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.


Journal Article

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/m(2) per day, with subsequent doses targeted to total systemic exposure of 100±20 ng h/mL and CY 750 mg/m(2) 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 III-IV toxicity was gastrointestinal (n=37). 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.

Full Text

Duke Authors

Cited Authors

  • Kasow, KA; Stewart, CF; Barfield, RC; Wright, NL; Li, C; Srivastava, DK; Leung, W; Horwitz, EM; Bowman, LC; Handgretinger, R; Hale, GA

Published Date

  • November 2012

Published In

Volume / Issue

  • 47 / 11

Start / End Page

  • 1448 - 1454

PubMed ID

  • 22426752

Pubmed Central ID

  • 22426752

Electronic International Standard Serial Number (EISSN)

  • 1476-5365

Digital Object Identifier (DOI)

  • 10.1038/bmt.2012.51


  • eng

Conference Location

  • England