Search Results (1,307)

Background: Late-onset neutropenia (LON) and hypogammaglobulinemia are recognized sequelae of rituximab therapy in B-cell non-Hodgkin lymphoma, and both may leave patients vulnerable to infection once treatment has ended. Methods: Fifty-three patients with newly diagnosed, unfavorable diffuse large B-cell lymphoma (DLBCL) who entered remission on dose-adjusted (DA) R-EPOCH immunochemotherapy were retrospectively evaluated. Neutropenia (absolute neutrophil count < 1.5 × 10⁹/L, CTCAE-graded), hypogammaglobulinemia and infections were registered at treatment completion and 6 and 12 months later. Results: All laboratory parameters changed significantly over time. Most reached their nadir at the end of treatment, whereas the absolute neutrophil count alone reached its lowest value later, at 6 months. Neutropenia, largely mild to moderate, affected 17.6% of patients at treatment completion, 22.4% at 6 months and 7.9% at 12 months. Neutropenia at 6 months was a new event, with no overlap with end-of-treatment neutropenia, and was mostly transient. Hypogammaglobulinemia (IgG < 5 g/L) occurred in 33.3%, 16.7% and 20.0%, respectively; median IgG declined to a nadir at the end of treatment and recovered thereafter, although the deficit tended to persist in the same patients. Post-treatment infections were recorded in 73.6% of patients (mostly respiratory); neutropenia was not associated with infection at any time point, whereas end-of-treatment hypogammaglobulinemia was associated with respiratory infection (p = 0.040). The independent predictors of 6-month neutropenia were a greater number of dose-escalated cycles, lower baseline leukocyte count and the absence of on-treatment infection, whereas 6-month hypogammaglobulinemia was predicted by autologous transplantation and the absence of B symptoms. In exploratory body composition analyses, lower baseline psoas muscle mass was associated with end-of-treatment neutropenia (p = 0.042) and greater muscle loss with other site (skin and gastrointestinal) infection (p = 0.004). Conclusions: After DA-R-EPOCH, LON is a delayed and largely transient event separate from end-of-treatment neutropenia, whereas hypogammaglobulinemia is more persistent and clinically relevant for respiratory infections. Full article

Background/Objectives: Hematological malignancies (HMs) are an important component of the cancer burden in adolescents and young adults (AYA, 15–39 years), requiring long-term specialized care. In Poland, recent healthcare reforms under the National Oncology Network (KSO) have not formally included haemato-oncology or AYA-specific needs. Methods: A population-based study was conducted using data from the Polish National Cancer Registry. AYAs diagnosed with HM between 2000 and 2022 were included. Descriptive analyses and projections were based on cases diagnosed between 2000 and 2022, whereas age-specific incidence trend analyses were restricted to the 2015–2022 period. Tumours were classified according to the HAEMCARE framework. Age-standardized incidence rates (ASIRs), annual percentage changes (APCs), and short-term projections through 2028 were estimated using generalized linear models. Additionally, data from the National Health Fund (NFZ) were analyzed to assess the geographical distribution of reimbursed drug programmes dedicated to selected HMs. Results: A total of approximately 23,000 AYA patients diagnosed with HMs were identified. Hodgkin lymphomas (HL) were the predominant tumour type across all age groups, while lymphoblastic leukemia/lymphoma was most common among younger AYAs and diffuse large B-cell lymphoma (DLBCL) increased in relative importance with age. Between 2015 and 2022, ASIRs remained stable only in two age groups (20–24 and 25–29), whereas statistically significant increases were observed among individuals aged 15–19, 30–34 and 35–39 years. Despite largely stable incidence patterns, projections indicated a growing absolute number of cases for DLBCL and follicular lymphomas. Analysis of NFZ data revealed substantial regional variation in the availability of reimbursed drug programmes, with up to six-fold differences in facility density between voivodships. Conclusions: HM epidemiology among AYAs in Poland is characterized by increasing incidence in selected lymphoma subtypes alongside declining mortality. Incorporating haemato-oncology and AYA-specific needs into national cancer planning frameworks should therefore be considered essential for future healthcare system preparedness. Full article

