The Follicular Lymphoma International Prognostic Index (FLIPI) and the histological subtype are the most important factors to predict histological transformation in follicular lymphoma

Giné, Eva; Montoto, Silvia; Bosch, Francesc; Arenillas, Leonor; Mercadal, Santiago; Villamor, Neus; Martı́nez, Antonio; Colomo, Lluı́s; Campo, Elı́as; Montserrat, Emili; López‐Guillermo, Armando

doi:10.1093/annonc/mdl162

Cited by 118 publications

(94 citation statements)

References 32 publications

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“…2,[27][28][29] However, these parameters do not address the underlying microenvironment and bi-directional crosstalk between FL B-cells and stromal cells that may herald aggressive disease biology in advance of clinical presentation and deterioration. 30 Cytokines present within the tumor microenvironment appear to contribute to growth and survival of malignant cells and also ensures a continued inflammatory milieu recruiting reactive cells to lymphoma tissue.…”

Section: Discussionmentioning

confidence: 99%

Elevated serum levels of IL-2R, IL-1RA, and CXCL9 are associated with a poor prognosis in follicular lymphoma

Mir¹,

Maurer²,

Ziesmer³

et al. 2015

Blood

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• Elevated IL-2R, IL-1RA, and CXCL9 are associated with shorter event-free survival in newly diagnosed FL, treated with chemoimmunotherapy.• Increased serum IL-12 and IL-1RA is associated with shorter event-free survival in patients who were observed or treated with rituximab alone.Serum cytokines and chemokines may reflect tumor biology and host response in follicular lymphoma (FL). To determine whether the addition of these biological factors may further refine prognostication, 30 cytokines and chemokines were measured in pretreatment serum specimens from newly diagnosed FL patients (n 5 209) and from 400 matched controls. Cytokine levels were correlated with clinical outcome in patients who were observed or received single agent rituximab, or those who received chemotherapy.Correlations with outcome in chemotherapy treated patients were further examined in a separate cohort of 183 South West Oncology Group (SWOG) patients and all patients were then included in a meta-analysis. Six cytokines were associated with outcome in the Molecular Epidemiology Resource (MER) after adjusting for the FL international prognostic index. In patients who were observed or treated with rituximab alone, increased serum IL-12 and interleukin 1 receptor antagonist (IL-1RA) (P 5 .005 and .02) were associated with a shorter event-free survival. In patients receiving chemotherapy, hepatocyte growth factor, IL-8, IL-1RA, and CXCL9 (P 5 .015, .048, .004, and .0005) predicted a shorter EFS. When the MER chemotherapy treated patients and SWOG patients were combined in a meta-analysis, IL-2R, IL-1RA, and CXCL9 (P 5 .013, .042, and .0012) were associated with a poor EFS. (Blood. 2015;125(6):992-998) Introduction Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma in the United States.1 While classified as an indolent B-cell lymphoma, the clinical course exhibits a spectrum based on the FL international prognostic index (FLIPI) score with a remarkable tendency for patients to relapse.2 The overall survival rate of patients with FL was previous reported as 75% at 5 years, and ranged from 71% at 10 years for patients with a FLIPI score between 0 to 1, and 36% for those with a FLIPI score of .3. Currently, the median survival of all newly diagnosed patients is approximately 9 years. 3Although the overall survival appears to have improved with advances in chemoimmunotherapy, the median event free survival (EFS) remains around 2 years for patients with advanced disease. 4 As a prognostic score, the FLIPI has several limitations. It focuses on clinical factors and does not take into account biological factors such as the tumor microenvironment and the host response. Indeed, some studies have found better prognostication of the very high-risk group with the international prognostic index (IPI) rather than with the FLIPI. 5,6 The FLIPI may potentially be further improved, particularly in the high-risk categories, if biological data are added. Gene expression profiling studies on pretreatment specimens from patients with FL hav...

