Management Of Primary Central Nervous System Lymphoma Research Articles

SPCR-11 DEMOGRAPHIC DISPARITIES AND PROGNOSTIC FACTORS IN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA: A SEER DATABASE ANALYSIS

Abstract Accounting for 3-4% of all central nervous system malignancies, primary CNS lymphoma (PCNSL) is a rare but aggressive form of extranodal non-Hodgkin lymphoma. Although recent studies have demonstrated an overall decline in the incidence, certain demographics are known to be more affected than others. We reviewed the queried Surveillance, Epidemiology, and End Results (SEER) database, 17 registries, Nov 2021 sub (2000-2019) for lymphoid neoplasm recode 2021 revision with primary site codes C69.1-69.4, C69.9-70.1, C70.9-72.5, C72.8-72.9. Patients of unknown race, ethnicity, and stage of the disease were excluded. We used Cox proportional hazard regression to assess the determinants of overall survival (OS) and cause-specific survival (CSS). Significance level was set to 0.05. Our search included 5910 patients. The mean age at diagnosis was 61.8 ± 15.8 years. Males accounted for 53.67% of the patients. Racial demographics showed a predominance of Whites (66.1%), followed by Hispanics (15.6%), Asian/pacific islanders (10.3%), Blacks (7.4%), and American Indians/Alaska Natives (0.45%). Most common histology was diffuse large B-cell lymphoma (67.74%). Most patients were diagnosed at stage I (76.5%), followed by stage IV (19.7%) of the disease. Older patients had worse OS (HR 1.03 [1.027;1.032]) and CSS (HR 1.021 [1.018;1.024]). Females had better OS 0.853 [0.803;0.9059]) and CSS (HR 0.8871 [0.8145;0.966]) compared to males. Indolent (follicular and marginal zone) lymphomas were associated with better OS (HR 0.3169 [0.2647-0.3759]) and CSS (HR 0.4265 [0.3494-0.5152]) compared to large B-cell lymphoma. Black patients had worse OS (1.608 [1.421-1.813]) and CSS (HR 1.385 [1.165-1.635]). While Hispanic ethnicity did not influence OS, it was associated with worse CSS (1.158 [1.025;1.304]). Stage at diagnosis did not have a statistically significant association with survival. These results suggest a need for additional research targeting high-risk demographics to develop tailored treatments, enhance care accessibility, and address possible inequities in the management of PCNSL.

Prognostic Factors of the Primary Central Nervous System Lymphoma: Clinical Experience from a Tertiary Care Center in the Middle East.

Aim Primary central nervous system lymphoma (PCNSL) is a rare extra nodal non-Hodgkin's lymphoma. The optimal treatment for PCNSL is still unclear. In this study, we present our experience with management of PCNSL in a tertiary care center in Iran. Methods In this retrospective study, 58 patients with tissue diagnosis of PCNSL were studied. All patients were treated with chemotherapy including intravenous high-dose methotrexate, rituximab and temozolomide and radiotherapy by the same oncologist. Statistical analysis was performed using SPSS. Results The mean overall survival (OS) in this study was 37.4 ± 13.6 months and the mean progression free survival (PFS) was 35.1 ± 9.8 months. The mean time to progression was 15.2 ± 8.79 months among 8 patients who experienced progression in this series. Finding of a positive CSF cytology was not linked with disease progression, while HIV infection and multifocal involvement at initial presentation were strongly linked to a lower PFS. The single most important factor affecting the OS was the histopathologic type of the PCNSL; two of the three patients who died from their disease in this series had non-B cell PCNSL, whereas only one patient with DLBCL died because of brainstem involvement. Conclusion The results of this study show a lower rate of HIV-infection in patients with PCNSL as compared to the series from the western countries. Non-B cell histopathology and HIV-infection were found to be associated with the dismal prognosis.

