scholarly journals IL10 and IL10:IL6 Ratio in CSF Is Useful at Diagnosis but Also in the Assessment of Therapeutic Response in Patients with Primary Central Nervous System Lymphoma (PCNSL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1619-1619
Author(s):  
Ludovic Nguyen ◽  
Myrto Costopoulos ◽  
Marie-Laure Tanguy ◽  
Caroline Houillier ◽  
Sylvain Choquet ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Response ◽  
Conflicts Of Interest ◽  
Neurological Diseases ◽  
Central Nervous System Lymphoma ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Mri Findings ◽  
Meningeal Dissemination

Abstract Reliable biomarkers of primary central nervous system lymphoma (PCNSL) are needed to support the magnetic resonance imaging (MRI) findings especially when the cerebral biopsy cannot be performed for pathologic examination. Biomarkers are also needed to optimize the assessment of therapeutic response, which so far relies only on gadolinium uptake on MRI, although large discrepancies of outcomes are observed in patients in complete remission assessed by MRI criteria. The aim of the present study was to evaluate the diagnostic and prognostic values of the cerebrospinal fluid (CSF) concentrations of interleukin (IL)-10 and IL-6 and of the IL-10:IL-6 ratio in patients with diffuse large B-cell type (DLBCL) PCNSL, at time of diagnosis and after treatment. IL-10 and IL-6 levels were measured in 120 patients with DLBCL-PCNSL and 36 control patients with other brain tumor or inflammatory neurologic diseases, using the quantitative Cytometric Bead Array® technique (human IL-10 CBA kit and human IL-6 CBA kit; BD BiosciencesTM) on a FACSCanto II cytometer (BD BiosciencesTM) according to the manufacturer’s recommendations. Serial measures of cytokines were performed in 57 patients. The IL-10:IL-6 ratio distinguishes PCNSL from other neurological diseases. Using a cutoff level of 1.0, the sensitivity and specificity are 94% and 80% respectively. Meningeal dissemination defined by cytological examination and/or flow cytometry analysis, is significantly associated with a higher IL-10 concentration (417 pg/ml vs 22 pg/ml; p = 0.0024) and a higher IL-10:IL-6 ratio (32 vs 6 ; p = 0.0011). Previous treatment with corticosteroids significantly reduces the IL-10:IL-6 ratio (ratio=7.6 with corticosteroids vs 21.9 without corticosteroids; p= 0.02). With a median follow-up of 25 months, the pre-therapeutic concentration of IL-10 has no prognostic value on overall and progression free survivals. After treatment, the median concentration of IL-10 is significantly decreased in patients entering complete (CR) or partial response (PR) compared to non-responder patients (median = 35.9 pg/ml and 235.5 pg/ml respectively, p = 0.01). We demonstrate for the first time that among patients in CR or PR (as per MRI criteria), a persistent detectable IL-10 level in CSF (> 2,5 pg/ml) has an impact on the progression free survival (1 year PFS: 21.2 % vs 53.6%; p= 0,004) (figure 1). Our study shows that IL-10:IL-6 ratio can be used as a diagnostic biomarker for PCNSL of DLBCL type . Analysis will be done to determine the cut off values of IL10 and IL-10:IL-6 ratio in a predictive model of meningeal dissemination. We also provide evidence that IL-10 concentration may be useful to complete the assessment of therapeutic response in PCNSL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Fotemustine-Based in Combination with Rituximab As First-Line Induction Chemotherapy for Newly Diagnosed Primary Central Nervous System Lymphoma:a Prospective Phaseii Trial

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 5-5
Author(s):  
Jingjing Wu ◽  
Fenghua Gao ◽  
Lei Zhang ◽  
Xin Li ◽  
Ling Li ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Median Overall Survival ◽  
Conflicts Of Interest ◽  
Objective Response ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival

Objective:To evaluate the safety, efficacy, and feasibility of rituximab, fotemustine, pemetrexed and dexamethasone (R-FPD) regimen for primary central nervous system lymphoma (PCNSL) patients. Methods:A prospective, single-center, single-arm, phase II clinical trial. Patients with newly diagnosed PCNSL diagnosed from the First Affiliated Hospital of Zhengzhou University from July 2018 to July 2020. R-FPD regimen consisted of rituximab (375 mg/m2 i.v. on D0), fotemustine (100mg/m2 i.v. on D1) ,pemetrexed (600mg/m2 i.v. on D1), and dexamethasone (40 mg i.v. on D1).(NCT04083066) Results: 30 patients were included. After two cycles, the objective response rate(ORR) was 96.4%(27/28,26 PR,1 CR,0 SD,0 PD,2 Censored),the disease control rate(DCR) was 96.4%(27/28); After four cycles, the ORR was 71.4% (15/21, 5PR,10 CR,1SD,5PD,7NR,2 Censored),DCR was 76.2%(16/21). The median progression-free survival (PFS) was 20.3 months (95%CI:5.2--35.4),The median overall survival (OS) was 22.0 months (95%CI:16.1-27.9).The grade III-IV toxicities were mainly leukopenia(17.9%), thrombocypenia(25%) and anemia(10.7%). Conclusion: Fotemustine-based in combination with Rituximab chemotherapy can improve outcomes with the progress free survival and the overall survival benefits, as well as with better tolerability for newly diagnosed PCNSL patients. Keywords: rituximab; primary central nervous system lymphoma; pemetrexed; fotemustine; efficacy Disclosures No relevant conflicts of interest to declare.

