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1.
Medicina (Kaunas) ; 57(11)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34833353

RESUMO

Mastocytosis is a rare hematological neoplasm characterized by the proliferation of abnormal clonal mast cells (MCs) in different cutaneous and extracutaneous organs. Its diagnosis is based on well-defined major and minor criteria, including the pathognomonic dense infiltrate of MCs detected in bone marrow (BM), elevated serum tryptase level, abnormal MCs CD25 expression, and the identification of KIT D816V mutation. The World Health Organization (WHO) classification subdivides mastocytosis into a cutaneous form (CM) and five systemic variants (SM), namely indolent/smoldering (ISM/SSM) and advanced SM (AdvSM) including aggressive SM (ASM), SM associated to hematological neoplasms (SM-AHN), and mast cell leukemia (MCL). More than 80% of patients with SM carry a somatic point mutation of KIT at codon 816, which may be targeted by kinase inhibitors. The presence of additional somatic mutations detected by next generation sequencing analysis may impact prognosis and drive treatment strategy, which ranges from symptomatic drugs in indolent forms to kinase-inhibitors active on KIT. Allogeneic stem cell transplant (SCT) may be considered in selected SM cases. Here, we review the clinical, diagnostic, and therapeutic issues of SM, with special emphasis on the translational implications of SM genetics for a precision medicine approach in clinical practice.

2.
Front Oncol ; 11: 777730, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765563

RESUMO

A total of 63 myeloproliferative neoplasms [MPN; 9 polycythemia vera (PV), 32 essential thrombocythemia (ET), and 22 myelofibrosis (MF)] underwent spleen stiffness (SS) measurement by vibration-controlled transient elastography equipped with a novel spleen-dedicated module. Higher SS values significantly correlated with grade 2-3 bone marrow (BM) fibrosis (p=0.035), with hemoglobin level <10 g/dl (p=0.014) and with white blood cells ≥10,000/µl (p=0.008). Median SS was significantly higher in MF patients compared to ET and PV (p=0.015). SS also correlated with higher JAK2 variant allele frequency (p=0.02). This study identifies SS as a potential noninvasive tool that reflects BM fibrosis and the mutational burden in MPN.

3.
Front Oncol ; 11: 739171, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513714

RESUMO

An observational prospective study was conducted by the CML Italian network to analyze the role of baseline patient characteristics and first line treatments on overall survival and CML-related mortality in 1206 newly diagnosed CML patients, 608 treated with imatinib (IMA) and 598 with 2nd generation tyrosine kinase inhibitors (2GTKI). IMA-treated patients were much older (median age 69 years, IQR 58-77) than the 2GTKI group (52, IQR 41-63) and had more comorbidities. Estimated 4-year overall survival of the entire cohort was 89% (95%CI 85.9-91.4). Overall, 73 patients (6.1%) died: 17 (2.8%) in the 2GTKI vs 56 (9.2%) in the IMA cohort (adjusted HR=0.50; 95% CI=0.26-0.94), but no differences were detected for CML-related mortality (10 (1.7%) vs 11 (1.8%) in the 2GTKIs vs IMA cohort (sHR=1.61; 0.52-4.96). The ELTS score was associated to CML mortality (high risk vs low, HR=9.67; 95%CI 2.94-31.74; p<0.001), while age (per year, HR=1.03; 95%CI 1.00-1.06; p=0.064), CCI (4-5 vs 2, HR=5.22; 95%CI 2.56-10.65; p<0.001), ELTS score (high risk vs low, HR=3.11; 95%CI 1.52-6.35, p=0.002) and 2GTKI vs IMA (HR=0.26; 95%CI 0.10-0.65, p=0.004) were associated to an increased risk of non-related CML mortality. The ELTS score showed a better discriminant ability than the Sokal score in all comparisons.

