scholarly journals TMOD-33. THE ROLE OF BAFF-R SIGNALING IN THE GROWTH OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii235-ii235
Author(s):  
Matthias Mulazzani ◽  
Xíaolan Zhou ◽  
Wenlong Zhang ◽  
Andreas Straube ◽  
Louisa von Baumgarten
Keyword(s):  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Cns Lymphoma ◽  
Orthotopic Mouse Model ◽  
Term Survival ◽  
Treatment Target ◽  
Therapeutic Algorithms

Abstract Primary CNS lymphoma (PCNSL) is an aggressive brain tumor. Despite improvements in therapeutic algorithms, long-term survival remains rare, illustrating an urgent need for novel therapeutic targets. BAFF-R is a pro-survival receptor expressed on most malignant B cells, including PCNSL. To date, its role in PCNSL growth remains elusive. Here, we created a BAFF-R knockout lymphoma cell line (BAFF-R-KO) using CRISPR-Cas9. In serum-starved conditions, BAFF-R-KO cells exhibit decreased viability in vitro compared to BAFF-R+ cells. Combining an orthotopic mouse model of PCNSL with chronic cranial windows and intravital microscopy, we demonstrate a significant delay in tumor growth in mice inoculated with BAFF-R-KO cells compared to BAFF-R+ PCNSL. Additionally, median survival of BAFF-R-KO mice was significantly prolonged. Altogether, our results indicate a potential of BAFF-R as a novel treatment target for PCNSL.

Solitary primary CNS lymphoma: long term survival following total resection

1998 ◽  
Vol 15 (1) ◽  
pp. 61-65 ◽  
Author(s):  
Wiliam Sonstein ◽  
Kamran Tabaddor ◽  
Josefina F Llena
Keyword(s):  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
Total Resection ◽  
Term Survival ◽  
Long Term Survival

Long-term survival in primary CNS lymphoma.

1998 ◽  
Vol 16 (3) ◽  
pp. 859-863 ◽  
Author(s):  
L E Abrey ◽  
L M DeAngelis ◽  
J Yahalom
Keyword(s):  
Primary Cns Lymphoma ◽  
Disease Free Survival ◽  
Cns Lymphoma ◽  
High Dose ◽  
Significant Prognostic Factor ◽  
Term Survival ◽  
Long Term Survival ◽  
Late Treatment ◽  
Historical Controls

PURPOSE We have previously reported on 31 patients with primary CNS lymphoma (PCNSL) treated between 1986 and 1992 with methotrexate (MTX), cranial radiotherapy (RT), and high-dose cytarabine who remained free of disease longer than historical controls. PATIENTS AND METHODS We performed a follow-up analysis of our original cohort and now report their long-term survival and late treatment-related toxicity. RESULTS The median cause-specific survival was 42 months, with a five-year survival of 22.3% compared with 3% to 4% in historical controls treated with RT alone. Age less than 50 years at diagnosis was a significant prognostic factor for survival (P = .01). Median disease-free survival was 40.3 months; 15 patients relapsed, all but one in the CNS. Late treatment-related toxicity was observed in nearly one third of patients and those more than 60 years of age were at substantially higher risk (P < .0001). CONCLUSION Combined modality therapy for PCNSL has improved survival, but relapse is common and late neurologic toxicity is a significant complication. Although this approach is highly effective for younger patients, efficacious but less neurotoxic regimens need to be developed for older patients.

scholarly journals A phase I/II study of thiotepa-based immunochemotherapy in relapsed/refractory primary CNS lymphoma: the TIER trial

2021 ◽  
Author(s):  
Christopher P. Fox ◽  
Ayesha S Ali ◽  
Graham W McIlroy ◽  
Stefanie Catherine Thust ◽  
Nicolás Martinez-Calle ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Dose Finding ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Term Survival ◽  
Overall Response