Radiation-free treatment for early-stage classic Hodgkin lymphoma (eHL) has been shown to be less effective than standard combined-modality treatment (CMT; chemotherapy plus involved-node radiotherapy (INRT)), which achieves long-term disease control of 94–95%. Approximately 70% of patients can be cured with chemotherapy alone, whereas about 5% fail CMT. Identifying patients who can safely receive chemotherapy alone and those requiring intensified CMT could enable a risk-adapted treatment strategy. The RAFTING trial (NCT04866654; EudraCT 2020-002382-33) is an international, prospective, phase 2, non-inferiority study enrolling patients 18–70 years, stage I–IIA eHL without bulky disease, B symptoms, or extranodal involvement. Low-risk (LR) patients are defined by total metabolic tumor volume (TMTV) <84 mL and negative PET-2. Those with at least one modified EORTC (mEORTC) risk factor, in which bulky disease is replaced by a large nodal mass (5–10 cm), receive four ABVD cycles, while those without risk factors receive two ABVD cycles alone. High-risk (HR) patients, defined by TMTV ≥84 mL and/or positive PET-2, receive “triple therapy”: 4 ABVD cycles, INRT (20/30 Gy), and nivolumab (240 mg q2w, ≤doses). LR patients are monitored using cfDNA. Limited relapse is treated with INRT (36 Gy) and nivolumab. The RAFTING trial is the first prospective eHL study to personalize treatment using TMTV and PET-2. It aims to omit radiotherapy in LR patients, intensify treatment in HR patients, and spare relapsed LR patients high-dose chemotherapy and autologous transplantation. CfDNA is being evaluated as a relapse marker. Despite the protocol’s complexity, this study exemplifies personalized medicine and could transform treatment practices. Full article

Background: Perinatal and early-life factors may influence non-Hodgkin lymphoma (NHL) risk, but study results have been mixed and exposure data for childhood ages are limited. Herein, we investigated associations of these exposures with risk of NHL and common subtypes. Methods: This case–control study included 2280 NHL cases and 2253 controls, enrolled from 2002 to 2014 at the Mayo Clinic Rochester. Self-reported perinatal and early-life exposures included maternal age at birth, birth order, birthweight, time breastfed, height and weight at ages 7, 12, and 18 years relative to peers, and age and weight when growth ceased. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for design variables and potential confounders. Linear trend tests were performed for ordinal variables, and heterogeneity tests were performed to evaluate whether associations varied across four NHL subtypes. Results: After multivariable adjustment, greater birth weight (OR = 1.15 for quartile 4 vs. 1; p-trend = 0.04), weight at age 7 relative to peers (compared to average, OR = 1.05 for heavy and OR = 0.87 for thin; p-trend = 0.002), and weight when growth ceased (OR = 1.30 for quartile 4 vs. 1; p-trend < 0.001) were associated with increased NHL risk. An inverse association was observed for breastfeeding duration with NHL risk (OR = 0.77 for >6 months vs. never; 95% CI 0.61–0.97). Associations did not significantly vary by major NHL subtype (p-heterogeneity > 0.05). Other perinatal and early-life exposures were not associated with NHL risk. Conclusions: Greater body weight at birth and through childhood may be associated with increased NHL risk, potentially extending the life-course perspective on adiposity and lymphomagenesis, with implications for prevention. Full article

