Abstract Primary mediastinal B-cell lymphoma (PMBL) is an uncommon aggressive lymphoma with generally favorable outcomes; however, 15% to 20% of patients develop refractory disease. Reliable baseline prognostic biomarkers remain lacking. We evaluated the prognostic value of radiomic parameters derived from baseline 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography in newly diagnosed PMBL. This post hoc analysis included 180 patients who were treatment naive from the multicenter Lymphoma Study Association (LYSA) cohort (2007-2017) treated with standard immunochemotherapy. Twelve 3-dimensional PET-derived radiomic features were extracted using Oncometer3D. Interparameter correlations were assessed using Spearman coefficients. Receiver operating characteristic analyses determined optimal cutoffs. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier estimates and Cox regression models. Four clusters of correlated features were identified: activity, tumor burden, massiveness/fragmentation, and dispersion. Among these, total metabolic tumor volume (TMTV), maximal interlesion distance (Dmax), and median peripheral centroid distance (medPCD) demonstrated the strongest prognostic associations. TMTV and Dmax were significantly associated with shorter PFS and OS, whereas medPCD predicted OS. In multivariable analysis adjusted for International Prognostic Index, bulky disease, B symptoms, and treatment regimen, a composite radiomic score (2-3 high-risk features vs 0-1) independently predicted OS (hazard ratio, 7.76 [95% confidence interval, 1.59-37.74]) and showed a strong trend for PFS. The composite score outperformed conventional clinical risk factors. Baseline PET-derived radiomic features capturing tumor burden, spatial dispersion, and compactness provide independent prognostic information in PMBL. A 3-parameter radiomic score outperformed conventional risk factors and identified a high-risk subgroup at diagnosis, warranting prospective and external validation before clinical implementation.

Objectives: Transcriptomic profiling has enabled the classification of Diffuse Large B-Cell Lymphoma (DLBCL) into distinct subtypes, such as Germinal Center B-cell-like (GCB) and Activated B-cell-like (ABC), primarily in HIV-negative patients. However, HIV-associated DLBCL may follow different molecular mechanisms due to immune dysregulation. This study aimed to characterize the transcriptomic landscape of HIV-related DLBCL to identify distinct subtypes and deregulated pathways with potential theranostic implications. Methods: Twelve formalin-fixed, paraffin-embedded DLBCL samples from HIV-positive patients were analyzed using Agilent's microarray. Quantile normalization and unsupervised hierarchical clustering were performed to classify tumors based on gene expression profiles. Results: Two distinct transcriptomic subgroups were identified. TP53 and BCL7A were overexpressed in cluster I, while BCL2 was overexpressed in cluster II. Notably, the "immune system development" pathway was under expressed in cluster I compared to cluster II. Conclusions: Our findings reveal two molecularly distinct subtypes of HIV-associated DLBCL, likely driven by differences in tumor microenvironment and immune status. These transcriptomic profiles may guide future targeted therapies. Further validation in larger cohorts and integration with proteomic and clinical data are warranted to develop a comprehensive theranostic framework.

Due to immunosuppressive treatment, COVID-19 vaccination is challenging in patients with B-cell lymphoma. We prospectively evaluated CD4, CD8 T-cell and serological responses to the COVID-19 mRNA vaccine in a cohort of patients treated for a B-cell lymphoma with anti-CD20 therapy. During lymphoma treatment, CD4, CD8, and CD19 cell dropped. While functional-specific CD4 and CD8 T-cell responses to SARS-CoV-2 were unaffected, vaccination in patients on treatment induced low specific antibody titers, contrasting with a preserved serological response when vaccination was completed before treatment initiation. Those findings reinforce a vaccinal strategy based on completion before lymphoma treatment, with a booster administered afterward.

