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PURPOSE: This phase II clinical trial evaluated the combination of Ibrutinib with rituximab, gemcitabine and oxaliplatin (R-GemOx) in patients with non-germinal centre B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: The IBDCL trial (NCT02692248) included patients with histological diagnosis of non-GCB DLBCL with relapsed or refractory disease and non-candidates for stem cell transplantation. Patients received an induction treatment consisting of 6 or 8 cycles of R-GemOx at standard doses every 2 weeks, in combination with ibrutinib (560 mg daily), followed by a maintenance treatment with ibrutinib for a maximum of 2 years. The primary objective was to evaluate the overall response rate (ORR) after 4 cycles. RESULTS: Sixty-four patients were included, 72% of them refractory to the last regimen. The ORR and CR rate after the 4th cycle were 53% (95% confidence interval [CI], 41-65) and 34% (95% CI, 24-46), respectively. Twenty-four (37%) patients started maintenance and 7 (11%) completed the planned 2 years. After a median follow-up of 29.7 months (range: 0.4-48.6), the estimated 2-year PFS and OS were 18% (95% CI, 8 - 28) and 26% (95% CI, 14 - 37), respectively. The most common grade ≥3 treatment-related adverse events (TRAEs) were thrombocytopenia (44%), neutropenia (30%) and anemia (14%). Grade ≥3 infectious and cardiovascular TRAEs were reported in 6 (9%) and 1 (2%) patient, respectively. CONCLUSIONS: Ibrutinib in combination with R-GemOx, followed by ibrutinib maintenance, demonstrated encouraging antitumor activity with durable responses and a manageable toxicity in patients with non-GCB DLBCL.
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PURPOSE: To analyze using Pentacam®, the corneal and anterior chamber changes following periocular botulinum toxin injection in patients with facial dystonia. METHODS: Prospective study that included patients with facial dystonia that were going to receive a periocular botulinum toxin injection for the first time or six months or more after the previous injection. A Pentacam® examination was carried out in all patients before and 4 weeks after the injection. RESULTS: Thirty-one eyes were included. Twenty-two had a diagnosis of blepharospasm and nine of hemifacial spasm. Analysis of corneal and anterior chamber parameters revealed a significant decrease in iridocorneal angle after botulinum toxin injection (from 35 ± 10º to 33.8 ± 9.7º, p = 0.022). No other corneal or anterior chamber parameters changed significantly after the injection. CONCLUSIONS: Periocular botulinum toxin injection causes narrowing of the iridocorneal angle.
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Blefarospasmo , Toxinas Botulínicas Tipo A , Toxinas Botulínicas , Distonia , Espasmo Hemifacial , Humanos , Blefarospasmo/tratamento farmacológico , Toxinas Botulínicas/efeitos adversos , Espasmo Hemifacial/tratamento farmacológico , Estudos Prospectivos , Distonia/tratamento farmacológico , Câmara Anterior , Injeções Intraoculares , Toxinas Botulínicas Tipo A/efeitos adversosRESUMO
BACKGROUND: To learn about the experiences and opinions of adolescent non-consumers and regular cannabis users about cannabis use and the factors that determine its use, using the I-Change explanatory model as a basis. METHODS: Qualitative methodology with a content analysis was used. Focus groups were conducted with adolescents who were non-regular cannabis users (those who had not tried cannabis or had only experimented with it before) and semi-structured interviews were conducted with adolescent and young adult in recovery who were in a detoxification program. A deductive analysis of the audio-recorded and transcribed interviews was performed, using the domains of the I-Change Model as a reference. RESULTS: Personal problems, social problems or family problems can lead to cannabis use. There was a lack of knowledge and low risk perception about consumption of this drug. There are other factors that influence consumption, the perception of advantages, such as the feeling of freedom and the influence of the peer group. The consumption of this substance in girls is changing, becoming more and more equal to that of boys. The family has an important role to play in preventing drug use. CONCLUSION: Knowledge of these factors is of vital importance as a prior step to the development of efficient intervention measures adjusted to the needs identified and the characteristics of the population.
