Primary Central Nervous Lymphoma Research Articles

Paired Circulating Tumor DNA in Cerebrospinal Fluid and Peripheral Blood: Reliable Technology for Diagnosing and Monitoring Primary and Secondary Central Nervous Lymphoma

Objective: This research delineates the temporal alterations of cell-free circulating tumor DNA (ctDNA) in the plasma and cerebrospinal fluid (CSF) of patients harboring primary and secondary central nervous system (CNS) lymphoma. The aim is to establish that CSF serves as a superior reservoir of ctDNA compared to plasma, thereby aiding in diagnostic processes and monitoring therapeutic efficacy. Concurrently, this study underscores the enhanced response and survival rates in patients administered Bruton's tyrosine kinase (BTK) inhibitors over an extended period exceeding three months. Methods: Data including cranial-enhanced magnetic resonance imaging (MRI) scans, leukocyte and protein concentrations in the CSF, exfoliated CSF cytology, flow cytometry, interleukin-10 to interleukin-6 ratios, ctDNA in plasma and CSF, were gathered from patients presenting primary and secondary CNS lymphoma（7 PCNSL,9 SCNSL）. The temporal ctDNA modifications in plasma and CSF during the patient's disease progression-initial onset, remission, and relapse-were scrutinized. Additionally, the implications of BTK inhibitor usage on patient response rates and survival rates were assessed. Results: Within the cohort of primary CNS lymphoma patients, ctDNA was detected in the CSF and plasma of 2 and 5 patients, respectively. Conversely, in patients with secondary CNS lymphoma, CSF and plasma ctDNA were discovered in 8 and 4 cases, respectively. The detection rate was contingent upon the central lesion's magnitude and position and the patient's surgical history related to the brain. Four patients, including two from each group, underwent cranial-enhanced MRI to appraise tumor burden at various disease stages, simultaneously with the monitoring of ctDNA in plasma and CSF. It was revealed that ctDNA levels in the CSF were in synchrony with the tumor burden, whereas plasma ctDNA levels remained relatively static. This indicates that CSF ctDNA may serve as a viable tool to assess therapeutic responses in CNS lymphoma patients. In two patients where surgical biopsy was unfeasible and both CSF exfoliation cytology and flow cytometry returned negative results, CSF ctDNA was positive, thereby underscoring its auxiliary role in diagnosing CNS lymphoma. Furthermore, the study indicated improved response and survival rates in patients subjected to BTK inhibitors for over three months. Conclusion: CSF ctDNA demonstrates potential in detecting CNS lymphoma and in the dynamic monitoring of therapeutic responses. Compared to cranial-enhanced MRI, exfoliated CSF cytology, and flow cytometry, CSF ctDNA testing offers superior sensitivity. For patients for whom brain surgical biopsy is not an option, CSF ctDNA testing emerges as a valuable supplementary diagnostic tool. CSF ctDNA allows for dynamic monitoring of therapeutic responses in CNS lymphoma patients, enabling the detection of residual lesions, and thereby guiding the formulation and duration of the treatment regimen. Patients administered oral BTK inhibitors for more than three months demonstrate higher treatment response and survival rates.

NCOG-39. DOSE-EFFECT RELATIONSHIP OF DEXAMETHASONE ON OUTCOMES OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA

Abstract BACKGROUND Dexamethasone is commonly used for symptomatic management in primary central nervous lymphoma (PCNSL). The optimal dosing scheme for dexamethasone is unknown and practice patterns widely vary among clinicians. In this study, we explored the dose-effect relationship of dexamethasone on PCNSL outcomes to better influence quality care for these patients. METHODS We retrospectively identified 24 Mayo Clinic patients (1/1/2018 – 12/31/2022) with pathologically confirmed PCNSL who received dexamethasone. All patients otherwise received standard oncologic care including methotrexate-based systemic chemotherapy and/or radiotherapy. The association between dexamethasone dosing regimens and clinical outcomes (performance status, clinical and radiographic response, survival) in addition to potential adverse effects were evaluated in the acute phase of presentation and at first post-treatment oncology follow up. RESULTS Nine patients received less frequent dexamethasone dosing (4 mg twice daily or less), while 15 received more frequent dexamethasone dosing (4 mg four times daily). Fourteen patients received dexamethasone prior to biopsy, 2 of which (1 in each cohort) had a non-diagnostic biopsy and required a second procedure 3 weeks to 3 months later to confirm PCNSL diagnosis. There were no statistically significant differences in time to diagnosis from presentation or clinical and radiographic improvement including Karnofsky Performance Status, reduction in seizures, or survival between the two cohorts. Additionally, there were no differences in the frequency of adverse events (e.g., hyperglycemia, hypertension, infection, psychosis) between the two dosing regimens. CONCLUSIONS These results suggest that more frequent dexamethasone dosing is not associated with better clinical outcomes in the symptomatic management of PCNSL. Twice daily or less frequent dosing can be considered without compromising patient outcomes.

