Risk factors for severe neutropenia following intra-arterial chemotherapy for intra-ocular retinoblastoma

PLoS One. 2014 Oct 10;9(10):e108692. doi: 10.1371/journal.pone.0108692. eCollection 2014.

Abstract

Purpose: Intra-arterial chemotherapy is a promising strategy for intra-ocular retinoblastoma. Neutropenia is the most commonly encountered systemic toxicity and in this study we aimed to determine the risk factors associated with the development of severe (≥ grade 3) neutropenia.

Methods: Retrospective review of 187 evaluable cycles of melphalan-containing intra-arterial chemotherapy from the first three cycles administered to 106 patients with intra-ocular retinoblastoma from May 2006 to June 2011. Cycles were considered to be evaluable if (1) blood count results were available in the 7 to 14 days post-treatment interval and (2) concurrent intravenous chemotherapy was not administered. Toxicity was assessed via the Common Terminology Criteria for Adverse Events version 4.0.

Results: 54 cycles (29%) were associated with grade 3 (n = 43) or grade 4 (n = 11) neutropenia. Multivariate stepwise logistic regression revealed that a higher melphalan dose (>0.40 mg/kg) was significantly associated with severe neutropenia during all 3 cycles (odds ratio during cycle one 4.11, 95% confidence interval 1.33-12.73, p = 0.01), but the addition of topotecan and/or carboplatin were not. Prior treatment with systemic chemotherapy was not associated with severe neutropenia risk in any analysis.

Conclusions: Intra-arterial melphalan-based chemotherapy can cause severe neutropenia, especially when a dose of greater than 0.40 mg/kg is administered. Further study with a larger sample may be warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Child, Preschool
  • Humans
  • Infant
  • Infusions, Intra-Arterial
  • Melphalan / administration & dosage
  • Melphalan / adverse effects*
  • Melphalan / therapeutic use
  • Neutropenia / chemically induced*
  • Neutropenia / pathology
  • Neutrophils / drug effects
  • Neutrophils / pathology
  • Retina / drug effects
  • Retinal Neoplasms / drug therapy*
  • Retinoblastoma / drug therapy*
  • Retrospective Studies
  • Risk Factors

Substances

  • Antineoplastic Agents, Alkylating
  • Melphalan