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INTRODUCTION: Vaccination is a fundamental intervention in disease prevention; therefore, the advice and recommendations of health professionals have a major influence on the population's decision to be vaccinated or not. Professionals must have sufficient competencies to carry out their work and recommend vaccination with evidence-based knowledge. The aim is to design and validate a strategy to improve professional competencies in vaccination to positively influence adherence and increase vaccination rates in the population. METHODS AND ANALYSIS: Training will be designed based on evidence and previous studies and piloted with healthcare providers. To test changes in knowledge, a pretest and post-test will be conducted. To test feasibility, a think-aloud method will be used with participants and triangulated with focus groups using SWOT (strengths, weaknesses, opportunities and threats) analysis. Transfer will be measured using the questionnaire 'factors for the indirect evaluation of transfer' and an efficacy questionnaire 1½ months later; for satisfaction, an ad hoc questionnaire will be used. A summative approach will be used for the analysis of the focus groups and descriptive and bivariate statistics for the questionnaires. ETHICS AND DISSEMINATION: This study was approved by the Andalusian Research Ethics Committee, Spain (approval number: 0524-N-20). The results will be made available to the public at journal publications and scientific conferences.
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Pessoal de Saúde , Vacinas , Educação Continuada , Pessoal de Saúde/educação , Humanos , Atenção Primária à Saúde , Projetos de PesquisaRESUMO
The gastrointestinal contents of twelve individuals from six odontocete species that stranded between 2018 and 2019 in the Macaronesian Region (Eastern North Atlantic) were examined for the presence of marine debris. In addition, concentrations of eleven organic persistent contaminants (nonylphenols, bisphenols, phthalates and pesticides) were analysed in muscle samples by liquid chromatography. No particles larger than 5 mm were found, except for two plastic labels that were found on the same dolphin. On the contrary, all animals contained microplastics of diverse sizes, most of them being fibres (98.06%, n = 708). The predominant detected pollutants were bisphenols (4-984 ng/g) and DEHP (102-1533 ng/g). Also, except for two individuals, all animals had pesticide levels in their tissues. This work has allowed the establishment of a protocol for the study of microplastic ingestion in cetaceans, and tests the potential of microRaman to improve the understanding of microplastic alteration processes.
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Praguicidas , Poluentes Químicos da Água , Animais , Monitoramento Ambiental , Microplásticos , Plásticos , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: Human papillomavirus (HPV) is one of the most common sexually transmitted infections and can be prevented by vaccination. The purpose of this study is to gain a better understanding, by analysing interview responses of adolescents and parents, of how adolescent sexual behaviour is approached in families, how widespread knowledge about HPV is in Andalusia, the autonomous region with the lowest vaccination rate in Spain, as well as to learn more about the interviewees' position regarding vaccination. METHODS: A qualitative study by means of 15 focus groups of adolescents (N = 137, aged 14-17 years) and five focus groups of parents with children of those ages (N = 37) was conducted in the provinces of Granada, Seville and Jaén (Andalusia, Spain). The audio data were transcribed verbatim, coded and analysed thematically using NVIVO-10 software. RESULTS: There were three major results: (1) There is a lack of communication between adolescents and parents regarding sexual behaviour; (2) In both groups, scarce knowledge about HPV and vaccination was found; (3) Parents mistrust vaccination due to a lack of qualified and verified information about its benefits. CONCLUSIONS: Healthy adolescent sexual behaviour is aided by communication within the family. Families need more information based on the evidence about HPV and vaccination. Health professionals are a key element in this process.