Methionine-PET to differentiate between brain lesions appearing similar on conventional CT/MRI scans.

11 C-Methionine (MET)-PET is a useful tool in neuro-oncology. This study aimed to examine whether a combination of diagnostic variables associated with MET uptake could help distinguish between brain lesions that are often difficult to discriminate in conventional CT and MRI. MET-PET was assessed in 129 patients with glioblastoma multiforme, primary central nervous lymphoma, metastatic brain tumor, tumefactive multiple sclerosis, or radiation necrosis. The accuracy of the differential diagnosis was analyzed using five diagnostic characteristics in combination: higher maximum standardized uptake value (SUV) of MET in the lesion/the mean normal cortical SUV of MET ratio, overextension beyond gadolinium, peripheral pattern indicating abundant MET accumulation in the peripheral region, central pattern denoting abundant MET accumulation in the central region, and dynamic-up suggesting increased MET accumulation during dynamic study. The analysis was conducted on sets of two of the five brain lesions. Significant differences in the five diagnostic traits were observed among the five brain lesions, and differential diagnosis could be achieved by combining these diagnostic features. The area under the curve between each set of two of the five brain lesions using MET-PET features ranged from .85 to 1.0. According to the findings, combining the five diagnostic criteria could help with the differential diagnosis of the five brain lesions. MET-PET is an auxiliary diagnostic technique that could help in distinguishing these five brain lesions.

Outcome of Brain Lymphoma in a High Epstein-Barr Virus–Prevalence Country After Kidney Transplantation

The incidence of post-transplant lymphoproliferative disorder (PTLD) in adult kidney transplant (KTx) recipients is less common in Taiwan. In our institute, we observed that brain lymphoma was the most notorious type. The study describes the clinical, histologic, and radiological features of primary central nervous lymphoma (PCNSL) and the outcomes and associations with Epstein-Barr virus (EBV) infection in our center. Among 1470 KTx recipients, 5 patients had tissue-proven brain lymphoma (0.34%). The brain pathology disclosed diffuse large B-cell lymphoma in all patients. EBV was detected through in situ hybridization for Epstein-Barr encoding region (EBER) to disclose the EBV inclusion in the nuclei of lymphoma cells. The first treatment step was the reduction of immunosuppressants; 4 patients received whole-brain radiotherapy after complete resection of PCNSL, and 1 received concurrent chemoradiotherapy. Only one patient had poor performance status at the time of diagnosis and had a poor response to treatment with steroids. Four patients survived (mean 36.5 months, range 8.6 to 57.6 months), but one died after rapid neurologic deterioration. Epstein-Barr virus inclusion was found in PCNSL in our patients; however, the role of EBV in PCNSL remains to be clarified. Post-transplant lymphoproliferative disorder is a rare malignancy after KTx with a predilection of brain involvement in Taiwan. We report a successful care experience in a patient with primary CNS lymphoma with better survival.