scholarly journals Treatment of secondary central nervous system involvement in systemic aggressive B cell lymphoma using R-MIADD chemotherapy: a single-center study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yuchen Wu ◽  
Xuefei Sun ◽  
Xueyan Bai ◽  
Jun Qian ◽  
Hong Zhu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Involvement ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Cns Involvement ◽  
The Central Nervous System ◽  
Secondary Central Nervous System

Abstract Background Secondary central nervous system lymphoma (SCNSL) is defined as lymphoma involvement within the central nervous system (CNS) that originated elsewhere, or a CNS relapse of systemic lymphoma. Prognosis of SCNSL is poor and the most appropriate treatment is still undetermined. Methods We conducted a retrospective study to assess the feasibility of an R-MIADD (rituximab, high-dose methotrexate, ifosfamide, cytarabine, liposomal formulation of doxorubicin, and dexamethasone) regimen for SCNSL patients. Results Nineteen patients with newly diagnosed CNS lesions were selected, with a median age of 58 (range 20 to 72) years. Out of 19 patients, 11 (57.9%) achieved complete remission (CR) and 2 (10.5%) achieved partial remission (PR); the overall response rate was 68.4%. The median progression-free survival after CNS involvement was 28.0 months (95% confidence interval 11.0–44.9), and the median overall survival after CNS involvement was 34.5 months. Treatment-related death occurred in one patient (5.3%). Conclusions These single-centered data underscore the feasibility of an R-MIADD regimen as the induction therapy of SCNSL, further investigation is warranted.

scholarly journals INNV-21. EFFECTIVE REGIMEN OF HIGH-DOSE METHOTREXATE PLUS TEMOZOLOMIDE FOR PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA: A SINGLE-CENTER RETROSPECTIVE STUDY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii120-ii121
Author(s):  
Jun-ping Zhang ◽  
Jing-jing Ge ◽  
Cheng Li ◽  
Shao-pei Qi ◽  
Feng-jun Xue ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Retrospective Study ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Better Than

Abstract OBJECTIVE To evaluate the efficacy and safety of high-dose methotrexate combined with temozolomide in the treatment of newly diagnosed primary central nervous system lymphoma. METHODS A retrospective study was performed to analyze the clinical data of patients with primary central nervous system lymphoma treated with high-dose methotrexate plus temozolomide in the Department of Neuro-oncology, Capital Medical University, Sanbo Brain Hospital from May 2010 to December 2018. RESULTS A total of 41 patients were identified. Median age was 57 years (range, 27–76 years). The maximal extent of surgery was total resection in 6, partial resection in 8, and biopsy in 27 patients. Of the 35 patients with evaluable lesions, 32 achieved complete response (CR) and 3 achieved partial response. CR rate was 91.4%. The median follow-up time was 36.5 months (range, 4.9–115.4 months). After treatment, the median progression-free survival (PFS) was 45.1 months. PFS rate at 1, 2, 5 years were 85.4%, 70.1% and 43.8%, respectively. The OS rate at 1, 2, 5 years were 92.7%, 82.4% and 66.5%, respectively. The median PFS of patients younger than 65 years was better than that of patients ≥65 years (98.8 months vs 27.9 months, p=0.039). There was no association between efficacy and extent of resection (p=0.836). After disease progression, 6 of the 21 patients received radiotherapy. There was no statistical difference in OS between the patients with or without radiotherapy (36.9 months vs 28.4 months). The main severe adverse events were myelosuppression (36.6%) and elevated transaminase (34.1%). Three patients were discontinued due to drug-related toxicities. CONCLUSIONS High-dose methotrexate combined with temozolomide is effective in the treatment of primary central nervous system lymphoma, with a low incidence of severe adverse reactions. This efficacy may be better than the historical control of methotrexate alone or methotrexate plus rituximab.

scholarly journals A Case of Primary T-Cell Central Nervous System Lymphoma: MR Imaging and MR Spectroscopy Assessment

