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1.
Cytometry A ; 95(9): 1008-1018, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31364809

RESUMO

Flow cytometry is broadly used for the identification, characterization, and monitoring of hematological malignancies. However, the use of clinical flow cytometry is restricted by its lack of reproducibility across multiple centers. Since 2006, the EuroFlow consortium has been developing a standardized procedure detailing the whole process from instrument settings to data analysis. The FranceFlow group was created in 2010 with the intention to educate participating centers in France about the standardized instrument setting protocol (SOP) developed by the EuroFlow consortium and to organise several rounds of quality controls (QCs) in order to evaluate the feasibility of its application and its results. Here, we report the 5 year experience of the FranceFlow group and the results of the seven QCs of 23 instruments, involving up to 19 centers, in France and in Belgium. The FranceFlow group demonstrates that both the distribution and applicability of the SOP have been successful. Intercenter reproducibility was evaluated using both normal and pathological blood samples. Coefficients of variation (CVs) across the centers were <7% for the percentages of cell subsets and <30% for the median fluorescence intensities (MFIs) of the markers tested. Intracenter reproducibility provided similar results with CVs of <3% for the percentages of the majority of cell subsets, and CVs of <20% for the MFI values for the majority of markers. Altogether, the FranceFlow group show that the 19 participating labs might be considered as one unique laboratory with 23 identical flow cytometers able to reproduce identical results. Therefore, SOP significantly improves reproducibility of clinical flow in hematology and opens new avenues by providing a robust companion diagnostic tool for clinical trials in hematology. © 2019 International Society for Advancement of Cytometry.


Assuntos
Citometria de Fluxo/métodos , Neoplasias Hematológicas/diagnóstico , Imunofenotipagem/normas , Bélgica , Citometria de Fluxo/instrumentação , Citometria de Fluxo/normas , Fluorescência , França , Neoplasias Hematológicas/sangue , Humanos , Imunofenotipagem/métodos , Linfócitos/citologia , Linfócitos/metabolismo , Monócitos/citologia , Monócitos/metabolismo , Controle de Qualidade , Padrões de Referência , Reprodutibilidade dos Testes
2.
Am J Hematol ; 94(10): 1123-1131, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31328307

RESUMO

Diagnosis of lymphoma leptomeningeal dissemination is challenging and relies on a wide array of methods. So far, no consensus biological guidelines are available. This increases the chance of intra- and interpractice variations, despite the shared concern to perform the minimum amount of tests while preserving clinically relevant results.We evaluated a training cohort of 371 cerebrospinal fluid (CSF) samples from patients with putative lymphomatous central nervous system (CNS) localization using conventional cytology (CC), flow cytometry (FCM), molecular clonality assesment by PCR and cytokine quantification (CQ). This led us to propose a biological algorithm, which was then verified on a validation cohort of 197 samples. The samples were classified according to the clinical context and the results of each technique were compared. Using all four techniques was not useful for exclusion diagnosis of CNS lymphoma (CNSL), but they proved complementary for cases with suspected CNSL. This was particularly true for CQ in primary CNSL. Overall, diagnosis can be obtained with a two-step approach. The first step comprises CC and FCM, as results are available quickly and FCM is a sensitive method. Both PCR and CQ can be postponed and performed in a second step, depending on the results from the first step and the clinical context.The proposed algorithm missed none of the CNSL samples of the validation cohort. Moreover, applying this algorithm would have spared 30% of PCR tests and 20% of CQ over a one-year period, without compromising clinical management.