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Alphapapillomavirus , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Adolescente , Criança , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Papillomaviridae , Infecções por Papillomavirus/prevenção & controle , Pais , Aceitação pelo Paciente de Cuidados de Saúde , Comportamento Sexual , Espanha , VacinaçãoRESUMO
INTRODUCTION AND OBJECTIVES: Since different PET/CT (Positron Emission Tomography/Computed Tomography) scanners give different qualitative readings, a program for clinical trial qualification (CTQ) is mandatory to guarantee a reliable and reproducible use of PET/CT in prospective multi-centre clinical trials. Within this work we will show the results carried out in performing CTQ in Spain. MATERIALS AND METHODS: We set up, under the auspices of Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GELTAMO), a CTQ program consisting of the acquisition and analysis of 18F uniformity and image quality phantoms for the reduction of inter-scanner variability (ISV). The ISV was estimated on background activity concentration (BAC) and sphere to background ratio (SBR) and defined as their 95% confidence level. RESULTS: Twenty-six out of 27 (96%) scanners fulfilled the CTQ requirements. The CTQ was fulfilled at the first round in 27% of the cases, while in 38%, 15% and 20%, two, three or more than three iterations, were required, respectively. The mean CTQ time was (1.8 ± 1.4) months (range: 0.3-4.6). The ISV in BAC and SBR were 20.3% and 67.7%. CONCLUSIONS: The CTQ proven to be a reliable tool to reduce ISV. This enabled to set-up clinical trials in which PET/CT was used to evaluate different clinical endpoints.
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The University Hospital of Salamanca, in Spain, had its first COVID-19 case on March 1st and as of May 11th, we had 1,100 positive cases. Based on the vulnerability of patients with blood cancers, on March 9th, the Hematology Department developed a protocol, amended as the new information was available, to maintain the Hematology Unit as a "free COVID-19 island." The protocol included symptom-based surveys and screening tests to patients, caregivers, and healthcare personnel to identify early potential positive cases and prevent its spread. Between March 9 and April 28, 32 asymptomatic patients and caregivers were tested and 68 rT-PCR diagnostic assays have been performed with two positive results. A 106 healthcare workers have been tested (208 rT-PCR) and seven of them were positive. In summary, the implementation of preemptive measures after the first case appeared allowed us to be able to provide treatment to our patients.
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BACKGROUND Paraneoplastic cerebellar degeneration (PCD) is a rare condition that can present as an acute or subacute cerebellar syndrome. PCD is most commonly associated with gynecological and breast cancer, small-cell lung cancer, and classical Hodgkin's lymphoma. The symptoms of PCD can arise several months before tumor diagnosis. This report is of a case of a 44-year-old man with PCD that preceded the diagnosis of classical Hodgkin's lymphoma by 16 months. CASE REPORT A 44-year-old man was admitted to hospital with a cerebellar syndrome that was initially diagnosed as vertebrobasilar insufficiency. Eight months later, cerebral magnetic resonance imaging (MRI) findings and serum anti-Tr antibodies supported the diagnosis of PCD, but no underlying malignancy was initially found. At 16 months after the initial diagnosis of PCD, the patient developed an enlarged inguinal lymph node. Histology of the excisional lymph node biopsy confirmed the diagnosis of classic mixed cellularity Hodgkin's lymphoma, Ann Arbor stage IIA. The patient responded to four cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. CONCLUSIONS This case illustrates that in patients who present with PCD, an associated malignancy, such as classical Hodgkin's lymphoma, may emerge several months later, which supports long-term follow-up. The presence of anti-Tr antibodies may support a diagnosis of classical Hodgkin's lymphoma in a patient with a history of PCD who develops lymphadenopathy.
