Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive myeloid neoplasm which shows a high rate of central nervous system (CNS) recurrence and overall survival (OS) of <1 year. ...Despite this, screening for CNS involvement is not routinely performed at diagnosis and intrathecal (IT) prophylaxis is not regularly administered in BPDCN. Here, we prospectively evaluated 13 consecutive BPDCN patients for the presence of CNS involvement by flow cytometry. Despite none of the patients presented with neurological symptoms, occult CNS involvement was detected in 6/10 cases evaluated at diagnosis and 3/3 studied at relapse/progression. BPDCN patients evaluated at diagnosis received IT treatment -either CNS prophylaxis (n = 4) or active therapy (n = 6)- and all but one remain alive (median follow-up of 20 months). In contrast, all three patients assessed at relapse/progression died. The potential benefit of IT treatment administered early at diagnosis on OS and CNS recurrence-free survival of BPDCN was further confirmed in a retrospective cohort of another 23 BPDCN patients. Our results show that BPDCN patients studied at diagnosis frequently display occult CNS involvement; moreover, they also indicate that treatment of occult CNS disease might lead to a dramatically improved outcome of BPDCN.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare subtype of leukemia/lymphoma, whose diagnosis can be difficult to achieve due to its clinical and biological heterogeneity, as well as ...its overlapping features with other hematologic malignancies. In this study we investigated whether the association between the maturational stage of tumor cells and the clinico-biological and prognostic features of the disease, based on the analysis of 46 BPDCN cases classified into three maturation-associated subgroups on immunophenotypic grounds. Our results show that blasts from cases with an immature plasmacytoid dendritic cell (pDC) phenotype exhibit an uncommon CD56- phenotype, coexisting with CD34+ non-pDC tumor cells, typically in the absence of extramedullary (e.g. skin) disease at presentation. Conversely, patients with a more mature blast cell phenotype more frequently displayed skin/extramedullary involvement and spread into secondary lymphoid tissues. Despite the dismal outcome, acute lymphoblastic leukemia-type therapy (with central nervous system prophylaxis) and/or allogeneic stem cell transplantation appeared to be the only effective therapies. Overall, our findings indicate that the maturational profile of pDC blasts in BPDCN is highly heterogeneous and translates into a wide clinical spectrum -from acute leukemia to mature lymphoma-like behavior-, which may also lead to variable diagnosis and treatment.
Current procedures for the assessment of chronic wound infection are time-consuming and require complex instruments and trained personnel. The incidence of chronic wounds worldwide, and the ...associated economic burden, urge for simple and cheap point-of-care testing (PoCT) devices for fast on-site diagnosis to enable appropriate early treatment. The enzyme myeloperoxidase (MPO), whose activity in infected wounds is about ten times higher than in non-infected wounds, appears to be a suitable biomarker for wound infection diagnosis. Herein, we develop a single-component foldable paper-based device for the detection of MPO in wound fluids. The analyte detection is achieved in two steps: (i) selective immunocapture of MPO, and (ii) reaction of a specific dye with the captured MPO, yielding a purple color with increasing intensity as a function of the MPO activity in infected wounds in the range of 20–85 U/mL. Ex vivo experiments with wound fluids validated the analytic efficiency of the paper-based device, and the results strongly correlate with a spectrophotometric assay.
Transformation of follicular lymphoma into an aggressive lymphoma (tFL) worsens the prognosis and the standard treatment is not completely defined. Allogeneic hematopoietic stem cell transplantation ...(alloSCT) could be a potentially curative option for these patients, but it has not been widely explored.
We designed a retrospective multicenter study to analyze the efficacy and toxicity of alloSCT in tFL patients and potential prognostic factors of survival.
A total of 43 patients diagnosed with tFL who underwent alloSCT in 14 Spanish centers between January 2000 and January 2019 were included. Median age was 44 (31-67) years. After a median follow-up of 58 months, estimated 5-year overall survival (OS) and progression-free survival (PFS) were both 35%. Estimated 100-day and 1-year non-relapse mortality (NRM) were 20% and 34%, respectively. The type of conditioning regimen (3-year OS of 52% vs. 20%, respectively, for reduced-intensity vs. myeloablative conditioning) and development of chronic graft versus host disease (cGVHD) (3-year OS of 75% vs. 40%) were the only factors significantly associated with OS. The only variable with an independent association with OS was cGVHD (HR, 3.4; 95% CI, 1.2-9.6).