Neurotoxicity Outcomes Following Whole Brain Radiation Therapy in Patients with Primary CNS Lymphoma

<h3>Purpose/Objective(s)</h3> The role of radiation therapy (RT) in the management of primary CNS lymphoma (PCNSL) remains controversial. RT is associated with high response rates and may contribute to improved overall survival (OS). RT may also provide CNS disease control that facilitates successful salvage with stem cell transplantation in patients with chemotherapy-refractory disease. However, the long-term effects and neurologic sequelae from whole brain radiation therapy (WBRT) in younger patients with PCNSL has not been demonstrated. This retrospective study aimed to examine the long-term neurotoxicity outcomes of patients with PCNSL who received WBRT. Oncologic outcomes were also analyzed. <h3>Materials/Methods</h3> We retrospectively reviewed medical records from patients with PCNSL who underwent WBRT from 2011-2022. Patient and tumor-related variables included demographics, immunosuppression, imaging, and toxicities during and after treatment. Cognitive disturbance was evaluated and graded according to the <i>Common Terminology Criteria for Adverse Events (CTCAE)</i> v 2.0 and 3.0. Statistical analysis was conducted using <i>JMP Pro 15.2</i>. <h3>Results</h3> A total of 98 patients were identified with PCNSL from 2011-2022. We excluded patients with orbital primary, which resulted in a cohort of 61 patients. Eleven patients underwent WBRT; 5 between the age of 18-60 years and 6 greater than 60 years. The average age was 53.3 years [Range: 35-87 years]. Among the 5 patients in the younger patient cohort, 3 had a history of HIV; all were non-reactive at evaluation prior to RT. All 6 patients in the older patient cohort were HIV negative. All patients had undergone WBRT as a salvage or consolidation regimen, with dose regimens varying from 27-45 Gy and dose per fraction varying from 1.8-3 Gy. Two of the 11 patients received a boost. Ten out of the 11 patients underwent RT as a salvage regimen, and 1 patient underwent consolidative WBRT. The median progression-free survival (PFS) and OS among patients who had undergone WBRT was 9.5 months and 8 years, respectively. For all ages, cognitive disturbance was grade 0, 1, 2, and 3 in 18.2%, 45.5%, 18.2%, and 9.1%, respectively, at 6 months. At 24 months, cognitive disturbance was detected as grade 0 in 27.3% patients and grade 1 in 27.3%. Among the younger cohort, at 6 months, cognitive disturbance grade 0, 1, 2, and 3 was noted in 0%, 60%, 20%, and 20% respectively. At 24 months, cognitive disturbance was grade 1 in 60%. In the elder cohort, at 6 months, cognitive disturbance was grade 0, 1, and 2 in 33%, 33%, and 17%, respectively. At 24 months, 50% of patients had grade 0 cognitive disturbance. <h3>Conclusion</h3> WBRT demonstrated acceptable levels of cognitive disturbance in patients with PCNSL while maintaining oncologic outcomes. PFS data may be limited by implementation of WBRT, as all patients underwent WBRT as a salvage or consolidative treatment. Even so, WBRT should be considered as an upfront management strategy for younger patients with PCNSL.

An Update on Neurosurgical Management of Primary CNS Lymphoma in Immunocompetent Patients.

Primary central nervous system lymphomas (PCNSL) are rare CNS tumors that harbor a conspicuously longer diagnostic delay compared to other malignant brain tumors. The gold standard for diagnosis is stereotactic biopsy to acquire tissue for histopathological analysis and therefore neurosurgery plays a central role when reducing the diagnostic period is mandated. However, histopathological diagnosis could be complicated if the patient was preoperatively exposed to corticosteroids. Besides the histopathological result, diagnosis of a PCNSL also requires full diagnostic workup to exclude cerebral metastatic disease of a systemic lymphoma. Most reviews of PCNSL discuss recent advancements in systemic treatment options from an (neuro-)oncologic viewpoint, whereas our intention was to discuss the optimization of the diagnostic period and therefore describe current standards of imaging, summarizing the diagnostic workup, discussing the surgical workup and future diagnostic prospects as well as the influence of preoperative corticosteroid therapy to reduce the diagnostic delay of PCNSL patients.

Primary Central Nervous System Lymphoma: How Do Neurologists Deal with its Management?

What are desirable roles of general neurologists in the diagnosis and treatment of primary central nervous system lymphoma (PCNSL)? These issues were discussed 7 years back in the special feature articles of this journal. In the last 7 years genome analyses using liquid biopsy specimens have progressed and are becoming popular in the management of PCNSL, thereby enabling neurosurgeons to avoid invasive brain biopsy. The role of general neurologists in this country is not to be directly engaged in the PCNSL management, but to make an early diagnosis of PCNSL and to refer patients with PCNSL to specialists for a combination of chemotherapy and irradiation therapy.

