Biology of Blood and Marrow Transplantation
Volume 14, Issue 1 , Pages 88-98 , January 2008

Once-Daily Intravenous Busulfan with Therapeutic Drug Monitoring Compared to Conventional Oral Busulfan Improves Survival and Engraftment in Children Undergoing Allogeneic Stem Cell Transplantation

  • Imke H. Bartelink

      Affiliations

    • Departments of Hematology, Immunology and Clinical Pharmacy, University Medical Center Utrecht, the Netherlands
    • Corresponding Author InformationCorrespondence and reprint requests: Imke Bartelink, University Medical Center, Department of Pharmacy, Room HP D00.218, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
  • ,
  • Robbert G.M. Bredius

      Affiliations

    • Departments of Hematology, Immunology and Clinical Pharmacy, Leiden University Medical Center, the Netherlands
  • ,
  • Tessa T. Ververs

      Affiliations

    • Departments of Hematology, Immunology and Clinical Pharmacy, University Medical Center Utrecht, the Netherlands
  • ,
  • Martine F. Raphael

      Affiliations

    • Departments of Hematology, Immunology and Clinical Pharmacy, University Medical Center Utrecht, the Netherlands
  • ,
  • Charlotte van Kesteren

      Affiliations

    • Departments of Hematology, Immunology and Clinical Pharmacy, University Medical Center Utrecht, the Netherlands
  • ,
  • Marc Bierings

      Affiliations

    • Departments of Hematology, Immunology and Clinical Pharmacy, University Medical Center Utrecht, the Netherlands
  • ,
  • Carin M.A. Rademaker

      Affiliations

    • Departments of Hematology, Immunology and Clinical Pharmacy, University Medical Center Utrecht, the Netherlands
  • ,
  • J. den Hartigh

      Affiliations

    • Departments of Hematology, Immunology and Clinical Pharmacy, Leiden University Medical Center, the Netherlands
  • ,
  • Cuno S.P.M. Uiterwaal

      Affiliations

    • Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands
  • ,
  • Juliette Zwaveling

      Affiliations

    • Departments of Hematology, Immunology and Clinical Pharmacy, Leiden University Medical Center, the Netherlands
  • ,
  • Jaap J. Boelens

      Affiliations

    • Departments of Hematology, Immunology and Clinical Pharmacy, University Medical Center Utrecht, the Netherlands

Received 23 July 2007 ,Accepted 24 September 2007.