4.
Blood Adv ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34592758

RESUMO

Evans syndrome (ES) is a rare condition, defined as the presence of two autoimmune cytopenias, more frequently autoimmune hemolytic anemia and immune thrombocytopenia, and rarely autoimmune neutropenia. ES can be classified as primary or secondary to various conditions, including lymphoproliferative disorders, other systemic autoimmune diseases, and primary immunodeficiencies, particularly in children. In adult ES, little is known about clinical features, disease associations and outcome. In this retrospective international study, we analyzed 116 adult patients followed at 13 European tertiary centers, focusing on treatment requirement, occurrence of complications and death. ES was secondary to or associated with an underlying condition in 24 cases (21%), mainly other autoimmune diseases and hematologic neoplasms. Bleeding occurred in 42% of subjects, mainly low grade and at ITP onset. Almost all patients received first line treatment (steroids+/-IVIG), and 23% needed early additional therapy for primary refractoriness. Further therapy lines included rituximab, splenectomy, immunosuppressants, thrombopoietin receptor agonists, and others, with response rates greater than 80%. However, a remarkable number of relapses occurred, requiring ≥3 therapy lines in 54% of cases. Infections and thrombotic complications occurred in 33% and 21% of subjects, respectively, mainly grade ≥3, and correlated with the number of therapy lines. Besides age, other factors negatively impacting on survival were severe anemia at onset and occurrence of relapse, infections and thrombosis. These data show that adult ES is often severe and marked by a relapsing clinical course and potentially fatal complications, pinpointing the need for high clinical awareness, prompt therapy, and anti-infectious/anti-thrombotic prophylaxis.

5.
Int J Food Microbiol ; 357: 109367, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34482184

RESUMO

Alternaria is one of the main fungal genera affecting the quality of barley grains. In this study, a polyphasic approach was carried out to characterise the Alternaria population infecting different cultivars of barley grains from the major producing regions of Argentina in the 2014 and 2015 seasons. Its relationship with Fusarium and correlations between predominant species, barley cultivars, and climatic conditions in the growing regions were evaluated. Alternaria incidence exceeded that of Fusarium in all the barley samples and was higher in the drier season (21% in 2014 and 42% in 2015 vs. 6% and 4%, respectively). The main Alternaria species-groups identified were present in both growing seasons in similar frequencies (A. tenuissima sp.-grp., 83.4% in 2014 and 81.7% in 2015; A. infectoria sp.-grp., 11.7% in 2014 and 11.3% in 2015). The dominant Alternaria species-group isolated and identified based on morphological characteristics, DNA sequencing, and metabolite profile was A. tenuissima (72.9%), followed by A. infectoria (14.6%). An association between their frequency and field temperature was observed; A. tenuissima sp.-grp. was more frequent in northern localities, where higher temperatures were registered, while the opposite was observed for A. infectoria sp.-grp. A smaller percentage of A. arborescens sp.-grp. (5%), A. alternata sp.-grp. (3.9%) and A. vaccinii (1.4%) were also identified. Both secondary metabolite profiles and phylogenetic analysis were useful to distinguish isolates from Alternaria section Alternaria and section Infectoriae. Regarding metabolite profiles, alternariol was the most frequent compound produced by isolates of the section Alternaria. Infectopyrones and novae-zelandins were produced by most of the isolates from section Infectoriae. The barley cultivars analysed in this study did not show a particular susceptibility regarding the Alternaria population composition, except for Andreia, which presented the highest frequency of contamination with A. tenuissima sp.-grp. The rest of the cultivars, when grown in different regions, showed different proportion of the Alternaria sp.-grps., suggesting that other factors were determinant in their distribution. The results obtained in the present study will be a valuable tool for health authorities to assess the need for regulations on Alternaria mycotoxins, given the high incidence of Alternaria spp. in barley and the diversity of metabolites that might contaminate the grains.