Assuntos
Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Linfoma não Hodgkin/líquido cefalorraquidiano , Algoritmos , Doenças do Sistema Nervoso Central/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/patologia , Líquido Cefalorraquidiano/citologia , Células Clonais , Citocinas/líquido cefalorraquidiano , Detecção Precoce de Câncer , Reações Falso-Negativas , Reações Falso-Positivas , Citometria de Fluxo , Rearranjo Gênico do Linfócito B , Genes de Imunoglobulinas , Humanos , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/patologia , Meninges/patologia , Reação em Cadeia da Polimerase Multiplex , Invasividade Neoplásica , Hipermutação Somática de Imunoglobulina , Coloração e Rotulagem/métodos
3.
Gastroenterology ; 152(8): 2052-2062.e2, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28274850

RESUMO

BACKGROUND & AIMS: Interferon-free direct-acting antiviral (DAA) therapies are effective in patients with hepatitis C virus-induced cryoglobulinemia vasculitis (HCV-CV). We analyzed blood samples from patients with HCV-CV before and after DAA therapy to determine mechanisms of these drugs and their effects on cellular immunity. METHODS: We performed a prospective study of 27 consecutive patients with HCV-CV (median age, 59 y) treated with DAA therapy (21 patients received sofosbuvir plus ribavirin for 24 weeks, 4 patients received sofosbuvir plus daclatasvir for 12 weeks, and 2 patients received sofosbuvir plus simeprevir for 12 weeks) in Paris, France. Blood samples were collected from these patients before and after DAA therapy, and also from 12 healthy donors and 12 individuals with HCV infection without CV. HCV load, cryoglobulins, and cytokines were quantified by flow cytometry, cytokine multiplex assays, and enzyme-linked immunosorbent assay. RESULTS: Twenty-four patients (88.9%) had a complete clinical response of CV to DAA therapy at week 24, defined by improvement of all the affected organs and the absence of relapse. Compared with healthy donors and patients with HCV infection without CV, patients with HCV-CV, before DAA therapy, had a lower percentage of CD4+CD25hiFoxP3+ regulatory T cells (P < .01), but higher proportions of IgM+CD21-/low memory B cells (P < .05), CD4+IFNγ+ cells (P < .01), CD4+IL17A+ cells (P < .01), and CD4+CXCR5+interleukin 21+ follicular T-helper (Tfh) cells (P < .01). In patients with HCV-CV, there was a negative correlation between numbers of IgM+CD21-/low memory B cells and T-regulatory cells (P = .03), and positive correlations with numbers of Tfh cells (P = .03) and serum levels of cryoglobulin (P = .01). DAA therapy increased patients' numbers of T-regulatory cells (1.5% ± 0.18% before therapy vs 2.1% ± 0.18% after therapy), decreased percentages of IgM+CD21-/low memory B cells (35.7% ± 6.1% before therapy vs 14.9% ± 3.8% after therapy), and decreased numbers of Tfh cells (12% ± 1.3% before therapy vs 8% ± 0.9% after therapy). Expression levels of B lymphocyte stimulator receptor 3 and programmed cell death 1 on B cells increased in patients with HCV-CV after DAA-based therapy (mean fluorescence units, 37 ± 2.4 before therapy vs 47 ± 2.6 after therapy, P < .01; and 29 ± 7.3 before therapy vs 48 ± 9.3 after therapy, P < .05, respectively). CONCLUSIONS: In a prospective clinical trial of patients with HCV-CV, DAA-based therapy restored disturbances in peripheral B- and T-cell homeostasis.


Assuntos
Antivirais/uso terapêutico , Subpopulações de Linfócitos B/efeitos dos fármacos , Crioglobulinemia/tratamento farmacológico , Hepatite C/tratamento farmacológico , Vírus de Hepatite/efeitos dos fármacos , Imidazóis/uso terapêutico , Tolerância Imunológica/efeitos dos fármacos , Imunidade Celular/efeitos dos fármacos , Ribavirina/uso terapêutico , Simeprevir/uso terapêutico , Sofosbuvir/uso terapêutico , Subpopulações de Linfócitos T/efeitos dos fármacos , Vasculite/tratamento farmacológico , Idoso , Antivirais/efeitos adversos , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Subpopulações de Linfócitos B/virologia , Biomarcadores/sangue , Carbamatos , Estudos de Casos e Controles , Crioglobulinemia/diagnóstico , Crioglobulinemia/imunologia , Crioglobulinemia/virologia , Citocinas/sangue , Quimioterapia Combinada , Feminino , Hepatite C/complicações , Hepatite C/diagnóstico , Hepatite C/imunologia , Vírus de Hepatite/imunologia , Humanos , Imidazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Prospectivos , Pirrolidinas , Ribavirina/efeitos adversos , Simeprevir/efeitos adversos , Sofosbuvir/efeitos adversos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/virologia , Fatores de Tempo , Resultado do Tratamento , Valina/análogos & derivados , Vasculite/diagnóstico , Vasculite/imunologia , Vasculite/virologia , Carga Viral
5.
Haematologica ; 102(1): 43-51, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27758817