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Doença de Hodgkin/diagnóstico , Degeneração Paraneoplásica Cerebelar/diagnóstico por imagem , Adulto , Antibióticos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Bleomicina/uso terapêutico , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Doença de Hodgkin/complicações , Doença de Hodgkin/tratamento farmacológico , Humanos , Imageamento por Ressonância Magnética , Masculino , Degeneração Paraneoplásica Cerebelar/complicações , Vimblastina/uso terapêuticoRESUMO
The biology and clinical impact of bone marrow (BM) infiltration in patients with diffuse large B-cell lymphoma (DLBCL) remains unclear in the rituximab era. We retrospectively analyzed 232 patients diagnosed with DLBCL at our center between 1999 and 2014. Concordant-presence of large cells similar to those of the lymph node biopsy- and discordant-infiltration by small cells forming lymphoid aggregates, lacking cytological atypia-BM infiltration was defined by histological criteria and further characterized by flow cytometry (FCM). Cell of origin (COO) was determined using Hans' algorithm. For the clonal relationship between tumor and discordant BM, the VDJH rearrangement was analyzed. Survival analyses were restricted to 189 patients treated with rituximab and chemotherapy. Thirty-six (16%) had concordant, and 37 (16%) discordant BM infiltration. FCM described different indolent lymphomas among discordant cases, clonally related with DLBCL in 10/13 available samples. Median follow-up was 58 months. 5-year-progression-free survival (PFS) for non-infiltrated, discordant and concordant groups was 68%, 65% and 30%, respectively (p < 0.001). Combining COO and BM infiltration, patients with discordant BM and non-germinal center B-cell COO also had decreased 5-year-PFS (41.9%). In multivariate analysis, concordant BM had an independent effect on PFS (HR 2.5, p = 0.01). Five-year cumulative incidence of central nervous system (CNS) relapse was 21%, 4% and 1% in concordant, discordant and non-infiltrated groups, respectively (p < 0.001). In conclusion, concordant BM infiltration represents a subset with poor prognosis, whereas the prognostic impact of discordant BM infiltration could be limited to non-CGB cases.
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BACKGROUND: Consensus is lacking regarding the optimal salvage therapy for patients with follicular lymphoma who relapse after or are refractory to immunochemotherapy. METHODS: This phase II trial evaluated the efficacy and safety of response-adapted therapy with rituximab, bendamustine, mitoxantrone, and dexamethasone (RBMD) in follicular lymphoma patients who relapsed after or were refractory to first-line immunochemotherapy. Sixty patients received three treatment cycles, and depending on their response received an additional one (complete/unconfirmed complete response) or three (partial response) cycles. Patients who responded to induction received rituximab maintenance therapy for 2 years. RESULTS: Thirty-three (55%) and 42 (70%) patients achieved complete/unconfirmed complete response after three cycles and on completing induction therapy (4-6 cycles), respectively (final overall response rate, 88.3%). Median progression-free survival was 56.4 months (median follow-up, 28.3 months; 95% CI, 15.6-51.2). Overall survival was not reached. Progression-free survival did not differ between patients who received four vs six cycles (P = .6665), nor between patients who did/did not receive rituximab maintenance after first-line therapy (P = .5790). Median progression-free survival in the 10 refractory patients was 25.5 months (95% CI, 0.6-N/A) and was longer in patients who had shown progression of disease after 24 months of first-line therapy (median, 56.4 months; 95% CI, 19.8-56.4) than in those who showed early progression (median, 42.31 months; 95% CI, 24.41-NA) (P = .4258). Thirty-six (60%) patients had grade 3/4 neutropenia. Grade 3/4 febrile neutropenia and infection were recorded during induction (4/60 [6.7%] and 5/60 [8.3%] patients, respectively) and maintenance (2/43 [4.5%] and 4/43 [9.1%] patients, respectively). CONCLUSIONS: This response-adapted treatment with RBMD followed by rituximab maintenance is an effective and well-tolerated salvage treatment for relapsed/refractory follicular lymphoma following first-line immunochemotherapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov # NCT01133158.