Nanomedicine Applications in Treatment of Primary Central Nervous System Lymphoma: Current State of the Art.

Primary central nervous system lymphoma (PCNSL) is a rare but highly aggressive subtype of extra nodal non-Hodgkin lymphoma (NHL), which is confined in the central nervous system (CNS). Despite recent advancements in treatment options, the overall prognosis of PCNSL remains poor. Among many unfavorable factors affecting efficacy, inadequate drug delivery into the CNS is still the thorniest challenge. Blood-brain barrier (BBB) constitutes a significant impediment, restricting entry of most therapeutics to the brain. Nanotechnology has offered great promise for brain diseases, as various nano-based drug delivery systems (NDDSs) have been developed for delivery of theranostic agents in to the CNS. These drug delivery systems possess significant advantages, including good feasibility, reliable safety profile, excellent BBB penetration and potent antitumor effects. As for treatment of PCNSL, numerous well-developed BBB-crossing nano-based strategies can be applied with proper modifications and improvements. Some exquisitely designed NDDSs specific for PCNSL have shown great potential. In this review, we provide a summary on current status of diagnosis and treatment of PCNSL, followed by an overview of BBB-crossing strategies applied in management of PCNSL, both novel and wellestablished. Finally, challenges and future perspectives in this field are also discussed.

Diagnosis, prognosis and treatment of primary central nervous system lymphoma in the elderly population (Review).

Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal non-Hodgkin lymphoma that is unique and different from systemic diffuse large B-cell lymphomas. The median age at diagnosis of PCNSL is 65 years and its incidence is rising rapidly in the elderly population. A total of ≥20% of all patients with PCNSL are ≥80 years old. Notably, age has been identified as an independent poor prognostic factor for PCNSL. Elderly patients have an inferior prognosis to that of younger patients and are more severely affected by iatrogenic toxicity; therefore, elderly patients represent a unique and vulnerable treatment subgroup. The present review summarized the available literature to provide an improved understanding of the epidemiology, clinical characteristics, diagnosis, prognosis and management of PCNSL in the elderly population. Notably, the incidence of PCNSL in immunocompetent elderly patients, predominantly in men, is increasing. For the diagnosis of CNSL, imaging-guided stereotactic biopsy is considered the gold standard. When stereotactic biopsy is not possible or conclusive, certain biomarkers have been described that can help establish a diagnosis. PCNSL has a very poor prognosis in the elderly, even though several prognostic scoring systems exist and several prognostic markers have been reported in patients with PCNSL. Furthermore, the treatment of elderly patients remains challenging; it is unlikely that a novel agent could be used as a curative monotherapy; however, a combination of novel agents with polychemotherapy or its combination with other novel drugs may have therapeutic potential.

Survival and Patient-Reported Outcomes of Older Adults with Primary Central Nervous System Lymphoma on Low-Dose Lenalidomide