RESUMO

Bing Neel syndrome is a rare disease manifestation of Waldenström's macroglobulinemia that results from infiltration of the central nervous system by malignant lymphoplasmacytic cells. In this guideline we describe the clinical symptoms, as well as the appropriate laboratory and radiological studies, that can aid in the diagnosis. The presentation of Bing Neel syndrome may be very diverse, and includes headaches, cognitive deficits, paresis, and psychiatric symptoms. The syndrome can present in patients with known Waldenström's macroglobulinemia, even in the absence of systemic progression, but also in previously undiagnosed patients. Diagnostic work-up should include cerebral spinal fluid analysis with multiparameter flow cytometry to establish B-cell clonality, protein electrophoresis and immunofixation for the detection and classification of a monoclonal protein as well as molecular diagnostic testing for immunoglobulin gene rearrangement and mutated MYD88. MRI of the brain and spinal cord is also essential. The second challenge is to expand our knowledge of prognosis and treatment outcome. Prospective clinical trials on Bing Neel syndrome patients that employ uniform treatment along with appropriate laboratory cerebral spinal fluid assessments and standardized MRI protocols will be invaluable, constituting a significant step forward in delineating treatment outcome for this intriguing disease manifestation.


Assuntos
Fenótipo , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/terapia , Algoritmos , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Diagnóstico Diferencial , Testes Diagnósticos de Rotina , Gerenciamento Clínico , Humanos , Imageamento por Ressonância Magnética/métodos , Técnicas de Diagnóstico Molecular , Síndrome , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/epidemiologia , Macroglobulinemia de Waldenstrom/etiologia
6.
J Neurooncol ; 133(2): 315-320, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28432587

RESUMO

Primary CNS lymphoma (PCNSL) is chemosensitive to high-dose methotrexate-based chemotherapy. However, responses in the elderly are short-lasting and outcome is poor. Given that radiotherapy and intensive chemotherapy expose elderly to severe toxicities, alternative consolidation approaches need to be evaluated. In this multicenter study, we retrospectively analyzed consecutive patients with newly-diagnosed PCNSL, aged >60, treated with a (R)-MPV-AAA regimen. The regimen consisted of three 28-day cycles of methotrexate (3.5 g/m2 D1, D15), procarbazine, vincristine, followed by three 28-day cycles of cytarabine consolidation (3 g/m2 D1-2). Addition of rituximab (375 mg/m2 D1) was optional. The results were compared with the historical MPV-A regimen. Ninety patients received the (R)-MPV-AAA regimen with (n = 39) or without (n = 51) rituximab. Median age was 68 and median KPS 60. 55% of patients achieved a complete response, 8% a partial response and 37% progressed. The median PFS was 10 months, the median OS 28.1 months. Toxicity was mainly hematological, with 54 and 51% of grade III-IV neutropenia and thrombopenia. The response rate was higher in patients receiving rituximab (77 vs. 53%; p = 0.03), whereas no difference was observed in terms of PFS or OS. When comparing the results to the historical MPV-A, there was no difference in terms of response rate, PFS or OS, but a higher rate of hematotoxicity. This study suggests that extending cytarabine consolidation after methotrexate-based chemotherapy does not improve the MPV-A efficacy but increases toxicity in the elderly. The addition of rituximab may improve the response rate, but its impact on final outcome remains unclear.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Linfoma/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Citarabina/uso terapêutico , Feminino , Seguimentos , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Procarbazina/uso terapêutico , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do Tratamento
7.
Ann Rheum Dis ; 75(10): 1777-82, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26567178