Recurrent Neuropsychiatric Systemic Lupus Erythematosus Presenting with Primary Central Nervous System Lymphoma

We report the case of a systemic lupus erythematosus (SLE) patient who was diagnosed with lupus cerebritis, vasculitis, Epstein-Barr virus infection, and consequently, lymphoma. The patient presented to the emergency department with dysarthria, dysphagia, left-sided hemiparesis, and hypesthesia. Initial brain magnetic resonance imaging (MRI) revealed multiple high signal intensities in the cortex and subcortex. Intravenous methylprednisolone and immunoglobulin administration did not improve her symptoms. However, intravenous rituximab improved the parenchymal and angiographic abnormalities. One month later, she developed another acute left-sided hypesthesia. Brain MRI revealed multiple rim-enhancing lesions with perilesional edema, different from the previous lesion. Intravenous methylprednisolone and cyclophosphamide did not improve her symptoms, and she was finally diagnosed with primary central nervous system lymphoma after brain biopsy. Neurological symptoms improved after chemotherapy. Since the incidence of primary central nervous lymphoma is relatively high in SLE patients, careful diagnosis and accurate treatment are needed.

Primary Central Nervous System ALK-Negative Anaplastic Large Cell Lymphoma: A Case Report and Literature Review

Primary Central Nervous System ALK-Negative Anaplastic Large Cell Lymphoma: A Case Report and Literature Review

First-line high-dose therapy and autologous blood stem cell transplantation in patients with primary central nervous system non-Hodgkin lymphomas\u2014a single-centre experience in 61 patients

Primary central nervous system non-Hodgkin lymphomas (PCNS-NHLs) are extranodal B-cell lymphomas with poor prognosis. The role of high-dose therapy (HDT) followed by autologous blood stem cell transplantation (ASCT) as first-line therapy is still not clear. We retrospectively collected long-term follow up data of 61 consecutive patients with PCNS-NHL at the University Hospital Düsseldorf from January 2004 to December 2016. Thirty-six patients were treated with conventional chemoimmunotherapy (cCIT) only (CT-group). Seventeen patients received an induction cCIT followed by HDT and ASCT. In the CT-group, the overall response rate (ORR) was 61% (CR 47%, PR 14%), and there were 8% treatment-related deaths (TRD). Progression-free survival (PFS) was 31.8 months, and overall survival (OS) was 57.3 months. In the HDT-group, the ORR was 88% (59% CR, 29% PR), and there were 6% TRD. Median PFS and OS were not reached at 5 years. The 5-year PFS and OS were 64.7%. After a median follow up of 71 months, 10 patients (59%) were still alive in CR/PR following HDT and ASCT, one patient was treated for progressive disease (PD), and 7 had died (41%, 6 PD, 1 TRD). All patients achieving CR prior to HDT achieved durable CR. In the CT-group, 8 patients (22%) were alive in CR/PR after a median follow-up of 100 months. Twenty-eight patients died (78%, 24 PD, 2 TRD, 2 deaths in remission). In the univariate analysis, the HDT-group patients had significantly better PFS (not reached vs 31.8 months, p = 0.004) and OS (not reached vs 57.3 months, p = 0.021). The multivariate analysis showed HDT was not predictive for survival. Treatment with HDT + ASCT is feasible and offers the chance for long-term survival with low treatment-related mortality in younger patients. In this analysis, ORR, PFS and OS were better with HDT than with conventional cCIT alone. This result was not confirmed in the multivariate analysis, and further studies need to be done to examine the role of HDT in PCNSL.

PRIMARY CNS LYMPHOMA MIMICKING TUBERCULOSIS INFECTION - A CASE REPORT

Primary central nervous system lymphoma (PCNSL) is a rare variety of extra nodal non-Hodgkin lymphoma that reportedly involves leptomeninges, the brain, spinal cord, eyes, or may involve other organs systemically. We present a case of 46-yearold woman with complaints of headache and fever for three weeks, associated with right-sided weakness & altered state of consciousness for one week. The most common presentation of primary central nervous lymphoma is diffuse or multifocal supratentorial masses causing cognitive deterioration and involvement of vitreous, retina, and optic nerve. Most cases ofPCNSL are left undiagnosed due to uncommon

Rituximab, Methotrexate, Procarbazine and Lomustine (R-MPL) for the Treatment of Primary CNS Lymphoma