Introduction: Current treatment strategy for HIV-associated Burkitt lymphoma (BL) typically rely on intensive chemotherapy regimens modeled on anti-leukemia protocols such as GMALL, LMB, and their regional derivatives. These are often resource-intensive, prolonged, and associated with dose-limiting toxicities, frequent interruptions, and high treatment-related mortality. The “CARMEN” protocol is a dose-dense regimen developed to improve tolerability while maintaining efficacy [Ferreri, Blood Adv 2022]. It includes a 36-day, single-course induction with weekly sequential doses of six anticancer drugs, plus intrathecal chemo, followed by high-dose cytarabine–based consolidation. Favorable safety and efficacy profiles with CARMEN and similar regimens have helped narrow the outcome gap between HIV-pos and HIV-neg patients (pts) with BL. However, systematic comparisons of efficacy across chemo regimens—particularly when stratified by prognostic scores—remain limited. In the absence of feasible prospective comparative trials, the HIV Lymphoma Network of the European Hematology Association launched an international study to assess feasibility and efficacy of GMALL (and its derivatives), CARMEN, and other regimens in HIV-pos pts with BL treated at 19 centers across Germany, Italy, Spain, France, and Croatia. Methods: HIV-pos adults with BL treated between 2005–2024 were included. All pts were eligible regardless of ECOG PS, stage, IPI, BLIPI [Olszewski, JCO 2021], or treatment. Pts with HBV/HCV infection were included; those lost to follow-up within 6 months of diagnosis were excluded. The primary endpoint was overall survival (OS), analyzed by treatment regimen and stratified by IPI (low: 0–1; intermediate: 2–3; high: 4–5) and BLIPI (low: 0; intermediate: 1; high: 2–4). Feasibility and tolerability were assessed by the incidence of treatment-related deaths, dose reductions or interruptions, grade ≥3 non-hematologic toxicities, and grade ≥3 infections. Variables significantly associated with OS were further evaluated using Cox proportional hazards models. Results: Of 247 consecutive HIV-pos pts with BL (median age 43; range 25–68; 227 males), 16 were excluded for early loss to follow-up, leaving 231 for analysis. Of these, 145 received GMALL or derivatives (BFM, BURKIMAB), 41 received CARMEN, 16 received LMB, and 20 received R-CHOP. Nine pts treated with other regimens were excluded from analyses. Baseline characteristics were comparable across groups, except for B symptoms, which were not recorded in the LMB cohort. At a median follow-up of 65 months (range 7–164), 73 pts experienced a PFS event, and 61 died: 41 from lymphoma, 17 from infections, and 2 from second cancers. The 5-yr PFS and OS were 70% (95%CI:69–71) and 71% (95%CI:70–72), respectively. Stratified by treatment regimen, 5-yr OS was 74% (95%CI:73–75) for GMALL and derivatives, 68% (95%CI:66–70) for CARMEN, 79% (95%CI:78–80) for LMB, and 45% (95%CI:25–62) for R-CHOP. IPI data were available for 212 pts (95%). Among 49 with IPI 0–1, only two events occurred, with a 5-yr OS of 95% (95%CI:94–96) and no significant differences across regimens. Among 163 pts with IPI 2–5, the 5-yr OS was 65% (95%CI:64–66), with comparable efficacy among GMALL and derivatives, CARMEN, and LMB, but significantly worse outcomes for R-CHOP. Similar findings were observed using BLIPI stratification. Multivariable analysis identified bulky disease, HIV-RNA levels, gender, and IPI as independent OS predictors. Notably, it confirmed equivalent efficacy among intensified regimens and their superiority over R-CHOP. In terms of feasibility, CARMEN had the most favorable profile: only 5 pts (12%) required dose reductions and 2 (5%) discontinued treatment due to toxicity. In comparison, dose reductions and discontinuations occurred in 30% and 16% of pts on GMALL, and 38% and 16% with LMB. Conclusions: OS rates are encouraging in HIV-pos pts with BL; however, nearly one-third of deaths are still attributable to iatrogenic toxicity. Despite the limitations of a retrospective design, our findings suggest that CARMEN regimen provides outcomes comparable to those of standard intensive protocols (GMALL, its derivatives, and LMB). Efficacy was consistent across all risk subgroups defined by IPI and BLIPI. In addition to its short duration and favorable tolerability, CARMEN may reduce the risk of chronic toxicity and secondary malignancies, owing to its use of single doses of chemotherapeutic agents.

