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Busulphan Conditioning

Accidental busulfan overdose during conditioning for stem cell transplantation

Bone Marrow Transplantation volume 35, pages 125–128 (2005)Cite this article

Abstract

Summary:

High dose busulfan is widely used in preparative regimens for bone marrow transplantation. We describe three cases of accidental busulfan overdosing. Two adults received a single dose of 8 and 18 mg/kg busulfan, respectively. Doses of 9 × 4 mg/kg were ingested by a 14-year-old girl, who experienced seizures. In all cases, no severe liver toxicity including veno-occlusive disease was observed. Plasma samples were obtained from two patients. Busulfan plasma concentrations were far above published values after high-dose busulfan treatment. Busulfan was eliminated by a first-order process. All patients survived these high doses of busulfan and successful transplantation was possible. Two patients died from refractory GvHD on days 91 and 80 after transplantation. One patient is alive in remission after an observation time of 18 months. These cases show that busulfan overdosing may occur and pharmacokinetic evaluation is warranted to estimate risk of early and late toxicity.

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References

  1. McDonald GB, Sharma P, Matthews DE et al. Venoocclusive disease of the liver after bone marrow transplantation: diagnosis, incidence, and predisposing factors. Hepatology 1984; 4: 116–122.

    Article  CAS  PubMed  Google Scholar 

  2. Jones RJ, Lee KS, Beschorner WE et al. Venoocclusive disease of the liver following bone marrow transplantation. Transplantation 1987; 44: 778–783.

    Article  CAS  PubMed  Google Scholar 

  3. McDonald GB, Hinds MS, Fisher LD et al. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Ann Intern Med 1993; 118: 255–267.

    Article  CAS  PubMed  Google Scholar 

  4. Grochow LB, Jones RJ, Brundrett RB et al. Pharmacokinetics of busulfan: correlation with veno-occlusive disease in patients undergoing bone marrow transplantation. Cancer Chemother Pharmacol 1989; 25: 55–61.

    Article  CAS  PubMed  Google Scholar 

  5. Schuler U, Schroer S, Kuhnle A et al. Busulfan pharmacokinetics in bone marrow transplant patients: is drug monitoring warranted? Bone Marrow Transplant 1994; 14: 759–765.

    CAS  PubMed  Google Scholar 

  6. Murphy CP, Harden EA, Thompson JM . Generalized seizures secondary to high-dose busulfan therapy. Ann Pharmacother 1992; 26: 30–31.

    Article  CAS  PubMed  Google Scholar 

  7. Fitzpatrick JE . New histopathologic findings in drug eruptions. Dermatol Clin 1992; 10: 19–36.

    Article  CAS  PubMed  Google Scholar 

  8. Pascual MJ, Maldonado J . Extramedullary toxicity in bone marrow transplantation using busulfan and cyclophosphamide conditioning. Sangre (Barc) 1995; 40: 191–197.

    CAS  Google Scholar 

  9. deMagalhaes SM, Bloom EJ, Donnenberg A et al. Toxicity of busulfan and cyclophosphamide (BU/CY2) in patients with hematologic malignancies. Bone Marrow Transplant 1996; 17: 329–333.

    Google Scholar 

  10. Albrecht M, Tackmann W, Pribilla W . Aplastic syndrome in myleran overdose. Med Klin 1971; 66: 126–130.

    CAS  PubMed  Google Scholar 

  11. Fiedler W, Goetz G, Weh HJ et al. GM-CSF in busulfan overdosage (letter). Eur J Haematol 1990; 45: 183–184.

    Article  CAS  PubMed  Google Scholar 

  12. Petersen FB, Sanders JE, Storb R et al. Inadvertent administration of a greater-than-usual pre-marrow transplant dose of busulfan – report of a case. Transplantation 1988; 45: 821–822.

    Article  CAS  PubMed  Google Scholar 

  13. Chen CS, Seidel K, Armitage JO et al. Safeguarding the administration of high-dose chemotherapy: a national practice survey by the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 1997; 3: 331–340.

    CAS  PubMed  Google Scholar 

  14. Stein J, Davidovitz M, Yaniv I et al. Accidental busulfan overdose: enhanced drug clearance with hemodialysis in a child with Wiskott–Aldrich syndrome. Bone Marrow Transplant 2001; 27: 551–553.

    Article  CAS  PubMed  Google Scholar 

  15. Slavin S, Nagler A, Naparstek E et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 1998; 91: 756–763.

    CAS  PubMed  Google Scholar 

  16. Schuler US, Renner UD, Kroschinsky F et al. Intravenous busulphan for conditioning before autologous or allogeneic human blood stem cell transplantation. Br J Haematol 2001; 114: 944–950.

    Article  CAS  PubMed  Google Scholar 

  17. Hassan M, Ljungman P, Bolme P et al. Busulfan bioavailability. Blood 1994; 84: 2144–2150.

    CAS  PubMed  Google Scholar 

  18. Heinzel G, Woloszczak R, Thomann P . Pharmacokinetic and Pharmacodynamic Data Analysis System for the PC, Gustav Fischer: Stuttgart/Jena/New York 1993.

  19. Shaw PJ, Scharping CE, Brian RJ et al. Busulfan pharmacokinetics using a single daily high-dose regimen in children with acute leukemia. Blood 1994; 84: 2357–2362.

    CAS  PubMed  Google Scholar 

  20. Weingart SN, Wilson RM, Gibberd RW et al. Epidemiology of medical error. BMJ 2000; 320: 774–777.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gaidys WG, Dickerman JD, Walters CL et al. Intrathecal vincristine. Report of a fatal case despite CNS washout. Cancer 1983; 52: 799–801.

    Article  CAS  PubMed  Google Scholar 

  22. Arico M, Nespoli L, Porta F et al. Severe acute encephalopathy following inadvertent intrathecal doxorubicin administration. Med Pediatr Oncol 1990; 18: 261–263.

    Article  CAS  PubMed  Google Scholar 

  23. Mortensen ME, Cecalupo AJ, Lo WD et al. Inadvertent intrathecal injection of daunorubicin with fatal outcome. Med Pediatr Oncol 1992; 20: 249–253.

    Article  CAS  PubMed  Google Scholar 

  24. Fernandez CV . Can we prevent cytotoxic disasters? Br J Haematol 2000; 108: 464–469.

    Article  CAS  PubMed  Google Scholar 

  25. Anderson RA, Wolff JE, Egeler RM et al. Infallible measures needed to prevent errors in the administration of chemotherapeutic agents (letter; comment). Med Pediatr Oncol 1999; 32: 401–402.

    Article  CAS  PubMed  Google Scholar 

  26. Reason J . Human error: models and management. West J Med 2000; 172: 393–396.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Medizinische Klinik I, Technische Universität Dresden, Germany

    A Jenke, J Freiberg-Richter, U D Renner, M Bornhäuser, E Schleyer, G Ehninger & U Schuler

  2. Klinik für Innere Medizin, Universität Rostock, Germany

    S Wilhelm & M Freund

Authors
  1. A Jenke
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  2. J Freiberg-Richter
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  3. S Wilhelm
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  4. M Freund
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  5. U D Renner
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  6. M Bornhäuser
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  7. E Schleyer
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  8. G Ehninger
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  9. U Schuler
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Correspondence to A Jenke.

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Jenke, A., Freiberg-Richter, J., Wilhelm, S. et al. Accidental busulfan overdose during conditioning for stem cell transplantation. Bone Marrow Transplant 35, 125–128 (2005). https://doi.org/10.1038/sj.bmt.1704697

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  • DOI: https://doi.org/10.1038/sj.bmt.1704697

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