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
G. Manenti ◽  
F. Di Giuliano ◽  
A. Bindi ◽  
V. Liberto ◽  
V. Funel ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mr Imaging ◽  
Mr Spectroscopy ◽  
Neuropsychiatric Symptoms ◽  
Central Nervous System Lymphoma ◽  
Mri Findings ◽  
Characteristic Appearance ◽  
The Right ◽  
Cns Lymphomas

Primary central nervous system lymphomas (PCNSLs) are mainly B-cells lymphomas. A risk factor for the development of PCNSL is immunodeficiency, which includes congenital disorders, iatrogenic immunosuppression, and HIV. The clinical course is rapidly fatal; these patients usually present signs of increased intracranial pressure, nausea, papilledema, vomiting, and neurological and neuropsychiatric symptoms. PCNSL may have a characteristic appearance on CT and MR imaging. DWI sequences and MR spectroscopy may help to differentiate CNS lymphomas from other brain lesions. In this paper, we report a case of a 23-year-old man with T-primary central nervous system lymphoma presenting with a mass in the right frontotemporal lobe. We describe clinical, CT, and MRI findings. Diagnosis was confirmed by stereotactic biopsy of the lesion.

Myeloablative versus non-myeloablative consolidative chemotherapy for newly diagnosed primary central nervous system lymphoma: Results of induction therapy in Alliance 51101.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8042-8042
Author(s):  
Tracy Batchelor ◽  
Sharmila Giri ◽  
Amy S. Ruppert ◽  
Nancy L. Bartlett ◽  
Eric D. Hsi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Induction Therapy ◽  
Significant Proportion ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
Whole Brain Radiation ◽  
Myeloablative Chemotherapy ◽  
Grade 3 ◽  
Dose Modifications

8042 Background: Optimal consolidative therapy for primary central nervous system lymphoma (PCNSL) is not defined. Avoidance of whole brain radiation may reduce risk of neurotoxicity. Non-radiation consolidative options include myeloablative chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) or non-myeloablative chemotherapy. Methods: This is a randomized phase 2, National Clinical Trials Network study of induction methotrexate (MTX) (8 g/m2days 1, 15), temozolomide (TMZ) (150-200 mg/m2 D7-11), and rituximab (RTX) (C1 D3, 10, 17, 24 and C2 D3, 10) in four 28-day cycles followed by one cycle of cytarabine (ARA-C) (2 g/m2 BID, D1, 2) (MTRA). Following induction, patients (pts) received consolidation with thiotepa (5 mg/kg BID, D -5, -4) plus carmustine (400 mg/m2, day -6) and ASCT (Arm A) or one cycle of ARA-C (2 g/m2 BID, D1-4) plus infusional etoposide (40 mg/kg over 96h) (Arm B). The primary endpoint was median progression-free survival (PFS), designed to compare consolidation regimens. This report describes the results of the 5 cycles of induction therapy. Results: 113 pts (median age 61 years, range 33-75) were randomized (Arm A: 57, Arm B: 56) across 27 centers. 108 eligible pts who received induction therapy were evaluated. 36 pts (33.3%) did not proceed to consolidation, mainly due to disease progression (17), pt withdrawal (8), or adverse events including death (6). Grade 3 or 4 febrile neutropenia occurred in 12 pts (11.1%) during induction. Dose modifications of MTX were required in 75% of pts and 63.3% of cycles, mainly due to renal adjustments. Dose delays of MTX were required in 52.8% of pts and 22.2% of cycles. Overall response rate (CR, CRu, PR) at the end of induction was 65.7% (95% CI, 56%, 74.6%). Conclusions: While MTRA is feasible and active a significant proportion of pts did not receive consolidation, supporting the need to develop more effective induction strategies. Clinical trial information: NCT01511562 .

scholarly journals High-dose methotrexate-based regimens with or without vincristine for the treatment of primary central nervous system lymphoma

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Tracelyn Freeman ◽  
Carlo S Legasto ◽  
M Alexandra Schickli ◽  
Eric M McLaughlin ◽  
Pierre Giglio ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Treatment Options ◽  
Group Versus ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
Adverse Event Rate ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

Abstract Background Primary central nervous system lymphoma (PCNSL) is a rare malignancy with few treatment options. One regimen used for induction is rituximab, high-dose methotrexate (HD-MTX), procarbazine, and vincristine (R-MPV). A common institutional practice is removing vincristine (VCR) from this regimen due to its poor CNS penetration and associated toxicities. The aim of this study was to evaluate how the omission of VCR from HD-MTX-based induction impacted clinical outcomes. Methods In a retrospective review, patients with PCNSL who received HD-MTX-based induction therapy between January 1, 2010 and May 31, 2018 were evaluated. Patients were stratified according to treatment into 2 groups, VCR-containing therapy versus no VCR. The primary endpoint was complete response (CR) rate following the completion of induction chemotherapy. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and adverse event rate. Results Twenty-nine patients were included: 16 patients in the VCR group and 13 in the non-VCR group. A CR was achieved in 7 (44%) and 5 (38%) (odds ratio [OR] = 1.24; 95% confidence interval [CI]: 0.28–5.53) patients, respectively. Median OS was 85.3 (95% CI: 20.2–85.3) versus 67.1 months (95% CI: 10.5–NR) and median PFS was 60.7 (95% CI: 9.4–NR) versus 23.7 months (95% CI: 4.7–NR) in the VCR group versus non-VCR group, respectively. The incidence of any grade peripheral neuropathy was higher in the VCR group. Conclusions CR rate, OS, and PFS were similar between groups regardless of VCR inclusion. Adverse events were higher in the VCR group. Larger studies are required to further evaluate the efficacy of VCR in PCNSL induction regimens.

