Rituximab Cerebrospinal Fluid Levels in Patients with Primary Central Nervous System Lymphoma Treated with Intravenous High Dose Rituximab

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1644-1644 ◽  
Author(s):  
Jean-Francois Larouche ◽  
Marc Bergeron ◽  
Grace Hampson ◽  
Tim Illidge ◽  
Robert Delage
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Primary Cns Lymphoma ◽  
Serum Levels ◽  
Cns Lymphoma ◽  
High Dose ◽  
Serum Samples ◽  
Cerebrospinal Fluid Levels ◽  
Fluid Levels

Abstract Abstract 1644 INTRODUCTION: Rituximab penetration in central nervous system is largely unknown in human. Experiments in monkeys showed that 0,1% of serum rituximab concentration was achieved in cerebrospinal fluid. Reports in patients are limited (Rubenstein JL, Blood 2003 and Petereit HF, Multiple Sclerosis 2009). They demonstrated similar low levels of cerebrospinal fluid penetration with standard dose (375 mg /m2) rituximab in patients with central nervous system (CNS) lymphoma or multiple sclerosis. METHOD: We conducted a phase 2 trial in patients with primary CNS lymphoma. Patients were treated with an intravenous combination of high dose methotrexate (8 g/m2), high dose cytarabine (2 g/m2) and high dose rituximab (750 mg/m2 every 1–2 weeks × 13 infusions). We obtained from four patients paired cerebrospinal fluid and serum samples and rituximab concentration were determined in each. Samples were collected at different time points just before rituximab infusion and represent trough levels. RESULTS: 11 cerebrospinal fluid samples were available and their 11 paired serum samples. Mean cerebrospinal fluid and serum levels were 2,04 ug/mL (0,49–4,08) and 297,09 ug/mL (211,26–504,47) respectively. Mean cerebrospinal fluid levels were 0,71% (0,18–1,5%) of serum levels. No relationship was made between cerebrospinal fluid level and the number of rituximab dose administered. CONCLUSION: In patients with primary CNS lymphoma receiving high dose 1–2 weekly rituximab. cerebrospinal fluid concentration achieve is low compared to serum levels. However, administration of higher dose of intravenous rituximab can increase penetration in central nervous system but its clinical impact is unknown as cerebrospinal fluid levels are still low. Disclosures: No relevant conflicts of interest to declare.

Lymphomatous meningitis in primary central nervous system lymphoma

2006 ◽  
Vol 21 (5) ◽  
pp. 1-7 ◽  
Author(s):  
Marc C. Chamberlain
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Drug Therapy ◽  
Mr Imaging ◽  
Primary Cns Lymphoma ◽  
Chemotherapeutic Agents ◽  
Cranial Computed Tomography ◽  
Cns Lymphoma ◽  
High Dose ◽  
Lymphomatous Meningitis

✓Lymphomatous meningitis (LM) due to primary central nervous system (CNS) lymphoma is an uncommon problem in neurooncology and can occur at time of diagnosis or recurrence. Notwithstanding frequent focal signs and symptoms, LM is a disease affecting the entire neuraxis, and therefore staging and treatment need to encompass all cere-brospinal fluid (CSF) compartments. Central nervous system staging of LM includes contrast agent–enhanced cranial computed tomography (CT) or Gd-enhanced magnetic resonance (MR) imaging, Gd-enhanced spinal MR imaging, CT myelography, and radionuclide CSF flow study. Treatment of LM includes involved-field radiotherapy of bulky or symptomatic disease sites and intra-CSF drug therapy. The inclusion of concomitant systemic therapy can benefit patients with LM and can obviate the need for intra-CSF chemotherapy. At present, intra-CSF drug therapy is confined to three chemotherapeutic agents (methotrexate, cytosine arabinoside, and thiotepa) administered by a variety of schedules either by intralumbar or intraventricular drug delivery. Although treatment of LM is palliative and the expected median survival of patients is 4 to 6 months, it often provides stabilization and protection from further neurological deterioration. In patients with primary CNS lymphoma, CNS prophylaxis has been recommended (using a combination of high-dose systemic chemotherapy and intra-CSF chemotherapy), but the strategy remains controversial because high-dose systemic methotrexate is commonly used as an adjuvant therapy. Patients with primary CNS lymphoma at high risk as defined by positive CSF cytology or neuroradiography consistent with LM may benefit from the inclusion of intra-CSF chemotherapy.