Assuntos
Fusarium , Hordeum , Micotoxinas , Alternaria , Filogenia
6.
Cancer J ; 27(4): 266-274, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34398553

RESUMO

ABSTRACT: The high degree of clinical heterogeneity of chronic lymphocytic leukemia (CLL) is influenced by the disease molecular complexity. Genetic studies have allowed to better understand CLL biology and to identify molecular biomarkers of clinical relevance. TP53 disruption represents the strongest prognosticator of chemorefractoriness and indicates the use of Bruton tyrosine kinase inhibitors (BTKis) and BCL2 inhibitors. Unmutated IGHV (immunoglobulin heavy variable) genes also predict refractoriness to chemoimmunotherapy; importantly, when treated with B-cell receptor inhibitors or BCL2 inhibitors, IGHV unmutated patients display an outcome similar to that of IGHV mutated CLL. Before choosing treatment, a comprehensive assessment of TP53 and IGHV status is recommended by all guidelines for CLL clinical management. In case of fixed-duration therapeutic strategies, monitoring of minimal residual disease may provide a tool to decide treatment duration. The current precision medicine management of CLL patients might be further improved by the adoption of novel biomarkers that are emerging as clinically meaningful for this disease.


Assuntos
Leucemia Linfocítica Crônica de Células B , Biologia , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/genética , Mutação , Prognóstico
8.
Br J Haematol ; 195(1): 108-112, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34291829

RESUMO

We aimed at molecularly dissecting the anatomical heterogeneity of small lymphocytic lymphoma (SLL), by analysing a cohort of 12 patients for whom paired DNA from a lymph node biopsy and circulating cells, as well as plasma-circulating tumour DNA (ctDNA) was available. Notably, the analyses of the lymph node biopsy and of circulating cells complement each other since a fraction of mutations (20·4% and 36·4%, respectively) are unique to each compartment. Plasma ctDNA identified two additional unique mutations. Consistently, the different synchronous sources of tumour DNA complement each other in informing on driver gene mutations in SLL harbouring potential prognostic and/or predictive value.

9.
Blood Cancer J ; 11(6): 115, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34135309
10.
BMC Geriatr ; 21(1): 320, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34011271

RESUMO

BACKGROUND: Age is considered as one of the most important risk-factor for many types of solid and hematological cancers, as their incidence increases with age in parallel to the ever-growing elderly population. Moreover, cancer incidence is constantly increasing as a consequence of the increase in life expectancy that favors the process of cellular senescence. Geriatric assessment has been increasingly recognized as predictive and prognostic instrument to detect frailty in older adults with cancer. In particular, the G8 score is a simple and reproducible instrument to identify elderly patients who should undergo full geriatric evaluation. Due to their frailty, elderly patients may be often under-treated and a therapeutic choice based also on a comprehensive geriatric assessment (CGA) is recommended. With these premises, we aim to test the impact of the CGA based interventions on the quality of life (QoL) of frail elderly onco-hematological patients, identified by the G8 screening, candidate for innovative target directed drugs or treatments including the combination of radiotherapy and chemotherapy (RT + CT). METHODS: Patients aged > 65 years, candidate to target directed agents or to RT + CT treatments are screened for frailty by the G8 test; those patients classified as frail (G8 ≤ 14) are randomized to receive a CGA at baseline or to conventional care. The primary endpoint is QoL, assessed by EORTC QLQ-C30C. As collateral biological study, the potential prognostic/predictive role of T-cell senescence and myeloid derived suppressor cells (MDSC) are evaluated on plasma samples. DISCUSSION: This trial will contribute to define the impact of CGA on the management of frail elderly onco-hematologic patients candidate to innovative biological drugs or to integrated schedules with the association of RT + CT. Furthermore, the use of plasma samples to assess the potential prognostic value of imbalance of immune-competent cells is expected to contribute to the individualized care of elderly patients, resulting into a fine tuning of the therapeutic strategies. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04478916 . registered July 21, 2020 - retrospectively registered.