Background and Objectives: The prognostic effect of the number of neoplastic cells in classic Hodgkin lymphoma (CHL) regardless of the histological subgroup has not been studied to date. We aimed to evaluate the prognostic impact of the number, ratio, and/or grouping of Hodgkin/Reed–Sternberg (HRS) cells in patients with CHL. Materials and Methods: 135 consecutive adult patients with CHL were included. The number, ratio, and grouping of HRS cells were evaluated on hematoxylin–eosin (HE) and CD30-stained slides. The ratio and group formation were scored. Results: Female:male ratio was 0.82. The median age was 36 ± 15.8 (range: 18–82 years). The number of HRS cells was significantly higher in nodular sclerosis CHL than in mixed-cellularity CHL and lymphocyte-rich CHL. Also, the number of HRS cells was significantly higher in syncytial variant nodular sclerosis CHL (SV-NSCHL). HRS cell ratio was in the range of 6–25% in more than 50% of the cases on both HE- and CD30-stained slides. The number of cases with a group score of 0 (no HRS groups) was significantly higher among men compared to women. HRS cells mostly did not form groups in EBER-positive patients. Confluent/large groups were more common in SV-NSCHL. Response to first-line therapy, gender, and EBER positivity were found to be independent prognostic factors. The number, ratio, and grouping of HRS cells were not associated with OS, stage, recurrence, and/or response to first-line treatment. Conclusions: The number, ratio, and/or grouping of HRS cells do not have any significant prognostic impact on CHL patients, however future studies are required to explore their pathogenetic implications. Full article

Diffuse large B-cell lymphoma (DLBCL) represents the most frequent subtype of non-Hodgkin lymphoma; however, conventional 2D cultures and murine models fail to fully recapitulate the complexity of the human tumor microenvironment (TME). To address these limitations, we developed and characterized three chitosan-based hydrogels with distinct physicochemical and mechanical properties as tunable three-dimensional (3D) platforms for DLBCL culture. U2932 lymphoma cells were encapsulated either alone or in co-culture with WPMY-1 stromal cells to investigate the effects of matrix stiffness and stromal support on lymphoma growth. Furthermore, co-culture with stromal cells promoted rapid spheroid formation and generated larger cellular aggregates than mono-cultures, with the most pronounced effect observed in the 2% chitosan hydrogel. Live/dead assays demonstrated high cell viability within the selected culture condition. Overall, the 2% chitosan formulation provided the most suitable microenvironment for supporting DLBCL growth and organization, highlighting its potential as a physiologically relevant 3D in vitro model for investigating lymphoma biology and evaluating novel therapeutic strategies. Full article

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of clinically aggressive mature T-cell and natural killer (NK)-cell neoplasms that account for approximately 10–15% of all non-Hodgkin lymphomas in Western countries . The most common subtypes include extranodal NK/T-cell lymphoma (ENKTL), nodal T-follicular helper cell lymphomas, peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), anaplastic large cell lymphoma (ALK-positive and ALK-negative), and T-cell lymphoblastic lymphoma. Non-coding RNAs (ncRNAs) constitute the majority of the human transcriptome and play critical roles in regulating gene expression, cellular proliferation, differentiation, migration, and apoptosis. Among these, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) have emerged as key regulators of lymphomagenesis and disease progression in PTCLs. These molecules modulate diverse oncogenic pathways through chromatin remodeling, transcriptional regulation, competing endogenous RNA activity, and interactions with RNA-binding proteins, thereby influencing proliferation, immune evasion, treatment resistance, and clinical outcomes. Representative examples include the lncRNA TCLlnc1, which promotes PTCL progression through activation of transforming growth factor-β (TGF-β) signaling, and the circRNAs circKIF4A, circADARB1, and circ-LAMP1, which regulate miRNA-dependent signaling networks involving PDK1/BCL11A, STAT3, and DDR2, respectively. In this review, we summarize the current understanding of the biological and clinical roles of lncRNAs and circRNAs in PTCL and related T-cell and NK-cell neoplasms and highlight their potential as diagnostic and prognostic biomarkers as well as therapeutic targets. We also discuss recent advances and future directions for integrating ncRNA-based approaches into precision medicine for T-cell lymphoma. Full article