scholarly journals Cerebrospinal Fluid Flow Cytometry: Utility in Central Nervous System Lymphoma Diagnosis

2020 ◽  
Vol 47 (3) ◽  
pp. 382-388
Author(s):  
Ka Loong Kelvin Au ◽  
Sarah Latonas ◽  
Afshin Shameli ◽  
Iwona Auer ◽  
Christopher Hahn
Keyword(s):  
Central Nervous System ◽  
Flow Cytometry ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Hematological Malignancy ◽  
Previous History ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
Csf Flow ◽  
Neurologic Symptoms

ABSTRACT:Background:Flow cytometry of the cerebrospinal fluid (CSF) is used in isolation or as an adjunct to cytology to increase the sensitivity of detecting central nervous system (CNS) lymphoma. We aimed to evaluate the sensitivity of CSF flow cytometry as a diagnostic screening tool for primary CNS lymphoma in patients presenting with undifferentiated neurologic symptoms.Methods:We retrospectively reviewed all CSF samples received by the Calgary Laboratory Services Flow Cytometry Laboratory from 2012 to 2015. Clinical data, laboratory investigations, radiologic imaging studies, and pathological data were analyzed. Clinical review extended to 2 years post-CSF flow cytometric testing.Results:Only 43/763 (5.6%) samples of CSF flow cytometry in 28/573 (4.9%) patients were found to be positive for a hematological malignancy in patients with undifferentiated neurologic symptoms. The overall sensitivity of the test was 13.8% with 25 patients with negative CSF flow cytometry later having a positive biopsy for CNS lymphoma. CSF flow cytometry was negative in all cases when at the time of CSF examination the patient did not have a previous hematological malignancy or findings of abnormal enhancement on MRI (n = 249).Conclusion:CSF flow cytometry has low utility in screening for primary CNS lymphoma in the absence of a previous history of hematologic malignancy or findings of abnormal enhancement on MRI.

Cerebrospinal fluid levels of chemokines in HIV infected patients with and without opportunistic infection of the central nervous system

2009 ◽  
Vol 287 (1-2) ◽  
pp. 79-83 ◽  
Author(s):  
Paulo Pereira Christo ◽  
Márcia de Carvalho Vilela ◽  
Thales Lage Bretas ◽  
Renan Barros Domingues ◽  
Dirceu Bartolomeu Greco ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Opportunistic Infection ◽  
Cerebrospinal Fluid Levels ◽  
The Central Nervous System ◽  
Fluid Levels

scholarly journals P14.84 Intraarterial chemotherapy and osmotic blood-brain barrier modification in the treatment of primary CNS lymphoma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii87-iii87
Author(s):  
D Fortin ◽  
G Gahide ◽  
C Iorio-Morin
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Primary Cns Lymphoma ◽  
Brain Barrier ◽  
Cns Lymphoma ◽  
High Dose ◽  
Left Internal Carotid Artery ◽  
Single Center ◽  
Blood Brain

