Dissecting follicular lymphoma: high versus low risk

Abstract

Progress in the management of follicular lymphoma (FL) has translated to improved outcomes, with most patients surviving a decade or more from the time of diagnosis. However, the disease remains quite heterogeneous and a substantial number of patients have more aggressive disease with short responses to therapy and/or transformation to higher-grade lymphomas. Given the lack of a single standard approach, it is important to understand sources of heterogeneity among patients that influence initial management, surveillance strategies, and overall prognosis. Most of the validated tools, such as the Follicular Lymphoma International Prognostic Index (FLIPI) and FLIPI-2, apply to the frontline setting, and there is an unmet need for prognostic tools in relapsed and refractory disease states. In particular, the number of prior treatment regimens may be less important than the duration of response to the most recent regimen and the type of prior therapy received. Furthermore, despite awareness of progressive genetic and epigenetic derangements and a growing appreciation of the microenvironment's role in FL outcomes, there is no validated means of incorporating biologic data into clinical prognostic indices. This review highlights the current state of knowledge regarding risk stratification in FL.

Disparate survival outcomes after front-line chemoimmunotherapy in older patients with follicular, nodal marginal zone and small lymphocytic lymphoma

“…Because it is not possible to distinguish R given as a maintenance treatment from therapy at progres sion, we could not adjust for maintenance strategy, which is known to extend PFS in FL [21,40]. FLIPI scores and other measures of tumor burden were not directly available, and our claims-based variables may not completely account for the clinical risk factors [13,41]. However, using more realis tic age group subdivisions (with cut-offs of 60 and 70 years) and comorbidity measures as implemented in our analysis has been shown to significantly improve prognostic predic tions over FLIPI alone in population-based cohorts [42], While FL, NMZL and SLL are usually distinguishable using their characteristic immunophenotypes, we cannot rule out some misclassifications in the absence of central histo pathologic review.…”

Common progenitor cells in mature B-cell malignancies

“…De-novo follicular lymphoma has an indolent disease course characterized by multiple relapses, with an estimated 2-3% annual risk of histological transformation to aggressive large cell histology [transformed follicular lymphoma (tFL)] [17][18][19]. The genetic hallmark of follicular lymphoma is the t(14;18)(q32;q21) translocation that places the BCL2 oncogene under control of the immunoglobulin heavy-chain enhancer and promotes its expression [20,21].…”

Computer‐assisted quantification of CD3+ T cells in follicular lymphoma

“…Many studies have been performed to determine the clinical significance of the nonmalignant cell populations using markers such as CD10, Bcl-6, CXCR5, FoxP3, PD1, CD25, and CD8, among others, to evaluate biologic and prognostic relevance of different T cell subsets (5)(6)(7)(8). However, the results of these studies were frequently contradictory with different cell subsets correlating with good prognosis in some studies and with poor or indifferent prognosis in others (5)(6)(7)9,10). This lack of correlation among studies may be related to many factors, including the inherent subjectivity of manual scoring of immunohistochemical stains (11).…”