Lymphomas are broadly categorized into Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Despite treatment advances, they remain a major cause of cancer-related morbidity and mortality in Canada. This study examined temporal trends in socioeconomic inequalities in lymphoma mortality in Canada from 2000 to 2019. Using a unique census division level dataset (n = 280) constructed by pooling information from the Canadian Vital Statistics Death Database, the Canadian Census of Population and the National Household Survey, we measured mortality in HL and NHL in Canada. The age-standardized Concentration index (C) was used to quantify income and education inequalities in lymphoma. Time trend analyses were conducted to examine the changes in the observed socioeconomic inequalities. Crude HL mortality declined significantly over the study period. Crude NHL mortality remained largely unchanged in Canada overall, although modest declines were observed in the Prairies. The age-standardized C indicated persistent income and education inequalities for both lymphoma types. For NHL, mortality became increasingly concentrated among lower-income and lower-education populations over time. The persistent and widening socioeconomic inequalities observed in HL and NHL mortality, respectively, in Canada underscore the need for targeted public health interventions and more equitable distribution of resources to address systematic and avoidable differences in cancer outcomes associated with socioeconomic disadvantage. Full article

Background and Objectives: Relapsed/refractory non-Hodgkin lymphoma (R/R NHL) remains a major therapeutic challenge, particularly in patients with peripheral T-cell lymphomas (PTCL), who frequently exhibit poor responses to salvage therapy and inferior survival outcomes. Achieving adequate disease control before autologous stem cell transplantation (ASCT) is a critical determinant of long-term survival. The bendamustine, gemcitabine, vinorelbine, and prednisolone (BEGEV) regimen has demonstrated high efficacy and favorable tolerability in relapsed/refractory classical Hodgkin lymphoma; however, data regarding its role in NHL are extremely limited. Materials and Methods: We conducted a retrospective, single-center analysis of patients with R/R NHL who received the BEGEV regimen as salvage therapy. Clinical characteristics, response rates, transplantation outcomes, progression-free survival (PFS), overall survival (OS), and safety data were evaluated. Treatment responses were assessed according to standard radiologic response criteria. Survival analyses were performed using the Kaplan–Meier method. Results: A total of 68 patients with R/R NHL were included in the analysis. Diffuse large B-cell lymphoma (DLBCL) was the predominant histological subtype, accounting for 49 patients (72.1%). BEGEV was administered predominantly in later salvage settings. Response assessments were available for 56 patients. Among evaluable patients, the objective response rate (ORR) was 73.2%, whereas the ITT ORR was 60.3% (41/68). Following BEGEV therapy, 25 patients (36.8%) proceeded to autologous stem cell transplantation (ASCT), while 8 patients (11.8%) underwent allogeneic stem cell transplantation (allo-SCT). Exploratory analyses demonstrated longer overall survival (log-rank p = 0.012) and progression-free survival (log-rank p = 0.011) among patients who subsequently underwent transplantation; however, these findings should be interpreted with caution because of the retrospective study design and the potential for selection and immortal time biases. Median PFS and OS were 4 and 26 months, respectively. Adverse events were predominantly hematologic and generally manageable. Conclusions: BEGEV may represent a reasonable salvage regimen for selected patients with R/R NHL and may facilitate disease control allowing subsequent transplantation in selected patients, including selected PTCL patients. Full article

Background: Post-treatment erythrocytosis (PT-E⁺)—an increase in red blood cell counts after therapy—is an uncommon but reproducible finding in a subset of Hodgkin lymphoma (HL) survivors, and its biological basis remains undefined. Methods: A targeted DNA sequencing panel of 33 genes was used at diagnosis and during follow-up in PT-E⁺ patients and HL controls who did not develop erythrocytosis (E⁻; those without increased red blood cells). Germline (inherited) and somatic (acquired) genetic variants were compared, and changes in variant frequency over time were assessed. Results: PT-E⁺ patients had a unique molecular profile. They showed inherited variants in genes that regulate oxygen sensing and red blood cell production (EPAS1, EGLN3, HIF3A, PKLR, SH2B3, and RAB4B-EGLN2). Rare, acquired mutations affecting hypoxia, HIF, and EPO pathways (EGLN1/2/3, EPAS1, HIF1A/3A, VHL, EPO, and PKLR) were also found. These changes did not appear in E⁻ controls, who instead had common clonal hematopoiesis mutations (DNMT3A, TET2, ASXL1, and JAK3). Most somatic variants in the hypoxia pathway in PT-E⁺ patients decreased or disappeared after treatment, which suggests these changes are temporary and influenced by the surrounding environment. Conclusions: PT-E⁺ is biologically different from polycythemia vera and from idiopathic or JAK2-unmutated erythrocytosis. Both inherited risk and HL-related hypoxic or inflammatory stress are present. This supports a two-hit model, in which genetically primed red blood cell pathways respond strongly to disease-related triggers. These results suggest a new way to understand erythrocytosis after HL treatment. Full article

Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis, affecting approximately 50 million people worldwide. An estimated 15–30% of individuals with chronic HCV infection progress to cirrhosis, which may subsequently develop into hepatocellular carcinoma. Beyond liver disease, HCV is associated with a broad spectrum of extrahepatic manifestations, particularly mixed cryoglobulinemia (MC) and B-cell non-Hodgkin lymphoma (B-NHL). Persistent viral infection induces chronic antigenic stimulation of B lymphocytes, a key pathogenic mechanism underlying the progression from MC to overt B-NHL. These observations have important therapeutic implications and support the use of antiviral therapy as a cornerstone of treatment. The efficacy of direct-acting antivirals (DAAs) has been well established in patients with HCV-related MC and cryoglobulinemic vasculitis. Several studies have shown that DAAs achieve sustained virologic response rates exceeding 90%, often approaching 100% in contemporary cohorts. Viral eradication is frequently associated with clinical and immunological improvement, as well as regression of cryoglobulinemia. Encouraging outcomes have also been reported in patients with HCV-associated indolent B-NHL, particularly marginal zone lymphoma, although confirmation in larger studies with longer follow-up is needed. In patients with HCV-positive aggressive lymphomas, DAAs have been safely administered in combination with immunochemotherapy, yielding promising results. This review summarizes the current evidence on HCV-associated MC and B-NHL and discusses the impact of DAA therapy on the clinical course and management of these disorders. Full article

Background: The prognostic significance of extranodal disease in classical Hodgkin lymphoma remains incompletely defined. Although contemporary models such as the Advanced Hodgkin International Prognostic Index (A-HIPI) improve systemic risk stratification, it remains unclear whether outcomes are more closely associated with specific extranodal organ involvement or with the overall burden of extranodal dissemination. Methods: This retrospective single-center study included 89 patients with predominantly advanced-stage classical Hodgkin lymphoma, including a minority of high-risk stage II bulky cases, and documented extranodal involvement at diagnosis. Extranodal disease was evaluated according to both organ-specific involvement and extranodal organ burden (EOB), defined as single extranodal organ involvement (single EO) versus involvement of two or more extranodal organs (≥2 EO). Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan–Meier analysis and Cox proportional hazard models. Risk stratification was examined using both the International Prognostic Score (IPS) and A-HIPI. Results: Patients with ≥2 EO had significantly inferior OS compared with those with single EO involvement (5-year OS, 66.8% vs. 96.7%; log-rank p = 0.018), whereas the difference in PFS did not reach statistical significance (5-year PFS, 49.6% vs. 73.5%; log-rank p = 0.108). A-HIPI-based stratification significantly discriminated OS (5-year OS, 92.2% vs. 78.2%; p = 0.001) and showed borderline discrimination for PFS (5-year PFS, 71.5% vs. 57.2%; p = 0.053). In the combined analysis, patients with high A-HIPI risk and ≥2 EO had the poorest outcomes, with a 5-year PFS of 34.1% and a 5-year OS of 25.0%. In a parsimonious multivariable Cox model including EOB and A-HIPI-predicted 5-year risk as a continuous variable, ≥2 EO remained associated with inferior OS (HR 3.83, 95% CI 1.34–10.97; p = 0.013), while its association with PFS was adverse but not statistically significant (HR 1.83, 95% CI 0.86–3.88; p = 0.114). Organ-specific extranodal involvement showed limited and inconsistent associations with survival across A-HIPI- and IPS-defined subgroups. Conclusions: In this retrospective single-center cohort, involvement of multiple extranodal organs was associated with inferior OS after adjustment for continuous A-HIPI-predicted risk, whereas its association with PFS did not reach statistical significance. Individual extranodal sites showed no consistent prognostic associations. These exploratory and hypothesis-generating findings suggest that quantitative assessment of extranodal organ burden may complement existing clinical risk measures; however, confirmation in larger, contemporary, externally validated cohorts is required before clinical application. Full article

