Navegando por Palavras-chave "Leucemia Linfocítica Crônica"

Agora exibindo 1 - 2 de 2
  • Imagem de Miniatura
    Item
    Restrito
    Avaliação da Expressão da Vimentina em Leucemia Linfocítica Crônica e sua importância como fator de prognóstico
    (Universidade Federal de São Paulo (UNIFESP), 2010-02-24) Siufi, Grazziella Curado [UNIFESP]; Yamamoto, Mihoko [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Purpose: In this study our purpose was to evaluate the prognostic significance of the vimentin expression on CLL cells, from peripheral blood (PB) and bone marrow (BM) biopsy samples, correlating with already well known prognostic markers in CLL such as mutational status of IgVH genes, expression of CD38, Zap-70 protein, and VEGFR, molecular cytogenetics (FISH) results and with Binet’s clinical stage and progression free survival (PFS) Methods: Sixty six patients with CLL from Hospital São Paulo-UNIFESP were studied. The CLL diagnosis was established by leukemic cells immunophenotyping using score system (Moreau et al). PB cells were collected at admission and evaluated by flow cytometry for CD38 (through positive cells percentage and mean fluorescence intensity –MFI- methods) and Zap-70, VEGFR and Vimentin expressions. For the last ones (Vimentin and VEGFR) mononuclear cells separated by Ficoll Hypaque gradient were used. The Vimentin expression was evaluated in fresh and/or cryopreserved blood samples and also in BM biopsy specimens obtained at the time of diagnosis, by immunohistochemistry.The BM infiltration pattern was also evaluated. The IgVH genes mutational status was evaluated by PCR techniques followed by sequencing. Results: Vimentin expression in both circulating and marrow cells was associated with VEGFR positive expression, unmutated IgVH genes, diffuse bone marrow infiltration and unfavourable cytogenetics abnormalities. Association of CD38 expression was observed only in BM. Advanced clinical stage, age>68 years, positive expression for CD38 and VEGFR, unmutated IgVH genes, unfavourable cytogenetics abnormalities, vimentin expression in PB and BM cells and diffuse marrow infiltration pattern were associated with short PFS. The impact of these prognostic markers was also observed in Binet A patients. In multivariate analysis, the Binet’s stages B+C (p=0,008), strong unimodal and bimodal IMF pattern of CD38 (p=0,03), diffuse marrow infiltration (p=0,02) and vimentin expression on BM cells by immunohistochemistry (p=0,002) were identified as independent risk factor for reduced PFS. Comparison of Vimentin expression in PB cells by flow cytometry and in BM cells by immunohistochemistry from the same patients, showed concordant results. When vimentin expression in fresh and thawed samples from the same patients was compared, concordant results were also observed. Conclusions: Vimentin expression in CLL cells from both PB and BM showed high impact as prognostic marker, predicting poor PFS, even in Binet A patients. Both flow cytometry and immunohistochemistry are relatively easy techniques and feasible in most flow cytometric or pathological laboratories, requiring the usual routine equipments. Our results were comparable to IgVH mutational status suggesting the usefulness of Vimentin as prognostic marker in CLL patients. In addition its evaluation might be useful for the better understanding of pathofisiology of CLL and also, for the therapeutic interventions, such as the use of EGCG (epigallocatechin galate – green tea).
  • Imagem de Miniatura
    Item
    Acesso aberto (Open Access)
    Comparação das características clínicas, laboratoriais e dos desfechos de pacientes com leucemia linfocítica crônica acompanhados em hospitais públicos ou privados no Brasil: uma análise retrospectiva do Registro Brasileiro de Leucemia Linfocítica Crônica
    (Universidade Federal de São Paulo (UNIFESP), 2020-12-18) Pfister, Verena [UNIFESP]; Silva, Celso Arrais Rodrigues Da [UNIFESP]; Universidade Federal de São Paulo
    Introduction: Chronic lymphocytic leukemia (CLL) typically occurs in elderly patients and has a highly variable clinical course. It is important to understand the aspects that affect the outcomes of CLL in a real-world setting. In addition to biological factors, socioeconomic and health system characteristics may also influence the clinical course and outcome of CLL. Data from the Brazilian Registry of CLL was analyzed to compare clinical and treatmentrelated characteristics in patients with CLL followed in public or private institutions in Brazil. Objective: To describe the clinical and laboratory characteristics and outcomes of a series of CLL patients followed in public or private hospitals in Brazil. Methods: The Brazilian Registry of CLL started in 2004 as a prospective non-interventional data collection tool. All patients with minimum available data required on patient and disease characteristics and survival were included. Results/discussion: From January 2004 to August 2020, 3053 patients from 37 centers met eligibility criteria for this analysis: 2449 (80%) were followed at public hospitals and 604 (20%) at private institutions. The majority were male (57%), with median age of 66 years (ranging from 23 to 106). Binet stage at diagnosis was A in 1678 (58%) patients, B in 652 (23%) and C in 540 (19%). FISH for del(17p) was performed in only 486 patients (16%), while FISH for the most common aberrations [del(13q), +12, del(11q), and del(17p)] was performed in 446 patients (15%). IGHV mutational status was performed in only 214 patients (7%), and karyotype in only 173 patients (6%). Comparing public and private hospitals, we observed that patients in public hospital are older (median age 66 years vs. 63 years for private hospitals, P<0.0001), had more advanced disease at diagnosis (frequency of Binet B or C was 44% in public vs. 33% in private hospital, P<0.0001), more frequently had elevated creatinine levels (18% vs. 10%, P<0.0001). All prognostic markers were performed more often in private than in public hospitals: FISH for del17p (42% of cases vs. 10%, respectively, P<0.0001), IGHV mutational status (13% vs. 6%, respectively,P<0.0001) and karyotype (16% vs. 3%, respectively, P<0.0001). The frequency of a positive FISH for del(17p) was similar between public and private hospitals (11% vs. 9%, P=0.65), as well as the frequency of unmutated IGHV status (60% vs. 49%, P=0.12). Analyzing 1080 patients who have been treated since 2008, treatment was performed after a median time follow up of 6 months (range: 0-290) after diagnosis. First line treatment was predominantly based on chlorambucil in 43% of cases and in fludarabine in 39%. Anti-CD20 monoclonal antibody was used in only 35% of cases (rituximab in 32% and obinutuzumab in 3%). Novel agents were used in first line in only 23 patients (2%) , 19 of which in the context of a clinical trial. In public hospitals there were significantly less patients receiving fludarabine-base regimens (36% vs. 52%, P<0.0001), and regimens containing anti-CD20 monoclonal antibodies (26% vs. 75%, P<0.0001). Overall survival at 7 years was significantly worse in public than in private hospitals (68% vs. 92%, respectively, P<0.0001). After a multivariate analysis, survival in patients from public hospitals remained significantly worse than in private hospitals (hazard ratio - HR 2.88, 95% confidence interval 1.59 – 5.24), after correcting for age, Binet staging and beta2-microglobulin. Treatment free survival at 7 years was also worse in public than in private hospitals (30% vs. 48%, respectively, P<0.0001), although the difference did not remain after correcting for Binet staging and beta2-microglobulin in a multivariate analysis (HR 0.91, 95%CI 0.50- 1.66, P=0.76). Conclusion: Our data indicate that there are striking differences among patients treated in public or private hospitals in Brazil. A worse clinical condition as well as the lack of accessibility to basic laboratory tests and adequate therapies may explain the worse outcome of patients treated in public institutions in Brazil.