Introduction: Primary central nervous lymphoma (PCNSL) is a rare type of non-Hodgkin lymphoma that may involve the brain, spinal cord, leptomeninges and vitreous. The median age at diagnosis is in the fifth decade and most patients (pts) present with significant neurologic deficit and a low performance status. The optimal treatment of PCNSL is controversial. High dose methotrexate (HDMTX) is a standard treatment of PCNSL and is more effective when given in combination with other CNS-penetrating medications, which, however, add to the toxicity of the treatment. We aimed to evaluate the effectiveness and the safety of the combination of rituximab, HDMTX, procarbazine and lomustine (R-MPL) in pts with PCNSL. Patients and methods: We retrospectively reviewed the files of PCNSL pts treated in Hadassah Medical Center, Jerusalem, Israel, between the years 2006-2019. The medical records were reviewed for demographic details and initial disease characteristics (age, sex, performance status, laboratory results, cerebrospinal fluid (CSF) content and tumor location), and for therapeutic details including chemotherapy protocol, toxicity, response to treatment and survival. We excluded pts who could not receive HDMTX. The R-MPL is a 42-day cycle protocol, consisting IV Rituximab 375 mg/m2 on days 1, 15 and 28, IV HDMTX 5 g/m2 (3.5 g/m2 for pts > 60 Years (y)) on days 2, 15 and 29, PO procarbazine 100 mg/m2 (60 mg/m2 for pts > 60 y) on days 3-9, PO lomustine 60 mg/m2 (40 mg/m2 for pts > 60 y) on day 2. Six to nine intrathecal (IT) injections of MTX / cytarabine were included for pts with positive CSF cytology, tumor adjacent to ventricles, or per physician's decision. Rituximab was given for no more than 8 doses in total. A total of 3-4 courses of R-MPL were given. Responsive pts could proceed to autologous stem cell transplant (ASCT) with TECAM conditioning or 2 cycles of intermediate dose cytarabine (IDAC, 1.5 g/m2), 2 doses in each cycle. Those who achieved less than CR or had significant toxicity to R-MPL received additional ifosfamide/etoposide or high dose cytarabine or temazolamide or topotecan. Radiation was given only for salvage. Results: Fifty-two pts were included in the study. Median age was 62 years (range 28-94). Three (6%) had leptomeningeal involvement, thirteen (25%) had vitreoretinal involvement, 30 (58%) had involvement of the deep brain. Mean ECOG, IELSG and MSKCC scores were 1.98, 2.53 and 1.94 respectively. The median number of HDMTX doses was 8 (range 3-16). Forty-five (87%) pts completed at least one 42-day cycle of R-MPL. Among this group, 29 (64%) pts received at least 3 IT injections, 12 (27%) underwent ASCT, 10 (22%) received IDAC, and 7 (16%) received other chemotherapies. The median follow-up was 27 months (m) (range 0.4-140m). The overall response rate (ORR) was 79% (41/52), and the complete response (CR) rate was 52% (27/52). The median progression free survival (PFS) was 15.5m and the median overall survival (OS) was 27m. Among the 45 pts who received at least one R-MPL cycle, the ORR was 87% (39/45), the CR rate was 60% (27/45), the median PFS was 84m and the median OS was not reached (figure 1). Known prognostic factors correlated with OS: age (p<0.01), ECOG performance status (p<0.01), CSF protein (p=0.01) and IELSG/MSKCC scores (p=0.05/0.04). Patients who received at least 3 IT injections had a trend to longer PFS (32.4m Vs 19.2m, p=0.09), and a significant OS benefit (48.6m Vs 20.8m, p<0.01). In a multivariable model, the effect of IT injections was independent of age, sex and IELSG score, and attenuated by number of HDMTX doses. ASCT/IDAC did not improve PFS/OS, however numbers were small. Achieving CR at the end of treatment strongly correlated with PFS/OS, but timing of best response (after one 42-day cycle Vs later) did not. Grade 3-4 adverse events included infections (21%) and kidney injury (13%). Two pts died during therapy, both in the 1st cycle due to disease progression. Ten pts (19%) discontinued therapy due to toxicity. No treatment related mortality (TRM) was documented. Conclusions: The R-MPL protocol achieved a favorable ORR/PFS/OS as described, with reasonable grade 3-4 toxicity and no TRM. The advantage of ASCT/IDAC could not be assessed due to small number of pts. IT injections (at least 3) and achievement of CR at the end of treatment correlated with survival. The R-MPL protocol was reported in previous trials only among the elderly, and should further be evaluated in all age groups. Disclosures Goldschmidt: Abbvie Inc: Consultancy, Research Funding.

