Objectives:Knowledge of health related quality of life of haematological patients is limited. This study aimed at investigating the prevalence and predictors of symptoms and problems in a representative sample of haematological patients in Denmark.Methods:A random sample of patients with leukaemia, multiple myeloma and advanced lymphoma (n = 732) received the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (EORTC QLQ-C30). Mean scores were calculated. In addition, scores were dichotomised using two thresholds: patients reporting at least ‘a little’ of each EORTC QLQ-C30 symptom/problem were classified as having a ‘symptom/problem’, and patients reporting at least ‘quite a bit’ were classified as having a ‘severe symptom/problem’. Multiple logistic regression was used to identify predictors.Results:In total, 470 (64%) patients participated. The most frequent symptoms/problems were fatigue (55%; severe 20%), reduced role function (49%; severe 23%), insomnia (46%; severe 15%), and pain (37%; severe 15%). Older patients and patients in active antineoplastic treatment had more symptoms and problems. There was only little evidence of social inequalities.Conclusion:This is probably the first nationally representative study of symptoms and problems in haematological patients. These patients have symptoms/problems that deserve attention. Health related quality of life is an important issue in haematological malignancies.
BackgroundThe prognostic value of aberrant DNA methylation of cell-free circulating DNA in plasma has not previously been evaluated in diffuse large B cell lymphoma (DLBCL). The aim of this study was to investigate if aberrant promoter DNA methylation can be detected in plasma from DLBCL patients and to evaluate this as a prognostic marker. Furthermore, we wanted to follow possible changes in methylation levels during treatment. Seventy-four patients were enrolled in the study, of which 59 received rituximab and CHOP-like chemotherapy. Plasma samples were collected from all patients at the time of diagnosis and from 14 healthy individuals used as controls. In addition, plasma samples were collected during and after treatment for surviving patients. In total, 158 plasma samples were analyzed for DNA methylation in the promoter regions of DAPK (DAPK1), DBC1, MIR34A, and MIR34B/C using pyrosequencing.ResultsAberrant methylation levels at the time of diagnosis were detected in 19, 16, 8, and 10 % of the DLBCL plasma samples for DAPK1, DBC1, MIR34A, and MIR34B/C, respectively. DAPK1 methylation levels were significantly correlated with DBC1 and MIR34B/C methylation levels (P < 0.001). For the entire cohort, 5-year overall survival (OS) rates were significantly lower in the groups carrying aberrant DAPK1 (P = 0.004) and DBC1 (P = 0.044) methylation, respectively. DAPK1 methylation status were significantly correlated with stage (P = 0.015), as all patients with aberrant DAPK1 methylation were stages III and IV. Multivariate analysis identified DAPK1 as an independent prognostic factor for OS with a hazard ratio of 8.9 (95 % CI 2.7–29.3, P < 0.0007). Patients with DAPK1 methylated cell-free circulating DNA at time of diagnosis, who became long-term survivors, lost the aberrant methylation after treatment initiation. Conversely, patients that maintained or regained aberrant DAPK1 methylation died soon thereafter.ConclusionsAberrant promoter methylation of cell-free circulating DNA can be detected in plasma from DLBCL patients and hold promise as an easily accessible marker for evaluating response to treatment and for prognostication. In particular, aberrant DAPK1 methylation in plasma was an independent prognostic marker that may also be used to assess treatment response.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0261-y) contains supplementary material, which is available to authorized users.