Introduction: Management of primary CNS lymphoma (PCNSL) in patients age &amp;gt;70 represents a significant challenge. In most clinical series, median OS for PCNSL patients age &amp;gt;70 is &amp;lt;1 year (Mendez et al., Neuro-Oncology 2018). Since late 2011, our group has used low-dose lenalidomide as maintenance therapy in older patients with newly-diagnosed PCNSL who had &amp;gt;partial response (PR) to induction chemotherapy or salvage chemotherapy for relapsed disease. A preliminary report by our group supported the feasibility and efficacy of low-dose lenalidomide maintenance for 13 older patients with PCNSL, in lieu of consolidation with radiation or high-intensity chemotherapy (Vu et. al., BJH 2019).Here, we present the outcomes of 22 consecutive older patients with PCNSL (inclusive of updated outcomes on the original 13 patients) treated with low-dose lenalidomide after achieving &amp;gt;PR following induction chemotherapy. In addition, we provide a first report on the impact of maintenance low-dose lenalidomide on quality of life (QOL), overall functioning, and symptom burden. Methods: We performed a retrospective analysis of consecutive patients age &amp;gt;65 years with PCNSL, who achieved &amp;gt;PR to induction methotrexate/rituximab+temozolomide (MTR) chemotherapy and were subsequently treated with low-dose lenalidomide maintenance (5-10 mg/dose) in PR1/CR1. We determined their clinical characteristics, progression-free survival (PFS) and overall survival (OS) by Kaplan-Meier. In addition, we obtained correlative data on QOL and symptom burden on a representative sample of older PCNSL patients who were treated with low-dose IMiDs over the course of &amp;gt; 2 months, via the European Organization of Research and Treatment of Cancer (EORTC) QOL questionnaire (QLQ)-C30. Our study was approved by the University of California San Francisco Institutional Review Board with patient informed consent. Results: The median age at diagnosis of the 22 consecutive older newly-diagnosed PCNSL patients was 77 (range 64 - 86). Median Karnofsky Performance Status was 70. Twenty patients received induction MTR (2 received M-R) without consolidative dose-intensive chemotherapy, autologous stem cell transplant, or whole brain irradiation. The median methotrexate dose was 2.5 gm/m2 (range 0.5 - 8). With median follow-up of 47 months, median time on low-dose lenalidomide maintenance was 14 months. Median PFS was 84 months, and median OS has not been reached. (Figure 1). At progression, patients received methotrexate followed by lenalidomide or pomalidomide. Thus far, there have been 3 deaths: one due to PCNSL, one by myocardial infarction, 4 years after discontinuation of lenalidomide, and one without definitive cause. To assess the tolerability of low-dose lenalidomide (and/or pomalidomide) in this population, we determined patient-reported outcomes with respect to quality of life, as measured by the EORTC QLQ-C30. We summarize our findings in Figure 2 on 8 consecutive PCNSL patients age &amp;gt;70 that received maintenance IMiD therapy for at least 2 months. Seven of the 8 patients were treated with maintenance low-dose lenalidomide for a median of 11 months, and one patient was on maintenance pomalidomide (1-2 mg/day) for a total of 76 months. Overall low-dose IMiDs were well-tolerated: mild-to-moderate fatigue and insomnia were the two most commonly reported symptoms. Conclusions: Our experience suggests that low-dose lenalidomide as maintenance therapy after induction chemotherapy in older patients with PCNSL may result in improved PFS and OS. Importantly, our data suggest that QOL and overall functioning as measured by the EORTC QLQ-C30 was comparable, if not better, than QOL as assessed for patients receiving high dose methotrexate-based therapy, autologous stem cell transplant, whole brain radiation therapy, and/or blood brain barrier disruption (Doolittle et. al., Neurology 2013). In conclusion, based on this preliminary assessment, maintenance low-dose lenalidomide (and pomalidomide) appear to be well-tolerated in older PCNSL, with patients reporting good quality of life, low symptom burden, and overall good level of functioning. Survival outcomes remain encouraging. A phase I trial in newly-diagnosed, non-transplant eligible PCNSL that evaluates combination nivolumab with lenalidomide, both as a component of induction therapy and as low-dose lenalidomide maintenance, is in development via Alliance (A051901). Disclosures Rubenstein: Kymera: Research Funding. OffLabel Disclosure: Low-Dose Lenalidomide as Maintenance in Older Patients with Primary CNS Lymphoma

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

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.

Recent advances in the management of primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal lymphoma primarily involving the brain, spinal cord, or leptomeninges. PCNSL is associated with a relatively poor prognosis compared to other extranodal diffuse large B-cell lymphomas. However, methotrexate-based induction chemotherapy followed by consolidative chemotherapy or high-dose therapy and autologous stem cell transplantation has improved the survival outcome, together with reduced neurotoxicity. Recent studies found that aberrant activation of the B-cell receptor-signaling pathway and activation of the NF-κB are frequent genetic alterations and could be good targets for the treatment of PCNSL. Herein, we have reviewed the current status and recent advances in the biology and management of PCNSL.

Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma.

Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma.

Updates on Primary Central Nervous System Lymphoma.

Primary central nervous system lymphoma (PCNSL) is an aggressive malignancy confined to the brain, spinal cord, leptomeninges, and eyes. Due to its rarity, there is a paucity of randomized trials and a varied approach to its management in the oncologic community. This review summarizes recent literature guiding current clinical practice. The presentation, work up, and management of PCNSL are discussed. Induction therapy incorporates a methotrexate-based chemotherapy regimen and is generally followed by a consolidation regimen including high dose chemotherapy (with or without autologous stem cell rescue). Whole brain radiation therapy (WBRT) is a potential additional consolidation strategy. Management of relapsed and refractory disease poses a special challenge due to poor outcomes. Immunotherapy and targeted treatments are promising novel strategies for recurrent/refractory patients. Currently, there is little consensus in the management of PCNSL. Treatment recommendations should be tailored to the individual patient, with consideration for risk of neurotoxicity. New, exciting strategies are in development and when feasible, enrollment in a clinical trial should be considered.

