Patient age at diagnosis is associated with the molecular characteristics of diffuse large B-cell lymphoma.
MMML - Molecular mechanisms in malignant lymphoma

Abstract (Expand)

Diffuse large B-cell lymphoma is the most frequent type of B-cell lymphoma in adult patients but also occurs in children. Patients are currently assigned to therapy regimens based on arbitrarily chosen … age limits only (eg, 18 or 60 years) and not biologically justified limits. A total of 364 diffuse large B-cell lymphomas and related mature aggressive B-cell lymphomas other than Burkitt lymphoma from all age groups were analyzed by comprehensive molecular profiling. The probability of several biologic features previously reported to be associated with poor prognosis in diffuse large B-cell lymphoma, such as ABC subtype, BCL2 expression, or cytogenetic complexity, increases with age at diagnosis. Similarly, various genetic features, such as IRF4 translocations, gains in 1q21, 18q21, 7p22, and 7q21, as well as changes in 3q27, including gains and translocations affecting the BCL6 locus, are significantly associated with patient age, but no cut-offs between age groups could be defined. If age was incorporated in multivariate analyses, genetic complexity lost its prognostic significance, whereas the prognostic impact of ABC subtype and age were additive. Our data indicate that aging is a major determinant of lymphoma biology. They challenge current concepts regarding both prognostic biomarkers and treatment stratification based on strict age cut-offs.

Authors: W. Klapper, M. Kreuz, C. W. Kohler, B. Burkhardt, M. Szczepanowski, I. Salaverria, M. Hummel, M. Loeffler, S. Pellissery, W. Woessmann, C. Schwanen, L. Trumper, S. Wessendorf, R. Spang, D. Hasenclever, R. Siebert

Date Published: 23rd Feb 2012

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

Neural processing of negative emotional stimuli and the influence of age, sex and task-related characteristics.
LIFE Adult

Abstract (Expand)

Negative emotional stimuli are particularly salient events that receive privileged access to neurocognitive resources. At the neural level, the processing of negative stimuli relies on a set of sensory, … limbic, and prefrontal areas. However, controversies exist on how demographic and task-related characteristics modulate this brain pattern. Here, we used activation likelihood estimation (ALE) meta-analysis and replicator dynamics to investigate the processing of negative visual stimuli in healthy adults. Our findings endorse the central role of the amygdala. This result might reflect how this structure modulates perceptual and attentional mechanisms in response to emotional stimuli. Additionally, we characterize how the neural processing of negative visual stimuli is influenced by the demographic factors of age and sex as well as by task-related characteristics like stimulus type, emotion category, and task instruction, with the amygdala showing comparable engagement across different sexes, stimulus types, and task instructions. Our findings practically inform experimentation in the affective neurosciences but also suggest brain circuits for neurobiological investigations of affective symptomatology.

Authors: I. Garcia-Garcia, J. Kube, M. Gaebler, A. Horstmann, A. Villringer, J. Neumann

Date Published: 12th May 2016

Publication Type: Not specified

Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas.
GGN - German Glioma Network

Abstract (Expand)

WHO grading of human brain tumors extends beyond a strictly histological grading system by providing a basis predictive for the clinical behavior of the respective neoplasm. For example, patients with … glioblastoma WHO grade IV usually show a less favorable clinical course and receive more aggressive first-line treatment than patients with anaplastic astrocytoma WHO grade III. Here we provide evidence that the IDH1 status is more prognostic for overall survival than standard histological criteria that differentiate high-grade astrocytomas. We sequenced the isocitrate dehydrogenase 1 gene (IDH1) at codon 132 in 382 patients with anaplastic astrocytoma and glioblastoma from the NOA-04 trial and from a prospective translational cohort study of the German Glioma Network. Patients with anaplastic astrocytomas carried IDH1 mutations in 60%, and patients with glioblastomas in 7.2%. IDH1 was the most prominent single prognostic factor (RR 2.7; 95% CI 1.6-4.5) followed by age, diagnosis and MGMT. The sequence from more favorable to poorer outcome was (1) anaplastic astrocytoma with IDH1 mutation, (2) glioblastoma with IDH1 mutation, (3) anaplastic astrocytoma without IDH1 mutation and (4) glioblastoma without IDH1 mutation (p < 0.0001). In this combined set of anaplastic astrocytomas and glioblastomas both, IDH1 mutation and IDH1 expression status were of greater prognostic relevance than histological diagnosis according to the current WHO classification system. Our data indicate that much of the prognostic significance of patient age is due to the predominant occurrence of IDH1 mutations in younger patients. Immunohistochemistry using a mutation-specific antibody recognizing the R132H mutation yielded similar results. We propose to complement the current WHO classification and grading of high-grade astrocytic gliomas by the IDH1 mutation status and to use this combined histological and molecular classification in future clinical trials.