References 

  1. Bolinger AM, Zangwill AB, Slattery JT, et al. An evaluation of engraftment, toxicity and busulfan concentration in children receiving bone marrow transplantation for leukemia or genetic disease. Bone Marrow Transplant. 2000;25:925–930
  2. Slattery JT, Sanders JE, Buckner CD, et al. Graft-rejection and toxicity following bone marrow transplantation in relation to busulfan pharmacokinetics. Bone Marrow Transplant. 1995;16:31–42
  3. Tran HT, Madden T, Petropoulos D, et al. Individualizing high-dose oral busulfan: prospective dose adjustment in a pediatric population undergoing allogeneic stem cell transplantation for advanced hematologic malignancies. Bone Marrow Transplant. 2000;26:463–470
  4. Michel G, Gluckman E, Esperou-Bourdeau H, et al. Allogeneic bone marrow transplantation for children with acute myeloblastic leukemia in first complete remission: impact of conditioning regimen without total-body irradiation–a report from the Societe Francaise de Greffe de Moelle. J Clin Oncol. 1994;12:1217–1222
  5. Bleyzac N, Souillet G, Magron P, et al. Improved clinical outcome of paediatric bone marrow recipients using a test dose and Bayesian pharmacokinetic individualization of busulfan dosage regimens. Bone Marrow Transplant. 2001;28:743–751
  6. Andersson BS, Madden T, Tran HT, et al. Acute safety and pharmacokinetics of intravenous busulfan when used with oral busulfan and cyclophosphamide as pretransplantation conditioning therapy: a phase I study. Biol Blood Marrow Transplant. 2000;6:548–554
  7. Cremers S, Schoemaker R, Bredius R, et al. Pharmacokinetics of intravenous busulfan in children prior to stem cell transplantation. Br J Clin Pharmacol. 2002;53:386–389
  8. Nguyen L, Fuller D, Lennon S, Leger F, Puozzo C. I.V. busulfan in pediatrics: a novel dosing to improve safety/efficacy for hematopoietic progenitor cell transplantation recipients. Bone Marrow Transplant. 2004;33:979–987
  9. Tran HT, Petropoulos D, Worth LL, ullen CA, adden T, ndersson BS, et al. Pharmacokinetics and individualized dose adjustment of intravenous busulfan in children with advanced hematologic malignancies undergoing allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2004;10(11):805–812Ref Type: Generic
  10. Vassal G, Michel G, Esperou H, et al. Prospective validation of a novel IV busulfan fixed dosing for paediatric patients to improve therapeutic AUC targeting without drug monitoring. Cancer Chemother Pharmacol. 2008;61:113–123
  11. Zwaveling J, Bredius RG, Cremers SC, et al. Intravenous busulfan in children prior to stem cell transplantation: study of pharmacokinetics in association with early clinical outcome and toxicity. Bone Marrow Transplant. 2005;35:17–23
  12. Zwaveling J, den Hartigh J, Lankester AC, et al. Once-daily intravenous busulfan in children prior to stem cell transplantation: study of pharmacokinetics and early clinical outcomes. Anticancer Drugs. 2006;17:1099–1105
  13. Dix SP, Wingard JR, Mullins RE, et al. Association of busulfan area under the curve with veno-occlusive disease following BMT. Bone Marrow Transplant. 1996;17:225–230
  14. 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
  15. Ljungman P, Hassan M, Bekassy AN, Ringden O, Oberg G. High busulfan concentrations are associated with increased transplant-related mortality in allogeneic bone marrow transplant patients. Bone Marrow Transplant. 1997;20:909–913
  16. McCune JS, Gibbs JP, Slattery JT. Plasma concentration monitoring of busulfan: does it improve clinical outcome?. Clin Pharmacokinet. 2000;39:155–165
  17. Slattery JT, Clift RA, Buckner CD, et al. Marrow transplantation for chronic myeloid leukemia: the influence of plasma busulfan levels on the outcome of transplantation. Blood. 1997;89:3055–3060
  18. Small TN, Young JW, Castro-Malaspina H, et al. Intravenous busulfan and melphalan, tacrolimus, and short-course methotrexate followed by unmodified HLA-matched related or unrelated hematopoietic stem cell transplantation for the treatment of advanced hematologic malignancies. Biol. Blood Marrow Transplant. 2007;13:235–244
  19. Ouachee-Chardin M, Elie C, de Saint BG, et al. Hematopoietic stem cell transplantation in hemophagocytic lymphohistiocytosis: a single-center report of 48 patients. Pediatrics. 2006;117:e743–e750
  20. Horne A, Janka G, Maarten ER, et al. Haematopoietic stem cell transplantation in haemophagocytic lymphohistiocytosis. Br J Haematol. 2005;129:622–630
  21. Henter JI, Samuelsson-Horne A, Arico M, et al. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood. 2002;100:2367–2373
  22. Boelens JJ, Wynn RF, O'meara A, et al. Outcomes of hematopoietic stem cell transplantation for Hurler's syndrome in Europe: a risk factor analysis for graft failure. Bone Marrow Transplant. 2007;
  23. Bolinger AM, Zangwill AB, Slattery JT, et al. Target dose adjustment of busulfan in pediatric patients undergoing bone marrow transplantation. Bone Marrow Transplant. 2001;28:1013–1018
  24. Bouligand J, Boland I, Valteau-Couanet D, et al. In children and adolescents, the pharmacodynamics of high-dose busulfan is dependent on the second alkylating agent used in the combined regimen (melphalan or thiotepa). Bone Marrow Transplant. 2003;32:979–986