Assuntos
Fragilidade , Avaliação Geriátrica , Idoso , Envelhecimento , Idoso Fragilizado , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/terapia , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
PLoS One ; 16(4): e0250081, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33878141

RESUMO

Dormancy of hematopoietic stem cells and formation of progenitors are directed by signals that come from the bone marrow microenvironment. Considerable knowledge has been gained on the murine hematopoietic stem cell microenvironment, while less so on the murine progenitor microenvironment and even less so on these microenvironments in humans. Characterization of these microenvironments is decisive for understanding hematopoiesis and finding new treatment modalities against bone marrow malignancies in the clinic. However, it is equally challenging, because hematopoietic stem cells are difficult to detect in the complex bone marrow landscape. In the present study we are characterizing the human hematopoietic stem cell and progenitor microenvironment. We obtained three adjacent bone marrow sections from ten healthy volunteers. One was used to identify a population of CD34+/CD38- "hematopoietic stem cells and multipotent progenitors" and a population of CD34+/CD38+ "progenitors" based on immunofluorescence pattern/intensity and cellular morphology. The other two were immunostained respectively for CD34/CD56 and for CD34/SMA. Using the combined information we performed a non-computer-assisted quantification of nine bone marrow components (adipocytes, megakaryocytes, bone surfaces, four different vessel types (arteries, capillaries, sinusoids and collecting sinuses), other "hematopoietic stem cells and multipotent progenitors" and other "progenitors") within 30 µm of "hematopoietic stem cells and multipotent progenitors", "progenitors", and "random cell profiles". We show that the microenvironment of the "hematopoietic stem cells and multipotent progenitors" is significantly enriched in sinusoids and megakaryocytes, while the microenvironment of the "progenitors" is significantly enriched in capillaries, other "progenitors", bone surfaces and arteries.


Assuntos
Células da Medula Óssea/citologia , Células-Tronco Hematopoéticas/citologia , Nicho de Células-Tronco/fisiologia , Adipócitos , Adulto , Idoso , Antígenos CD34 , Medula Óssea/metabolismo , Células da Medula Óssea/metabolismo , Células da Medula Óssea/fisiologia , Diferenciação Celular , Separação Celular , Células Cultivadas , Feminino , Citometria de Fluxo , Hematopoese , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/fisiologia , Humanos , Imunofenotipagem , Megacariócitos , Glicoproteínas de Membrana , Pessoa de Meia-Idade
12.
Blood ; 138(7): 571-583, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-33889952

RESUMO

The efficacy and safety of thrombopoietin receptor agonists (TRAs) in older patients with primary immune thrombocytopenia (ITP) are unknown. We investigated TRA response and switch, thrombotic/hemorrhagic risk, and sustained responses off-treatment (SROTs) in 384 patients with ITP aged ≥60 years. After 3 months, 82.5% and 74.3% of eltrombopag- and romiplostim-treated patients, respectively, achieved a response; 66.7% maintained the response (median follow-up, 2.7 years). Eighty-five (22.2%) patients switched to the alternative TRA; although no cross-toxicity was observed, 83.3% of resistant patients had a response after the switch. Thirty-four major thromboses (3 fatal) and 14 major hemorrhages (none fatal) occurred in 18 and 10 patients, respectively, while on TRAs and were associated with thrombosis history (subdistribution hazard ratio, 2.04, P = .05) and platelet count <20 × 109/L (subdistribution hazard ratio, 1.69; P = .04), respectively, at TRA start. A recurrent event occurred in 15.6% of patients surviving thrombosis, in all cases but 1 during persisting TRA treatment (incidence rate, 7.7 per 100 patient-years). All recurrences occurred in the absence of adequate antithrombotic secondary prophylaxis. Sixty-two (16.5%) responding patients discontinued TRAs; 53 (13.8%) patients maintained SROTs, which were associated with TRA discontinuation in complete response (P < .001). Very old age (≥75 years; 41.1%) was associated with the more frequent start of TRAs in the persistent/acute phase but not with response or thrombotic/hemorrhagic risk. TRAs are effective in older patients with ITP, with no fatal hemorrhages and with SROTs in a significant portion of patients. Caution is warranted in patients with a history of thrombosis, and a careful risk/benefit balance should be considered.