Abstract BACKGROUND Primary central nervous system lymphomas (PCNSL) are considered a rare and aggressive form of central nervous system (CNS) tumors. High-dose methotrexate has become the backbone of PCNSL treatment, and is recommended by the EANO guidelines. In most recent protocols, investigators tend to postpone or even avoid the use of radiotherapy; indeed, its use has become controversial with findings of associated severe neuro-toxicity, especially in elderly patients. To maximize delivery across the BBB, we use cerebral intra-arterial chemotherapy (CIAC) coupled with osmotic blood-brain barrier disruption (OBBBD). We hereby report our single-center experience over 18 years with the CIAC + BBBD technique using 2 different HD-MTX protocols. MATERIAL AND METHODS This phase II study was conducted at the Centre hospitalier Universitaire de Sherbrooke (CHUS) from November 1999 to May 2018. The protocol was approved by the institutional review board, and informed consent was obtained in accordance to institutional regulation in every patient After enrollment and initial evaluation, patients were treated every four weeks (1 cycle) for 12 cycles, unless progression. After general anesthesia, a transfemoral approach was used to catheterize either the right or left internal carotid artery or the dominant vertebral artery, depending on tumor(s) location. OBBBD was performed by infusing 20% mannitol in the selected vascular distribution for 30 seconds at a rate that fills the vascular distribution so as to maximize the contact of the mannitol with the endothelial cells.Two different chemotherapy regimens were sequentially used in this study. High-dose MTX (5 g IV) was the cornerstone of both regimens: the first regimen (1999 to 2007) also included etoposide phosphate IV (400 mg/m²) and cyclophosphamide IV (660 mg/m²), whereas the 2nd regimen (1998 to 2018) also included carboplatin IA (400 mg/m²). RESULTS The present analysis therefore concerns a cohort of 44 naive patients recruited over 18 years in a single center. Median follow-up was 38 months. Overall, a CR was induced in 34 patients (79%). Themedian time to CR was 7.3 months (IQR: 7.8). Of these 34 patients, 11 (25.6%) are still alive, and 9 of these are disease-free after treatment discontinuation. The actuarial median survival (MS) was 46.5 months (95% CI: 30.9–62.2) for the cohort. Survival was 88%, 64%, 54%, 39% and 18% at 1, 2, 3,5 and 10 years (Figure 1 and Table 2).The progression-free survival was 43.4 months (95% CI: 17.9–68.9). Five occurrences of vascular complications related to the treatment were observed (11.6%). Conclusion: CIAC HD-MTX-based protocols with OBBBD is a safe and well-tolerated procedure for the management of primary CNS lymphoma. Our single center data suggests better PFS and survival outcomes compared to IV protocols with less hematologic toxicity and good tolerability, especially in the elderly.

Cerebrospinal Fluid Levels of IL-6 in Patients with Acute Infections of the Central Nervous System

1992 ◽  
Vol 24 (6) ◽  
pp. 787-791 ◽  
Author(s):  
Donato Torre ◽  
Claudia Zeroli ◽  
Giorgio Ferraro ◽  
Filippo Speranza ◽  
Roberto Tambini ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Cerebrospinal Fluid Levels ◽  
Acute Infections ◽  
The Central Nervous System ◽  
Fluid Levels

scholarly journals Cerebrospinal fluid flow cytometry: utility in central nervous system lymphoma diagnosis

2021 ◽  
Vol 48 (s1) ◽  
pp. S2-S3
Author(s):  
KLK Au ◽  
S Latonas ◽  
A Shameli ◽  
I Auer ◽  
C Hahn
Keyword(s):  
Central Nervous System ◽  
Flow Cytometry ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Hematological Malignancy ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
List Type ◽  
Csf Flow ◽  
Testing Algorithm

Flow cytometry of the cerebrospinal fluid (CSF) is used in isolation or as an adjunct to cytology to increase the sensitivity of detecting primary central nervous system (CNS) lymphoma. We aim to evaluate the sensitivity of CSF flow cytometry as a diagnostic tool for primary CNS lymphoma in patients presenting with undifferentiated neurologic symptoms. We retrospectively reviewed all CSF samples received by the Calgary Laboratory Services Flow Cytometry Laboratory from 2012- 2015. Clinical data, laboratory investigations, radiologic imaging studies, and pathological data were analyzed. Clinical review extended to 2 years post CSF flow cytometric testing. The number of samples of CSF flow cytometry that were positive for a hematological malignancy was 43/763 (5.6%). The overall sensitivity of the test was 69.4%. A positive result was more likely to occur in patients with a prior history of a hematological malignancy or abnormal enhancement on MRI (p<0.0001). CSF flow cytometry was negative in all patients who did not have a previous hematological malignancy or abnormal enhancement on MRI (n = 247). CSF flow cytometry has a limited role in screening for primary CNS lymphoma, unless a strictly endorsed testing algorithm is applied. It is, however, an invaluable tool in evaluating CNS involvement in patients with a previous diagnosis of hematolymphoid malignancy or abnormal enhancement on MRI.LEARNING OBJECTIVESThis presentation will enable the learner to:Discuss the costs and benefits of using CSF flow cytometry to diagnose CNS lymphoma 1.Identify appropriate clinical indications for using CSF flow cytometry as a first-line test2.Apply a testing algorithm to increase the diagnostic yield of CSF flow cytometry