Primary Central Nervous System Lymphoma.

Primary central nervous system (CNS) lymphoma is a rare and aggressive extranodal non-Hodgkin lymphoma confined to the brain, eyes, spinal cord, or leptomeninges without systemic involvement. This article provides an overview of the clinical features, diagnosis, and management of primary CNS lymphoma in patients who are immunocompetent, focusing on recent advances in treatment. Primary CNS lymphoma is sensitive to radiation therapy; however, whole-brain radiation therapy inadequately controls the disease when used alone and causes delayed neurotoxicity with significant neurocognitive impairment, especially in patients who are elderly. A number of clinical trials have demonstrated durable disease control and less neurotoxicity with methotrexate-based induction chemotherapy with or without autologous stem cell transplantation or reduced-dose whole-brain radiation therapy. Prompt diagnosis and initiation of treatment are vital to improving clinical outcomes in patients with primary CNS lymphoma. The optimal treatment has yet to be defined, but high-dose methotrexate-based induction chemotherapy is considered standard for newly diagnosed primary CNS lymphoma. Ongoing randomized trials will attempt to address the roles of rituximab and consolidative treatment using autologous stem cell transplantation or reduced-dose whole-brain radiation therapy. Despite high tumor response rates to initial treatment, many patients will relapse. The choice of salvage treatment will depend on age, previous treatment and response, performance status, and comorbidities at the time of relapse.

Outcomes of primary central nervous system lymphoma in the era of immunotherapy: Cleveland Clinic experience.

e13516 Background: Primary central nervous system lymphoma (PCNSL), a form of extranodal non-Hodgkin lymphoma represents 3% of primary CNS tumors. It is aggressive but typically confined to the CNS. Despite improvements in the management of PCNSL, more than 50% of patients eventually relapse. There are limited data on PCNSL from larger cohort studies. Methods: With IRB approval, the Cleveland Clinic Neuro-Oncology Center database was used to identify patients treated between 2006-2015 for PCNSL. Overall survival (OS) from the diagnosis of PCNSL and progression free survival (PFS) were the primary and secondary end points respectively. Cox proportional hazards models were used for data analysis. Results: 86 PCNSL patients were included in the analysis. Only 5% (4/76) were HIV positive. The median age of diagnosis was 63 (range 15 - 86) and 50% were males. 88% of patients presented only with brain lesion, 8% only in eye and 4% had both brain and eye involvement. 15% of patients (12/81) had positive CSF findings. Treatment included: chemotherapy (CT) alone (39% of patients); chemoimmunotherapy (CIT) (32%); CIT with radiotherapy (RT) (13%); RT alone (11%); CT with RT (4%); and immunotherapy (IT) alone (1%). Among 23 patients (31%) who received RT upfront, 74% had WBRT (n = 17). The most common upfront therapy was high dose methotrexate (HD MTX) (44%), followed by HD MTX with rituximab (23%), RTOG 0227 (12%), RTOG 1114 (11%) and rest 14% included rituximab or temozolomide or other cytotoxic chemotherapy alone or in combinations. The most common relapse site was brain (72%), followed by eyes (12%) and spine (8%). The median follow-up was 26 months. At last follow up, 41% had died and 93% of which were PCNSL-related. The median PFS and OS were 17.7 months and 84 months, respectively. There was a trend towards superior PFS in upfront IT vs. no IT (20 vs. 14 months, p 0.08). Better performance status (KPS &gt; 80 vs. &lt; 80, HR 0.42 (p = 0.033)) and PFS ≥ 24 months compared to ≤ 24 months (p = 0.0012) were associated with improved OS. Conclusions: We report a large single institution cohort of PCNSL patients treated in the era of immunotherapy. In our cohort, better KPS (≥80) and PFS ≥ 24 months had improved OS. Upfront IT showed a trend towards improved PFS.