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Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cloridrato de Bendamustina/uso terapêutico , Dexametasona/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Mitoxantrona/uso terapêutico , Rituximab/uso terapêutico , Terapia de Salvação , Adulto , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina/efeitos adversos , Dexametasona/efeitos adversos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imunoterapia , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Mitoxantrona/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Intervalo Livre de Progressão , Rituximab/efeitos adversosAssuntos
Doença de Hodgkin/genética , Carioferinas/genética , Mutação de Sentido Incorreto , Proteínas de Neoplasias/genética , Mutação Puntual , Receptores Citoplasmáticos e Nucleares/genética , Adulto , Distribuição por Idade , Idoso , Feminino , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/patologia , Humanos , Linfonodos/química , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Índice de Gravidade de Doença , Distribuição por Sexo , Espanha/epidemiologia , Análise de Sobrevida , Proteína Exportina 1RESUMO
Plitidepsin is a cyclic depsipeptide that was first isolated from a Mediterranean marine tunicate (Aplidium albicans) and, at present, is manufactured by total synthesis and commercialized as Aplidin®. Its antitumor activity, observed in preclinical in vitro and in vivo studies has prompted numerous clinical trials to be conducted over the last 17 years, alone or in combination with other anticancer agents. Single-agent plitidepsin has shown limited antitumor activity and a tolerable safety profile in several malignancies, such as noncutaneous peripheral T-cell lymphoma, melanoma, and multiple myeloma. In patients with relapsed or refractory multiple myeloma, plitidepsin activity seems to be enhanced after addition of dexamethasone while remaining well tolerated, and a Phase III trial comparing plitidepsin plus dexamethasone vs dexamethasone alone is underway. Additional studies are required to better define the role of plitidepsin in combination with other active agents in these indications. Results of plitidepsin activity in other hematological malignancies or solid tumors have been disappointing so far. Further studies analyzing its mechanisms of action and potential biomarkers will help select patients who may benefit most from this drug. In this review, we critically analyze the published studies on plitidepsin in hematological malignancies and solid tumors and discuss its current role and future perspectives in treating these malignancies. We also review its design, pharmaceutical data, and mechanism of action.
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Antineoplásicos Fitogênicos/uso terapêutico , Depsipeptídeos/uso terapêutico , Desenho de Fármacos , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/química , Depsipeptídeos/síntese química , Depsipeptídeos/química , Humanos , Peptídeos CíclicosRESUMO
Prognostic factors in Hodgkin lymphoma (HL) still fail to accurately identify high-risk patients. Tumor microenvironment in HL is a current focus of research for risk definition but few studies have focused on infiltrating lymphocytes. Here, we analyzed the number of tumor infiltrating lymphocytes by flow cytometry in diagnostic biopsies from 96 HL homogeneously treated patients with ABVD with or without radiotherapy. Most lymph node cells were lymphocytes (90 ± 17), with a median T/B/NK distribution of 74%/26%/0.7%, and CD4+ T-cell predominance. The amount of CD19+ B cells, and NK cells did not show association with disease features. However, high numbers of CD8+ and CD4+ cells were associated with better and poorer outcomes, respectively. Patients with ≥15% cytotoxic CD8+ cells among the total cell population had a longer 10-year freedom from treatment failure (FFTF) (93% vs. 73%, p=.04). In turn, cases with ≥75% of CD4+ infiltrating cells showed a significantly decreased FFTF (73% vs. 96%, p=.021). Consequently, CD4/CD8 ratio ≥5 associated with a poorer 10-year FFTF (69.5% vs. 94%, p=.02). This deleterious effect was particularly prominent in advanced disease (n = 58, p=.01). In multivariate analysis, a CD4/CD8 ratio ≥5 was the only independent variable to predict for treatment failure (HR = 4.5, 95% confidence interval, 1.2-16.8). In conclusion, our study shows that high CD4+ and low CD8+ T-cells infiltrates of tumor specimens associate with poor prognosis in HL patients, and CD4/CD8 ratio might be potentially useful for tailoring therapy.
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Doença de Hodgkin/imunologia , Doença de Hodgkin/mortalidade , Linfonodos/imunologia , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/imunologia , Subpopulações de Linfócitos T/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Bleomicina/efeitos adversos , Bleomicina/uso terapêutico , Relação CD4-CD8 , Criança , Dacarbazina/efeitos adversos , Dacarbazina/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Imunofenotipagem , Estimativa de Kaplan-Meier , Linfonodos/metabolismo , Linfonodos/patologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Prognóstico , Curva ROC , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia , Resultado do Tratamento , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , Adulto JovemRESUMO
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.