Existing epidemiological evidence regarding the potential role of (poly)phenol intake in lymphoma development is limited. We investigated the associations between the intake of total and individual classes and subclasses of (poly)phenols and the risk of lymphoma, including main frequent subtypes in the EPIC cohort using multivariable-adjusted Cox proportional hazards models. During a mean 14-year follow-up (time frame: from 1990–1994 to 2008–2013), 2394 incident lymphoma cases were diagnosed from a total of 367,463 individuals. No significant associations were observed between total intakes of (poly)phenols, flavonoids, and phenolic acids and overall lymphoma risk. Total (poly)phenols, phenolic acid and hydroxycinnamic acid intakes were positively associated with Hodgkin lymphoma (HL) risk [HRlog2 = 2.56 (95

Primary mediastinal large B-cell lymphoma (PMBL) is a rare entity that predominantly affects young female patients and typically presents as a large and compressive anterior mediastinal mass. Accumulating evidence suggests relationships among PMBL patient body composition (BC), cancer outcomes, and treatment-related toxicities. The aim of this study was to evaluate the impact of BC on PMBL patients using PET-CT images acquired pretreatment. Two hundred nineteen patients were included in an ancillary analysis of a multicenter retrospective LYSA cohort of treatment-naïve adult PMBL patients who received first-line treatment with ACVBP, CHOP14 or CHOP21 plus anti-CD20. Anthropometric parameters were assessed from the baseline PET-CT image using two methods: (i) manual segmentation at the L3 level and (ii) automatic software-based multislice measurements with Anthropometer3DNet. The median age was 35.4 years (range 18-88 years), and the median body mass index was 23.8 kg/m2 (15.6; 40.8). Overall, 137 patients were treated with R-ACVBP, 44 received R-CHOP14, and 38 were treated with R-CHOP21. Patients with low lean body mass had a higher incidence of febrile neutropenia, both in the overall cohort (25% vs. 12.6%, p = 0.02) and in the R-ACVBP subgroup (35.7% vs. 19.4%, p = 0.03). Univariate analysis showed that in patients treated with R-ACVBP, subcutaneous low adiposity, determined by 3D measurements, was associated with overall survival (OS) (p = 0.04). At 3 years, the OS (95% CI) was 96% (93-100) in above-median adiposity patients and 86% (78-95) in below-median adiposity patients. Low lean body mass (LBM), assessed from the pretreatment PET-CT images using automatic Anthropometer3DNet software, may serve as a predictive marker for acute treatment-related toxicity in PMBL patients, particularly those receiving the dose-intensive R-ACVBP regimen. Additionally, depletion of the subcutaneous fat mass was correlated with an increased risk of mortality, highlighting the importance of a comprehensive BC assessment in this patient population.

Background/Objectives: Transcriptomic studies of diffuse large cell lymphoma (DLCL) have made it possible to distinguish several profiles, including Germinal Centres (GC) and Activated B-Cells. These different types present a different pathophysiology and evolution, which may lead to different treatments. However, these profiles were determined in patients not infected with the human immunodeficiency virus (HIV), whereas lymphomas in the immunocompromised present certain specific characteristics. We therefore set out to determine the transcriptomic profile of DLCL occurring in HIV patients, in order to more precisely determine the pathophysiology of the different subtypes and to identify deregulated molecular pathways that could have a theragnostic value. Methods: We analysed 12 paraffin-embeddd samples of DLCL linked to HIV infection (two replicates per biological samples) using the Agilent's SurePrint G3 Human GE 8x60K v2 transccriptome chip. Unsupervised hierarchical clustering was performed on the normalized data (quantile normalization) to define the groups that separate the samples according to their gene expression profile. Results: From this sample of 12 DLCLs, we were able to clearly define two transcriptomic subgroups. Among the differences in gene expression, TP53 and BCL7A were overexpressed in cluster I, and BCL2 in cluster II. In terms of signalling pathways, the ‘immune system development’ pathway was under-expressed in cluster I and over-expressed in cluster II. Conclusions: Our results strongly suggest the existence of two different transcriptomic signatures which certainly underlie significant differences in pathophysiology. These differences may be due to the specific tumour environment associated with HIV infection. Our very preliminary study will need to be continued with a larger number of patients, and integrate proteomic, metabolomic and clinical data in order to define a theragnostic approach.