Systemic Approach to Recurrent Primary CNS Lymphoma: Perspective on Current and Emerging Treatment Strategies.

There is no uniform standard of care for the treatment of refractory or recurrent primary central nervous lymphoma (r/r PCNSL). Many different systemic treatment regimens have been studied, but available data are based on small prospective or retrospective reports. There have been no randomized controlled trials in r/r PCNSL to date. Here, we provide an overview of published systemic regimens for the treatment of r/r PCNSL, as well as therapies that are under investigation. In addition, based on available data, we propose strategies of how to approach choice of therapy for different groups of patients in this disease setting. Patients can be mainly divided into three groups: 1) patients suitable for a re-challenge with high-dose methotrexate (HD-MTX)-based regimens and that may or may not be candidates for consolidation with high-dose chemotherapy with autologous stem cell transplant, 2) patients refractory to HD-MTX or that had early relapse, but suitable for an aggressive treatment strategy with re-induction with non-MTX-based therapy, possibly followed by high-dose chemotherapy with autologous transplant, and 3) patients not suitable for re-treatment with HD-MTX and that are not candidates for aggressive therapy. As PCNSL is a rare disease and as there is urgent need for better outcomes in r/r PCNSL, clinical trial participation is encouraged, especially in elderly or frail patients who are not candidates for high-dose chemotherapy and transplant.

Serum levels of soluble programmed death-ligand 1 (sPD-L1) in patients with primary central nervous system diffuse large B-cell lymphoma

BackgroundThe interaction of programmed death-1 protein (PD-1) and programmed death-1 ligand (PD-L1) produces immunosuppressive activity, protecting tumor cells from anti-tumor immunity and possibly releasing soluble PD-L1 (sPD-L1) from PD-L1 expressing tumor cells. Therefore, we measured serum levels of sPD-L1 in patients with primary central nervous system lymphoma (PCNSL) and explored its clinical implications.MethodsSixty-eight patients with newly diagnosed PCNSL had diffuse large B-cell lymphoma and were treated with high-dose methotrexate-containing chemotherapy. The measurement of sPD-L1 and cytokines was performed using serum samples archived at diagnosis, and the tissue expression of PD-L1 was also analyzed from archived paraffin-embedded tissue blocks. Disease relapse, progression-free survival (PFS), and overall survival (OS) were analyzed according to the extent of sPD-L1 in serum and PD-L1 in tissue.ResultsThe median level of serum sPD-L1 (0.429 ng/mL) was higher than in healthy control patients (0.364 ng/mL). The occurrence of relapse was more frequent in the high sPD-L1 (78%) than the low sPD-L1 group (50%), though the groups did not have different clinical or pathological characteristics at diagnosis. As a result, the OS and PFS for the high sPD-L1 group were significantly lower than those in the low group. PD-L1-positive tumor cells were found in 35 patients (67%), and the extent of PD-L1-postive tumor cells was positively associated with serum sPD-L1 levels (r = 0.299, P = 0.031). Among the 34 cytokines analyzed, only the serum level of IL-7 correlated with the serum level of sPD-L1 (r = 0.521, P < 0.001).ConclusionsSerum levels of sPD-L1 could reflect the expression of PD-L1 in PCNSL tumor cells and predict patient survival outcomes. Therefore, sPD-L1 in serum could be a feasible biomarker for determining a risk-adapted treatment strategy for PCNSL patients.Trial registrationThe study population was patients who were diagnosed with PCNSL between January 2009 and February 2017 and registered for our prospective cohort studies after providing written informed consent (ClinicalTrials.gov: NCT00822731 [date of registration - January 14, 2009] and NCT01877109 [date of registration - June 13, 2013]).

