institution between 2004 and 2016 and receiving treatment with chemoimmunotherapy. Progression-free survival (PFS) and global survival (OS) rates were estimated using the method of Kaplan-Meier. Univariate and multiple Cox regression models were used to assess the effect of covariates on PFS and OS. Results: Median (range) age at diagnosis was 62 years (32-83). Forty-eight percent of patients had high-risk FLIPI and 36.7% were high-risk FLIPI-2. Patient characteristics are shown in the Table 1. The most commonly front-line therapies administered were R-CHOP (56.9%) and R-CVP (40%). Rituximab maintenance was administered to 48 patients (73.8%). Overall, 67.2% of patients achieved complete remission (CR) and 12.5% partial remission (PR) with no significant differences between both regimens. After a median follow-up of 60 months (range, 0-185), 67.7% of patients are still in CR, 15.4% have relapsed, and 23.1% have died. Neither the median PFS nor the median OS were reached. The estimated 5-year PFS and OS among all patients were 67.4% and 83.4%, respectively. Variables influencing PFS and OS in the univariate analysis were age > 60 years (p = 0.02), Hb <12 g/dL (p = 0.036), raised serum LDH (p = 0.001), albumin <3 mg/dL (p = 0.029), high-risk FLIPI (p = 0.01), high-risk FLIPI-2 (p = 0.001), not receive Rituximab maintenance (p = 0.04), disease progression <2 years after diagnosis (p < 0.0001), and disease refractoriness (p < 0.0001). Multivariate analysis confirmed raised serum LDH (p = 0.034) and refractoriness to front-line therapy (p = 0.021) as the two variables affecting OS while disease progression <2 years after diagnosis was the only variable affecting PFS (p = 0.007). Conclusions: Our results show that refractoriness to chemoimmunotherapy and early progression after treatment were the most relevant variables affecting outcome of patients. Both factors should be used to stratify the risk of patients with FL. Likewise, we did not found any OS and PFS advantage among patients receiving maintenance. UNL, upper normal limit.
Chronic lymphocytic leukemia (CLL) is unique among B cell malignancies in that the malignant clones can be featured either somatically mutated or unmutated IGVH genes. CLL cells that express unmutated immunoglobulin variable domains likely underwent final development prior to their entry into the germinal center, whereas those that express mutated variable domains likely transited through the germinal center and then underwent final development. Regardless, the cellular origin of CLL remains unknown. The aim of this review is to summarize immunological aspects involved in this process and to provide insights about the complex biology and pathogenesis of this disease. We propose a mechanistic hypothesis to explain the origin of B-CLL clones into our current picture of normal B cell development. In particular, we suggest that unmutated CLL arises from normal B cells with self-reactivity for apoptotic bodies that have undergone receptor editing, CD5 expression, and anergic processes in the bone marrow. Similarly, mutated CLL would arise from cells that, while acquiring self-reactivity for autoantigens—including apoptotic bodies—in germinal centers, are also still subject to tolerization mechanisms, including receptor editing and anergy. We believe that CLL is a proliferation of B lymphocytes selected during clonal expansion through multiple encounters with (auto)antigens, despite the fact that they differ in their state of activation and maturation. Autoantigens and microbial pathogens activate BCR signaling and promote tolerogenic mechanisms such as receptor editing/revision, anergy, CD5+ expression, and somatic hypermutation in CLL B cells. The result of these tolerogenic mechanisms is the survival of CLL B cell clones with similar surface markers and homogeneous gene expression signatures. We suggest that both immunophenotypic surface markers and homogenous gene expression might represent the evidence of several attempts to re-educate self-reactive B cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.