Proliferative Activity Of Neoplastic B Cells - Impact On The Prognosis Of Follicular Lymphoma
Authors: Pereira Dulcineia , Chacim Sergio Pereira , Brito Margarida dantas , Abreu Miguel , Mesquita Edgar , Marques Margarida , Viterbo Luisa , Oliveira Isabel , Domingues Nelson , Moreira Ilidia , Espirito-Santo Ana , Correia Cecilia , Palmeira Carlos , Sousa Emilia , Godinho Ines , Pires Marta , Henrique Rui , Teixeira Manuel R. , Martins Gabriela , Martins Angelo , Mariz Jose Mario 
Published: October 2019

Abstract

Introdution
Follicular Lymphoma (FL) presents a recurrent clinical behavior. The proliferative activity of B-cells in NHL subtypes varies amongst different subtypes, being higher in high grade NHL. In FL without t(14; 18), high proliferative activity appears to be a better predictor of progression free survival (PFS).

Objectives
Evaluation of proliferative activity of neoplastic B cells in patients with FL and its association with underlying cytogenetic changes (such as t(14;18)). Determination of the prognostic value of proliferative activity of neoplastic B cells and t(14, 18) in patients with FL.

Methods
Retrospective analysis of 139 patients with FL, followed in our center from 2006 to 2011. Evaluation of the cytogenetic changes and percentage of cells in S phase at the time of diagnosis, performed on lymph nodes. The cell cycle analysis was evaluated by flow cytometry, resorting to DNA labeling kit B-NHL (Cytognos) ModFit software (Verity). The adopted cut-off of S phase cells was based on the median value. The type of response was defined in accordance with the criteria proposed by the NCCN. The patients´ characteristics were compared with a X2 test for binary variables and a Mann-Whitney test for continuous variables. The survival curves were estimated based Kaplan-Meier curves and the data for the various groups were compared with a log-rank test. The multivariate analysis was carried out using a Cox model, after the proportional hazard assumption was checked. A p value below 0.05 was considered as being statistically significant.

Results
The median follow-up was 34 months ([8-75]). The S phase was analysed in 45 patients with an median age of 56 years ([31-78]). 89% (n = 40) of the patients presented an Ann Arbor stage III-IV, 86.7% (n = 39) a follicular pattern, 89% (n = 40) a grade 1/2 and 57.8% (n = 26) a FLIPI ≥ 3. The t(14;18) was found in 25 patients (55.6%), in 9 patients cytogenetic analyses was not performed. In this study was given immunochemotherapy to 82.2% (n = 37) patients. Thirty patients (66.7%) achieved CR and 15.6% (n = 7) PR, with a PFS of 22 months in 53.3% of patients. In univariate Cox regression analysis, the histological pattern, the number of S-phase cells and the t(14;18) are independent predictors of PFS (p<0.05). Quantification of S-phase cells was done in 86.7% (n = 39) patients. The PFS was better in patients with S ≥ 2.3%, in comparison to patients with S< 2.3% (median 38 vs. 28 months, p = 0.03), without impact in overall survival (p = 0.67). Patients without t(14;18) presented better PFS (p = 0.008) and higher proliferative activity (54.5% S ≥ 2.3% vs. 36.4% S< 2.3%). Analysing the number of S-phase cells in relation to the presence or absence of t(14; 18), it was noted that patients with S ≥ 2.3% and without t(14; 18) (n = 14) have better PFS (p = 0.004).

Conclusion
Quantification of cells in S phase in FL, by flow cytometry, arises as a simple, fast and reproducible method with a prognosis impact on PFS. Cells in S phase ≥ 2.3% and absence of t(14;18) at diagnosis are associated with reduced risk of progression (p<0.05).

Disclosures:
No relevant conflicts of interest to declare.