Risk Factors for Severe Neutropenia following Intra-Arterial Chemotherapy for Intra-Ocular Retinoblastoma

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.