13.
Int J Mol Sci ; 22(5)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802366

RESUMO

Myelodysplastic syndromes (MDS) arising in the context of inherited bone marrow failure syndromes (IBMFS) differ in terms of prognosis and treatment strategy compared to MDS occurring in the adult population without an inherited genetic predisposition. The main molecular pathways affected in IBMFS involve telomere maintenance, DNA repair, biogenesis of ribosomes, control of proliferation and others. The increased knowledge on the genes involved in MDS pathogenesis and the wider availability of molecular diagnostic assessment have led to an improvement in the detection of IBMFS genetic predisposition in MDS patients. A punctual recognition of these disorders implies a strict surveillance of the patient in order to detect early signs of progression and promptly offer allogeneic hematopoietic stem cell transplantation, which is the only curative treatment. Moreover, identifying an inherited mutation allows the screening and counseling of family members and directs the choice of donors in case of need for transplantation. Here we provide an overview of the most recent data on MDS with genetic predisposition highlighting the main steps of the diagnostic and therapeutic management. In order to highlight the pitfalls of detecting IBMFS in adults, we report the case of a 27-year-old man affected by MDS with an underlying telomeropathy.


Assuntos
Predisposição Genética para Doença/genética , Síndromes Mielodisplásicas/genética , Adulto , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Mutação/genética
14.
Blood ; 137(11): 1438-1439, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33734337
15.
J Clin Epidemiol ; 137: 31-44, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33753228

RESUMO

BACKGROUND: The aim was to investigate the relative validity of the preference-based measure EORTC QLU-C10D in comparison with the EQ-5D-3L in myelodysplastic syndromes (MDS) patients. METHODS: We used data from an international multicentre, observational cohort study of MDS patients. Baseline EORTC QLU-C10D and EQ-5D-3L scores were used and index scores calculated for Italy, Australia, and the UK. Criterion validity was established by Spearman and intraclass correlations (ICC) and Bland-Altman plots. Construct validity was established by the instruments' ability to discriminate known groups, i.e. groups whose health status is expected to differ. RESULTS: We analyzed data from 619 MDS patients (61.1% male; median age 73.8 years). Correlations between theoretically corresponding domains were largely higher than between unrelated domains. ICCs and Bland-Altman plots indicated moderate to good criterion validity. Ceiling effects were lower for the QLU-C10D (4.7%) than for the EQ-5D-3L (22.6%). The EQ-5D-3L failed to discriminate known-groups in two and the QLU-C10D in one of the comparisons; the QLU-C10D's efficiency in doing so was higher in clinical known-groups. Results were comparable between the countries. CONCLUSIONS: The QLU-C10D may be suitable to generate health utilities for economic research in MDS. Responsiveness and minimal important differences need yet to be established.


Assuntos
Síndromes Mielodisplásicas , Qualidade de Vida , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Síndromes Mielodisplásicas/diagnóstico , Reprodutibilidade dos Testes
16.
Food Microbiol ; 97: 103741, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33653520

RESUMO

Tomato fruit is susceptible to Alternaria spp. spoilage, which poses a health risk due to their mycotoxin production. Biopreservation relies on the use of whole microorganisms or their metabolites to manage spoilage microorganisms including filamentous fungi. However, the use of treatments at fungistatic level might activate intracellular pathways, which can cause an increment in mycotoxin accumulation. The objective of this work was to evaluate the effect of two strains of Debaryomyces hansenii and the antifungal protein PgAFP at 10 and 40 µg/mL. Both growth and production of two of the most common mycotoxins (tenuazonic acid and alternariol monomethyl ether) by Alternaria tenuissima sp.-grp. and Alternaria arborescens sp.-grp. on a tomato-based matrix, were analysed at 12 °C. Additionally, the impact of these biocontrol agents on the stress-related RHO1 gene expression was assessed. All treatments reduced mycotoxin accumulation (from 27 to 92% of inhibition). Their mode of action against Alternaria spp. in tomato seems unrelated to damages to fungal cell wall integrity at the genomic level. Therefore, the two D. hansenii strains (CECT 10352 and CECT 10353) and the antifungal protein PgAFP at 10 µg/mL are suggested as biocontrol strategies in tomato fruit at postharvest stage.


