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Solid Cancers

Toxicities of busulfan/melphalan versus carboplatin/etoposide/melphalan for high-dose chemotherapy with stem cell rescue for high-risk neuroblastoma

Bone Marrow Transplantation volume 51, pages 1204–1210 (2016)Cite this article

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Abstract

The optimal autologous stem cell rescue (HDC-SCR) regimen for children with high-risk neuroblastoma (HR-NBL) is not defined. Carboplatin/etoposide/melphalan (CEM) is the current US standard; however, European data suggest busulfan/melphalan (Bu/Mel) may have less toxicity. Published data regarding toxicities associated with CEM and Bu/Mel are limited. We conducted a single-institution retrospective cohort study of children with HR-NBL who received CEM or Bu/Mel preparative regimens. Toxicity data were analyzed using χ2 or Fisher’s exact, Wilcoxon two-sample or log-rank tests. Sinusoidal obstruction syndrome (SOS) was observed in 7/44 CEM (15.9%) and 5/21 (24%) Bu/Mel patients (P=0.50). Median time to SOS was longer following Bu/Mel than CEM (20 versus 9 days, P=0.02). Pulmonary hypertension (PHTN) was observed in ~20% of children after Bu/Mel and none after CEM (P=0.01). CEM patients had more nephrotoxicity (P=0.001), packed red blood cell (P=0.02) and platelet transfusions (P=0.008), and days on maximum pain support (P=0.0007). Time to engraftment, length of stay, documented infection rates and HDC-SCR-related mortality were similar. Nephrotoxicity and resource utilization associated with cytopenias and mucositis were greater after CEM. Pulmonary toxicities were more severe after Bu/Mel, and increased vigilance for PHTN may be warranted, particularly in children with hypoxemia out of proportion to respiratory distress.

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Acknowledgements

This study was supported by an Alex’s Lemonade Stand Foundation Center of Excellence Grant (Developmental Therapeutics Scholar, AVD) and an American Cancer Society Mentored Research Scientist Grant in Applied and Clinical Research, Grant number: MRSG-12-215-01-LIB (AES).

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Authors and Affiliations

  1. Division of Oncology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    A V Desai, Y Li, N J Bunin, S A Grupp, R Bagatell & A E Seif

  2. Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    A V Desai, M B Heneghan, N J Bunin, S A Grupp, R Bagatell & A E Seif

  3. Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Y Li, N J Bunin, S A Grupp, R Bagatell & A E Seif

  4. Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Y Li

  5. Department of Pathology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    S A Grupp

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  1. A V Desai
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Correspondence to A V Desai.

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Desai, A., Heneghan, M., Li, Y. et al. Toxicities of busulfan/melphalan versus carboplatin/etoposide/melphalan for high-dose chemotherapy with stem cell rescue for high-risk neuroblastoma. Bone Marrow Transplant 51, 1204–1210 (2016). https://doi.org/10.1038/bmt.2016.84

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