Our results indicate that alloSCT continues to be a potentially curative option for patients with tFL.
Follicular lymphoma (FL) is a heterogeneous disease whose pathogenesis remains partially unknown. Around 20% of FL patients experience early progression or treatment-refractory disease and 2-3% of ...patients per year experience histological transformation (HT) into a more aggressive lymphoma (tFL). Here, we evaluate the immunoglobulin heavy chain variable (IGHV) gene usage and mutational status in 187 FL cases to assess its impact on clinical outcome and histological transformation. The IGHV gene repertoire was remarkably biased in FL. The IGHV4-34 (14%), IGHV3-23 (14%), IGHV3-48 (10%), IGHV3-30 (9%) and IGHV3-21 (7%) genes accounted for more than half of the whole cohort. IGHV3-48 was overrepresented in cases of tFL (19%) compared with non-transformed FL at 5 years (5%, P = 0.05). Patients with the IGHV3-48 gene were significantly more likely to have had HT after 10 years than those who used other genes (71% vs. 25%, P < 0.05), irrespective of the therapy they received. Moreover, IGHV3-30 was also overrepresented in cases of FL (9%) and tFL (13%) compared with diffuse large B-cell lymphoma in which it was nearly absent. In conclusion, our results indicate a role for antigen selection in the development of FL, while the use of IGHV3-48 could help predict histological transformation.
An exploratory analysis of 75 follicular lymphoma patients treated with obinutuzumab or rituximab induction therapy (IT) for 4 weeks in the phase II GAUSS study aimed to determine whether positron ...emission tomography (PET) results could predict progression-free survival (PFS) and tumor response. The proportion of patients with a PFS event (progression or death) was higher in those who were PET-positive after IT (assessed using Deauville five-point scale criteria; 35/52, 67%) than PET-negative (5/20, 25%); the hazard ratio for progression or death was 0.25 (95%CI: 0.01-0.64; p = 0.0018). A significant association was also found when PET results were assessed using International Harmonization Project and European Organisation for Research and Treatment of Cancer criteria. Change between baseline and end of IT in values of standardized uptake value and other PET parameters were associated with PFS and response. Validation of these results in prospective studies of larger cohorts is warranted.
From a contextual transdiagnostic approach, this study focuses on the importance of the processes of Experiential Avoidance and Activation in explaining and treating psychological problems. There ...exists widespread empirical evidence to suggest that the response pattern known as Experiential Avoidance, a general unwillingness to remain in contact with particular private experiences through the use of maladaptive avoidance strategies, acts as a functional dimension in various psychological problems. Activation, that is, maintaining contact with experiences/conditions of life and consequently with associated sources of reward, is a condition present in most therapeutic processes. Although a great deal of research has analyzed the relationship of the value of reward with the etiology and maintenance of psychological problems, Activation, as a transdiagnostic factor, has been studied less. The aim of this paper is to carry out an empirical study of the relationship between Activation, EA and emotional state and analyze the capacity of these two conditions to discriminate the intensity and symptomatology type in subjects with emotional distress.
The Hospital Anxiety and Depression Scale (HADS), Environmental Reward Observation Scale (EROS) and Behavioral Activation for Depression Scale (BADS) were completed by 240 health center users.
Of the participants, 55% showed clinically relevant emotional distress. All cases of depression showed clinical anxiety. To discriminate between subjects without (
= 109) and with emotional distress (
= 131), analyses of the ROC curves and logistic regression analysis identified the BADS-Avoidance/Rumination followed by the EROS. To discriminate between subjects with anxiety but without depression (
= 61) and with anxiety and depression (
= 70), the most efficient scales were EROS followed by BADS-Social Impairment.
It was shown that people with no emotional complaints maintained greater contact with life experiences and with environmental sources of reward than those with emotional distress. Response patterns showing Experiential Avoidance and a reduction in Activation responses were associated with clinical distress. A reduction in Activation was the condition which distinguished those people with the greatest distress and also the greatest comorbidity of symptoms of depression and anxiety. These data support the transdiagnostic nature of Activation and suggest greater attention should be paid to this concept.
