High-dose chemotherapy with autologous hematopoietic stem cell rescue for stage 4b retinoblastoma

Background. Stage 4b retinoblastoma (central nervous system metastatic disease) has been lethal in virtually all cases reported. Here we describe a series of eight patients treated with intensive chemotherapy, defined as the intention to include highdose chemotherapy with autologous hematopoietic stem cell rescue. Procedure. Induction chemotherapy included cyclophosphamide and/or carboplatin with a topoisomerase inhibitor. Highdose chemotherapy regimens were carboplatin and thiotepa with or without etoposide (n=3) or carboplatin, etoposide, and cyclophosphamide (n=2). Results. Seven patients had leptomeningeal disease and one patient had only direct extension to the CNS via the optic nerve. Three patients had stage 4b disease at the time of original diagnosis of the intra-ocular retinoblastoma; five had later onset at a median of 12 months (range 3-69 months). One patient died of toxicity (septicemia and multi-organ system failure) during induction and two had disease progression prior to high-dose chemotherapy. Five patients received high-dose chemotherapy at a median of 6 months (range 4-6) post-diagnosis of stage 4b disease. Two patients survive event-free at 40 and 101 months; one was irradiated following recovery from the high-dose chemotherapy. Conclusions. Intensive multimodality therapy may be beneficial for some patients with stage 4b retinoblastoma. Longer follow-up will determine whether it has been curative.