RESUMO

BACKGROUND: Hepatitis C virus (HCV) is the aetiological agent for most cases of cryoglobulinaemia vasculitis. Interferon-containing regimens are associated with important side effects and may exacerbate the vasculitis. OBJECTIVE: To evaluate safety and efficacy of an oral interferon-free regimen, sofosbuvir plus ribavirin, in HCV-cryoglobulinaemia vasculitis. PATIENTS AND METHODS: We enrolled 24 consecutive patients (median age of 56.5 years and 46% of women) with HCV-cryoglobulinaemia vasculitis. Sofosbuvir (400 mg/day) was associated with ribavirin (200-1400 mg/day), for 24 weeks. The primary efficacy end point was a complete clinical response of the vasculitis at the end of treatment (week 24). RESULTS: Main features of HCV-cryoglobulinaemia vasculitis included purpura and peripheral neuropathy (67%), arthralgia (58%), glomerulonephritis (21%) and skin ulcers (12%). Twenty-one patients (87.5%) were complete clinical response at week 24. Complete clinical response was achieved in six (25%) patients at week 4, four (16.6%) at week 8, seven (29.2%) at week 12, three (12.5%) at week 16 and one (4.2%) at week 20. The cryoglobulin level decreased from 0.35 (0.16-0.83) at baseline to 0.15 (0.05-0.45) g/L at week 24. The C4 serum level increased from 0.10 (0.07-0.19) to 0.17 (0.09-0.23) g/L at week 24. Seventy-four per cent of patients had a sustained virological response at week 12 post treatment. The most common side effects were fatigue, insomnia and anaemia. Two serious adverse events were observed. CONCLUSIONS: Sofosbuvir plus ribavirin combination was associated with a high rate of complete clinical response and a low rate of serious adverse events in HCV-cryoglobulinaemia vasculitis.


Assuntos
Antivirais/administração & dosagem , Crioglobulinemia/tratamento farmacológico , Ribavirina/administração & dosagem , Sofosbuvir/administração & dosagem , Vasculite/tratamento farmacológico , Crioglobulinemia/virologia , Quimioterapia Combinada , Feminino , Hepacivirus , Hepatite C/complicações , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Vasculite/virologia
10.
J Neurol ; 268(8): 2890-2894, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33609156

RESUMO

BACKGROUND: Interleukin 6 (IL-6) is a pleomorphic cytokine that can be found in the cerebrospinal fluid (CSF) in a wide spectrum of inflammatory pathologies of the central nervous system (CNS). OBJECTIVE: Our aim was to characterize the diagnostic significance of CSF IL-6 among various CNS inflammatory diseases with pseudotumoral lesions (CNSID) and primary CNS lymphoma (PCNSL). METHODS: We retrospectively analyzed the CSF IL-6 concentrations in 43 consecutive patients with suspected PCNSL. A total of 28 patients were positively diagnosed with PCNSL and 15 with CNSID. We verified the results with CSF IL-10, an established biomarker for PCNSL. RESULTS: In the PCNSL group, the median CSF IL-6 concentration was 8 pg/ml, interquartile range (IQR) 5-18.5. For the patients with CNSID, the median concentration was 70 pg/ml, IQR 5-1368. A group comparison showed significantly higher CSF IL-6 levels in patients with CNSID than in those with PCNSL (p = 0.032). Moreover, IL-6 was correlated with CSF cell count in the CNSID group (r = 0.56, p = 0.028), but not in the PCNSL group (r = 0.3, p = 0.13). We found significantly higher CSF IL-10 levels in patients with PCNSL than in patients with CNS inflammatory lesions (p < 0.001). DISCUSSION AND CONCLUSIONS: Our study suggests that CSF IL-6 levels could represent, in addition to CSF IL-10, a useful biomarker in the differential diagnosis of CNSID and suspected PCNSL.