scholarly journals Consolidation Treatment for Primary Central Nervous System Lymphoma: Which Modality for Whom?

2020 ◽  
pp. 1-14
Author(s):  
Osnat Bairey ◽  
Liat Shargian-Alon ◽  
Tali Siegal
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Real Life ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
The Elderly ◽  
High Dose ◽  
Brain Radiotherapy ◽  
Randomized Studies

Primary central nervous system lymphoma is a rare aggressive disease that largely affects elderly patients and is associated with poor prognosis. The optimal treatment approach is not yet defined and it consists of induction and consolidation phases. The combination of high-dose (HD) methotrexate-based chemotherapy followed by whole-brain radiotherapy (WBRT) prolongs the median progression-free survival (PFS) and overall survival 2- to 3-fold as compared to WBRT alone but is associated with significant delayed neurotoxicity. Alternative strategies are being investigated in order to improve disease outcomes and spare patients the neurocognitive side effects. These include reduced-dose WBRT, non-myeloablative HD chemotherapy, or HD chemotherapy with autologous stem cell transplantation (HDC/ASCT). There are no randomized studies that compare all these consolidation regimens head to head but recently HDC/ASCT has been evaluated versus WBRT in prospective randomized studies. These studies proved that WBRT and HDC/ASCT yield similar 2-year PFS with preserved or improved cognitive function after HDC/ASCT. Yet, the proportion of patients treated with such intensive consolidation is low, both in real life and in specialized centers, leaving many unsettled issues. This review is appraising current dilemmas related to the choice of consolidating therapeutic modalities, their associated acute and delayed toxicity, and future prospects for alternative approaches in the elderly.

scholarly journals ML-21 Tirabrutinib monotherapy for relapsed/refractory primary central nervous system lymphoma

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii18-ii18
Author(s):  
Keiichi Kobayashi ◽  
Nobuyoshi Sasaki ◽  
Kuniaki Saito ◽  
Yuki Yamagishi ◽  
Yoshie Matsumoto ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Cell Receptor ◽  
Median Number ◽  
Grade 3

Abstract Backgrounds & purpose: Prognosis of patients with primary central nervous system lymphoma (PCNSL) remains poor despite multiagent immunochemotherapy, and standard of care for relapsed or refractory (r/r) PCNSL has not been established. Recent progresses on molecular genetics and biology of PCNSL have led to development of novel molecular targeted therapies, especially targeting Bruton’s tyrosine kinase (BTK), located in the B-cell receptor and Toll-like receptor signaling pathways. Tirabrutinb, a second generation BTK inhibitor, was approved for r/rPCNSL in March 2020 in Japan. Methods: Patients with r/rPCNSL treated with tirabrutinib since December 2017 were eligible for this retrospective study. Tirabrutinib was given orally at doses 320–480 mg/day daily until progression or unacceptable toxicity. Results: A total of 7 patients were enrolled (6 relapses, 1 refractory), 4 males, median age was 73 (range, 54–80 years), and median KPS was 70 (70–90). Three patients had received prior whole brain radiotherapy. Median number of prior therapies was 1 (1–2). Best overall response rate was 57.1%; 42.9% with a complete response (CR/CRu), 14.3% with a partial response (PR), while there were 3 PDs (42.9%). Four patients experienced PD and estimated median progression-free survival (mPFS) was 29.6 months. All patients were alive at the data cutoff with median follow up of 21.4 months (2–30.4). Common adverse events (AEs) include grade 4 neutropenia (n=1), grade 3 lymphopenia (n=3), and hepatic dysfunction (n=1). Toxic rash was observed in four patients (grade 3 in one, grade 2 in three) leading to discontinuation of tirabrutinib in two patients, while others continued on TIR with dose reduction and steroid use. The median time to rash presentation was 28 days (12–28). Conclusions: Tirabrutinib was well tolerated with frequent minor to moderate skin rash emerging within one month and active for r/rPCNSL. Long-term efficacy and safety profile need to be determined with a larger cohort.

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