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Conditioning Regimens

A phase II trial of liposomal busulphan as an intravenous myeloablative agent prior to stem cell transplantation: 500 mg/m2 as a optimal total dose for conditioning

Bone Marrow Transplantation volume 30, pages 833–841 (2002)Cite this article

Abstract

We conducted a phase I/II trial, to evaluate the efficacy and safety of an intravenous liposomal formulation of busulphan (LBu) as a myeloablative agent for stem cell transplantation (SCT). The liposomal busulphan was administered as a 3 h infusion twice daily over 4 consecutive days. Six adults received 1.6–2 mg/kg/dose and 18 children received 1.8–3 mg/kg/dose. Pharmacokinetic parameters were studied after the first and the last dose of busulphan. No significant difference in clearance, AUC, elimination half-lives or distribution volume between the first and the last dose was found in either groups. A significantly (P < 0.005) higher clearance was observed in children after the first and the last dose (3.61 and 3.79 ml/min/kg, respectively) compared to adults (2.40 and 2.33 ml/min/kg, respectively). The elimination half-lives after the first and the last dose were significantly (P < 0.005) shorter in children (2.59 and 2.72 h, respectively) compared to adults (3.35 and 3.61 h, respectively). Clearance correlated significantly with age. However, no significant correlation with age was observed when clearance was adjusted to the body surface area. Two cases of VOD following a total dose of 24 mg/kg were observed. Six patients experienced mucositis. No other organ toxicity was observed. We conclude that intravenous liposomal busulphan pharmacokinetics is age dependent. A dosage schedule based on body surface area should be used especially in young children to reduce the age-dependent difference in kinetics. An intravenous liposomal dose of busulphan of 500 mg/m2 is suggested to reach a similar systemic exposure and myeloablative effect in both children and adults. Moreover, the novel liposomal form of busulphan showed a favorable toxicity profile and seems safe as a part of the high-dose therapy prior to SCT.

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Acknowledgements

The authors thank the nursing staff on wards B87, B78 and M72, Huddinge University Hospital and nursing staff at University Children's Hospital in Zurich for all their help during the study. This study was supported by grants from the Swedish Children's Cancer Society (grant 1997/035, 1999/033) and King's Gustav V Jubilee Fund (grant 00:510).

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Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Laboratory of Hematology, Huddinge University Hospital, Stockholm, Sweden

    M Hassan, C Nilsson & Z Hassan

  2. Division of Hematology, Department of Medicine, Huddinge University Hospital, Stockholm, Sweden

    J Aschan & P Ljungman

  3. Division of Immunology, Hematology and Bone Marrow Transplantation, University Children's Hospital, Zurich, Switzerland

    T Gungor, S Eber & R Seger

  4. Center for Allogeneic Stem Cell Transplantation (CAST), Huddinge University Hospital, Stockholm, Sweden

    J Aschan, P Hentschke & O Ringdén

  5. Department of Pediatrics, Huddinge University Hospital, Stockholm, Sweden

    J Winiarski

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Hassan, M., Nilsson, C., Hassan, Z. et al. A phase II trial of liposomal busulphan as an intravenous myeloablative agent prior to stem cell transplantation: 500 mg/m2 as a optimal total dose for conditioning. Bone Marrow Transplant 30, 833–841 (2002). https://doi.org/10.1038/sj.bmt.1703739

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