Article | Published:

Use of busulfan in conditioning for allogeneic hematopoietic stem cell transplantation in adults: a survey by the Transplant Complications Working Party of the EBMT


A survey was carried out among EBMT centers about the use of busulfan for conditioning in allogeneic stem cell transplantation. Of 109 responding centers, 106 used busulfan for conditioning, 102 in conventional myeloablative doses, and 93 in reduced doses (RIC). The route of administration was mostly intravenous, but ~10% of the centers gave the drug orally. The number of doses in i.v. administration varied and was in myeloablative conditioning mostly one (50 centers) or four (43 centers) doses a day. Seventeen of the 106 centers used pharmacokinetics for dose adjustment in myeloablative conditioning, nine in RIC. The details of pharmacokinetic monitoring varied markedly. Three quarters of the centers reported adjusting the dose based on obesity in myeloablative conditioning and about 60% in RIC. The most common method for dose calculation was ideal body weight + 0.25 × (actual body weight − ideal body weight). In conclusion, the present survey showed marked heterogeneity in the current practices of busulfan administration for conditioning. The impact of the heterogeneity is not well known. Due to this and the scarcity of support from controlled clinical studies, no clear guidelines can be presented, but some prevailing policies to be recommended were identified.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    Ciurea SO, Andersson BS. Busulfan in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2009;15:523–36.

  2. 2.

    Palmer J, McCune JS, Perales M-A, Marks D, Bubalo J, Mohty M, et al. Personalizing busulfan-based conditioning: considerations from the American Society for Blood and Marrow Transplantation Practice Guidelines Committee. Biol Blood Marrow Transplant. 2016;22:1915–25.

  3. 3.

    Passweg JR, Baldomero H, Bader P, Bonini C, Duarte RF, Dufour C, et al. Use of haploidentical stem cell transplantation continues to increase: the 2015 European Society for Blood and Marrow Transplant activity survey report. Bone Marrow Transplant. 2017;52:811–7.

  4. 4.

    Nguyen L, Leger F, Lennon S, Puozzo C. Intravenous busulfan in adults prior to haematopoietic stem cell transplantation: a population pharmacokinetic study. Cancer Chemother Pharmacol. 2006;57:191–8.

  5. 5.

    de Lima M, Couriel D, Thall PF, Wang X, Madden T, Jones R, et al. Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS. Blood. 2004;104:857–64.

  6. 6.

    Madden T, de Lima M, Thapar N, Nguyen J, Roberson S, Couriel D, et al. Pharmacokinetics of once-daily i.v. busulfan as part of pretransplantation preparative regimens: a comparison with an every 6-hour dosing schedule. Biol Blood Marrow Transplant. 2007;13:56–64.

  7. 7.

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

  8. 8.

    Grochow LB. Busulfan disposition: the role of therapeutic monitoring in bone marrow transplantation induction regimens. Semin Oncol. 1993;20(4 suppl 4):18–25.

  9. 9.

    Slattery JT, Sanders JE, Buckner CD, Schaffer RL, Lambert KW, Langer FP, et al. Graft-rejection and toxicity following bone marrow transplantation in relation to busulfan pharmacokinetics. Bone Marrow Transplant. 1995;16:31–42.

  10. 10.

    Dix SP, Wingard JR, Mullins RE, Jerkunica I, Davidson TG, Gilmore CE, et al. Association of area under the curve with veno-occlusive disesase following BMT. Bone Marrow Transplant. 1996;17:225–30.

  11. 11.

    Bleyzac N, Souillet G, Magron P, Janoly A, Martin P, Bertrand Y, 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;28:743–51.

  12. 12.

    Andersson BS, Thall PF, Madden T, Couriel D, Wang X, Tran HT, et al. Busulfan systemic exposure relative to regimen-related toxicity and acute graft-versus-host disease: defining a therapeutic window for i.v. BuCy2 in chronic myelogenous leukemia. Biol Blood Marrow Transplant. 2002;8:477–85.

  13. 13.

    O´Donnell PH, Artz AS, Undevia SD, Pai RK, Del Cerro P, Horowitz S, et al. Phase I study of dose-escalated busulfan and alemtuzumab as conditioning for allogeneic hematopoietic stem cell transplant: reduced clearance at high doses and occurrence of late sinusoidal obstruction syndrome/ veno-occlusive disease. Leuk Lymphoma. 2010;51:2240–9.

  14. 14.

    Bartelink IH, Lalmohamed A, van Reij EML, Dvorak CC, Savic RM, Zwaveling J, et al. A new harmonized approach to estimate busulfan exposure predicts survival and toxicity after hematopoietic cell transplantation in children and young adults: a multicenter retrospective cohort analysis. Lancet Haematol. 2016;3:e526–e536.