Global hypomethylation has been linked to disease progression in several cancers, but has not been reported for Diffuse Large B Cell Lymphoma (DLBCL). This study aimed to assess global methylation in DLBCL and describe its prognostic value. Mean LINE1 methylation, a validated surrogate measure for global methylation, was measured in DNA from 67 tumor biopsies. Additionally, cell-free circulating DNA (cfDNA) in plasma samples from 74 patients was tested to assess the feasibility of global hypomethylation as a biomarker in liquid biopsies. LINE1 methylation was assessed using a commercially available kit, based on pyrosequencing of PCR amplified bisulfite-treated DNA. Global hypomethylation was detected in a subset of cases and was associated with poor overall survival in both tumor biopsies (P = .001) and cfDNA (P = .009). It was the strongest risk factor in multivariate analysis in both biopsies (HR: 10.65, CI: 2.03-55.81, P = .005) and cfDNA (HR: 11.87, CI: 2.80-50.20, P = .001), outperforming conventional clinical risk factors. Finally, hierarchical cluster analyses were performed for the cfDNA samples using previously published gene-specific methylation data. This analysis shows that global hypomethylation co-occurs with other epigenetic abnormalities, including DAPK1 promoter hypermethylation. In conclusion, we have shown that global hypomethylation is strongly associated with poor survival in DLBCL both when present in tumor biopsy DNA and when detected in plasma cfDNA, and has potential for clinical application as a prognostic biomarker.
(R)-CHOP-14 has substantially improved outcome in DLBCL, but may have increased morbidity and reduced quality of life (QoL). Our aim was to evaluate QoL during (R)-CHOP-14-based chemotherapy. Twenty-six patients participated (small single-center study). EORTC QLQ-C30 was completed pre-treatment, mid-treatment, 14 days post-treatment, and 3 months post-treatment. Scores were compared to a reference population, and analyzed separately. Pre-treatment, global health status (p = 0.004), physical functioning (p = 0.036), role functioning (p = 0.017), and emotional functioning (p = 0.040) were reduced, and fatigue (p = 0.009) and appetite loss (p = 0.007) increased compared to the reference population. During treatment, physical functioning and role functioning decreased significantly, whereas emotional functioning, fatigue, and diarrhea increased. Three months post-treatment, scores were generally equivalent to those of the reference population, and lower for nausea/vomiting (p < 0.001) and constipation (p < 0.001). Disease-related symptoms were frequent in high-risk DLBCL. Treatment-related symptoms were normalized 3 months post-treatment. In conclusion, QoL is only temporarily affected during (R)-CHOP-14-based chemotherapy, and the treatment regimen is therefore feasible.
MicroRNAs are small regulatory RNAs that are deregulated in a wide variety of human cancers, including different types of B-cell lymphoma. Nevertheless, the feasibility of circulating microRNA for early diagnosis of B-cell lymphoma has not been established. To address the possibility of detecting specific circulating microRNAs years before a B-cell lymphoma is diagnosed, we studied the plasma expression of microRNA first in pre-treatment samples from patients with diffuse large B-cell lymphoma and subsequently in repository samples from blood donors who later developed B-cell lymphomas. In addition, we studied the microRNA expression in the diagnostic lymphoma biopsy. The most strongly induced (miR-326) and suppressed (miR-375) plasma microRNA at diagnosis, when compared with healthy blood donors, were also substantially up-or down-regulated in plasma repository samples taken from several months to up to two years before the blood donors were diagnosed with B-cell lymphoma. Importantly, at these time points the donors had no signs of disease and felt healthy enough to donate blood. In conclusion, this first study of plasma microRNA profiles from apparently healthy individuals, taken several years before B-cell lymphoma diagnosis, suggests that plasma microRNA profiles may be predictive of lymphoma development. B cell lymphomas are the most common hematological cancer in adults with reported annual incidence rates of around 21/100,000 persons in DK 1. A wide variety of B-cell lymphoma subtypes are recognized by the WHO classification, the most common of which are diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) 2. Despite significant improvements in outcome, DLBCL as such still carry considerable mortality with an overall three year survival of around 75% 3. Accordingly, there is a need for biomarkers that are readily applicable in the clinic to facilitate early detection and treatment of patients. Circulating microRNAs may be of potential interest in this regard. MicroRNAs are small RNA strands, consisting of 18 to 23 nucleotides, that regulate the activity of messenger RNA (mRNA) 4. They are detectable-and have been shown to be quite stable in plasma samples despite the presence of RNases 5,6. Therefore, microRNAs have attracted considerable attention in recent years, and multiple studies have repeatedly demonstrated that they are dysregulated in virtually all malignancies 7. In particular, aberrant serum levels of different microRNAs have been reported in patients with various types of lymphoma 8-13 .
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