Assuntos
Neoplasias do Sistema Nervoso Central , Granuloma de Células Plasmáticas/diagnóstico , Interleucina-6/líquido cefalorraquidiano , Linfoma , Biomarcadores Tumorais , Neoplasias do Sistema Nervoso Central/diagnóstico , Diagnóstico Diferencial , Humanos , Linfoma/diagnóstico , Estudos Retrospectivos
11.
Ann Biol Clin (Paris) ; 78(5): 527-536, 2020 10 01.
Artigo em Francês | MEDLINE | ID: mdl-33026348

RESUMO

We report the case of a man with a primary diagnosis of Waldenström macroglobulinemia. He secondarily presented a diffuse large B cell lymphoma (DLBCL) located in the nasal fossae, which relapsed later in the eye. The diagnosis of these two malignancies is based on a multidisciplinary biological approach using new sensitive and specific techniques. These techniques revealed that the two diseases harbor different B cell clones, indicating a distinct origin. This observation highlights the importance of targeted biological techniques for the diagnosis of these two rare hemopathies. It also shows that it is possible to prove the independent nature of the two tumor clones, thus allowing optimized therapeutic management.


Assuntos
Carcinoma de Células de Transição/diagnóstico , Neoplasias Oculares/secundário , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/patologia , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Macroglobulinemia de Waldenstrom/diagnóstico , Idoso , Carcinoma de Células de Transição/sangue , Carcinoma de Células de Transição/complicações , Diagnóstico Diferencial , Neoplasias Oculares/sangue , Neoplasias Oculares/diagnóstico , Testes Hematológicos , Humanos , Imunoglobulina M/análise , Imunoglobulina M/sangue , Imunofenotipagem , Achados Incidentais , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/complicações , Masculino , Gamopatia Monoclonal de Significância Indeterminada/sangue , Gamopatia Monoclonal de Significância Indeterminada/complicações , Gamopatia Monoclonal de Significância Indeterminada/patologia , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/complicações , Urotélio/patologia , Baixa Visão/diagnóstico , Baixa Visão/etiologia , Macroglobulinemia de Waldenstrom/sangue , Macroglobulinemia de Waldenstrom/complicações , Macroglobulinemia de Waldenstrom/patologia
12.
Neurology ; 94(10): e1027-e1039, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-31907289

RESUMO

OBJECTIVE: Real-life studies on patients with primary CNS lymphoma (PCNSL) are scarce. Our objective was to analyze, in a nationwide population-based study, the current medical practice in the management of PCNSL. METHODS: The French oculo-cerebral lymphoma network (LOC) database prospectively records all newly diagnosed PCNSL cases from 32 French centers. Data of patients diagnosed between 2011 and 2016 were retrospectively analyzed. RESULTS: We identified 1,002 immunocompetent patients (43% aged >70 years, median Karnofsky Performance Status [KPS] 60). First-line treatment was high-dose methotrexate-based chemotherapy in 92% of cases, with an increasing use of rituximab over time (66%). Patients <60 years of age received consolidation treatment in 77% of cases, consisting of whole-brain radiotherapy (WBRT) (54%) or high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) (23%). Among patients >60 years of age, WBRT and HCT-ASCT consolidation were administered in only 9% and 2%, respectively. The complete response rate to initial chemotherapy was 50%. Median progression-free survival was 10.5 months. For relapse, second-line chemotherapy, HCT-ASCT, WBRT, and palliative care were offered to 55%, 17%, 10%, and 18% of patients, respectively. The median, 2-year, and 5-year overall survival was 25.3 months, 51%, and 38%, respectively (<60 years: not reached [NR], 70%, and 61%; >60 years: 15.4 months, 44%, and 28%). Age, KPS, sex, and response to induction CT were independent prognostic factors in multivariate analysis. CONCLUSIONS: Our study confirms the increasing proportion of elderly within the PCNSL population and shows comparable outcome in this population-based study with those reported by clinical trials, reflecting a notable application of recent PCNSL advances in treatment.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Antineoplásicos Imunológicos/farmacologia , Neoplasias do Sistema Nervoso Central/terapia , Irradiação Craniana/estatística & dados numéricos , Linfoma/terapia , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Transplante de Células-Tronco/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Neoplasias do Sistema Nervoso Central/epidemiologia , Terapia Combinada , Bases de Dados Factuais , França/epidemiologia , Humanos , Linfoma/epidemiologia , Metotrexato/farmacologia , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Rituximab/farmacologia , Transplante Autólogo , Adulto Jovem
13.
Semin Hematol ; 55(4): 179-181, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30502843

