Diagnosis Of non-Hodgkin Lymphoma Research Articles

Factors influencing timely diagnosis in neurolymphomatosis.

Neurolymphomatosis refers to infiltration of the peripheral nervous system (PNS) by non-Hodgkin lymphoma (NHL). Diagnostic intervals in neurolymphomatosis and factors delaying diagnosis have not been evaluated. We therefore aimed to analyze diagnostic intervals in a large cohort. The quality control database at Yale Cancer Center, Section of Neuro-Oncology, was searched for neurolymphomatosis cases diagnosed between 2001 and 2021. Univariate analyses were performed to identify parameters influencing diagnostic intervals. We identified 22 neurolymphomatosis cases including 7 with primary and 15 with secondary disease, which occurred a median (range: 4-144) of 16 months after initial NHL diagnosis. Patients typically presented with painful polyneuropathy (73%), that was asymmetrical and rapidly progressive. Diagnosis was based on PNS biopsy (50%) or integration of neuroimaging findings (50%) with NHL history and diagnostic cerebrospinal fluid examinations. Median interval from symptom onset to diagnosis was 3 months (range: 1-12). Secondary neurolymphomatosis compared to primary disease (median 2 vs. 6 months, p = 0.02), and cases with rapidly-progressive asymmetrical neuropathy as opposed to other presentations (median 2 vs. 6 months; p < 0.001) were diagnosed earlier. Upfront conventional CT compared to other modalities (median 2 vs. 5 months p = 0.04) and nerve root localization as opposed to other disease sites (median 1.5 vs. 4 months; p = 0.04) delayed diagnosis. NL type and localization, neuropathy course and distribution, and imaging modality selected for initial evaluation influence diagnostic intervals in neurolymphomatosis. Knowledge of this rare entity is critical for early suspicion, and diagnosis.

Evaluation of the incidence, predictors, risk assessment scores and outcomes of thromboembolism in a cohort of Egyptian NHL patients - Real World Experience.

Non-Hodgkin's Lymphoma (NHL) is the most common subtype of lymphoma. The incidence of venous thromboembolism (VTE) in aggressive NHL was estimated recently to be 11%. Several risk assessment scores and factors are available to help identify cancer patients at risk for developing VTE. Patients with a pathologically confirmed diagnosis of NHL were identified at the Oncology Center of Mansoura University. The study included 777 patients: 719 with DLBCL-NOS, 26 with Anaplastic-B-cell, and 32 with T-cell-rich-NHL. Data were retrospectively collected from electronic medical records, including clinical, radiological, and laboratory information related to VTE and NHL. The median age at NHL diagnosis was 53 years, (range: 18-98). There was a male predominance, 51.4% of the cases. At initial lymphoma diagnosis, VTE was identified in 46 (5.9%) patients, and 61 (7.9%) patients experienced VTE while undergoing chemotherapy. According to logistic regression analysis, a PS (performance status) ≥ 2, bulky lesions, and mediastinal masses were significant predictors of VTE at presentation, with P-values of 0.022, 0.002, and < 0.001, respectively. Meanwhile, NHL patients who developed VTE during chemotherapy had significantly poorer PS, higher absolute neutrophilic counts (ANC), neutrophil/lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lactate dehydrogenase (LDH) levels than lymphoma patients without VTE, with P-values of 0.003, 0.034, 0.049, 0.01and 0.007, respectively, as determined by multivariate analysis. The ROC curve identified the cut-off values of 4.875 × 109/L for ANC, 2.985 for NLR, 144.85 for PLR, and 417.5 U/L for LDH as potential markers for predicting VTE in NHL patients. Patients with a PS ≥ 2 and values exceeding these cut-offs for ANC, NLR, and PLR experienced significantly higher incidences of VTE than other groups, with P-values of 0.003, < 0.001, < 0.001, and < 0.001, respectively. At the end of the follow-up, the overall survival was significantly shortened by VTE occurring during chemotherapy, hypoalbuminemia, intermediate-high and high international prognostic index (IPI) scores (intermediate-high and high), responses other than CR and relapse, all with P-values < 0.05. ECOG PS and Inflammatory markers such as NLR, PLR, and neutrophilic count could serve as predictors of the development of thrombotic events in patients with NHL-DLBCL. Additionally, the occurrence of VTE during chemotherapy is an independent poor prognostic marker for overall survival (OS).