PURPOSE:This study questions the quality of life of young to mid-life hematology patients during lockdowns in France. METHOD:Fifteen semi-structured interviews were conducted in 2022. FINDINGS:Thematic content analysis identified three main themes: (1) regulating fear of COVID-19 during the health crisis, (2) maintaining relationships and fostering social support during the pandemic, and (3) removing the stigma of cancer with COVID-19: a positive factor for patients' quality of life. INTERPRETATION:Study participants experienced the restrictions imposed on the entire population in the face of COVID-19 in various ways, including positive events. In fact, for some, the lockdown situation allowed them to better "fit in" and feel less stigmatized because of their patient status. Indeed, lifestyles specific to them became common barrier gestures to the whole population. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS OR POLICY:The results underline the importance of broadening the communication fields and fostering psychosocial skills in these patients.

Since the beginning of the COVID-19 pandemic, there has been an overall improvement in patient mortality. However, haematological malignancy patients continue to experience significant impacts from COVID-19, including high rates of hospitalization, intensive care unit (ICU) admissions, and mortality. In comparison to other haematological malignancy patients, individuals with chronic myeloid leukemia (CML) generally have better prognosis. This study, conducted using a large haematological malignancy patient database (EPICOVIDEHA), demonstrated that the majority of CML patients experienced mild infections. The decline in severe and critical infections over the years can largely be attributed to the widespread administration of vaccinations and the positive response they elicited. Notably, the mortality rate among CML patients was low and exhibited a downward trend in subsequent years. Importantly, our analysis provided confirmation of the effectiveness of vaccinations in CML patients.

HIV infection is associated with an increased risk of diffuse large B-cell lymphoma (DLBCL). In this prospective study, we analyzed the evolution of B-cell activating cytokines (interleukin-6 [IL-6], IL-10, and B-cell activating factor [BAFF]) and main functional subsets of circulating B and T cells in 51 patients with HIV-associated DLBCL treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, Oncovin [vincristine], and prednisone). R-CHOP therapy was associated with a decrease of IL-10, whereas IL-6 levels fluctuated, and BAFF levels increased during the first 3 months and decreased thereafter. We observed a rapid rise in CD19+ B cells composed mostly of na & iuml;ve B cells whereas marginal zone-like B cells and memory B cells recovered gradually. With a median follow-up of 41 months, progression-free survival and overall survival at 5 years were 61.8% (95% confidence interval [CI], 47.6-80.4) and 67.4% (95% CI, 53.4-85.0), respectively. Progression (17.5%) and sepsis (12.5%) were the main causes of death. Baseline risk factors for death and progression were poor revised International Prognostic Index (P = .049), natural killer cell lymphopenia (P = .001), lower proportion of na & iuml;ve B cells (P = .017), and higher IL-6 serum levels (P = .001). Our data suggest that patients treated with R-CHOP for HIV-associated DLBCL have a disturbed peripheral Bcell compartment and that the low pool size of circulating na & iuml;ve B cells negatively affects their clinical outcome. In an era of development of B-cell-depleting therapies including B-cell- targeting chimeric antigen receptor T cells, assessment of perturbations within nontumoral Bcell counterparts are warranted for risk profiling in HIV-associated DLBCL. This trial was registered at www.ClinicalTrials.gov as #NCT01164436.

