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Evaluation of immunologic crossreaction of antiasparaginase antibodies in acute lymphoblastic leukemia (ALL) and lymphoma patients

Abstract

To evaluate how well antibodies to one asparaginase preparation predict or correlate with antibodies to another preparation in acute lymphoblastic leukemia (ALL) and lymphoma patients who did and did not have hypersensitivity reactions during chemotherapy. In all, 24 children with newly diagnosed ALL or lymphoma, who received Escherichia coli asparaginase 10 000 IU/m2 IM thrice weekly for nine doses as part of multiagent induction and reinduction chemotherapy, and seven monthly doses during the first 7 months of continuation treatment, were studied. Plasma samples were collected at postinduction and at postreinduction. Six of 24 patients had no overt clinical reactions (nonreacting) and received only the E. coli preparation. Of these, 18 patients who had allergic reactions were switched to Erwinia asparaginase. A total of 18 patients had an anaphylactoid reaction to Erwinia asparaginase and were switched to receive polyethylene glycol (PEG) asparaginase. Antibody levels were measured by enzyme-linked immunoadsorbent assay against all the three asparaginase preparations. At postinduction, antibodies against E. coli were higher in reacting patients (0.063±0.066) than in nonreacting patients (0.019±0.013) (P=0.03). At postreinduction, anti-Erwinia antibodies were significantly higher in reacting patients (0.431±0.727) than in nonreacting patients (0.018±0.009) (P=0.007). Anti-E. coli antibodies correlated with anti-PEG antibodies at postinduction (r=0.714, P<0.001) and at postreinduction (r=0.914, P<0.001), but did not correlate with anti-Erwinia antibodies at postinduction (r=0.119, P=0.580) and at postreinduction (r=0.078, P=0.716). The results indicate a crossreactivity between patient antibodies raised against natural E. coli and PEG asparaginase but not Erwinia asparaginase.

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References

  1. Capizzi RL, Bertino JR, Skeel RT, Creasey WA, Zanes R, Olayon C et al. L-asparaginase: clinical, biochemical, pharmacological, and immunological studies. Ann Intern Med 1971; 74: 893–901.

    Article  CAS  Google Scholar 

  2. Asselin BL, Ryan D, Frantz CN, Bernal SD, Leavitt P, Sallan SE et al. In vitro and in vivo killing of acute lymphoblastic leukemia cells by L-asparaginase. Cancer Res 1989; 49: 4363–4368.

    CAS  PubMed  Google Scholar 

  3. Asselin BL, Lorenson MY, Whitin JC, Coppola DJ, Kende AS, Blakley RL et al. Measurement of serum L-asparagine in the presence of L-asparaginase requires the presence of an L-asparaginase inhibitor. Cancer Res 1991; 51: 6568–6573.

    CAS  PubMed  Google Scholar 

  4. Capizzi RL, Bertino JR, Handschumacher RE . L-asparaginase. Ann Rev Med 1970; 21: 433–444.

    Article  CAS  Google Scholar 

  5. Capizzi RL . Asparaginase revisited. Leukemia Lymphoma 1993; 19(Suppl): 147–150.

    Article  Google Scholar 

  6. Capizzi RL, Holcenberg JS . Asparaginase. In: Holland JF et al. Cancer Medicine, 3rd edn, Vol. XVI-9. Philadelphia: Lea & Febiger, 1993, pp 796–806.

    Google Scholar 

  7. Evans WE, Tsiatis A, Rivera G, Murphy SB, Dahl G.V. Denison M et al. Anaphylactoid reactions to Escherichia coli and Erwinia asparaginase in children with leukemia and lymphoma. Cancer 1982; 49: 1378–1383.

    Article  CAS  Google Scholar 

  8. Asselin BL, Whitin JC, Coppola DJ, Rupp IP, Sallan SE, Cohen HJ . Comparative pharmacokinetic studies of three asparaginase preparations. J Clin Oncol 1993; 11: 1780–1786.

    Article  CAS  Google Scholar 

  9. Asselin BL . The three-asparaginases: comparative pharmacology and optimal use in childhood leukemia. In: Kaspers et al. Drug Resistance in Leukemia and Lymphoma, Vol. III. New York: Kluwer Academic/Plenum Publishers, 1999, pp 621–629.

    Chapter  Google Scholar 

  10. Peterson RG, Hanschumacher RE, Mitchell MS . Immunological responses to L-asparaginase. J Clin Invest 1971; 50: 1080–1090.

    Article  CAS  Google Scholar 

  11. Keating MJ, Holmes R, Lerner S, Ho DH . L-asparaginase and PEG asparaginase – past, present, and future. Leukemia Lymphoma 1993; 10: 153–157.

    Article  Google Scholar 

  12. Killander D, Dohlwitz A, Engstedt L, Franzen S, Gahrton G, Gullbring B et al. Hypersensitivity reactions and antibody formation during L-asparaginase treatment of children and adults with acute leukemia. Cancer 1976; 37: 220–228.

    Article  CAS  Google Scholar 

  13. Cheung N-KV, Chau IY, Coccia PF . Antibody response to Escherichia coli L-asparaginase: prognostic significance and clinical utility of antibody measurement. Am J Pediatr Hematol/Oncol 1986; 8: 99–104.

    CAS  Google Scholar 

  14. Woo MH, Hak LJ, Storm MC, Evans WE, Sandlund JT, Rivera GK et al. Anti-asparaginase antibodies following E. coli asparaginase therapy in pediatric acute lymphoblastic leukemia. Leukemia 1998; 12: 1527–1533.

    Article  CAS  Google Scholar 

  15. Park YK, Abuchowski A, Davis S, Davis F . Pharmacology of Escherichia coliL-asparaginase polyethylene glycol adduct. Anticancer Res 1981; 1: 373–376.

