Intra-arterial Chemotherapy for Retinoblastoma

Inclusion Criteria: * Patients diagnosed with retinoblastoma \>4 months of age16 * Patients whose other treatment options would require systemic chemotherapy, radiotherapy, or enucleation * Patient or parent/legal guardian must sign a written informed consent * One of a, b, or c: * Patients who have bilateral COG stage B, C, D, or E retinoblastoma (refer to Appendix A) who have undergone systemic chemotherapy without resolution (meaning either has not had CR or has progressed despite systemic chemotherapy) and would have the following treatment options remaining: * IAC * enucleation of one eye * local radiation * Patients with non-germline retinoblastoma with unilateral disease who have COG A, B, C, or D tumors (refer to Appendix A). * Other patients may be considered on a case by case basis after discussion with pediatric ophthalmology, hematology/oncology, and interventional neuroradiology. Exclusion Criteria: * Opaque or hazy media which precluded visualization of the fundus. * New or recurrent retinoblastoma that can be controlled with other conservative measures such as cryotherapy, thermotherapy, or plaque radiotherapy. * Unilateral COG group E retinoblastoma (refer to Appendix A) with very poor visual prognosis as defined by pediatric ophthalmologist. * Patients who would benefit from systemic chemotherapy. * Patients with clinical or radiological evidence suggestive of retinoblastoma invasion of the optic nerve, choroid, sclera, orbit or metastatic sites. * Currently receiving any other investigational agents. * A history of allergic reactions attributed to compounds of similar chemical or biologic composition to melphalan or other agents used in the study. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. * Pregnant and/or breastfeeding. Participants of childbearing potential must have a negative pregnancy test within 14 days of study entry. * Patients with HIV are eligible unless their CD4+ T-cell counts are \< 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.