Retinoblastoma is the most common intraocular malignancy in infancy and childhood. The overall survival rate of retinoblastoma was reported to exceed 95% when children were early diagnosed with localized intraocular phase. The advanced retinoblastoma cases with central nervous system metastasis (CNS)is associated with exceedingly poor prognosis. CNS metastasis is the main cause of death in retinoblastoma. Meningeal involvement combined with spinal cord membrane involvement might be due to the meninges invasion and/or the spreading of CSF.

As the most sensitive drug to retinoblastoma tumor cells in vitro, melphalan is the most important drug in the local treatment of retinoblastoma, and it is also an irreplaceable drug in the current eye preservation treatment, which greatly improves the success rate of eye preservation for advanced retinoblastoma. According to the research and the practice of vitreous injection (melphalan), the drug concentration in vitreous can effectively kill retinoblastoma tumor cells.

It is reasonable to speculate that the tumor cells in CSF can be effectively killed by melphalan. Therefore, based on the above background, this study will explore the effectiveness and feasibility of intrathecal injection of melphalan in patients with CNS metastasis of retinoblastoma through a multicenter prospective study.

Inclusion Criteria:

• The pathological diagnosis was retinoblastoma. According to the IRSs (International retinoblastoma staging system) staging system, the stage was IVB
• CSF tumor cells on cytology, or radiographic evidence of NM on MRI scans and histologic diagnosis of systemic malignancy needed
• KPS≥60%
• Adequate bone marrow and organ function
• The parents signed the informed consent and were willing to accept the treatment and follow-up.

Exclusion Criteria:

• 1.Eye diseases other than retinoblastoma
• The eyes were infected within 30 days before screening
• There was a history of surgery and / or unhealed wound within 1 month before enrollment .
• Those who have allergic reaction or allergic history to chemotherapeutic drugs.
• Infectious diseases requiring oral, intramuscular or intravenous administration.
• Patients with systemic immune diseases.
• Active disseminated intravascular coagulation.
• Abnormal coagulation function.
• Abnormal bone marrow and organ function.
• Uncontrollable clinical problems.
• The researchers believe that those who need to be excluded.