    CAS  PubMed  Google Scholar 

  16. Yoshimoto T, Nishimura H, Saito Y, Sakurai K, Kamisaki Y, Wada H et al. Characterization of polyethylene glycol-modified L-asparaginase from Escherichia coli and its application to therapy of leukemia. Jpn J Cancer Res (Gann) 1986; 77: 1264–1270.

    CAS  Google Scholar 

  17. Billett AL, Carls A, Gelber RD, Sallan SE . Allergic reactions to Erwinia asparaginase in children with acute lymphoblastic leukemia who had previous allergic reactions to Escherichia coli asparaginase. Cancer 1992; 70: 201–206.

    Article  CAS  Google Scholar 

  18. The Medical Letter. Pegaspargase for acute lymphoblastic leukemia. Med Lett Drugs Ther 1995; 37: 23–24.

  19. Stone DH, DiPiro C, Davis CP, Meyer CF, Wray BB . Hypersensitivity reactions to Escherichia coli-derived polyethylene glycolated-asparaginase associated with subsequent immediate skin test reactivity to E. coli-derived granulocyte colony-stimulating factor. J Allergy Clin Immunol 1998; 101: 429–431.

    Article  Google Scholar 

  20. Woo MH, Hak LJ, Storm MC, Sandlund JT, Ribeiro RC, Rivera GK et al. Hypersensitivity or development of antibodies to asparaginase does not impact treatment outcome of childhood acute lymphoblastic leukemia. J Clin Oncol 2000; 18: 1525–1532.

    Article  CAS  Google Scholar 

  21. Oettgen HF, Stephenson PA, Schwartz MK, Leeper RD, Tallal L, Tan CC et al. Toxicity of E. coli L-asparaginase in man. Cancer 1970; 25: 253–278.

    Article  CAS  Google Scholar 

  22. Oncaspar prescribing information. Physicians' Desk Reference®, Montvale, NJ: Tomson PDR, 2002, pp 756–758.

  23. Holle LM . Pegaspargase: an alternative? Ann Pharmacotherapy 1997; 31: 616–624.

    Article  CAS  Google Scholar 

  24. Wada H, Imamura I, Sako M, Katagiri S, Tarui S, Nishimura H et al. Antitumor enzyme: polyethylene glycol-modified asparaginase. Ann NY Acad Sci 1990; 613: 95–108.

    Article  CAS  Google Scholar 

  25. Ettingger LJ, Kurtzberg J, Voute PA, Jurgens H, Halpern SL . An open-label, multicenter study of polyethylene glycol-L-asparaginase for the treatment of acute lymphoblastic leukemia. Cancer 1995; 75: 1176–1181.

    Article  Google Scholar 

  26. Pui C-H, Relling MV, Behm FG, Hancock ML, Boyett JM, Raimondi SC et al. L-asparaginase may potentiate the leukemogenic effect of the epipodophyllotoxins. Leukemia 1995; 9:1680–1684.

    CAS  PubMed  Google Scholar 

  27. Wang B, Hak LJ, Relling MV, Pui C-H, Woo MH, Storm MC . ELISA to evaluate plasma anti-asparaginase IgG concentrations in patients with acute lymphoblastic leukemia. J Immunol Methods 2000; 237: 75–83.

    Article  Google Scholar 

  28. Roitt I, Brostoff J, Male D . Immunology: Antigen Recognition, 3rd edn. London-New York: Gower Medical Publishing, 1996, p 7.4.

  29. Ho DH, Brown NS, Yen A, Holmes R, Keating M, Abuchowski A et al. Clinical pharmacology of polyethylene glycol-L-asparaginase. Drug Metab Dispos 1986; 14: 349–352.

    CAS  PubMed  Google Scholar 

  30. Asselin BL, Kreissman S, Coppola DJ, Bernal SD, Leavitt PR, Gelber RD et al. Prognostic significance of early response to a single dose of asparaginase in childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol 1999; 21: 6–12.

    Article  CAS  Google Scholar 

  31. Abshire TC, Pollock BH, Billett AL, Bradley P, Buchanan GR . Weekly polyethylene glycol conjugated L-asparaginase compared with biweekly dosing produces superior induction remission rates in childhood relapsed acute lymphoblastic leukemia: a pediatric oncology group study. Blood 2000; 96: 1709–1715.

    CAS  PubMed  Google Scholar 

  32. Duval M, Suciu S, Ferster A, Rialland X, Nelken B, Lutz P et al. Comparision of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: results of a randomized European Organisation for Research and Treatment of Cancer, Children's Leukemia Group phase 3 trail. Blood 2002; 15: 2734–2739.

    Article  Google Scholar 

  33. Boo J, Weber G, Ahlke E, Schulze-Westhoff P, Nowak-Dottl U, Wurthwein G et al. Monitoring of asparaginase activity and asparagine levels in children on different asparaginase preparations. Euro J Cancer 1996; 32: 1544–1550.

    Article  Google Scholar 

  34. Ettinger LJ . Asparaginases: where do we go from here? J Pediatr Hematol Oncol 1999; 21: 3–5.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by a grant from Aventis Pharmaceuticals, a grant from the state of Tennessee Center of Excellence in Pediatric Pharmacokinetics and Therapeutics, the National Institutes of Health, Bethesda, MD, Cancer Center CORE Grant No. CA-21765, CA-51001, and American Lebanese Syrian Associated Charities (ALSAC).

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Wang, B., Relling, M., Storm, M. et al. Evaluation of immunologic crossreaction of antiasparaginase antibodies in acute lymphoblastic leukemia (ALL) and lymphoma patients. Leukemia 17, 1583–1588 (2003). https://doi.org/10.1038/sj.leu.2403011

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