Effects and outcomes of tumor lysis syndrome in patients admitted with Hodgkin and non-Hodgkin lymphoma: A National Inpatient Sample study (2019-2020).

e19032 Background: Tumor Lysis Syndrome (TLS) is a life-threatening oncologic emergency. The newer advancement in therapeutic approaches in oncology has widened the range of malignancies associated with TLS. A lot of literature on the incidence of TLS in various solid malignancies exists. However, the effects of TLS on hematological malignancies, especially Hodgkin’s Lymphoma (HL) and Non-Hodgkin’s Lymphoma (NHL) have rarely been analyzed. Our study aims to identify the impact of TLS in patients hospitalized with HL and NHL and draw a comparison between HL and NHL. Methods: We analyzed the National Inpatient Sample database from 2019 - 2020 to identify patients &gt; 18 years old with a primary diagnosis of HL and NHL. We compared the TLS prevalence and all-cause in-hospital mortality, length of hospital stay (LOS), and total costs in patients admitted with HL and compared it with NHL. Categorical variables were compared using the chi-square test, and the t-test compared continuous variables. Multivariable regression analyses were performed adjusting for demographics, hospital-level characteristics, and relevant comorbidities. Results: Among 24,550 Hodgkin’s Lymphoma (HL) hospitalizations and 108,060 Non-Hodgkin’s Lymphoma (NHL) hospitalizations, TLS was diagnosed in 0.69% of HL patients and 0.89% of NHL patients. In-hospital mortality was significantly higher in both HL (44.1%) and NHL (28.3%) patients with TLS compared to those without TLS (HL: 4.5%, NHL: 5.1%). Multivariate regression analysis revealed that TLS presence increased the chance of mortality among both HL (OR 17.9) and NHL (OR 7.3) patients. TLS also significantly impacted secondary outcomes including Acute Kidney Injury (AKI) and Hyperkalemia in both HL and NHL patients. No statistically significant differences were found in the odds of cardiac arrhythmias between HL and NHL patients with TLS (Table). TLS was associated with longer Length of Stay and higher total hospital costs in both HL and NHL patients compared to those without TLS. Conclusions: TLS is significantly associated with increased mortality in patients with HL and NHL, more in HL compared to NHL. In patients with HL, and NHL, TLS is an independent risk factor for in-patient mortality, the longer LOS, and the total cost, thereby incurring an increased burden on healthcare resources. Our study aims to highlight the need for greater vigilance in this vulnerable group when TLS occurs. [Table: see text]

STAT3 Expression and Its Correlation with PD-L1 Expression in Non-Hodgkin's Lymphoma and Hodgkin's Lymphoma at Dr. Saiful Anwar Regional Public Hospital in Malang, Indonesian Population.

Lymphomas are malignant lymphocyte neoplasms that globally account for 10% of cancers in individuals aged <20 years. Malignant lymphomas are divided into Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). Despite the availability of many therapeutic modalities for lymphoma, such as Brentuximab vedotin, Nivolumab, and Pembrolizumab, it is still necessary to identify appropriate strategies with minimal side effects. Immunotherapy is a promising approach, exemplified by targeting JAK/STAT3 signaling, which can inhibit tumor growth and enhance antitumor immune responses. Hence, STAT3 (signal transducer and activator of transcription 3) is a promising therapeutic target. PD-L1 (programmed death-ligand 1), an immune checkpoint molecule, is used as a frontline treatment for various cancers. This study aims to determine STAT3 expression and its correlation with PD-L1 expression in NHL and HL to serve as a basis for further research on anti-STAT3 and its combination with other therapy targets. Samples were obtained from paraffin blocks of patients with confirmed diagnoses of NHL and HL, and then immunohistochemical staining was carried out with PD-L1 and STAT3 antibodies. The collected data were then analyzed using SPSS. Among the 10 HL patients, no patients (0%) expressed STAT3, while nine patients (90%) expressed PD-L1. Among the 10 NHL patients, 1 patient (10%) expressed STAT3, while six patients (60%) expressed PD-L1. There were no significant differences in STAT3 expression and PD-L1 expression between HL patients and NHL patients. There was no correlation between STAT3 and PD-L1 expression in HL and NHL because almost all STAT3 expressions were negative. Although this study revealed no differences between STAT3 and PD-L1 expression in HL and NHL and no significant correlation between STAT3 and PD-L1 expression in HL and NHL, this may serve as the basis for understanding the role of STAT3 and PD-L1 in the regulation of HL and NHL, which may be useful for further research targeting STAT3 and PD-L1 immunotherapy in HL and NHL.