RESUMO

We here report for the first time that low levels of interleukin (IL)-10 do not exclude lymphomatous meningitis (LM) in B-cell lymphoproliferative disorders (CLPD). Unexpectedly, IL-10 levels and IL-10:IL-6 ratio in CLPD differed from the levels observed in diffuse large B-cell lymphoma (DLBCL). We report the usefulness of adding the IL-10:IL-6 ratio in order to potentially reveal more aggressive lymphomas: either a transformation or an association with another "hidden" lymphoma such as primary CNS lymphoma (PCNSL).


Assuntos
Biomarcadores/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/diagnóstico , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Ann Biol Clin (Paris) ; 75(3): 339-347, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28540857

RESUMO

We report the case of a 31 year-old man diagnosed with an atypical acute leukemia difficult to characterize cytologically. The immunophenotyping identified a blastic population co-expressing myeloid, lymphoid B and lymphoid T markers suggesting the diagnosis of either a mixed phenotype acute leukemia (MPAL) or an early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Because of the poor prognosis linked to these leukemias, the patient benefited from chemotherapy targeting both myeloid and lymphoid components, followed by allogeneic hematopoietic stem cell transplantation. DNA-based techniques analyzing B and T-cell clonality identified partial rearrangements in immunoglobulin and TCR genes, allowing the monitoring of minimal residual disease. This observation highlights the difficulty to classify some atypical cases of acute leukemias. It emphasizes on the complementarity of cytomorphology, immunophenotyping by flow cytometry and molecular techniques in order to promptly characterize and treat these leukemias.


Assuntos
Leucemia Aguda Bifenotípica/diagnóstico , Leucemia/patologia , Doença Aguda , Adulto , Linfócitos B/patologia , Humanos , Imunofenotipagem , Leucemia/imunologia , Leucemia Aguda Bifenotípica/imunologia , Leucemia Aguda Bifenotípica/patologia , Masculino , Células Mieloides/patologia , Linfócitos T/patologia
15.
Res Pract Thromb Haemost ; 1(1): 120-127, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30046680

RESUMO

INTRODUCTION: The complex hemostatic changes associated with Berlin Heart (BH) implantation in children require a challenging antithrombotic treatment. The aim of this retrospective analysis was to evaluate the thromboelastography (TEG)-platelet mapping (PM) assay to monitor antiplatelet therapy in children implanted with a BH. METHODS: TEG-PM was performed in 4 BH-implanted patients receiving dipyridamole and aspirin, and 9 healthy volunteers. Patients' antiplatelet therapy was adjusted to TEG-PM results. Light transmission aggregometry (LTA) was also available for 2 of these patients. RESULTS: Between 2009 and 2014, 4 BH-implanted patients received a dual antiplatelet therapy monitored by TEG-PM. In 2 patients, 18 of 34 tracings were atypical, because the maximum amplitude due to fibrin never stabilized, which made difficult antiplatelet therapy adjustment as recommended by BH's guidelines. To overcome this difficulty, TEG-PM and LTA were next performed in parallel. However, both methods led to different decisions to adjust antiplatelet therapy in 57% of the cases. In order to better understand this atypical tracing, TEG-PM was also performed in 9 volunteers and surprisingly 3 of them had the same atypical tracing. This atypical tracing was corrected by adding apyrase, suggesting that adenosine diphosphate (ADP) participates to spontaneous platelet activation in heparinized samples. In addition, we evidenced a high variability in the responses of TEG-PM with ADP in volunteers. CONCLUSIONS: Antiplatelet therapy monitoring in BH-implanted children remains challenging, as TEG-PM is sensitive to several preanalytical and analytical conditions.