  25. Aggarwal C, Gupta S, Vaughan WP, et al. Improved outcomes in intermediate- and high-risk aggressive non-Hodgkin lymphoma after autologous hematopoietic stem cell transplantation substituting intravenous for oral busulfan in a busulfan, cyclophosphamide, and etoposide preparative regimen. Biol Blood Marrow Transplant. 2006;12:770–777
  26. Pawlowska AB, Blazar BR, Angelucci E, et al. Relationship of plasma pharmacokinetics of high-dose oral busulfan to the outcome of allogeneic bone marrow transplantation in children with thalassemia. Bone Marrow Transplant. 1997;20:915–920
  27. Fernandez HF, Tran HT, Albrecht F, et al. Evaluation of safety and pharmacokinetics of administering intravenous busulfan in a twice-daily or daily schedule to patients with advanced hematologic malignant disease undergoing stem cell transplantation. Biol Blood Marrow Transplant. 2002;8:486–492
  28. Russell JA, Tran HT, Quinlan D, et al. Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes. Biol Blood Marrow Transplant. 2002;8:468–476
  29. Ryu SG, Lee JH, Choi SJ, et al. Randomized Comparison of Four-Times-Daily versus Once-Daily Intravenous Busulfan in Conditioning Therapy for Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2007;13:1095–1105
  30. Andersson BS, Kashyap A, Gian V, et al. Conditioning therapy with intravenous busulfan and cyclophosphamide (IV BuCy2) for hematologic malignancies prior to allogeneic stem cell transplantation: a phase II study. Biol Blood Marrow Transplant. 2002;8:145–154
  31. Shaw PJ, Nath C, Berry A, Earl JW. Busulphan given as four single daily doses of 150 mg/m2 is safe and effective in children of all ages. Bone Marrow Transplant. 2004;34:197–205
  32. Bartelink IH, Rademaker CM, Schobben AF, van den Anker JN. Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations. Clin.Pharmacokinet. 2006;45:1077–1097
  33. Pineiro-Carrero VM, Pineiro EO. Liver. Pediatrics. 2004;113:1097–1106
  34. Strolin BM, Baltes EL. Drug metabolism and disposition in children. Fundam Clin Pharmacol. 2003;17:281–299
  35. Kearns GL. Impact of developmental pharmacology on pediatric study design: overcoming the challenges. J.Allergy Clin.Immunol. 2000;106:S128–S138
  36. de Wildt SN, Kearns GL, Leeder JS, van den Anker JN. Glucuronidation in humans. Pharmacogenetic and developmental aspects. Clin.Pharmacokinet. 1999;36:439–452
  37. de Wildt SN, Kearns GL, Leeder JS, van den Anker JN. Cytochrome P450 3A: ontogeny and drug disposition. Clin Pharmacokinet. 1999;37:485–505
  38. Proost JH, Meijer DK. MW/Pharm, an integrated software package for drug dosage regimen calculation and therapeutic drug monitoring. Comput Biol Med. 1992;22:155–163
  39. Bearman SI. The syndrome of hepatic veno-occlusive disease after marrow transplantation. Blood. 1995;85:3005–3020
  40. S.Corbacioglu and M.Lacobelli. VOD-DF study, prospective study of the incidence and outcome of venoocclusive disease (VOD) with the prophylactic use of defibrotide in pediatric stem cell transplantation. Version 4.0. 2-11-2004.
  41. Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18:295–304
  42. Kurth T, Walker AM, Glynn RJ, et al. Results of multivariable logistic regression, propensity matching, propensity adjustment, and propensity-based weighting under conditions of nonuniform effect. Am J Epidemiol. 2006;163:262–270
  43. Hassan M, Ljungman P, Bolme P, et al. Busulfan bioavailability. Blood. 1994;84:2144–2150
  44. Ryu SG, Lee JH, Choi SJ, et al. Randomized Comparison of Four-Times-Daily versus Once-Daily Intravenous Busulfan in Conditioning Therapy for Hematopoietic Cell Transplantation. Biol. Blood Marrow Transplant. 2007;13:1095–1105
  45. Boelens JJ, Wynn RF, O'Meara A, et al. Outcomes of Haematopoietic Stem Cell Transplantation for Hurler's Syndrome in Europe: a Risk Factor Analysis for Graft-Failure. Bone marrow transplantation. 2007;In Press
  46. Jones RJ, Lee KS, Beschorner WE. Venocclusive disease of the liver following bone marrow transplantation. Transplantation. 1975;44:778–783
  47. Ryu SG, Lee JH, Choi SJ, et al. Randomized comparison of four-times-daily versus once-daily intravenous busulfan in conditioning therapy for hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2007;13:1095–1105
  48. Tiedemann K, Waters KD, Tauro GP, Tucker D, Ekert H. Results of intensive therapy in childhood acute myeloid leukemia, incorporating high-dose melphalan and autologous bone marrow transplantation in first complete remission. Blood. 1993;82:3730–3738
  49. McDonald GB, Sharma P, Matthews DE, Shulman HM, Thomas ED. Venocclusive disease of the liver after bone marrow transplantation: diagnosis, incidence, and predisposing factors. Hepatology. 1984;4:116–122
  50. Hempel G, Oechtering D, Lanvers-Kaminsky C, et al. Cytotoxicity of dimethylacetamide and pharmacokinetics in children receiving intravenous busulfan. J Clin Oncol. 2007;25:1772–1778

PII: S1083-8791(07)00486-7

doi: 10.1016/j.bbmt.2007.09.015

Biology of Blood and Marrow Transplantation
Volume 14, Issue 1 , Pages 88-98 , January 2008