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Neoplasias do Sistema Nervoso Central/secundário , Neoplasias do Sistema Nervoso Central/terapia , Sistema Nervoso Central/patologia , Células Dendríticas/patologia , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Adolescente , Adulto , Idoso , Criança , Feminino , Neoplasias Hematológicas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Experience is limited with regard to antithrombotic therapy in patients with venous thromboembolism (VTE) following allogeneic hematopoietic stem cell transplantation (HSCT). DESIGN AND METHODS: We described a cohort of patients presenting with symptomatic VTE following allogeneic HSCT, including management patterns and outcomes. RESULTS: Twenty-four patients developed a deep vein thrombosis and/or pulmonary embolism unrelated to a catheter. Median time of VTE diagnosis and duration of antithrombotic therapy were 9.5 and 6months. Eleven patients were treated with full-dose low molecular weight heparin (LMWH). Eleven patients with minor bleeding, thrombocytopenia or renal failure received prophylactic dose LMWH. In two patients an inferior vena cava filter was inserted due to thrombocytopenia and bleeding. There were 2 major and 4 life-threatening bleeding episodes, so LMWH was discontinued permanently. Two deaths were directly attributable to bleeding. Ten patients developed a catheter-associated VTE. Median time to diagnosis and duration of anticoagulation was 2.5 and 3months. Catheter was removed in all patients. LMWH was administered at therapeutic-dose in 4 patients, and was reduced by bleeding in 2 of them. LMWH was administered at prophylactic-dose in 6 patients, and was reduced by renal failure in one patient. There were three episodes of minor bleeding. Rate of clot recurrence was 29.4% (n=10). Patients at recurrence were without antithrombotic treatment (n=4), intermediate-dose LMWH (n=2), low-dose LMWH (n=2) or acenocumarol (n=2). Eight patients with recurrence VTE had extensive chronic graft versus host disease (GVHD). CONCLUSIONS: LMWH was used in most HSCT recipients but half of them may not receive full-dose LMWH. Thrombocytopenia, renal impairment and bleeding were the reasons for reducing LMWH. Also, rates of clinically relevant hemorrhage or recurrent VTE were highly significant. The development of GVHD could mainly explain these findings.
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Anticoagulantes/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Adulto , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Gerenciamento Clínico , Feminino , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Trombocitopenia/induzido quimicamente , Resultado do Tratamento , Adulto JovemRESUMO
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.
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Células Dendríticas/patologia , Neoplasias Hematológicas/classificação , Neoplasias Cutâneas/classificação , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/patologiaRESUMO
INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity, showing a highly variable outcome. In patients with DLBCL relapsed/refractory to first-line treatment with rituximab the usefulness of the revised International Prognostic Index (R-IPI) as a prognostic tool remains unexplored. Some biological parameters (B-cell lymphoma 6 [Bcl-6], Bcl-2, p53, and multiple myeloma 1 [MUM1]) and blood populations (lymphocyte and monocyte counts) have been described as International Prognostic Index-independent prognostic factors. The objective was to evaluate the R-IPI to predict the outcome of DLBCL patients at the time of relapse after a front-line treatment with chemotherapy and rituximab and to establish in this population the relationship between biological parameters and outcome. PATIENTS AND METHODS: We included patients with refractory/relapsed DLBCL after first-line treatment with rituximab-containing regimens; patients must have already finished a rescue treatment also including rituximab. Immunohistochemical assessment of Bcl-2, Bcl-6, p53, and MUM1 expression were undertaken in available biopsies. R-IPI factors were identified from the clinical data at diagnosis and at relapse. Response was assessed using National Cancer Institute-sponsored Working Group guidelines. RESULTS: R-IPI prognosis at relapse was not significantly associated with overall response rate (ORR) after Rituximab-chemotherapy rescue therapy. None of the immunohistochemical parameters analyzed correlated with rescue therapy results. In contrast, patients with absolute lymphocyte count (ALC) ≥ 1 × 10(9)/L at relapse were more likely to respond than patients with ALC < 1 × 10(9)/L (P = .05). CONCLUSION: The R-IPI score calculated at relapse could not predict the ORR to second-line treatment. Lymphopenia is a simple and useful predictor for outcome in relapsed/refractory DLBCL and the only prognostic factor that in our hands could predict the overall response to a second-line treatment with rituximab and chemotherapy.