A phase I/II study of CY and topotecan in patients with high-risk malignancies undergoing autologous hematopoietic cell transplantation: The St Jude long-term follow-up

K. A. Kasow, C. F. Stewart, R. C. Barfield, N. L. Wright, Chin-Shang Li, D. K. Srivastava, W. Leung, E. M. Horwitz, L. C. Bowman, R. Handgretinger, G. A. Hale

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Fifty-eight consecutive children with high-risk malignancies were treated with CY, and targeted topotecan followed by autologous hematopoietic cell transplantation (AHCT) in a phase I/II Institutional Review Board-approved study. Twelve participants enrolled in phase I; 5 received dose level 1 of topotecan 3 mg/m2 per day, with subsequent doses targeted to total systemic exposure of 100±20 ng h/mL and CY 750 mg/m2 per day. Seven participants received dose level 2. CY dose escalation to 1 g/m 2 per day was considered excessively toxic; one died from irreversible veno-occlusive disease and two experienced reversible hepatotoxicity. These adverse events halted further dose escalation. A total of 46 participants were enrolled in phase II; results are on the 51 participants who received therapy at dose level 1, the maximum tolerated dose. Diagnoses included neuroblastoma (26), sarcoma (9), lymphoma (8), brain tumors (5), Wilms (2) and retinoblastoma (1). Twenty participants (39.3%) were in CR1 at enrollment; median age was 5.1 years. Most common non-hematological grade IIIIV toxicity was gastrointestinal (n37). Neutrophil and platelet engraftment occurred at a median of 15 and 24 days, respectively. Twenty-six (51%) participants remain alive at a median of 6.4 years after AHCT. CY 3.75 g/m 2, and targeted topotecan followed by AHCT are feasible and produce acceptable toxicity in children with high-risk malignancies.

Original languageEnglish (US)
Pages (from-to)1448-1454
Number of pages7
JournalBone Marrow Transplantation
Volume47
Issue number11
DOIs
StatePublished - Nov 2012
Externally publishedYes

Keywords

  • autologous BMT
  • CY
  • lymphoma
  • neuroblastoma
  • sarcoma
  • topotecan

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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  • Cite this

    Kasow, K. A., Stewart, C. F., Barfield, R. C., Wright, N. L., Li, C-S., Srivastava, D. K., Leung, W., Horwitz, E. M., Bowman, L. C., Handgretinger, R., & Hale, G. A. (2012). A phase I/II study of CY and topotecan in patients with high-risk malignancies undergoing autologous hematopoietic cell transplantation: The St Jude long-term follow-up. Bone Marrow Transplantation, 47(11), 1448-1454. https://doi.org/10.1038/bmt.2012.51