Primary central nervous system small lymphocytic lymphoma in the bilateral ventricles: two case reports

BackgroundPrimary central nervous system (CNS) small lymphocytic lymphoma (SLL), as a type of low-grade lymphoma, is extremely rare. The diagnosis of CNS SLL is challenging due to its variable clinical and radiological features, which may overlap with those of diffuse large B-cell lymphoma (DLBCL). Primary CNS SLL differs from DLBCL in that it has an indolent clinical course and a good prognosis. Thus, it is important to distinguish SLL from DLBCL. By reviewing the literature, only two cases of low-grade SLL, primarily located in the CNS and involving the brain parenchyma and dura, have been reported. To our knowledge, primary CNS SLL in the bilateral ventricles has never been reported. Interestingly, the two cases in our report are identical in terms of the clinical presentations, magnetic resonance imaging (MRI) features, pathological results and prognoses.Case presentationBoth patients presented with headaches. MRI suggested solid lesions located in the bilateral ventricles that were isointense on T1-weighted images and hypointense on T2-weighted images. After the injection of contrast agent (gadolinium, Gd), the intraventricular lesions were homogeneously enhanced and hyperperfused. CSF cytology revealed malignant cells. Brain biopsy revealed diffuse proliferation of small lymphocytes with positive labelling of B-cell immunomarkers. The primary origin in the CNS was confirmed with no evidence of systemic lymphoma. Two patients were given high doses of methotrexate-based chemotherapy and were free from symptoms and progression for more than 1-year of follow-up.ConclusionsThe presence of homogeneously enhanced intraventricular MRI lesions should raise the suspicion of primary CNS SLL.

Primary central nervous lymphoma of cerebellopontine angle germinal center type: Report of a rare case

Lymphoma of the central nervous system is uncommon, accounting for approximately 0.2-2% of all brain tumors. Primary lymphoma of the cerebellopontine angle (CPA) is rare in the central nervous system. Computed tomography (CT) and magnetic resonance imaging (MRI) reliably describe the typical features of vestibular schwannomas and meningiomas. In various types of cerebellopontine angle mass lesions lymphoma should be considered one of the differential diagnosis. To our knowledge, there have only been 20 cases reported worldwide so far.

Primary Intraocular Lymphoma: Relevance of Diagnostic Vitrectomy

Primary intraocular lymphomas are rare tumours that can be further subdivided into primary vitreoretinal and the even rarer primary uveal lymphoma. The incidence of primary vitreoretinal lymphoma (PVRL) has increased during the last few decades. Differential diagnostic distinction between lymphoma and posterior uveitis is often difficult, so that adequate diagnosis and treatment is often delayed. This is fatal, because PVRL is often associated with primary central nervous lymphoma. To confirm the diagnosis, prior treatment of cytological or histological detection of lymphoma cells is the gold standard. Therefore, a diagnostic vitrectomy should be performed with vitreous biopsy and sometimes transretinal biopsy. Cytokine analysis, as well as flow cytometry and molecular tests, are only additional methods that can be employed in case enough tumour material is available. After the diagnosis has been made, an interdisciplinary treatment concept must be developed by oncologists and ophthalmologists together.

333PD - Meta-analysis of the effect of rituximab in the treatment of primary central nervous system lymphoma

Background: Primary central nervous system lymphoma (PCNSL) is a rare subtype of agressive non-hodgkin lymphoma (NHL), and is most commonly of B cell phenotype. The standard treatment is not well established but high dose methotraxate is the most commonly used regimen. Intravenous rituximab (iv Rtx) treatment is integrated into the protocols for systemic B cell lymphomas. However there are mixed results with the use of Rtx. The aim of this meta-analysis is to investigate the role of iv Rtx in the treatment of PCNSL. Methods: PubMed and EBSCOhost databases are searched for rituximab, primary central nervous lymphoma, rituximab, survival. Browsing databases was done in English. Results: 580 patients were included to meta-analysis. Pooled hazard ratio showed that overall survival is correlated with iv Rtx (HR, 0,498; 95% CI, 0,366 - 0,678; p:<0,001). Pooled hazard ratio was calculated by using fixed effect model. The quality determinations of 7 studies were done by using Newcastle-Ottowa Scale. The studies were counted low quality with the score 1-3, average quality with the score 4-6, high quality with the score7-9. Median score of the studies was calculated as 5. Conclusions: In this meta-analysis, we showed that the addition of iv Rtx as part of a treatment protocol for PCNSL has a positive impact on survival. Legal entity responsible for the study: Mustafa Yıldırım Funding: None Disclosure: All authors have declared no conflicts of interest.