This EHA-ESMO Clinical Practice Guideline provides key recommendations for managing HIV-associated lymphomas.The guideline covers clinical, imaging and pathological diagnosis; staging and risk assessment; treatment and follow-up.The author group encompasses a multidisciplinary group of experts from different institutions and countries in Europe.Recommendations are based on available scientific data and the authors' collective expert opinion.

Supplementary Data from Stereotyped B-Cell Receptor Is an Independent Risk Factor of Chronic Lymphocytic Leukemia Transformation to Richter Syndrome

Background: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients. Aims: We aime to discover factors associated with mortality in patients receiving nirmatrelvir/ritonavir for the COVID-19 treatment. Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Additionally, a Cox regression was modelled to detect factors associated with mortality. Results: A total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, versus 74% in patients with no nirmatrelvir/ritonavir (p=0.003). Nirmatrelvir/ritonavir recipients were more likely to have received a 2nd vaccine booster than patients without (13% versus 7%, p=0.04), 5% were admitted to ICU, less than patients not receiving nirmatrelvir/ritonavir (12%, p=0.021). Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448-4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619-8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093-0.732) and obesity (aOR 0.105, 95%CI 0.014-0.776) were not associated with nirmatrelvir/ritonavir use. Overall mortality rate was 11%, and COVID-19 attributable mortality was 9%. In patients treated with nirmatrelvir/ritonavir the mortality rate was 7%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (15%, p=0.023). No other factor was observed explaining the mortality difference. Summary/Conclusion: Haematological malignancy patients were more likely to receive nirmatrelvir/ritonavir when reporting extrapulmonary symptoms or 2nd vaccine booster at COVID-19 onset, as opposed to chronic pulmonary disease and obesity. The mortality rate in patients treated with nirmatrelvir/ritonavir was significantly lower than in patients with targeted drugs other than nirmatrelvir/ritonavir. Keywords: Hematological malignancy, Immune deficiency, COVID-19, Infection

Patients with relapsed or refractory (R/R) peripheral T-cell lymphomas (PTCL) have a poor prognosis. Bendamustine (B) and brentuximab-vedotin (Bv) have shown interesting results in this setting. However, little information is available about their efficacy in combination. This multicenter and retrospective study aimed to evaluate the efficacy and safety of the combination of BBv in patients with noncutaneous R/R PTCL among 21 LYSA centers in France and Belgium. The primary objective was the overall response rate. A total of 82 patients with R/R PTCL were included. The best overall response rate (ORR) was 68%, with 49% of patients in complete response (CR). In multivariable analysis, only the disease status after the last regimen (relapse vs refractory) was associated with the response with an ORR of 83% vs 57%. Median duration of response was 15.4 months for patients in CR. With a median follow-up of 22 months, the median progression free survival (PFS) and overall survival (OS) were 8.3 and 26.3 months respectively. Moreover, patients in CR, who underwent an allogeneic transplant, had a better outcome than patients who did not with a median PFS and OS of 19.3 vs 4.8 months and not reached vs 12.4 months, respectively. Fifty-nine percent of patients experienced grade 3/4 adverse events that were mainly hematologic. BBv is highly active in patients with R/R PTCL and should be considered as a one of the best options of immunochemotherapy salvage combination in this setting and particularly as a bridge to allogeneic transplant for eligible patients.

In this journal, we recently reported the limited capacity of patients' sera, a month after initiation of 300 mg of AZD7442 (150 mg tixagevimab and 150 mg cilgavimab) as pre-exposure prophylaxis (PrEP), to neutralize the Omicron variant, particularly its BA.1 and BA.5 sublineages.1 PrEP was associated in immunocompromised patients to a reduction in the risk of SARS-CoV-2 infection, and of symptomatic and severe COVID-19 in the Omicron BA.1 and BA.2 era.2 However, the rate of breakthrough infections increased in some studies after the emergence of the BA.5 sublineage,3 even after AZD7442 dosage was increased to 600 mg (300 mg tixagevimab and 300 mg cilgavimab).