Incidence and Risk Factors for Neutropenia After Intra-Arterial Chemotherapy for Retinoblastoma

Abstract

Intra-arterial chemotherapy (IAC) has quickly gained popularity as a mainstay of treatment for retinoblastoma. Intra-arterial chemotherapy has been described as having several advantages over systemic chemotherapy, including reducing systemic toxicity and neutropenia; however, studies on the risk of neutropenia after IAC remain limited. To estimate the incidence of neutropenia after IAC, as well as identify risk factors associated with the development of neutropenia. This case series included pediatric patients with unilateral or bilateral retinoblastoma who were treated with IAC at a single quaternary care center from July 13, 2013, to January 6, 2023. All patients were treated with IAC and underwent multiple IAC cycles depending on treatment response. The primary chemotherapy agent used was melphalan, but topotecan or carboplatin could be used along with melphalan. Melphalan doses were kept to 0.4 mg/kg or less per cycle. After each IAC cycle, complete blood cell counts were obtained within 10 to 12 days and repeated until the absolute neutrophil count (ANC) was greater than or equal to 1000/μL. The primary outcome was the minimum ANC after each IAC cycle. The secondary outcome was the development of severe (grade 3 or 4) neutropenia (ANC <1000/μL). Regression analyses were used to identify associations between variables and outcomes. Receiver operating characteristic curves were used to calculate threshold dose for each chemotherapy agent potentially associated with the development of severe neutropenia. A total of 64 eyes of 49 patients (mean [SD] age, 1.7 [1.2] years; 25 females [51.0%]) with retinoblastoma were treated with 171 cycles of IAC. The mean (SD) nadir ANC was 1325.3 (890.7)/μL and occurred a median (IQR) of 10 (10-14) days (range, 6-28 days) after IAC administration. The frequency distribution of post-IAC neutropenia grades 0, 1, 2, 3, 4, and missing was 31 (18.1% of cycles), 25 (14.6%), 40 (23.4%), 37 (21.6%), 26 (15.2%), and 12 (7.0%), respectively. Factors weakly correlated with a lower ANC were higher melphalan dose (β = -2356 [95% CI, -4120.6 to -611.2]; adjusted R2 = 0.251; P = .01) and higher topotecan dose (β = -4056 [95% CI, -7003.6 to -1344.5]; adjusted R2 = 0.251; P = .006). In this case series of patients with retinoblastoma, the incidence of severe neutropenia after IAC was nearly 40%, which is higher than previously reported. Extended laboratory monitoring may aid in capturing previously overlooked cases of neutropenia. Topotecan may be associated with the development of neutropenia; limiting topotecan doses, especially in the setting of a high melphalan dose, may be beneficial in reducing the risk of neutropenia.