16.
Expert Rev Hematol ; 9(11): 1081-1091, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27677656

RESUMO

INTRODUCTION: Making the diagnosis of secondary CNS involvement in lymphoma can be difficult due to unspecific signs and symptoms, limited accessibility of brain/myelon parenchyma and low sensitivity and/or specifity of imaging and cerebrospinal fluid (CSF) examination currently available. Areas covered: MRI of the total neuroaxis followed by CSF cytomorphology and flow cytometry are methods of choice when CNS lymphoma (CNSL) is suspected. To reduce the numerous pitfalls of these examinations several aspects should be considered. New CSF biomarkers might be of potential diagnostic value. Attempts to standardize response criteria are presented. Expert commentary: Diagnosing CNSL remains challenging. Until diagnostic methods combining high sensitivity with high specifity are routinely introduced, high level of awareness and optimal utilization of examinations currently available are needed to early diagnose this potentially devastating disease.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/secundário , Linfoma/patologia , Biomarcadores , Neoplasias do Sistema Nervoso Central/terapia , Citodiagnóstico/métodos , Diagnóstico Diferencial , Detecção Precoce de Câncer , Humanos , Imagem Multimodal/métodos , Avaliação de Resultados em Cuidados de Saúde , Fenótipo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
Eur J Cancer ; 61: 69-76, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27156226

RESUMO

INTRODUCTION: We aimed to confirm the diagnostic value and to evaluate the pre- and post-therapeutic prognostic value of cerebrospinal fluid (CSF) concentrations of interleukin (IL)-10 and IL-6 in patients with diffuse large B-cell primary central nervous system lymphoma (PCNSL). PATIENTS AND METHODS: IL-10 and IL-6 concentrations were measured in 79 patients with PCNSL at diagnosis and in 40 control individuals. Fifty-four PCNSL patients underwent repeat assessments starting at diagnosis. RESULTS: The IL-10 concentration distinguished PCNSL from other neurologic diseases with a sensitivity of 88.6% and a specificity of 88.9% with a cutoff of 4 pg/ml. In a multivariate analysis of PCNSL patients, CSF involvement was associated with a higher IL-10 concentration (mean log (IL-10) of 4.4 versus 2.5 pg/ml, respectively, p = 0.0004). The pre-therapeutic IL-10 concentration had no prognostic impact on outcome. The IL-10 concentration decreased after treatment for most patients tested. Among patients with complete remission or partial remission, as evaluated by magnetic resonance imaging (MRI), a persistent detectable IL-10 level in the CSF at the end of treatment was associated with a negative impact on progression-free survival (PFS) (1-year PFS: 15%, 95% confidence interval [CI]: 2.5-38% versus 59%, 95% CI: 32-78%, respectively, p = 0.0004). CONCLUSION: Our study confirmed that IL-10 is a useful biomarker for the diagnosis of PCNSL. We highlight new findings showing that the IL-10 level in the CSF could be used as a surrogate marker for CSF involvement and that the post-treatment IL-10 concentration could complement standard MRI for therapeutic response assessment in PCNSL.


Assuntos
Biomarcadores Tumorais/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/diagnóstico , Interleucina-10/líquido cefalorraquidiano , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Intervalo Livre de Doença , Feminino , Humanos , Interleucina-6/líquido cefalorraquidiano , Modelos Logísticos , Linfoma não Hodgkin , Masculino , Pessoa de Meia-Idade , Prognóstico , Sensibilidade e Especificidade , Adulto Jovem
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