scholarly journals Case-based review: primary central nervous system lymphoma

2017 ◽  
Vol 4 (1) ◽  
pp. 46-59 ◽  
Author(s):  
Agnieszka Korfel ◽  
Uwe Schlegel ◽  
Derek R. Johnson ◽  
Timothy J. Kaufmann ◽  
Caterina Giannini ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
B Cell Lymphoma ◽  
The Elderly ◽  
Cns Lymphoma ◽  
High Dose ◽  
Tumor Biopsy

Abstract Primary CNS lymphoma (PCNSL) is a rare diffuse large B-cell lymphoma originating within the central nervous system. The overall incidence of PCNSL is rising, particularly in the elderly population. Immunosuppression is a strong risk factor, but most patients with this tumor are apparently immunocompetent. Diagnosis of PCNSL can be challenging. Non-invasive or minimally invasive tests such as ophthalmological evaluation and spinal fluid analysis may be useful, but the majority of patients require tumor biopsy for definitive diagnosis. Our knowledge concerning optimum treatment of PCNSL is fragmentary due to paucity of adequately sized trials. Most patients are now initially treated with high-dose-methotrexate-based chemotherapy alone, as the addition of whole-brain radiotherapy at standard doses has not been shown to increase survival and does increase the risk of neurological toxicity. Ongoing trials are addressing issues such as the roles of reduced-dose radiotherapy, the addition of the CD20 antibody rituximab to chemotherapy, high-dose chemotherapy followed by autologous stem cell transplantation, and maintenance therapy in the primary management of PCNSL.

scholarly journals Improving the antitumor activity of R-CHOP with NGR-hTNF in primary CNS lymphoma: final results of a phase 2 trial

2020 ◽  
Vol 4 (15) ◽  
pp. 3648-3658
Author(s):  
Andrés J. M. Ferreri ◽  
Teresa Calimeri ◽  
Maurilio Ponzoni ◽  
Flavio Curnis ◽  
Gian Marco Conte ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Primary Cns Lymphoma ◽  
Human Tumor ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Phase 2 ◽  
Phase 2 Trial

Abstract Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment of diffuse large B-cell lymphoma (DLBCL). Primary DLBCL of the central nervous system (CNS) (primary central nervous system lymphoma [PCNSL]) is an exception because of the low CNS bioavailability of related drugs. NGR–human tumor necrosis factor (NGR-hTNF) targets CD13+ vessels, enhances vascular permeability and CNS access of anticancer drugs, and provides the rationale for the treatment of PCNSL with R-CHOP. Herein, we report activity and safety of R-CHOP preceded by NGR-hTNF in patients with PCNSL relapsed/refractory to high-dose methotrexate-based chemotherapy enrolled in a phase 2 trial. Overall response rate (ORR) was the primary endpoint. A sample size of 28 patients was considered necessary to demonstrate improvement from 30% to 50% ORR. NGR-hTNF/R-CHOP would be declared active if ≥12 responses were recorded. Treatment was well tolerated; there were no cases of unexpected toxicities, dose reductions or interruptions. NGR-hTNF/R-CHOP was active, with confirmed tumor response in 21 patients (75%; 95% confidence interval, 59%-91%), which was complete in 11. Seventeen of the 21 patients with response to treatment received consolidation (ASCT, WBRT, and/or lenalidomide maintenance). At a median follow-up of 21 (range, 14-31) months, 5 patients remained relapse-free and 6 were alive. The activity of NGR-hTNF/R-CHOP is in line with the expression of CD13 in both pericytes and endothelial cells of tumor vessels. High plasma levels of chromogranin A, an NGR-hTNF inhibitor, were associated with proton pump inhibitor use and a lower remission rate, suggesting that these drugs should be avoided during TNF-based therapy. Further research on this innovative approach to CNS lymphomas is warranted. The trial was registered as EudraCT: 2014-001532-11.

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