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Unexpectedly high AUC levels in a child who received intravenous busulfan before stem cell transplantation

Bone Marrow Transplantation volume 45, pages 602–604 (2010)Cite this article

A 6-year-old boy underwent a craniotomy with subtotal resection of the cerebellar vermian tumor. Microscopic examination showed medulloblastoma. Brain magnetic resonance imaging after resection did not show residual disease. He subsequently received four cycles of ICE (ifosfamide, cisplatin, and etoposide) chemotherapy followed by whole craniospinal (24 Gy) and local (30 Gy) radiation therapy. He eventually received tandem high-dose chemotherapy. Conditioning regimens for the first and the second were carboplatin (1200 mg/m2)+thiotepa (750 mg/m2) and busulfan 1.1 mg/kg/dose intravenous every 6 h for total 16 doses (17.6 mg/kg)+melphalan 70 mg/m2 once daily intravenous for 2 days (140 mg/m2), respectively. Autologous PBSC were infused after high-dose chemotherapy. The numbers of CD-34-positive cells were 5.2 × 106/kg in the first and 7.0 × 106/kg in the second, respectively. Engraftment after the second autologous PBSCT was achieved on day 11. Brain magnetic resonance imaging on day 25 of the second autologous PBSCT showed no evidence of recurrence.

An autopsy was performed with the consent of his parents. Microscopically, organizing diffuse alveolar damage was seen, and nuclear enlargement, hyperchromasia, and pleomorphism were seen along alveolar and bronchial epithelium. This cytologic atypia was seen not only in the lung, but also in the urothelium of the renal pelvis. There was no evidence of bacterial, fungal, or viral infection. These pathological findings were consistent with busulfan-induced lung disease. Organizing diffuse alveolar damage is the most common manifestation of busulfan lung toxicity and is associated with bronchiolar and alveolar epithelium atypia.1 This cytologic atypia is often seen extrapulmonary sites, including urinary bladder, breast, and uterine cervix.1 The incidence of pulmonary toxicity after high-dose oral busulfan therapy before stem cell transplantation has been reported to be 3.6%.2 Corticosteroids are effective for treating this disease to various degrees. Although some patients improve, others progress and die.1

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Acknowledgements

This work was supported in part by funds for Clinical Cancer Research from the Health and Labour Sciences Research Grants.

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Authors and Affiliations

  1. Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

    T Nishikawa, Y Okamoto, T Tanabe, Y Shinkoda, Y Kodama & Y Kawano

  2. Department of Human Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

    M Higashi

  3. Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

    H Hirano & K Arita

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  1. T Nishikawa
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Correspondence to T Nishikawa.

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Nishikawa, T., Okamoto, Y., Tanabe, T. et al. Unexpectedly high AUC levels in a child who received intravenous busulfan before stem cell transplantation. Bone Marrow Transplant 45, 602–604 (2010). https://doi.org/10.1038/bmt.2009.195

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