Impact of treatment variability on survival in immuno-competent and immuno-compromised patients with primary central nervous lymphoma.

Patients with primary central nervous system lymphoma (PCNSL) treated in the 'real-world' setting do not represent those treated on clinical trials and might not be treated similarly. We studied characteristics and variability in care for 113 newly diagnosed PCNSL patients treated at 5 institutions in the Chicago area between 2000 and 2012. In 111 patients, single modality therapy with a high dose methotrexate (HD-MTX) regimen +/- rituximab, was most commonly employed (n=65), and 34 underwent radiotherapy (+/- systemic therapy). Fifty-eight of 108 patients received rituximab. Twenty-nine of 110 patients (26%) received intrathecal chemotherapy (ITC). Overall response rate was 80% (47% complete responses). With a median follow-up of 18·7months, median overall survival (OS) was 65·2months. In univariate analysis, HD-MTX (median OS 72·7 vs. 2·7months, P<0·001) and rituximab (median not reached versus 28·4months, P=0·005) impacted OS favourably. This significance was sustained regardless of immune status and in multivariate analysis. Whole brain radiotherapy (WBRT) resulted in a trend for improved OS as compared with systemic therapy alone (P=0·09), while ITC did not impact survival. Clinical practice has evolved to exclude WBRT and ITC while incorporating rituximab with clinical outcomes comparable in immuno-competent/compromised patients and similar to those achieved in recent clinical trials.

Primary central nervous system diffuse large B-cell lymphoma (DLBCL) can rarely mimic an acute peripheral neuropathy.

Primary central nervous system diffuse large B-cell lymphoma (DLBCL) can rarely mimic an acute peripheral neuropathy.

Fluorescein sodium-guided surgery in cerebral lymphoma

ObjectivesGrowth and progress of primary central nervous lymphoma (PCNSL) severely disrupt the blood brain barrier (BBB). Such disruptions can be intraoperatively visualized by injecting fluorescein sodium (FL) and applying a YELLOW 560nm surgical microscope filter. Here, we report a small cohort of patients with PCNSL that mimicked high grade gliomas (HGG) or cerebral metastases (CM), who had been operated on with the use of FL. Patients and methodsRetrospectively, seven patients with PCNSL were identified, who had been operated on by means of microsurgery after intravenous FL injection. The surgical reports were screened for statements on the grade of fluorescent staining in the tumor area. One representative case was chosen to show the staining under white light as well as under filtered light at different distances to the tumor area. ResultsAll patients had shown bright and homogenous fluorescent staining of the tumor (n=7. 100%). No adverse effects had been observed. ConclusionSimilar to patients with HGG or CM, patients with PCNSL may benefit from use of FL and the dedicated YELLOW 560nm filter in open surgery.

III. Current concepts in primary central nervous lymphoma.

III. Current concepts in primary central nervous lymphoma.

Constant pattern of relapse in primary central nervous lymphoma patients treated with high-dose methotrexate combinations. A Finnish retrospective study

Background. Primary central nervous system lymphoma (PCNSL) is a rare brain tumour with a dismal prognosis. Several phase II studies with high-dose methotrexate-based regimens have shown promising early results, but in all hospital-based data published so far, the disease outcome is poor.Material and methods. We performed a hospital-based retrospective analysis to evaluate the long-term results of the Nordic type of Bonn chemotherapy regimen in PCNSL patients. The study included 54 patients with newly diagnosed PCNSL who received chemotherapy with curative intent as their first-line treatment.Results. We found promising response rates, 76% of the patients achieving CR and 22% patients achieving PR, with corresponding two-year EFS 53% and OS 76%. However, with longer follow-up a constant pattern of relapses was observed with only one patient remaining in primary remission after 60 months.Discussion. The finding suggests that basic biological differences exist between PCNSL and systemic diffuse large B-cell lymphoma and there is a need for consolidation or maintenance therapy after achieving a remission in patients with PCNSL.