Assuntos
Alternaria/efeitos dos fármacos , Alternaria/metabolismo , Debaryomyces/metabolismo , Proteínas Fúngicas/metabolismo , Micotoxinas/biossíntese , Doenças das Plantas/microbiologia , Alternaria/genética , Alternaria/crescimento & desenvolvimento , Debaryomyces/química , Debaryomyces/genética , Frutas/microbiologia , Proteínas Fúngicas/genética , Fungicidas Industriais
17.
Fungal Biol ; 125(2): 153-159, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33518205

RESUMO

Wheat is one of the most important crops in Argentina and worldwide. One of the major diseases affecting the crop is the Fusarium Head Blight (FHB). It is an endemic disease caused mainly by Fusarium graminearum, the most common agent of FHB around the world. The infection is strongly influenced by environmental parameters and occurs mostly when there are favourable conditions of moisture and temperature during wheat anthesis or flowering. This destructive disease affects wheat, barley and other small grains and has the capability of destroying crops, causing great economic losses due to reduced grain quality, and the accumulation of significant levels of mycotoxins such as trichothecenes. The aim of this study was to evaluate the influence of temperature on mycotoxin biosynthesis, on three strains of F. graminearum of 15-ADON genotype and one of 3-ADON genotype, with different capacity of synthesizing DON, 3-ADON and 15-ADON. Trichothecene production of the strains at different temperatures (5, 10, 15, 20, 25, 30 and 35 °C) was evaluated after 7, 14, 21, 28 and 35 d of incubation. The optimum temperature to produce DON and 3-ADON was between 25 and 30 °C, but the maximum production of 15-ADON occurred at a lower temperature (10 °C) for all the strains. Conversely, the minimum production of DON and 3-ADON was recorded between 5 and 10 °C and of 15-ADON between 30 and 35 °C. A possible explanation for the similar accumulation of both acetyl derivatives by strains of different chemotype and genotypes could be that the acetyl derivatives biosynthesis is regulated by temperature.


Assuntos
Fusarium , Temperatura , Tricotecenos , Argentina , Fusarium/química , Fusarium/genética , Genótipo , Tricotecenos/metabolismo
18.
Br J Haematol ; 193(2): 386-396, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33618438

RESUMO

Up to 30% immune thrombocytopenia (ITP) patients achieve a sustained remission off-treatment (SROT) after discontinuation of thrombopoietin receptor agonists (TPO-RAs). Factors predictive of response are lacking. Patients aged ≥18 years with newly diagnosed or persistent ITP were treated with eltrombopag for 24 weeks. Primary end-point was SROT: the proportion of responders that were able to taper and discontinue eltrombopag maintaining the response during a period of observation (PO) of six months. Secondary end-points included the association between some immunological parameters (TPO serum levels, cytokines and lymphocyte subsets) and response. Fifty-one patients were evaluable. Primary end-point was achieved in 13/51 (25%) treated patients and 13/34 (38%) patients who started the tapering. Baseline TPO levels were not associated with response at week 24 nor with SROT. Higher baseline levels of IL-10, IL-4, TNF-α and osteopontin were negative factors predictive of response (P = 0·001, 0·008, 0·02 and 0·03 respectively). This study confirms that SROT is feasible for a proportion of ITP patients treated with eltrombopag. Some biological parameters were predictive of response.


