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Treatment of lymphoma can be associated with cognitive challenges, and some patients may fear development of dementia as long-term complication. Studies report a lower risk of dementia after cancer. Some believe this difference to be a protective mechanism of cancer, others believe it to be driven by bias. The risk of developing dementia after lymphoma has not been investigated in a population-based setting. The aim of this study was to identify the risk of being diagnosed with dementia after lymphoma treatment. This Danish nationwide matched cohort study included patients aged ≥65 years with a first-time diagnosis of a non-central nervous system lymphoma between 2005 and 2018 in complete remission after treatment with chemotherapy. Patients diagnosed with dementia or treated with dementia medication before lymphoma diagnosis were excluded. Each patient was matched 1:5 on sex, year of birth, and a modified Charlson comorbidity index. Patients and matched comparators were followed from the corresponding patient's date of complete remission. The risk of developing dementia was calculated using cause-specific hazard ratios (HR), and the cumulative risk was estimated by Aalen-Johansen with death as the competing risk. A total of 3,244 patients and 16,220 matched comparators were included in the study. There was no difference in risk of all-cause dementia among patients with lymphoma compared to matched comparators with cause-specific HR of 0.85 (95% confidence interval [CI]: 0.70;1.04). The risk of both Alzheimer's disease and non-Alzheimer's dementia was equal among patients and comparators: HR 0.89 (95% CI: 0.66;1.21) and 0.82 (95% CI: 0.63;1.07), respectively. Stratified by lymphoma subtype, age, or year of diagnosis, the risk of all-cause dementia remained equal among patients and matched comparators. The cumulative risk of all-cause dementia was significantly lower among patients with lymphoma compared to matched comparators (Gray's test p < 0.001), probably reflecting higher mortality in patients with lymphoma. The risk of all-cause dementia, Alzheimer's disease, and non-Alzheimer's dementia was equal among older patients with lymphoma compared to matched comparators. Our data suggests that risk of developing dementia is not changed after lymphoma treatment. [ABSTRACT FROM AUTHOR]

Abstract: Essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) are hematopoietic stem cell neoplasms that may be associated with autoimmune or chronic inflammatory disorders. Earlier gene expression profiling studies have demonstrated aberrant expression of genes involved in inflammatory responses, mainly being performed on granulocytes or CD34+ cells. Using gene expression profiling of whole blood from patients with ET (n =16), PV (n =36), and PMF (n =9), several genes involved in inflammation and immune regulation were found to be significantly deregulated. Our findings may reflect chronic inflammation to be of pathogenetic importance for the progression of these neoplasms toward the myelofibrotic end-stage and may also account for the increased frequency of second cancer in these diseases. [Copyright &y& Elsevier]

Abstract: Chromosomal aberrations in polycythemia vera (PV) are heterogenous and nonrandom. A prognostic predictive value of these aberrations has not been established. The V617F mutation in the JAK2 gene on chromosome 9p24.1 was identified recently in peripheral blood leukocytes in the majority of patients with PV and in approximately half of patients with essential thrombocythemia and idiopathic myelofibrosis. Within the JAK2 V617F-positive PV patients, however, clinical presentation and degree of myeloproliferation varies to a great extent. Here we report four cases of chronic myeloproliferative disorders [two with PV, one with PV in transformation to idiopathic myelofibrosis (IMF) and one IMF patient], with the distinct karyotypic abberations der(18) t(9;18) (p13;p11) and der(9;18)(p10;q10). Two patients had hyperproliferative PV and two had “transitional PV” and IMF, respectively. All four patients harbored the JAK2 V617F mutation. Our data, together with previously published data, clearly indicate an association of these chromosomal abnormalities with a highly proliferative PV phenotype with a propensity to transform into postpolycythemic myelofibrosis. Cytogenetic analysis seems to identify a subgroup of patients with a distinct prognostic profile, and should be performed in conjunction with a JAK2 mutation analysis in patients suspected of a chronic myeloproliferative disease. [Copyright &y& Elsevier]

