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Patients with follicular lymphoma (FL) refractory to front-line immunochemotherapy (ICT) have a poor overall survival (OS). Gene mutation analysis may be more accurate than classical risk factors to pick out these patients before treatment. This study aimed to describe the prevalence of selected genetic mutations in a cohort of patients with high-risk FL. Twenty-five patients with FL refractory to front-line ICT and 10 non-refractory patients matched for age, sex, and FLIPI score were included. We sequenced 18 genes (custom targeted sequencing panel) previously reported to potentially have prognostic impact, including the seven genes necessary to determine m7FLIPI risk. The 35 patients had a median age of 62. The FLIPI and FLIPI2 were high in 27 (84%) and 14 (48%), respectively. Three-year progression-free survival (PFS) and OS probabilities were 25% (95% CI, 13%-41%) and 53% (34%-69%), respectively. There were 73 variants in the 18 genes among the 35 patients. The median number of mutations per patient was 1 (interquartile range, 0-3). The most commonly mutated genes were CREBBP (11 of 35, 31%) and EP300 (10 of 35, 29%). EP300 mutations were associated with refractoriness to treatment (10 of 25 among refractory and 0 of 10 among non-refractory). In conclusion, in this study, patients with high-risk follicular lymphoma were genetically heterogeneous., (©2019 John Wiley & Sons, Ltd.)

Diffuse large B-cell lymphoma (DLBCL) prognostication requires additional biologic markers. miRNAs may constitute markers for cancer diagnosis, outcome, or therapy response. In the present study, we analyzed the miRNA expression profile in a retrospective multicenter series of 258 DLBCL patients uniformly treated with chemoimmunotherapy. Findings were correlated with overall survival (OS) and progression-free survival (PFS). miRNA and gene-expression profiles were studied using microarrays in an initial set of 36 cases. A selection of miRNAs associated with either DLBCL molecular subtypes (GCB/ABC) or clinical outcome were studied by multiplex RT-PCR in a test group of 240 cases with available formalin-fixed, paraffin-embedded (FFPE) diagnostic samples. The samples were divided into a training set (123 patients) and used to derive miRNA-based and combined (with IPI score) Cox regression models in an independent validation series (117 patients). Our model based on miRNA expression predicts OS and PFS and improves upon the predictions based on clinical variables. Combined models with IPI score identified a high-risk group of patients with a 2-year OS and a PFS probability of < 50%. In summary, a precise miRNA signature is associated with poor clinical outcome in chemoimmunotherapy-treated DLBCL patients. This information improves upon IPI-based predictions and identifies a subgroup of candidate patients for alternative therapeutic regimens.

Retrospective series have reported many clinical and biological significant prognostic factors in chronic lymphocytic leukemia (CLL). We describe a prospective cohort of 135 patients with CLL homogeneously studied at diagnosis for prognostic factors. Biological variables analyzed were CD38 and ZAP-70 expression, fluorescence in situ hybridization (FISH) for 13q-, +12, 11q-, and 17p-, and conventional cytogenetics. Univariate and multivariate analysis for progression-free survival (PFS) were performed in patients with early stage (Rai 0-1) CLL. CD38 was positive in 42 (31.6%) patients and ZAP-70 in 47 (35.9%). The most frequent FISH finding was isolated 13q- in 50 (38.5%) patients, and 17p- -was found in 11 (8.4%). Among 135 patients, 114 (84.4%) were Rai 0-1 at diagnosis and 39 (28.9%) presented adenopathies. With a median follow-up of 39 months, the presence of lymphadenopathy in patients with Rai 0-1 stage CLL was the only significant variable for predicting PFS in multivariate analysis (odds ratio [OR] 7, 95% confidence interval [CI] 2.2-22, p = 0.001). When only biological factors were analyzed, CD38 expression (OR 3.2, 95% CI 1.1-9.3, p = 0.03) and 17p- (OR 3.5, 95% CI 0.95-13.1, p = 0.05) correlated with worse PFS. A longer follow-up is necessary to analyze the prognostic value of these variables regarding overall survival.