scholarly journals MYD88 L265P mutation in primary central nervous system lymphoma is associated with better survival: A single centre experience

2021 ◽  
Author(s):  
Olimpia E Curran ◽  
Michael T C Poon ◽  
Louise Gilroy ◽  
Antonia Torgersen ◽  
Colin Smith ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Survival Data ◽  
Cox Regression ◽  
Central Nervous System Lymphoma ◽  
Primary Response ◽  
Current Evidence ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Myd88 L265p Mutation

Abstract Background The Myeloid differentiation primary response gene (MYD88) mutation in primary central nervous system lymphomas (PCNSL) may be associated with unfavourable prognosis, however current evidence remains limited. We aimed to characterise PCNSLs by integration of clinicopathological, molecular, treatment and survival data. Methods We retrospectively identified and validated 57 consecutive patients with PCNSLs according to the 2017 WHO classification of lymphoid neoplasms over 13 years. Formalin-fixed paraffin-embedded tumour samples underwent polymerase chain reaction assay to detect MYD88 mutation. We used Cox regression for survival analysis including age, treatment and MYD88 as covariates. We searched the literature for studies reporting demographics, treatment, MYD88 and survival of PCNSL patients, and incorporated individual-patient data into our analyses. Results The median age was 66 years and 56% were women. All 57 patients had PCNSL of non-germinal centre cell subtype and the majority (81%) received either single or combined therapies. There were 46 deaths observed over the median follow-up of 10 months. MYD88 mutation status was available in 41 patients of which 36 (88%) were mutated. There was an association between MYD88 mutation and better survival in the multivariable model (hazard ratio [HR] 0.277; 95% confidence interval [CI] 0.09-0.83; p=0.023) but not in a univariable model. After incorporating additional 18 patients from the literature, this association was reproducible (HR 0.245, 95% CI 0.09-0.64, p=0.004). Conclusions Adjusting for confounders, MYD88-mutant PCNSL appears to show improved survival. While further validation is warranted, detection of MYD88 mutation will aid identification of patients who may benefit from novel targeted therapies.

scholarly journals MYD88 L265P mutation in primary central nervous system lymphoma is associated with better survival: A single centre experience.

2020 ◽  
Author(s):  
Olimpia E. Curran ◽  
Michael T. C. Poon ◽  
Louise Gilroy ◽  
Antonia Torgersen ◽  
Colin Smith ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Survival Data ◽  
Cox Regression ◽  
Central Nervous System Lymphoma ◽  
Primary Response ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Allele Specific ◽  
Myd88 L265p Mutation

Background: The Myeloid differentiation primary response gene (MYD88) mutation in primary central nervous system lymphomas (PCNSL) may be associated with unfavourable prognosis, however the evidence remains limited. We aimed to comprehensively characterise PCNSLs by integration of clinicopathological, molecular, treatment and survival data. Methods: We retrospectively identified and validated 57 consecutive patients with PCNSLs according to the 2017 WHO classification of lymphoid neoplasms over a 13-year period. Formalin-fixed paraffin-embedded tumour samples underwent real-time allele-specific polymerase chain reaction assay to detect MYD88 mutation. We used multivariable Cox regression for survival analysis including age, treatment, and MYD88 as covariates. We searched the literature for studies reporting demographics, treatment, MYD88 and survival of PCNSL patients, and incorporated individual-patient data into our analyses. Results: The median age was 66 years and 56% were women. All 57 patients had PCNSL of non-germinal centre cell subtype and the majority (81%) received either single or combined therapies. There were 46 deaths observed over the median follow-up of 10 months. MYD88 mutation status was available in 41 patients of which 36 (88%) were mutated. There was an association between MYD88 mutation and better survival in the multivariable model (hazard ratio [HR] 0.34; 95% confidence interval [CI] 0.12-0.95; p=0.039) but not in a univariable model. After incorporating additional 18 patients from the literature, this association was reproducible (HR 0.31, 95% CI 0.13-0.77, p=0.012). Conclusions: Adjusting for confounders, MYD88 mutation is associated with better survival. While further validation is warranted, identification of MYD88 mutation can identify patients who may benefit from novel targeted therapies.

scholarly journals Multi-modality Therapy Leads to Longer Survival in Primary Central Nervous System Lymphoma Patients

2002 ◽  
Vol 29 (2) ◽  
pp. 147-153 ◽  
Author(s):  
Dhruv Singhal ◽  
Timothy F. Witham ◽  
Anand Germanwala ◽  
John C. Flickinger ◽  
David Schiff ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Radiation Therapy ◽  
Median Survival ◽  
Survival Data ◽  
Cox Regression ◽  
Central Nervous System Lymphoma ◽  
Treatment Modalities ◽  
Cox Regression Analysis ◽  
Single Modality