Autologous Stem Cell Transplantation (ASCT) As Upfront Treatment in Primary Central Nervous System Lymphoma (PCNSL): A Systematic Review and Comparative Analysis in Clinical Trials Setting

Purpose PCNSL standard treatment encompass 2 phases: induction and consolidation. Induction consists of high-dose methotrexate-based polychemotherapy for most patients and consolidation is still to be defined. ASCT is an effective treatment and despite the advancements in this technique for other disease sites, its role in PCNSL remains unclear. This systematic review aims to evaluate toxicity and outcomes of ASCT as upfront treatment in PNCSL.Material and Methods In accordance to PRISMA guidelines, a systematic review of the literature was conducted on studies reporting ASCT in PCNSL. EMBASE, MEDLINE and Cochrane databases were systematically searched for relevant studies until May 2016. All clinical trials (CT) evaluating the role of ASCT as up front treatment for PCNSL (excluding recurrence or salvage) were included. Studies were classified into 2 groups for statistical analysis: (1) Regimens containing thiotepa (either on induction or intensification regimen or conditioning regimen; (2) Regimens without thiotepa. Dichotomous outcomes were summarized as risk ratios (RRs). The size effect of the intervention for time-to-event outcomes was calculated by the pooled hazard ratio (HR), followed by the confidence interval (CI) of 95%. For determining derivative of expected events, the Z-Score for two-tailed p-value was calculated based on relative risk of each study.Results From 1803 references, 7 articles (6 phase 2; 1 pilot trial) from 2006 to 2016 were selected, comprising a total of 181 patients. For up front treatment of PCNSL with ASCT regimens containing thiotepa plus or minus WBRT: total of 128 patients were identified in 5 studies. Patient's median age was 54,5 (range, 54 to 57), KPS ranged from 70 to 90, WBRT was allowed in 3 studies and a median of 81% of the patients completes the ASCT protocol. Median complete response rate (CRR) was 69% (range, 54 to 81%), 2-years progression free survival (2PFS) 69% (range, 54 to 81%) and 2-years overall survival (2OS) 84% ranging from 83 to 91% in a median follow-up time of 15 to 63 months. Median neurotoxicity rates (NR) and treatment related mortality (TRM) were 3% (0 to 33%) and 3% (0 to 13%), respectively. (2) Up front ASCT regimens without thiotepa plus or minus WBRT: total of 53 patients were identified in 2 studies. Patient's median age was 52,5 (range, 52 to 53), KPS ranged from 70 to 80, WBRT was allowed in 1 study and a median of 59% of the patients completes the ASCT protocol. Median CRR was 31% (range, 18 to 44%), 2PFS 44% (range, 25 to 62%), 2OS of 65% ranging from 60 to 70% in a median follow-up time of 28 to 34 months. Median NR and TRM were 4% (0 to 8%) and 4%, respectively. Regimens containing thiotepa were associated with better 2OS (RR 0.46; IC95 0.27 to 0.80; P=0.006; Z=2.76) and increased 2PFS (RR 0.52; IC95 0.37 to 0.74; P=0.0002; Z=3.69). The addition of WBRT wasn't associated with better 2OS (RR 0.94; IC95 0.53 to 1.67; P=0.082; Z=0.22)Conclusions Up front ASCT in the management of PCNSL is associated with high CRR and excellent 2OS and 2PFS when thiotepa is added to the regimen. Close to 200 patients treated in CT settings with up front ASCT for PCNSL were found in the literature and at least 4 different treatment scenarios were described. An important rate (>10%) of TRM was seen in two studies however ASCT was seem to be safe in most of the publications. DisclosuresNo relevant conflicts of interest to declare.

The Role of Subretinal Aspiration in the Diagnosis and Management of Primary CNS Lymphoma

Primary intraocular lymphoma is a rare type of primary CNS lymphoma that can present with just eye symptoms. The case is presented of a patient who had recurrent bilateral uveitis that was treated with topical steroids. Magnetic Resonance imaging done of the head because of neurological symptoms which developed one year later revealed a diffuse infiltrative process in the brain. He was treated with methyprednisolone for a presumptive diagnosis of sarcoidosis. The diagnosis of intra- ocular lymphoma was made from a subretinal aspiration showing a population of monoclonal Blymphoplasmacytoid lymphocytes. Primary Intra-ocular lymphoma is a condition which is difficult to diagnose as it can mimic other conditions. There is usually a delay in diagnosis as empirical steroid therapy is commonly instituted which interferes with the dynamics of the disease process.