Relapsed or refractory primary central nervous system lymphoma (rrPCNSL) confers a poor prognosis with no accepted standard of care. Very few prospective studies have been conducted in this patient group. This multicenter, phase I/II study investigated thiotepa in combination with ifosfamide, etoposide and rituximab (TIER), for the treatment of PCNSL relapsed or refractory to high-dose methotrexate-based chemotherapy. A 3+3 design investigated the recommended phase II dose of thiotepa for a single-stage phase II cohort, assessing activity of two cycles of TIER against rrPCNSL. The primary outcome was overall response rate. The dose-finding study demonstrated 50mg/m2 of thiotepa could be safely delivered within the TIER regimen. No dose-limiting toxicities were encountered in phase I, and TIER was well-tolerated by the 27 patients treated in phase II. The most common Grade 3/4 toxicities were neutropenia (56% of patients) and thrombocytopenia (39%). An overall response was confirmed in 14 (52%) patients, meeting the pre-specified threshold for clinically relevant activity. The median progression-free survival was 3 months (95% confidence interval 2 to 6 months) and overall survival 5 months (3 to 9 months). Exploratory analyses suggest a greater benefit for thiotepa-naïve patients. Six patients successfully completed autologous stem cell transplant consolidation (ASCT), with 4 experiencing durable remissions after median follow-up of 50 months. The TIER regimen can be safely delivered and is active against rrPCNSL, and followed by ASCT can provide durable remission and long-term survival. However, for the majority of patients, prognosis remains poor and novel treatment strategies are urgently needed.

Long-term survival in patients with primary CNS lymphoma: Results from the G-PCNSL-SG1 trial.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 2032-2032 ◽  
Author(s):  
Patrick Roth ◽  
Peter Martus ◽  
Eckhard Thiel ◽  
Agnieszka Korfel ◽  
Michael Weller ◽  
...  
Keyword(s):  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
Term Survival ◽  
Long Term Survival

Long-term AIDS-related PCNSL outcomes with HD-MTX and combined antiretroviral therapy

Neurology ◽  
2017 ◽  
Vol 89 (8) ◽  
pp. 796-804 ◽  
Author(s):  
Antoine Moulignier ◽  
Cédric Lamirel ◽  
Hervé Picard ◽  
Marie-Gisèle Lebrette ◽  
Corinne Amiel ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Group Performance ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Short Term ◽  
Term Survival ◽  
Long Term Survival ◽  
Combined Antiretroviral Therapy

Objective:To assess the characteristics and outcomes of patients with AIDS-related primary CNS lymphoma (AR-PCNSL) in the combined antiretroviral therapy (cART) era systematically treated with high-dose methotrexate (HD-MTX).Methods:We retrospectively analyzed (intention-to-treat analysis) 51 consecutive patients with AR-PCNSL (median age 39 years) who were diagnosed from 1996 to 2014 and treated with a median of 6 (range 1–15) infusions of HD-MTX (3 g/m2) combined with cART.Results:Median all-patients' and survivors' follow-up lasted 23 (range 0–186) and 76 (range 23–186) months, respectively. At PCNSL diagnosis, 83% of the patients were on cART, median plasma HIV load was 175,600 copies/mL, and median CD4+ T-cell count was 24/μL. Median Eastern Cooperative Oncology Group performance status was 2 (range 1–4). Median overall survival (OS) was 5.7 years, with 5- and 10-year rates of 48% and 41%. Median time to progression was not reached (69% at 10 months). PCNSL was the direct cause of 14 deaths, all observed within the 10 months after its diagnosis: 6 patients died before HD-MTX could be administered, 4 had refractory disease, and 4 relapsed. Multivariate analyses retained time interval between AIDS diagnosis and PCNSL diagnosis, age at AR-PCNSL diagnosis, and deep brain structure involvement as independent OS-predictive factors. To restore effective immune function, cART tailored to HIV genotypes was started and combined with HD-MTX; no interactions and no immune reconstitution inflammatory syndrome occurred. No patient died of acute treatment-related toxicity, and 21 of 51 (41%) patients experienced grade 3/4 toxicity.Conclusions:Combined short-term HD-MTX monochemotherapy and optimal cART simply and effectively treat AR-PCNSL, achieving long-term survival with few relapses.Classification of evidence:This study provides Class IV evidence that short-term HD-MTX monochemotherapy improves long-term survival of patients with AIDS with primary CNS lymphoma receiving cARTs.