Copy number analysis can be useful for assessing prognosis in diffuse large B cell lymphoma (DLBCL). We analyzed copy number data from tumor samples of 60 patients diagnosed with DLBCL de novo and ...their matched normal samples. We detected 63 recurrent copy number alterations (CNAs), including 33 gains, 30 losses, and nine recurrent acquired copy number neutral loss of heterozygosity (CNN-LOH). Interestingly, 20 % of cases acquired CNN-LOH of 6p21 locus, which involves the HLA region. In normal cells, there were no CNAs but we observed CNN-LOH involving some key lymphoma regions such as 6p21 and 9p24.1 (5 %) and 17p13.1 (2.5 %) in DLBCL patients. Furthermore, a model with some specific CNA was able to predict the subtype of DLBCL, 1p36.32 and 10q23.31 losses being restricted to germinal center B cell-like (GCB) DLBCL. In contrast, 8p23.3 losses and 11q24.3 gains were strongly associated with the non-GCB subtype. A poor prognosis was associated with biallelic inactivation of
TP53
or 18p11.32 losses, while prognosis was better in cases carrying 11q24.3 gains. In summary, CNA abnormalities identify specific DLBCL groups, and we describe CNN-LOH in germline cells from DLBCL patients that are associated with genes that probably play a key role in DLBCL development.
Distributions of dissolved (DOM) and suspended (POM) organic matter, and their chromophoric (CDOM) and fluorescent (FDOM) fractions, are investigated at high resolution (< 10 km) in the Cape Verde ...Frontal Zone (CVFZ) during fall 2017. In the epipelagic layer (< 200 m), meso- and submesoscale structures (meanders, eddies) captured by the high resolution sampling dictate the tight coupling between physical and biogeochemical parameters at the front. Remarkably, fluorescent humic-like substances show relatively high fluorescence intensities between 50 and 150 m, apparently not related to local mineralization processes. We hypothesize that it is due to the input of Sahara dust, which transports highly re-worked DOM with distinctive optical properties. In the mesopelagic layer (200-1500 m), our results suggest that DOM and POM mineralization occurs mainly during the transit of the water masses from the formation sites to the CVFZ. Therefore, most of the local mineralization seems to be due to fast-sinking POM produced
in situ
or imported from the Mauritanian upwelling. These local mineralization processes lead to the production of refractory CDOM, an empirical evidence of the microbial carbon pump mechanism. DOM released from these fast-sinking POM is the likely reason behind the observed columns of relatively high DOC surrounded by areas of lower concentration. DOM and POM dynamics in the CVFZ has turned out to be very complex, in parallel to the complexity of meso- and submesoscale structures present in the area. On top of this high resolution variability, the input of Sahara dust or the release of DOM from sinking particles have been hypothesized to explain the observed distributions.
Preliminary data on the use of autologous stem cell transplantation (ASCT) as a salvage therapy for peripheral T-cell lymphoma (PTCL) indicate that the results are similar to those obtained in ...aggressive B-cell lymphomas. The aim of our study was to analyze outcomes of a large series of patients with PTCL with a prolonged follow-up who received ASCT as salvage therapy.
Between 1990 and 2004, 123 patients in this situation were registered in the GELTAMO database. The median age at transplantation was 43.5 years; in 91% of patients the disease was chemosensitive.
Seventy-three percent of the patients achieved complete remission, 11% partial remission and the procedure failed in 16%. At a median follow-up of 61 months, the 5-year overall and progression-free survival rates were 45% and 34%, respectively. The presence of more than one factor of the adjusted International Prognostic Index (a-IPI) and a high beta2-microglobulin at transplantation were identified as adverse prognostic factors for both overall and progression-free survival and allowed the population to be stratified into three distinct risk groups.
Our data show that approximately one third of patients with PTCL in the salvage setting may enjoy prolonged survival following ASCT, provided they are transplanted in a chemosensitive disease state. The a-IPI and beta2-microglobulin level predict the outcome after ASCT in relapsing/refractory PTCL.
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