Abstract:Background:Primary central nervous system lymphoma (PCL) is more frequently encountered by neurosurgeons given the increasing incidence among both nonimmunocompromised and immunocompromised patients. The most frequent surgery is stereotactic biopsy. Historically, radiation therapy has been the standard treatment modality for this disease and median survival was in the 15-month range. More recently, multi-modality therapy combining radiation therapy with chemotherapy (systemic, intrathecal, and/or intra-arterial) have resulted in longer survivals. We reviewed survival data for our series of patients treated for PCL over the last decade.Methods:Thirty-four patients with histologically confirmed PCL were treated at our center. Multivariate Cox regression analysis was performed to determine which factor(s) (age, gender, HIV status, Karnofsky Performance Scale, chemotherapy, single modality therapy, histology, location, number of lesions, surgical resection) had a significant impact on survival.Results:The overall median survival was 19 months. Patients receiving multi-modality therapy (n=17) (chemotherapy and radiation) had a median survival of 34 months compared to four months for patients receiving single modality therapy (n=17 including seven HIV positive patients). Multi-modality therapy was the only significant factor affecting survival in this multivariate analysis (p<0.0001).Conclusions:Chemotherapy plus radiotherapy significantly enhances survival over patients treated with single modality therapy alone. Quality of life issues should be addressed on a case by case basis as additional treatment modalities are initiated.

MYD88 (L265P) mutation is associated with an unfavourable outcome of primary central nervous system lymphoma

2016 ◽  
Vol 177 (3) ◽  
pp. 492-494 ◽  
Author(s):  
Keiichiro Hattori ◽  
Mamiko Sakata-Yanagimoto ◽  
Yasushi Okoshi ◽  
Yuki Goshima ◽  
Shintaro Yanagimoto ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Lymphoma ◽  
Unfavourable Outcome ◽  
Myd88 L265p Mutation ◽  
Myd88 L265p

Hyperglycemia is Associated with Poor Survival in Primary Central Nervous System Lymphoma Patients

2016 ◽  
Vol 103 (3) ◽  
pp. 272-278 ◽  
Author(s):  
Ayumi Debata ◽  
Koichi Yoshida ◽  
Kenta Ujifuku ◽  
Haruna Yasui ◽  
Kensaku Kamada ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Glucose Transporter ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Central Nervous System Lymphoma ◽  
Poor Performance Status ◽  
Poor Survival ◽  
Glut1 Expression

Purpose Primary central nervous system lymphoma (PCNSL) is a type of non-Hodgkin lymphoma (NHL), and it has been postulated that metabolic disorder may contribute to NHL etiology. We retrospectively investigated the prognostic significance of hyperglycemia in patients with PCNSL. We evaluated glucose transporter type 1 (GLUT1) expression by immunohistochemistry and analyzed its association with hyperglycemia and survival. Methods The medical and neuroradiologic records of 50 patients with PCNSL at our institution over the past 15 years were analyzed. Patients were divided into 3 groups based on mean fasting plasma glucose (FPG) levels: normal (<110 mg/dL), prediabetes (110-125 mg/dL), and diabetes (≥126 mg/dL). We defined prediabetes and diabetes groups as hyperglycemia. Results Forty-four percent of patients were in the prediabetes and diabetes groups. One-year survival rates were 73%, 66%, and 43% in normal, prediabetes, and diabetes groups, respectively. Univariate analysis revealed that high age, female sex, poor performance status, high mean FPG, and monotherapy were associated with shorter survival. Multivariable Cox regression analyses showed that high mean FPG and monotherapy were significant predictors of shorter survival (p = 0.036 and p = 0.000, respectively). The GLUT1 immunohistopathologic staining was performed in 34 cases, 20 of which (58%) showed variable levels of GLUT1 expression at the cell membrane and/or cytoplasm. Prediabetes and diabetes groups had a higher percentage of GLUT1-positive cells compared with the normal group (p = 0.015). Conclusions These findings indicate that hyperglycemia is associated with poor survival. The putative biological mechanism might involve differential GLUT1 expression between hyperglycemic and normal states in patients with PCNSL.

scholarly journals Clinicopathologic correlates of MYD88 L265P mutation and programmed cell death (PD-1) pathway in primary central nervous system lymphoma