Treatment of primary CNS lymphoma (PCNSL) following successful treatment of systemic non-Hodgkin’s lymphoma (NHL): a case series

Management of PCNSL occurring after successful treatment of systemic non-Hodgkin's lymphoma (NHL) is poorly defined. Illustrate a treatment approach for PCNSL following prior treatment of a systemic NHL. A retrospective case series of 6 patients (mean age 60 years; range 46-65) diagnosed with a diffuse large B cell lymphoma of the CNS following prior successful treatment of a systemic NHL (low-grade in 2; high-grade in 4). Mean interval to diagnosis of PCNSL after diagnosis of systemic NHL was 12 months (range 7-18). In 4/6 patients in whom genetic analysis could be performed, the PCNSL and NHL differed. Treatment utilized high-dose methotrexate and rituximab (immunochemotherapy) followed in patients with a radiographic complete response by autologous peripheral stem cell transplant (ASCT) with total body irradiation (TBI) and multi-agent conditioning chemotherapy (BEAM: carmustine, etoposide, cytarabine, melphalan). 5/6 patients had a radiographic complete response to immunochemotherapy and were treated with ASCT. 4/5 patients were free of disease following ASCT with a mean follow-up of 3 years (range 0.5-4 years). There were no toxic deaths and all patients transplanted successfully engrafted within 28 days (mean 18). Using a treatment paradigm similar to that utilized for recurrent systemic NHL (induction chemotherapy followed by ASCT) for PCNSL occurring metachronously after successful treatment of systemic NHL appears safe and effective.

Pathogenesis and management of primary CNS lymphoma

Primary CNS lymphoma (PCNSL), a rare variant of extranodal non-Hodgkin’s lymphoma, may cause various neurological symptoms and signs. The best therapeutic strategy is still a matter of debate. High-dose methotrexate (HD-MTX) is the most active compound and should be used as the backbone for any chemotherapy applied. Several other chemotherapeutic drugs have been assessed in combination with HD-MTX, but no standard has yet been defined. Whole-brain radiotherapy is active against PCNSL, but typically does not confer long-lasting remission and is associated with significant neurotoxicity in many patients. The recently published G-PCNSL-SG1 trial has shown that consolidating whole-brain radiotherapy after HD-MTX-based chemotherapy does not prolong overall survival and may therefore be deferred. Combined systemic and intraventricular polychemotherapy, or high-dose chemotherapy followed by stem cell transplantation may offer cures to younger patients. Improving treatment regimens without adding significant (neuro-)toxicity should be the focus of ongoing and future studies.

Primary central nervous system lymphoma

This review will summarize recent advances in the understanding and treatment of primary central nervous system lymphoma (PCNSL). The molecular and genetic characteristics that distinguish PCNSL are beginning to be elucidated. New tools such as flow cytometry and PET are improving the diagnosis and management of PCNSL. Although the current standard of care is high-dose methotrexate-based chemotherapy alone or in combination with whole brain radiotherapy, multiple questions remain regarding the optimal treatment of PCNSL, in general, and unusual variants of PCNSL. Although recent advances have improved our understanding of PCNSL, the need for additional collaborative research is critical.

Treatment options for central nervous system lymphomas in immunocompetent patients

Despite recent advances in diagnosis and treatment, the prognosis of primary CNS lymphoma (PCNSL) and CNS relapse of systemic non-Hodgkin lymphoma remains poor, and the optimal treatment is yet to be defined. This review presents an overview of the current status of CNS lymphoma treatment. Treatment options include radiotherapy alone, intravenous conventional chemotherapy alone, intrathecal chemotherapy, high-dose chemotherapy with autologous stem cell transplantation, combined modality treatment (i.e., chemotherapy plus radiotherapy), immunotherapy, radioimmunotherapy and ocular radiation and/or chemotherapy for intraocular lymphoma. High-dose methotrexate remains an essential part of most first-line treatments for PCNSL and CNS relapse of systemic non-Hodgkin lymphoma. Treatment standardization is hampered by the rarity of the disease and the difficulty of conducting trials with a higher number of patients. However, a recently closed Phase III/IV trial will most likely define the role of adjuvant whole-brain radiation treatment in PCNSL. Future directions in the management of PCNSL and CNS relapse of systemic lymphoma may include treatment stratification according to patient age and clinical and biological prognostic factors.