Use of Intrathecal Liposomal Cytarabine (DepoCyte) as Treatment of Lymphomatous Meningitis.
Authors: Cascavilla Nicola , Bodenizza Carlo , Carella Angelo Michele , Dell’Olio Matteo , Falcone Antonietta , Greco Michele Mario , La Sala Antonio , Mantuano Saverio , Melillo Lorella , Merla Emanuela , Nobile Michele , Sanpaolo Grazia , Scalzulli Potito 
Published: April 2020

Abstract
The Lymphomatous Meningitis (LM) is an uncommon event, either as an initial diagnosis and in the course (or as an outcome) of a front line treatment. In the latter cases the LM has a poor prognosis and a median survival of few months in untreated patients. Its occurrence is tightly related to the histology, the response to the therapy and the introduction of a proper prophylaxis. Currently, high doses of Methotrexate (HD-MTX) (3 g/sqm) followed by radiotherapy (WBRT: 50 Gy) represents the elective treatment. The role of the intrathecal therapy (IT-T) isn’t well defined: as a matter of facts, it doesn’t seem more effective than the systemic treatment with HD-MTX and it is burdened by a higher neurotoxicity. Furthermore, more frequent intrathecal administrations, a proper concentration and a prolonged exposition to the drugs are required.
Recently, an important role both in the prophylaxis and in the therapy of LM is played by the IT-T of Cytarabine in liposomal formulation (DepoCyte): the slow release from the multivescicular lipidic particles improves the distribution in the liquor, allows a lesser number of IT-T, reduces the undesired effects due to the treatment and increases the compliance of patients. Randomized studies have shown a significant better effectiveness and a reduced toxicity of liposomal formulation treatment with respect to the traditional one.
In the present work 9 cases of LM treated with systemic chemotherapy and with DepoCyte (50 mg IT every 15 days x 6 times) are shown. Male/Female ratio is 6/3; average age is 46 years (range 24–78). In all patients neurological symptoms were present; lymphomatous cells were identified in the CSF of 5 patients and Central Nervous System (CNS) localizations were detected by NMR in 7 patients.
The 5 CSF-positive cases were heterogeneous, as follows:
B-lineage CD10+ ALL meningeal relapse (after two marrow relapses), already undertaken to allogeneic stem cells transplantation, treated only with DepoCyte; Lymphoblastic T-Cell Lymphoma meningeal localization, with mediastinic mass, treated with DepoCyte associated to LSA2L2 Protocol and autologous stem cells tranplantation; DLBCL meningeal localization treated with DepoCyte associated to R-CHOP Protocol; LM at diagnosis in a 78 years old patient with inadequate compliance to systemic therapy, treated with DepoCyte; Mantle Cell Lymphoma meningeal (and systemic) relapse treated with DepoCyte associated to Codox-M Protocol.
In patients 1) to 4) the CR was obtained and they are still alive; only the latter patient, namely, case 5), died for disease progression. The remaining 4 CSF-negative cases had been diagnosed as DLBCL (3 at diagnosis and 1 at relapse) CNS solitary localizations. In all cases L-VAMP Protocol (modified with HD-MTX) was associated to IT-T with DepoCyte. With the only exception of the relapsed patient, the remaining 3 patients had a good response to therapy and they are still alive and in CR.Overall, DepoCyte was shown to be mostly effective, well tolerated by all patients and devoid of undesired side effects. The association with various systemic chemotherapy protocols had been demonstrated to be suitable and endowed with synergic effects. Studies with higher number of patients might validate the effectiveness of DepoCyte also in those CSF-negative cases with solitary CNS localization.