Existing Phase I studies have identified a maximally tolerated dose. administered intrathecally is well tolerated in patients with CNS lymphoma, including those with indolent forms of this disease. Cerebrospinal fluid parameters can provide a measure of disease response and SPL-B in this case, lumbar cerebrospinal fluid glucose trended most closely with response to intrathecal-rituximab (IT-R). Despite progression with intravenous rituximab, responses to IT-R do occur. Further study is required to define optimal use of IT-R. Approximately 95% of CNS lymphomas (CNSLs) are aggressive large B-cell lymphomas with only a small minority presenting as indolent neoplasms. Given their rarity, no set guidelines for management exist. Prognosis for these indolent neoplasms remains more favorable with prolonged survival despite less aggressive therapies?. This is the first report of the safety and SPL-B tolerability of intrathecal rituximab (IT-R) in an indolent CNSL. Case report ??Initial presentation A 78-year-old man presented in February 2008 with 2 months of progressive ataxia. Neuroimaging revealed bilateral, homogenously enhancing periventricular masses in the posterior fossa (Figure 1A). Cerebrospinal fluid (CSF) flow cytometry revealed a CD20+ monoclonal B-cell population with lambda light-chain restriction and the patient was started on dexamethasone (4 mg thrice daily) and transferred to our institution for evaluation. Systemic workup including SPL-B PET and bone marrow biopsy was unremarkable SPL-B and there was strong suspicion for CNSL. Biopsy was planned to confirm the presence of a lymphoproliferative process; however, after treatment with glucocorticoids a complete remission was observed. The yield of subsequent diagnostic biopsy was felt to be low and though initial CSF flow cytometry was worrisome for a lymphoproliferative disorder it was not diagnostic and radiographic surveillance was pursued without further treatment. The patient remained disease free for over 2 years. Open in a separate window Figure 1.? Serial neuroimaging results. Axial T1-weighted gadolinium enhanced brain MRI showing (A) bilateral, homogenously enhancing periventricular masses in the posterior fossa in February 2008; (B) recurrent leptomeningeal enhancement within the cerebellar folia in June 2010 and (C) no abnormal enhancement or parenchymal involvement in April 2013 with isolated cerebrospinal fluid disease. ??First & second recurrence C systemic treatment In April 2010, he suffered first relapse manifesting as progressive ataxia with nodular leptomeningeal enhancement on MRI (Figure 1B) and CSF which demonstrated monocytic pleocytosis (73 cells/mm3), glucose 6 mg/dl and protein 115 mg/dl. CSF cytology showed two abnormal monoclonal B-cell populations including a small CD5+, CD19+, CD20+, dim CD38+ kappa-light-chain-restricted population and a medium-to-large CD19+, CD20+, CD5-, CD10- lambda-restricted population. Serum studies showed corresponding IgM biclonal gammopathy and macroglobulinemia (IgM: 1240 mg/dl). BingCNeel syndrome, a rare form of Waldenstrom’s macroglobulinemia characterized by neoplastic infiltration into the CNS, was considered though bone marrow biopsy showed only hypercellular marrow with a single small lymphoid aggregate of small lymphocytes and predominance of kappa-light-chain-positive B cells without neoplasia?. As his clinical course and CSF results strongly supported an indolent CNSL, he was started on weekly systemic rituximab (375 mg/m2) and glucocorticoids (dexamethasone 4 mg four times daily for 2 weeks) with clinical, cytologic and radiographic partial response after four treatments but subsequent cytologic progression by 8 weeks. Serum studies to determine the status of the systemic monoclonal gammopathy were not repeated and biweekly intrathecal-methotrexate (IT-MTX) was initiated by Ommaya reservoir. This resulted in a complete radiographic Rabbit Polyclonal to MPRA remission which persisted after eight doses despite discontinuing therapy after 12 doses due to severe infusional reaction (e.g.,?confusion, agitation, nausea and hyperthermia). ??Third recurrence C intrathecal treatment He remained clinically, radiographically and cytologically stable until May 2013, when he developed recurrent progressive ataxia, aphasia and abulia. Neuroimaging was unremarkable (Figure 1C) but CSF showed monocytic pleocytosis (32 cells/mm3), protein 83 mg/dl and markedly reduced glucose of 2 mg/dl. CSF cultures were negative for infection. Flow cytometry revealed 10% phenotypically abnormal monoclonal B-cell and lambda-light-chain-restricted population consistent with recurrent disease. Radiation therapy and systemic chemotherapy (i.e.,?high-dose methotrexate) were considered; however, given his age, modest renal insufficiency, intolerance to prior IT-MTX, isolated leptomeningeal dissemination without bulky or radiographically measurable disease and indolent course, IT-R (25 mg once weekly, 5ml of a 10 mg/ml solution without dilution, no concurrent glucocorticoids) was initiated in August 2013. Treatments were extremely well tolerated without toxicity. Cytology, CSF protein and cells did not normalize but marked improvement in CSF glucose trended most closely with clinical improvement (Figure 2 & Table 1). At peak clinical improvement, CSF by lumbar dural puncture showed WBC 11 cells/mm3, glucose 27 mg/dl, and protein 70 mg/dl. Open in a separate window Figure 2.? Association between cerebrospinal fluid glucose by.