Authors: C. Hartmann, B. Hentschel, W. Wick, D. Capper, J. Felsberg, M. Simon, M. Westphal, G. Schackert, R. Meyermann, T. Pietsch, G. Reifenberger, M. Weller, M. Loeffler, A. von Deimling

Date Published: 20th Nov 2010

Publication Type: Not specified

Human Diseases: brain glioma, glioblastoma multiforme

Age and cellular composition influence overall survival in a collective of non-immunocompromised patients with EBV-positive diffuse large B-cell lymphoma from a German lymphoma center.
GLA - German Lymphoma Alliance

Abstract (Expand)

We investigated 41 diffuse large B-cell lymphomas (DLBCL) diagnosed at one center harboring >/=50% of latently Epstein-Barr virus (EBV)-infected neoplastic cells occurring in 34 patients aged >/=50 … years and in 7 patients younger than 50 years in the absence of any known immunodeficiency for the expression patterns of EBV latent and immediate-early proteins, for the differentiation stage of the neoplastic cells, the presence of cytogenetic alterations and a possible co-infection with the human herpes virus (HHV)-8. Here, we show that EBV-positive DLBCLs rarely arise from naive and more frequently from post-germinal center B-cells that often contain crippling immunoglobulin gene mutations. Most of the lymphomas did not exhibit breaks in the BCL2, BCL6, and MYC genes and none of the cases investigated contained HHV-8 sequences. Patients aged <50 years performed better than older ones while in patients aged >/=50 years only the cellular composition had an impact on overall survival.

Authors: K. Johrens, R. U. Trappe, D. Lenze, M. Pfreundschuh, M. Ziepert, M. Hummel, I. Anagnostopoulos

Date Published: 29th Apr 2016

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

The Speaking Voice in the General Population: Normative Data and Associations to Sociodemographic and Lifestyle Factors.
LIFE Adult

Abstract (Expand)

OBJECTIVES: Normative data concerning the speaking voice in the general population were gathered with the aim to establish standard values for clinical diagnostics. Associations between the speaking … voice and sociodemographic factors were examined. STUDY DESIGN: This is a prospective cross-sectional population-based study. METHODS: Speaking voice profiles were measured for 2472 (1154 male and 1318 female) participants between the ages of 40 and 79 years, using four speaking voice intensity levels: softest speaking voice (I), conversational voice (II), classroom voice (III), and shouting voice (IV). Smoking status and socioeconomic status were assessed. Data were analyzed using multivariate regression. RESULTS: The mean voice frequencies were 111.8 Hz for male and 161.3 Hz for female participants (I), 111.9 Hz for male and 168.5 Hz for female participants (II), 130.2 Hz for male and 198.0 Hz for female participants (III), and 175.5 Hz for male and 246.2 Hz for female participants (IV). Frequencies increased significantly with age for male but not for female participants. Sound pressure levels rose significantly with age at intensity levels I-III for both sexes, but decreased at intensity level IV. Frequencies and sound pressure levels were similar between nonsmokers and former smokers. Current smokers showed significantly lower frequencies as opposed to non- and former smokers. Speaking voice range and dynamics increased with higher socioeconomic status. CONCLUSIONS: The data are suitable as age-adjusted normative values for clinical measurement of the speaking voice. The mean fundamental speaking voice frequency of female participants was six to seven semitones lower than previously described.

Authors: M. Berg, M. Fuchs, K. Wirkner, M. Loeffler, C. Engel, T. Berger

Date Published: 3rd Jul 2016

Publication Type: Journal article

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