  15. 15.

    McCune JS, Gibbs JP, Slattery JT. Plasma concentration monitoring of busulfan: does it improve clinical outcome? Clin Pharmacokinet. 2000;39:155–65.

  16. 16.

    Bolinger AM, Zangwill AB, Slattery JT, Risler LJ, Sultan DH, Glidden DV, et al. Target dose adjustment of busulfan in pediatric patients undergoing bone marrow transplantation. Bone Marrow Transplant. 2001;28:1013–8.

  17. 17.

    Russell JA, Kangarloo SB, Williamson T, Chaudhry MA, Savoie ML, Turner AR, et al. Establishing a target exposure for once-daily intravenous busulfan given with fludarabine and Thymoglobulin before allogeneic transplantation. Biol Blood Marrow Transplant. 2013;19:1381–6.

  18. 18.

    Ansari M, Theoret Y, Rezgui MA, Peters C, Mezziani S, Desjean C, et al. Association between busulfan exposure and outcome in children receiving intravenous busulfan before hematopoietic stem cell transplantation. Ther Drug Monit. 2014;36:93–99.

  19. 19.

    Geddes M, Kangarloo SB, Naveed F, Quinlan D, Chaudhry MA, Stewart D, et al. High busulfan exposure is associated with worse outcomes in a daily i.v. busulfan and fludarabine allogeneic transplant regimen. Biol Blood Marrow Transplant. 2008;14:220–8.

  20. 20.

    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;20:909–13.

  21. 21.

    Slattery JT, Clift RA, Buckner CD, Radich J, Storer B, Bensinger WI, et al. Marrow transplantation for chronic myeloid leukemia: the influence of plasma busulfan levels on the outcome of transplantation. Blood. 1997;89:3055–60.

  22. 22.

    Andersson BS, Thall PF, Valdez BC, Milton DR, Al-Atrash G, Chen J, et al. Fludarabine with pharmacokinetically guided IV busulfan is superior to fixed-dose delivery in pretransplant conditioning of AML/MDS patients. Bone Marrow Transplant. 2017;52:580–7.

  23. 23.

    Bubalo J, Carpenter PA, Majhail N, Perales MA, Marks DI, Shaughnessy P, et al. Conditioning chemotherapy dose adjustment in obese patients: a review and position statement by the American Society for Blood and Marrow Transplantation Practice Guidelines Committee. Biol Blood Marrow Transplant. 2014;20:600–16.

  24. 24.

    Lindley C, Shea T, McCune J, Shord S, Decker J, Harvey D, et al. Intraindividual variability in busulfan pharmacokinetics in patients undegoing a bone marrow transplant: assessment of a test dose and first dose strategy. Anticancer Drugs. 2004;15:453–9.

  25. 25.

    Kangarloo SB, Naveed F, Ng ES, Chaudhry MA, Wu J, Bahlis NJ, et al. Development and validation of a test dose strategy for once-daily i.v. busulfan: importance of fixed infusion rate dosing. Biol Blood Marrow Transplant. 2012;18:295–301.

  26. 26.

    Effting C, de Moraes Arantes A, Queiroz Labre LV, Carneiro WJ, de Oliveira Neto JR, Bariani C, et al. Individualizing oral busulfan dose after using a test dose in patients undergoing hematopoietic stem cell transplantation: pharmacokinetic characterization. Ther Drug Monit. 2015;37:66–70.

  27. 27.

    de Castro FA, Simoes BP, Godoy AL, Bertagnoli Trigo FM, Coelho EB, Lanchote VL. Use of oral busulfan test dose in patients undergoing hematopoietic stem cell transplantation treated with or without fludarabine. J Clin Pharmacol. 2016;56:1555–62.

  28. 28.

    Weil E, Zook F, Oxencis C, Canadeo A, Urmanski A, Waggoner M, et al. Evaluation of the pharmacokinetics and efficacy of a busulfan test dose in adult patients undergoing myeloablative hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2017;23:952–7.

  29. 29.

    Copelan EA, Hamilton BK, Avalos B, Ahn KW, Bolwell BJ, Zhu X, et al. Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI. Blood. 2013;122:3863–70.

  30. 30.

    Shem-Tov N, Labopin M, Moukhtari L, Ciceri F, Esteve J, Giebel S, et al. Chemotherapy dose adjustment for obese patients undergoing hematopoietic stem cell transplantation: a survey on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Oncologist. 2015;20:50–55.

Download references

Author information

Correspondence to Tapani Ruutu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplemental Material, Table 1 legend

Supplementary Table 1

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark
Fig. 1