Human thymic epithelial cells maintain long-term survival of clonogenic myeloid and erythroid progenitor cells in vitro

2000 ◽  
Vol 111 (1) ◽  
pp. 363-370 ◽  
Author(s):  
Katsuto Takenaka ◽  
Mine Harada ◽  
Tomoaki Fujisaki ◽  
Koji Nagafuji ◽  
Shinichi Mizuno ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Progenitor Cells ◽  
Thymic Epithelial Cells ◽  
Erythroid Progenitor ◽  
Term Survival ◽  
Long Term Survival ◽  
Erythroid Progenitor Cells

THE ROLE OF POLYETHYLENIMINE IN ENHANCING PERFORMANCE OF GLUTAMATE BIOSENSORS

2018 ◽  
Vol 8 (3) ◽  
pp. 36-41
Author(s):  
Diep Do Thi Hong ◽  
Duong Le Phuoc ◽  
Hoai Nguyen Thi ◽  
Serra Pier Andrea ◽  
Rocchitta Gaia
Keyword(s):  
First Generation ◽  
Good Reproducibility ◽  
Complex Matrices ◽  
Long Term Stability ◽  
In Vitro Characterization ◽  
Glutamate Oxidase

Background: The first biosensor was constructed more than fifty years ago. It was composed of the biorecognition element and transducer. The first-generation enzyme biosensors play important role in monitoring neurotransmitter and determine small quantities of substances in complex matrices of the samples Glutamate is important biochemicals involved in energetic metabolism and neurotransmission. Therefore, biosensors requires the development a new approach exhibiting high sensibility, good reproducibility and longterm stability. The first-generation enzyme biosensors play important role in monitoring neurotransmitter and determine small quantities of substances in complex matrices of the samples. The aims of this work: To find out which concentration of polyethylenimine (PEI) exhibiting the most high sensibility, good reproducibility and long-term stability. Methods: We designed and developed glutamate biosensor using different concentration of PEI ranging from 0% to 5% at Day 1 and Day 8. Results: After Glutamate biosensors in-vitro characterization, several PEI concentrations, ranging from 0.5% to 1% seem to be the best in terms of VMAX, the KM; while PEI content ranging from 0.5% to 1% resulted stable, PEI 1% displayed an excellent stability. Conclusions: In the result, PEI 1% perfomed high sensibility, good stability and blocking interference. Furthermore, we expect to develop and characterize an implantable biosensor capable of detecting glutamate, glucose in vivo. Key words: Glutamate biosensors, PEi (Polyethylenimine) enhances glutamate oxidase, glutamate oxidase biosensors

The Role of SBA Loans in Small Business Survival after Disaster Events

2021 ◽  
pp. 0739456X2110282
Author(s):  
Maria Watson
Keyword(s):  
Small Business ◽  
Small Businesses ◽  
Conditional Logistic Regression ◽  
Small Business Administration ◽  
Confounding Factors ◽  
Term Survival ◽  
Business Survival ◽  
Quasi Experimental

Local businesses are important for recovering communities, yet program analyses of the effectiveness of Federal disaster loans—particularly for businesses—are limited and contradictory. This study looks at the role U.S. Small Business Administration (SBA) Disaster Loans played in the long-term survival of small businesses in Galveston County, Texas after the 2008 Hurricane Ike. This research uses quasi-experimental design, matching methods, and conditional logistic regression to tease out the effect of the loan from potential confounding factors. The results show that businesses that received a disaster loan were significantly more likely to survive than their controls, and businesses that moved were also more likely to survive.

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