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Section: Discussionmentioning

confidence: 99%

Elevated serum levels of IL-2R, IL-1RA, and CXCL9 are associated with a poor prognosis in follicular lymphoma

Mir¹,

Maurer²,

Ziesmer³

et al. 2015

Blood

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“…4,5,9 It remains challenging to predict subsequent transformation at the time of FL diagnosis although certain clinical parameters, such as elevated lactate dehydrogenase levels, advanced stage, and high Follicular Lymphoma International Prognostic Index (FLIPI) scores are correlated with a higher risk of transformation in some, but not all studies. [4][5][6]10 Similarly, certain genomic features have been associated with an increased likelihood of transformation. These include BCL6 translocations, 11 FAS mutations, 12,13 or deletions of 1p36.3.…”

Section: Introductionmentioning

confidence: 99%

Cell of origin of transformed follicular lymphoma

Kridel

Mottok

Farinha

et al. 2015

Blood

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Key Points• TFL is most commonly of the germinal center B-cell-like phenotype, but a significant minority of cases is of the ABC phenotype (16%).• The absence of BCL2 translocation in FL at diagnosis is associated with transformation into ABC-like large cell lymphoma.Follicular lymphoma (FL) is an indolent disease but transforms in 2% to 3% of patients per year into aggressive, large cell lymphoma, a critical event in the course of the disease associated with increased lymphoma-related mortality. Early transformation cannot be accurately predicted at the time of FL diagnosis and the biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort of 126 diagnostic FL specimens including 40 patients experiencing transformation (<5 years) and 86 patients not experiencing transformation for at least 5 years. In addition, we assembled an overlapping cohort of 155 TFL patients, including 114 cases for which paired samples were available, and assessed temporal changes of routinely available biomarkers, outcome after transformation, as well as molecular subtypes of TFL. We report that the expression of IRF4 is an independent predictor of early transformation (Hazard ratio, 13.3; P < .001). We also show that composite histology at the time of transformation predicts favorable prognosis. Moreover, applying the Lymph2Cx digital gene expression assay for diffuse large B-cell lymphoma (DLBCL) cell-of-origin determination to 110 patients with DLBCL-like TFL, we demonstrate that TFL is of the germinal-center B-cell-like subtype in the majority of cases (80%) but that a significant proportion of cases is of the activated B-cell-like (ABC) subtype (16%). These latter cases are commonly negative for BCL2 translocation and arise preferentially from BCL2 translocation-negative and/or IRF4-expressing FLs. Our study demonstrates the existence of molecular heterogeneity in TFL as well as its relationship to the antecedent FL. (Blood. 2015;126(18):2118-2127

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“…It includes patients' age (older than 60 years versus 60 years and younger), Ann Arbor stage (III/IV versus I/II), number of lymph node sites affected (more than 4 versus up to 4), hemoglobin level (less versus at least 120 g/L) and serum LDH level (above normal versus normal). 7,8 However, it does not include intrinsic tumor properties. For a long time, the only Page 4/28 prognostic features within the tumor itself were histological grading according to WHO criteria or determination of the proliferation index.…”

Section: Introductionmentioning

confidence: 99%

Intratumoral plasmacytoid dendritic cells associate with increased survival in patients with follicular lymphoma

Butsch¹,

waelti²,

Schaerer³

et al. 2011

Leukemia & Lymphoma

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The Follicular Lymphoma International Prognostic Index (FLIPI) and the histological subtype are the most important factors to predict histological transformation in follicular lymphoma

Abstract: FLIPI and histology were the most important variables predicting HT. Upon HT, only patients achieving CR reached prolonged survival, thus emphasizing the need for effective therapies once this event occurs.

Cited by 118 publications

References 32 publications

Elevated serum levels of IL-2R, IL-1RA, and CXCL9 are associated with a poor prognosis in follicular lymphoma

Elevated serum levels of IL-2R, IL-1RA, and CXCL9 are associated with a poor prognosis in follicular lymphoma

Cell of origin of transformed follicular lymphoma

Intratumoral plasmacytoid dendritic cells associate with increased survival in patients with follicular lymphoma

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