2019 ◽  
Vol 60 (12) ◽  
pp. 2880-2889 ◽  
Author(s):  
Tarsheen K. Sethi ◽  
Alexandra E. Kovach ◽  
Natalie S. Grover ◽  
Li-Ching Huang ◽  
Laura A. Lee ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cell Death ◽  
Nervous System ◽  
Programmed Cell Death ◽  
Central Nervous System Lymphoma ◽  
Myd88 L265p Mutation ◽  
Myd88 L265p

scholarly journals ML-09 The REAL-WORLD of Elderly PCNSL Therapy in Tohoku and Niigata Area According to Retrospective Analysis: A Collaborative Investigation of the Tohoku Brain Tumor Study Group

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii17-ii17
Author(s):  
Kenichiro Asano ◽  
Yoji Yamashita ◽  
Takahiro Ono ◽  
Manabu Natsumeda ◽  
Takaaki Beppu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Central Nervous System ◽  
Nervous System ◽  
Real World ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Central Nervous System Lymphoma ◽  
Rank Test ◽  
Cox Regression Analysis ◽  
The Real

Abstract Introduction: Recently, the number of cases of primary central nervous system lymphoma in elderly patients(EL-PCNSL) has been increasing. However, the treatment may be insufficient because of poor performance status and pre- and posttreatment complications. Therefore, we analyzed the risk factors for EL-PCNSL in the Tohoku and Niigata areas of Japan and clarified the REAL-WORLD of EL-PCNSL therapy. Materials & Methods: We investigated surgical and nonsurgical cases of patients aged 71 years or older from eight facilities during the last 8 years. We analyzed patient information, radiotherapy/chemotherapy or not, PFS, OS, RRs, second-line therapy, pre- and posttreatment complications, outcomes, and risk factors for poor prognosis. The log-rank test was used for univariate analysis, and Cox regression analysis was used for a multivariate analysis of risk factors. Results: Of the 142 cases registered, five differed from PCNSL pathologically, three receiving BSC were excluded, 31 were treated without biopsy, three were treated based on CSF-findings, and 100 were treated with biopsy. Total 134 cases were followed. The median age was 76 years, pretreatment KPS was 50%, and 118 cases(88%) had 217 pretreatment complications. The treatment contents consisted of various combinations depending on the attending physician. The retrospective overall PFS was 16 months and OS was 24 months. In the early treatment phase, out of 16 cases with dropout, four tumor and four complication deaths occurred. There were 77 deaths(58%), 39 internal tumor deaths(51%), and 33 complication deaths(43%). Poor prognostic risk factors were &lt;60% posttreatment KPS, complications involving pretreatment cardiovascular and central nervous system disease, posttreatment pneumonia or severe infection, and absence of radiation or chemotherapy. Conclusions: Pretreatment KPS did not affect poor outcomes, but posttreatment KPS &lt;60% and pre- and posttreatment complications did. Radiotherapy and chemotherapy are reportedly effective, but additional research to clarify the details of these modalities is needed.

scholarly journals Histopathological, immunohistochemical, and molecular study of BHV-5 infection in the central nervous system of experimentally infected calves

2015 ◽  
Vol 35 (4) ◽  
pp. 337-343 ◽  
Author(s):  
Didier Q. Cagnini ◽  
Paulo H.J. Cunha ◽  
José C.F. Pantoja ◽  
Peres R. Badial ◽  
José Paes de Oliveira-Filho ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Study ◽  
Histological Changes ◽  
Enveloped Virus ◽  
Double Stranded Dna ◽  
Formalin Fixed Paraffin ◽  
The Family ◽  
Formalin Fixed Paraffin Embedded ◽  
The Central Nervous System

Bovine meningoencephalitis caused by BHV-5, a double-stranded DNA enveloped virus that belongs to the family Herpesviridae and subfamily Alphaherpesvirinae, is an important differential diagnosis of central nervous diseases. The aim of this study was to describe the histological changes in the central nervous system of calves experimentally infected with BHV-5 and compare these changes with the PCR and IHC results. Formalin-fixed paraffin-embedded central nervous system samples from calves previously inoculated with BHV-5 were microscopically evaluated and tested using IHC and PCR. All the animals presented with nonsuppurative meningoencephalitis. From 18 evaluated areas of each calf, 32.41% and 35.19% were positive by IHC and PCR, respectively. The telencephalon presented more accentuated lesions and positive areas in the PCR than other encephalic areas and was the best sampling area for diagnostic purposes. Positive areas in the IHC and PCR were more injured than IHC and PCR negative areas. The animal with neurological signs showed more PCR- and IHC-positive areas than the other animals.

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