The association between Down syndrome (DS) and Hodgkin lymphoma (HL) is rare, with only a few cases reported in the literature. Here, we report the case of a pediatric patient with DS diagnosed with HL. In addition, a literature review was conducted, identifying only seven pediatric cases. We highlight treatment-related toxicity in this group of patients. Given the high survival rates of patients with HL, current strategies focus on individualizing treatment intensity based on the initial disease characteristics and the patient’s response. This consideration becomes even more important in patients with DS. The patient described in this report achieved complete metabolic remission after chemotherapy, experienced manageable grade 3 treatment-related toxicities, and remains in complete remission after 27 months of follow-up. Full article

Background: Interim PET after two cycles (PET2) has historically guided risk-adapted therapy in Hodgkin lymphoma (HL). Its value with frontline brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (BV + AVD) is uncertain, as BV + AVD improves progression-free survival and may reduce the prognostic relevance of early metabolic response. Our aim was to assess whether PET2 retains prognostic utility in HL patients treated with BV + AVD. Methods: We retrospectively reviewed 55 newly diagnosed classical HL patients treated with frontline BV + AVD. The primary endpoint was PET2 performance for predicting EOT PET positivity. Sensitivity, specificity, predictive values, and likelihood ratios were calculated with 95% confidence intervals. Results: Median age was 22 years (range 11–77), 49% were male, and 73% had stage III–IV disease. PET2 was negative in 51 patients (92.7%) and positive in 4 (7.3%). EOT PET was negative in 48 (87.3%) and positive in 7 (12.7%). Of seven EOT PET-positive patients, three were PET2-positive and four PET2-negative. Of 48 EOT PET-negative patients, 47 were PET2-negative and 1 PET2-positive. PET2 sensitivity was 42.9%, specificity 97.9%, positive predictive value 75.0%, and negative predictive value 92.2%. Positive likelihood ratio was 20.6; negative likelihood ratio was 0.58. Conclusions: In HL patients treated with BV + AVD, most achieve PET2 negativity, limiting interim PET discrimination. Negative PET2 adds little reassurance beyond the high baseline success rate, while positive PET2 is uncommon and identifies only a subset of eventual treatment failures. These findings question the routine use of PET2 to guide therapy in the BV + AVD era. Full article

Glyphosate-based herbicides are widely used agricultural chemicals. Concerns regarding carcinogenicity, particularly non-Hodgkin lymphoma (NHL), persist. We conducted a systematic review and meta-analysis to better evaluate glyphosate exposure and NHL risk. MEDLINE and EMBASE were searched for eligible cohort, case–control, and pooled studies. Risk of bias was assessed using recommended criteria. Random- and fixed-effects meta-analyses were performed, with sensitivity analyses addressing overlapping cohorts, hazard ratio inclusion, exposure definitions, and model overfitting. Evidence certainty was graded using GRADE. Ten primary datasets were analyzed. Ever-exposure was associated with an odds ratio of 1.11. Highest-exposure analyses demonstrated a significant association with NHL. Ever-exposure associations were modest, whereas a higher glyphosate exposure was consistently associated with an increased NHL risk. The findings were robust across sensitivity analyses. Full article