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In addition, FL patients had a significantly lower percentage of naïve T lymphocytes, a higher percentage of effector memory and effector lymphocytes, both CD4 SP + sp and CD8 SP + sp . Of note, regulatory T lymphocytes (Treg) and Th1 cells were increased in FL patients, while NK-cells were diminished. The aim of this study was to characterise the PB immune profile of FL patients at diagnosis, first relapse (R1) and subsequent relapses (> I R i SP 2 sp ) and compare them with healthy controls. [Extracted from the article]

Patients with advanced-stage Hodgkin lymphoma treated with ABVD who have a positive interim FDG-PET (iPET) have a poor prognosis. Escalation to BEACOPP has been shown to improve progression-free survival (PFS). However, randomized trials are lacking to determine the best strategy for intensification. We report on A-AVD escalation treatment outcomes for 15 iPET-positive patients post-ABVD. Overall response and complete response rates were 80% and 60%, respectively. Four patients underwent salvage therapy followed by autologous stem cell transplantation. At a median 17-month follow-up, all patients are alive, 87% in complete remission, and 1-year PFS was 57.8%. For patients ineligible for BEACOPP due to age, comorbidities, or preference, A-AVD escalation may be a viable alternative., (© 2024 John Wiley & Sons Ltd.)

Watchful waiting is an acceptable management strategy for advanced-stage, low tumor burden (LTB) patients with follicular lymphoma (FL). However, the prediction of how long this treatment-free observation period will last remains imperfect. We explored whether total metabolic tumor volume (TMTV) and other positron emission tomography parameters were predictive of time to first treatment (TTFT). We analyzed 97 grade 1-3A advanced-stage LTB FL patients and found that a high TMTV was associated with other tumor burden features at diagnosis. Patients with a TMTV above our established cutoff of 50 mL had a significantly shorter median duration of observation (2.6 vs. 8.8 years; p = 0.001). At 5 years, 77% of patients with a high TMTV and 46% of patients with a low TMTV required treatment. In the multivariable analysis, a high TMTV was the only independent factor predicting TTFT (hazard ratio = 2.09; p = 0.017). Overall, TMTV is a strong predictor of the duration of observation in LTB FL patients. Upon validation of our cutoff in external series and standardization of the methodology, the TMTV could become an additional factor to consider deferring or initiating treatment in otherwise LTB patients., (© 2023 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

While some follicular lymphoma (FL) patients do not require treatment or experience prolonged responses, others relapse early, and little is known about genetic alterations specific to patients with a particular clinical behavior. We selected 56 grade 1-3A FL patients according to their need of treatment or timing of relapse: never treated (n = 7), non-relapsed (19), late relapse (14), early relapse or POD24 (11), and primary refractory (5). We analyzed 56 diagnostic and 12 paired relapse lymphoid tissue biopsies and performed copy number alteration (CNA) analysis and next generation sequencing (NGS). We identified six focal driver losses (1p36.32, 6p21.32, 6q14.1, 6q23.3, 9p21.3, 10q23.33) and 1p36.33 copy-neutral loss of heterozygosity (CN-LOH). By integrating CNA and NGS results, the most frequently altered genes/regions were KMT2D (79%), CREBBP (67%), TNFRSF14 (46%) and BCL2 (40%). Although we found that mutations in PIM1, FOXO1 and TMEM30A were associated with an adverse clinical behavior, definitive conclusions cannot be drawn, due to the small sample size. We identified common precursor cells harboring early oncogenic alterations of the KMT2D, CREBBP, TNFRSF14 and EP300 genes and 16p13.3-p13.2 CN-LOH. Finally, we established the functional consequences of mutations by means of protein modeling (CD79B, PLCG2, PIM1, MCL1 and IRF8). These data expand the knowledge on the genomics behind the heterogeneous FL population and, upon replication in larger cohorts, could contribute to risk stratification and the development of targeted therapies., (© 2023 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

Serum soluble CD23 (sCD23) levels have been acknowledged as a prognostic factor in patients with chronic lymphocytic leukemia (CLL), but their potential relevance has not been analyzed in recent times. We retrospectively studied 338 CLL, small lymphocytic lymphoma, or CLL-type monoclonal B-cell lymphocytosis patients from a single institution, with available sCD23 levels at diagnosis. Baseline features and outcomes were compared between patients with sCD23 ≤/>1000 UI/L. The 140 patients (41%) who had sCD23 > 1000 UI/L showed adverse-risk clinical and biological characteristics. High sCD23 levels were predictive of a shorter time to first treatment (5-year probability of requiring treatment: 60 vs. 20%, p < 0.0001; hazard ratio (HR) = 1.72, p = 0.003 in a multivariable model also including the CLL International Prognostic Index and the absolute lymphocyte count), and a poorer 5-year overall survival (70 vs. 82%, p = 0.0009). These data suggest the potential of sCD23 to predict treatment-free survival and to shed light on mechanisms of activity and resistance to CD23-directed therapies., (© 2022 John Wiley & Sons Ltd.)

With the intention of identifying follicular lymphoma (FL) patients at higher risk of progression, early relapse (POD24), histological transformation (HT) or death, multiple risk scores (RS) have been proposed. However, it has not yet been established whether any of them globally outperforms the others. We evaluated the clinical utility and statistical performance of the five most widely used clinical scores (IPI, ILI, FLIPI, FLIPI2, PRIMA-PI) in a single-center series of 414 grade 1-3A FL patients diagnosed in the rituximab era. Overall concordance (proportion of patients allocated to the same risk category by all five RS) was 24%. FLIPI and FLIPI2 were predictive of time to first treatment. All five scores were predictive of response, POD24, progression-free, and OS, while only FLIPI predicted HT. IPI identified a small subset (7%) of truly high-risk patients (10-year OS of 16%). In subgroup analyses, we showed that ILI is useful in the prognostication of limited-disease patients, and PRIMA-PI is an age-independent score that can identify a high-risk subset of older patients. Performance metrics were slightly better for IPI in terms of calibration (Harrell's c-index 0.73), without major differences among RS regarding other parameters. Although the incorporation of molecular and imaging data will continue to refine the stratification of FL patients, FLIPI remains the most powerful clinical prognostic index in the rituximab era, predicting the greatest number of endpoints., (© 2021 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)