):554-63. https://doi.org/10.1097/MPH.0b013e3181e6f003
  7. Hijiya N, van der Sluis IM. Asparaginase-associated toxicity in children with acute lymphoblastic leukemia. Leuk Lymphoma 2016;57(4):748-57. https://doi.org/10.3109/10428194.2015.1101098
  8. Marquet K, Claes N, De Troy E, et al. A multicenter record review of in-hospital adverse drug events requiring a higher level of care. Acta Clin Belg 2017;72(3):156-62. https://doi.org/10.1080/17843286.2017.1283759
  9. Pirmohamed M, James S, Meakin S, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ (Clinical research ed) 2004;329 (7456):15-9. https://doi.org/10.1136/bmj.329.7456.15
  10. Ladewski LA, Belknap SM, Nebeker JR, et al. Dissemination of information on potentially fatal adverse drug reactions for cancer drugs from 2000 to 2002: first results from the research on adverse drug events and reports project. J Clin Oncol 2003;21(20):3859-66. https://doi.org/10.1200/JCO.2003.04.537
  11. Brewer T, Colditz GA. Postmarketing surveillance and adverse drug reactions: current perspectives and future needs. JAMA 1999;281(9):824-9. https://doi.org/10.1001/jama.281.9.824
  12. Jong-Mi Seong, Byung-Joo Park. Recent advance in pharmacovigilance activities of World Health Organization and U.S Food and Drug Administration. Korean Public Health Research 2015;41(2):19-28.
  13. Bushman JE, Palmieri D, Whinna HC, et al. Insight into the mechanism of asparaginase-induced depletion of antithrombin III in treatment of childhood acute lymphoblastic leukemia. Leuk Res 2000;24(7):559-65. https://doi.org/10.1016/S0145-2126(00)00017-5
  14. Medical Dictionary for Regulatory Activities. International Conference on Harmonization. Available from https://www.meddra.org/browsers. Accessed Oct. 1, 2016.
  15. WHO-Uppsala Monitoring Center causality category. World Health Organization. Available from https://www.who-umc.org. Accessed Jan. 1, 2014.
  16. Common Terminology Criteria for Adverse Events version 4.0. National Health Institute. Available from https://evs.nci.nih.gov/ftp1/CTCAE. Accessed Oct. 1, 2016.
  17. Buchanan GR, Holtkamp CA. Reduced antithrombin III levels during L-asparaginase therapy. Med Pediatr Oncol 1980;8(1):7-14. https://doi.org/10.1002/mpo.2950080103
  18. Merlen C, Bonnefoy A, Wagner E, et al. L-Asparaginase lowers plasma antithrombin and mannan-binding-lectin levels: Impact on thrombotic and infectious events in children with acute lymphoblastic leukemia. Pediatr Blood Cancer 2015;62(8):1381-7. https://doi.org/10.1002/pbc.25515
  19. Hunault Berger M, Chevallier P, Delain M, et al. Changes in antithrombin and fibrinogen levels during induction chemotherapy with L-asparaginase in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Use of supportive coagulation therapy and clinical outcome: the CAPELAL study. Haematologica 2008;93(10):1488-94. https://doi.org/10.3324/haematol.12948
  20. Ranta S, Heyman M, Jahnukainen K, et al. Antithrombin deficiency after prolonged asparaginase treatment in children with acute lymphoblastic leukemia. Blood Coagul Fibrinolysis. 2013;24(7):749-56. https://doi.org/10.1097/MBC.0b013e328363b147
  21. Stock W, Douer D, DeAngelo D, et al. Prevention and management of asparaginase/pegasparaginase-associated toxicities in adults and older adolescents: recommendations of an expert panel. Leuk Lymphoma 2011;52(12):2237-53. https://doi.org/10.3109/10428194.2011.596963
  22. Bodmer M, Sulz M, Stadlmann S, et al. Fatal liver failure in an adult patient with acute lymphoblastic leukemia following treatment with Lasparaginase. Digestion 2006;74(1): 28-32. https://doi.org/10.1159/000095827
  23. Sahoo S, Hart J. Histopathological features of L-asparaginase-induced liver disease. Semin Liver Dis 2003;23(3):295-9. https://doi.org/10.1055/s-2003-42647
  24. Durden DL, Salazar AM, Distasio JA. Kinetic analysis of hepatotoxicity associated with antineoplastic asparaginases. Cancer Res 1983;43(4):1602-5.
  25. Murakawa M, Okamura T, Shibuya T, et al. Use of a synthetic protease inhibitor for the treatment of L-asparaginase-induced acute pancreatitis complicated by disseminated intravascular coagulation. Ann Hematol 1992;64(5):249-52. https://doi.org/10.1007/BF01738305
  26. Cohen H, Bielorai B, Harats D, et al. Conservative treatment of Lasparaginase- associated lipid abnormalities in children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2010;54(5):703-6. https://doi.org/10.1002/pbc.22305
  27. Nesheli HM, Tamaddoni A, Nesheli MM, et al. L-asparaginase induced hyperlipidaemia in acute lymphoblastic leukaemia. J Pak Med Assoc 2013;63(3):324-6.
  28. Bhojwani D, Darbandi R, Pei D, et al. Severe hypertriglyceridaemia during therapy for childhood acute lymphoblastic leukaemia. Eur J Cancer 2014;50(15):2685-94. https://doi.org/10.1016/j.ejca.2014.06.023