We welcome the publication of a score (Follicular Lymphoma International Prognostic Index [FLIPI]) assisting in the choice of treatment for patients with newly diagnosed follicular lymphoma (FL). 1 As the authors state, treatment options for this disease range from "watch and wait" to allogeneic bone marrow transplantation, and the selection of the best available option will be favored by a realistic estimation of the expected survival for each particular patient.The 5 independent prognostic factors retained in the FLIPI reflect important characteristics of the patient (age), of the disease extension and clinical aggressiveness (stage and number of nodal sites involved, lactose dehydrogenase [LDH]), and of the tumorhost interaction (hemoglobin level). Surprisingly enough, histology grade, a disease characteristic considered by many clinicians to be of paramount importance for prognosis and choice of treatment, is missing from the index and was not even significant in the univarate analysis.The absence of this parameter from the index and the omission of any discussion about this fact in the paper could suggest that histologic grade is indeed not relevant to patient survival and should therefore not be taken as an important information.We believe that this misunderstanding results from a bias that is not sufficiently covered in the article and that should be clarified.It was long recognized that an important proportion of large cells (centroblasts) at histologic examination (an observation referred to as grade 3 in the current World Health Organization [WHO] classification) does confer to FL a worse prognosis, despite apparently favorable clinical prognostic features. 2,3 Nevertheless, the outcome of these cases can be similar to the forms with less centroblasts when they are treated with an anthracycline-containing regimen. 4,5 This information was known in 1985 6 (the year of the start of data collection for the FLIPI) and, although details on treatment are not given in the paper, it is probable that the majority of grade 3 FLs of this data set were treated with anthracyclines, thus influencing the prognosis.Even though the article states that "none of the treatments given during the period of inclusion has significantly changed the natural history of the disease," 1(p1264) this only applies to cases with histologic grades 1 and 2, while for WHO grade 3 we have reason to think that treatment did indeed influence survival, and therefore interacted with other prognostic factors.The FLIPI could have been a more reliable index if grade 3 FLs were not included in the analysis. We believe that for grades 1 and 2 FL, treatment should be selected based on a number of factors, including the FLIPI score, but an anthracycline-containing regimen should still be favored for patients with grade 3 FL, independent of their FLIPI index. References1. Solal-Cé ligny P, Roy P, Colombat P, White, et al. Follicular Lymphoma International Prognostic Index. Blood. 2004;104:1258-1265. 2. Martin AR, Weisenburger DD, Chan WC, et al. Progn...
Systemic lupus erythematosus is associated with increased risk of atherosclerosis; endothelial dysfunction is believed one of the most important initial steps of the atherosclerosis process. The aim of this study is to evaluate endothelial microparticles (EMPs) (VCAM-1/CD105) in addition to Carotid intima-media thickness (cIMT), as biomarkers of atherosclerosis, among Egyptian Systemic lupus erythematosus (SLE) patients and its correlation to SLE related risk factors. We compared data obtained from 60 Egyptian SLE patients neither of them had diabetes, hypertension nor smokers, with 30, age and sex matched healthy volunteers. Both patients and controls were subjected to full history taking and clinical examination as well as basic laboratory investigations in addition to VCAM-1 ELISA, CD105 by flow cytometer and Carotid arteries ultrasound to assess intima-media thickness and the presence of plaques. Our results revealed highly significant increase of cIMT, CD105, VCAM-1, total cholesterol and LDL-cholesterol in SLE patients compared to normal controls (P<0.001). In comparing SLE patients with increased cIMT with those with normal cIMT, we found significant increase in LDL cholesterol, steroid duration and highly significant increase of steroid cumulative dose and disease duration. Also, SLE patients with positive anti-dsDNA showed significant increase in cIMT (P<0.05) in comparison to anti-dsDNA negative patients at the time of sampling. Our results also demonstrated no correlation between Anti-Cardiolipin antibodies (ACL) and cIMT, VCAM-1 or CD105. We found that SLE patients had a significant increase in cIMT, VCAM-1 and CD105 compared with the controls. This significant increase in these atherosclerotic biomarkers was not correlated with indices of disease activity or presence of anti-dsDNA or ACL antibodies but correlated with disease and steroid duration, steroid cumulative dose, age and LDL-C level.
The expression of cytokines and chemokines are under control of several factors, including the bone marrow (BM) microenvironment. The aim of this work was to study the chemokine receptor expression on normal and neoplastic PCs and to investigate the relationship between the BM microenvironment and plasma cell behaviour. The study included 20 patients with reactive disorders or normal BM, 20 individuals with MGUS (monoclonal gammopathy of undetermined significance) and 19 patients with multiple myeloma at presentation. A large panel of chemokine receptor-specific antibodies directed against CCR1, CCR2, CCR3, CCR5, CCR6, CXCR1, CXCR2, CXCR3, CXCR4 and CXCR5 was characterized employing a four-colour flow cytometry approach. We demonstrate that normal and myeloma PCs have a specific chemokine receptor profile expressing 7/10 of the receptors studied. CCR2, CCR6, and CXCR1 showed decreased expression on myeloma PCs in comparison to normal PCs (average 3.3, 1.5 and 1.8-fold difference in expression level respectively). In contrast CXCR4 was upregulated on myeloma PCs on average 2.2-fold in comparison to normal PCs. There was no significant difference in expression between normal (CD19+) and neoplastic (CD19−) PCs from the same bone marrow environment in MGUS patients with respect to CCR6, CXCR1 and CXCR4. In contrast there was a significant difference in expression of CCR2 between CD19+ and CD19− PCs from the same BM (P=0.002). The level of expression on CD19− PCs was on average 1.6-fold lower than on their CD19+ counterparts (range 1.1 6.8-fold lower). In conclusion these data demonstrate that normal and myeloma PCs have a specific chemokine receptor profile. Myeloma PCs have a reduced level of some chemokine receptors compared to normal PCs which may account for their abnormal localization within the BM. Differences in expression of CXCR1, CXCR4, and CCR6 are not specific to the neoplastic process, as both normal and neoplastic plasma cells from the same marrow in MGUS patients show corresponding levels of expression. It is probable that feedback loops between neoplastic plasma cells and bone marrow stroma also influence normal plasma cell expression of these chemokine receptors. However, differences in CCR2 expression are not influenced by the marrow microenvironment, therefore downregulation of CCR2 expression is either a function of the neoplastic process or of the stage of differentiation of the originating neoplastic cell. Interfering with chemokines and their receptors which are related to the malignant transformation, particularly CCR2, may prove useful as adjunct to chemotherapy approaches.
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