Assuntos
Benzoatos/uso terapêutico , Redução da Medicação/estatística & dados numéricos , Hidrazinas/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/uso terapêutico , Receptores de Trombopoetina/agonistas , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzoatos/administração & dosagem , Benzoatos/toxicidade , Citocinas/imunologia , Redução da Medicação/métodos , Feminino , Humanos , Hidrazinas/administração & dosagem , Hidrazinas/toxicidade , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Púrpura Trombocitopênica Idiopática/diagnóstico , Pirazóis/administração & dosagem , Pirazóis/toxicidade , Receptores de Trombopoetina/imunologia , Indução de Remissão , Suspensão de Tratamento/estatística & dados numéricos
19.
Leukemia ; 35(8): 2325-2331, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33542480

RESUMO

The prognostic significance of lymphocyte doubling time (LDT) in chronic lymphocytic leukemia (CLL) was identified when the biology of the disease was poorly understood and therapy was not effective. We assessed the clinical and biological significance of LDT in 848 CLL patients in a real-life setting and the context of new biomarkers and effective therapy. A short LDT (≤12 months) was enriched for adverse biomarkers. Patients with a rapid LDT did need therapy shortly after diagnosis (median 23 months vs. not reached; p < 0.001) and had a poorer overall survival (median 95 months vs. not reached p < 0.001). LDT, IGHV mutational status, Beta-2 microglobulin, and Rai clinical stage were independent predictors for time to first treatment in the whole series and in Binet stage A patients. No correlation was observed between LDT and response to chemoimmunotherapy. However, a short LDT along with age ≥65 years, high-risk FISH (del(17p), del(11q)), unmutated IGHV, increased Beta-2 microglobulin, and TP53 mutations predicted short survival. Moreover, the prognostic significance of LDT was independent of the CLL-IPI and the Barcelona/Brno prognostic model. LDT remains an important outcome marker in the modern CLL era and should be incorporated into the clinical assessment and stratification of CLL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunoterapia/métodos , Leucemia Linfocítica Crônica de Células B/patologia , Linfócitos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/imunologia , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
20.
Blood Cancer J ; 11(2): 21, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33563901

RESUMO

In a multicenter European retrospective study including 162 patients with COVID-19 occurring in essential thrombocythemia (ET, n = 48), polycythemia vera (PV, n = 42), myelofibrosis (MF, n = 56), and prefibrotic myelofibrosis (pre-PMF, n = 16), 15 major thromboses (3 arterial and 12 venous) were registered in 14 patients, of whom all, but one, were receiving LMW-heparin prophylaxis. After adjustment for the competing risk of death, the cumulative incidence of arterial and venous thromboembolic events (VTE) reached 8.5% after 60 days follow-up. Of note, 8 of 12 VTE were seen in ET. Interestingly, at COVID-19 diagnosis, MPN patients had significantly lower platelet count (p < 0.0001) than in the pre-COVID last follow-up.This decline was remarkably higher in ET (-23.3%, p < 0.0001) than in PV (-16.4%, p = 0.1730) and was associated with higher mortality rate (p = 0.0010) for pneumonia. The effects of possible predictors of thrombosis, selected from those clinically relevant and statistically significant in univariate analysis, were examined in a multivariate model. Independent risk factors were transfer to ICU (SHR = 3.73, p = 0.029), neutrophil/lymphocyte ratio (SHR = 1.1, p = 0.001) and ET phenotype (SHR = 4.37, p = 0.006). The enhanced susceptibility to ET-associated VTE and the associated higher mortality for pneumonia may recognize a common biological plausibility and deserve to be delved to tailor new antithrombotic regimens including antiplatelet drugs.


Assuntos
Neoplasias da Medula Óssea/epidemiologia , COVID-19/epidemiologia , Transtornos Mieloproliferativos/epidemiologia , Trombocitemia Essencial/epidemiologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Medula Óssea/complicações , COVID-19/complicações , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/complicações , Pandemias , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/fisiologia , Trombocitemia Essencial/complicações
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