Abstract: Primary myelofibrosis (PMF) is characterized by leukoerythroblastic anemia with circulating immature myeloid cells, including CD34+ cells, progressive splenomegaly and accumulation of connective tissue and neoangiogenesis in the bone marrow. Altered bone marrow stroma and cell adherence account for the egress of CD34+ cells from the bone marrow. Carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 6 has been implicated in cell adhesion, cellular invasiveness, angiogenesis, and inflammation, which are all key processes in the pathophysiology of PMF. Accordingly, CEACAMs may play an important role in these processes in patients with myelofibrosis as well. Using a genome-wide approach, several genes of the CEACAM family were found to be deregulated in patients with PMF and related myeloproliferative neoplasms (n =69). In PMF patients, the CEACAM6 and 8 were significantly upregulated (fold change (FC) 12.5 and 14.0, respectively and FDR adjusted p values 7.71×10−7 and 1.48×10−5, respectively). The elevated expression of CEACAM genes may reflect clonal myeloid expansion and neutrophil activation being most exaggerated in patients with PMF. Alternatively, the highly elevated gene expression of CEACAM6 and 8 in PMF may be molecular markers of myelofibrotic transformation, implying enhanced proteolytic activity, egress of CD34+ cells into the circulation, and neoangiogenesis. [Copyright &y& Elsevier]

Background Optimal treatment strategy for the oldest patients with diffuse large B-cell lymphoma (DLBCL) remains controversial, as this group often is precluded from clinical trials, and population-based studies are limited. Methods All Danish DLBCL-patients ≥75 years diagnosed from 2003 to 2012 were identified, using the Danish National Lymphoma Registry (LYFO). Information regarding baseline characteristics, treatment, comorbidities and outcomes was retrieved from LYFO, the Danish National health registries and medical records. Patients were stratified by age (75–79; 80–84 and 85 + years), comorbidity score and treatment modality (standard treatment [R-CHOP/CHOP-like], less intensive regimens or palliative treatment). Findings A total of 1011 patients were included. Standard treatment was initiated in 64%, ranging from 83% among patients aged 75–79 years to 32% among patient aged 85 + years. With standard treatment, median overall survival (OS) estimates were 4·6, 2·6, and 1·9 years for the age groups 75–79, 80–84 and 85+ years. Among patient aged 75–79 and 80–84 years, OS was superior with standard treatment, although high comorbidity scores attenuated this association. Among patients aged 85+ years, survival was not influenced by treatment intensity. Patients ≥80 years had similar OS regardless of intended (R-)CHOP dosing, whereas patients of 75–79 years scheduled for full dose had higher OS. Standard treatment was not associated with increased hospitalisation. Interpretation Standard treatment is feasible with good outcomes in a large proportion of elderly DLBCL-patients. Planned dose reduction in patients aged ≥80 years had no negative impact on OS. [ABSTRACT FROM AUTHOR]

The recent discovery of the Janus activating kinase 2 V617F mutation in most patients with polycythemia vera (PV) and half of those with essential thrombocythemia (ET) and primary myelofibrosis (PMF) has favored the hypothesis of a biological continuum from ET over PV to PMF. We performed gene expression profiling of whole blood from control subjects (n = 21) and patients with ET (n = 19), PV (n = 41), and PMF (n = 9) using DNA microarrays. Applying an unsupervised method, principal component analysis, to search for patterns in the data, we demonstrated a separation of the four groups with biological relevant overlaps between the different entities. Moreover, the analysis separates Janus activating kinase 2-negative ET patients from Janus activating kinase 2-positive ET patients. Functional annotation analysis demonstrates that clusters of gene ontology terms related to inflammation, immune system, apoptosis, RNA metabolism, and secretory system were the most significantly deregulated terms in the three different disease groups. Our results yield further support for the hypothesis of a biological continuum originating from ET over PV to PMF. Functional analysis suggests an important implication of these gene ontology clusters in the pathogenesis of these neoplasms and in disease evolution from ET over PV to PMF. [Copyright &y& Elsevier]