Abstract Infiltration of cancer cells into the cerebrospinal milieu remains a challenge to oncologists. Thus, prophylactic therapy to avoid CNS tumors is now standard of care to avoid the development of tumors in the central nervous system (CNS). Despite the advances in oncological care, this issue remains poorly understood. In this regard, we have created a model of CNS chloroleukemia using Fischer 344 rats, in which chloroleukemic cells were injected when they are newborns and lipopolysaccharide (LPS) is given as a first-line of treatment. The cure rate with this regimen is 50%, and approximately 10% of survivors develop CNS leukemia as judged by their motor skills and the presence of quadriplegia and paraplegia. For this study, we injected 2400 Fischer 344 neonates with MIAC51 and treated them with LPS. All animals with overt signs of leukemia were sacrificed by day 26. By day 35, survivors started exhibiting CNS abnormalities. Of that cohort, we selected 150 animals with hind leg paraplegia on day 40. These animals were then re-randomized into 5 groups: group 1 received no treatment, group 2 received excipient control IV, group 3 received 5mg/kg API 31510 IV, group 4 received 25mg/kg IV, and group 5 received 100 mg/kg IV for 4 weeks, 3 times daily. Rats in groups 1, 2, 3 and 4 did not exhibit any signs of improvement and were sacrificed due to metastatic malignancy. These findings were recorded by MRI positive for tumor cells. In sharp contrast, animals injected with 100mg/kg IV exhibited a significant recovery of their motor skills and regained their ability to walk. MRI distinctly shows the lack of tumor cells in this group. Taken together, these results strongly indicate that API 31510 may provide a cure for CNS leukemia and may also be an effective prophylactic agent to prevent the extravasation of leukemic cells into the CNS. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1565. doi:10.1158/1538-7445.AM2011-1565