#2367 Membranoproliferative glomerulonephritis preceding non-Hodgkin lymphoma recurrence : a case report

Abstract Background and Aims Glomerulonephritis (GN) have been known to be associated with both chronic lymphocytic leukemia and non-Hodgkin's lymphoma. Membranoproliferative Glomerulonephritis (MPGN) is the most commonly reported histological diagnosis in these diseases. Method This report presented a rare case of membranoproliferative glomerulonephritis preceding non- Hodgkin lymphoma recurrence. Results In September 2023, we report the case of a 75-year-old woman with Sjögren's syndrome, systemic lupus erythematosus and hypertension history. Two years prior, she developed non Hodgkin lymphoma requiring chemotherapy with cyclophosphamide, prednisone, rituximab, and vincristine. It has remained in remission. She was admitted to our department with peripheral edema complaint. Physical examination showed edema in the lower extremities. The blood pressure was 130/85 on her antihypertensive regimen. No lymphadenopathies were found. She had mild proteinuria, microhematuria and reduced estimated glomerular filtration rate. The serum creatinine level was 190 µmol/l. She had 1.8 gr/day proteinuria. Laboratory data showed decreased levels of serum C3, C4. Anti-nuclear antibody (ANA) screens were negative. The cryoglobulins test was negative. Hepatitis B, hepatitis C, and HIV serologies were negative. Renal biopsy was performed and resulted as membranoproliferative glomerulonephritis with positive IgM immunofluorescence stain (Figs 1 and 2). We therefore concluded to a membranoproliferative glomerulonephritis with monotypic immunoglobulin deposits. After investigations, she got recurrent non-Hodgkin lymphoma diagnosis. Discussion GN may precede, coexist, or follow the diagnosis of lymphoma by several years. The pathogenesis of paraneoplastic GN remains uncertain, although autoimmune mechanisms and T-lymphocyte dysfunction may be important in this respect. Conclusion Secondary membranoproliferative glomerulonephritis can be observed in non-Hodgkin lymphoma patients but there are few reports about clinical results of lymphoma treatment. There is limited information available concerning the effects of treatment of non-Hodgkin's lymphoma on the progression of non-Hodgkin's lymphoma associated membranoproliferative glomerulonephritis.

Racial Disparities in Cardiovascular and Cerebrovascular Adverse Events in Patients with Non-Hodgkin Lymphoma: A Nationwide Analysis.

Background and Objectives: Non-Hodgkin lymphoma (NHL) has the sixth-highest malignancy-related mortality in the United States (US). However, inequalities exist in access to advanced care in specific patient populations. We aim to study the racial disparities in major adverse cardiovascular and cerebrovascular events (MACCEs) in NHL patients. Materials and Methods: Using ICD-10 codes, patients with NHL were identified from the US National Inpatient Sample 2016-2019 database. Baseline characteristics, comorbidities, and MACCE outcomes were studied, and results were stratified based on the patient's race. Results: Of the 777,740 patients with a diagnosis of NHL, 74.22% (577,215) were White, 9.15% (71,180) were Black, 9.39% (73,000) were Hispanic, 3.33% (25,935) were Asian/Pacific Islander, 0.36% (2855) were Native American, and 3.54% (27,555) belonged to other races. When compared to White patients, all-cause mortality (ACM) was significantly higher in Black patients (aOR 1.27, 95% CI 1.17-1.38, p < 0.001) and in Asian/Pacific Islander patients (aOR 1.27, 95% CI 1.12-1.45, p < 0.001). Sudden cardiac death was found to have a higher aOR in all racial sub-groups as compared to White patients; however, it was statistically significant in Black patients only (aOR 1.81, 95% CI 1.52-2.16, p < 0.001). Atrial fibrillation (AF) risk was significantly lower in patients who were Black, Hispanic, and of other races compared to White patients. Acute myocardial infarction (AMI) was noted to have a statistically significantly lower aOR in Black patients (0.70, 95% CI 0.60-0.81, p < 0.001), Hispanic patients (0.69, 95% CI 0.59-0.80, p < 0.001), and patients of other races (0.57, 95% CI 0.43-0.75, p < 0.001) as compared to White patients. Conclusions: Racial disparities are found in MACCEs among NHL patients, which is likely multifactorial, highlighting the need for healthcare strategies stratified by race to mitigate the increased risk of MACCEs. Further research involving possible epigenomic influences and social determinants of health contributing to poorer outcomes in Black and Asian/Pacific Islander patients with NHL is imperative.

Baseline immunoglobulin G and immune function in non-Hodgkin lymphoma: a retrospective analysis.

Non-Hodgkin's lymphoma (NHL) encompasses a diverse group of lymphoma subtypes with a wide range in disease course. Previous studies show that hypogammaglobulinemia in treatment-naïve patients is associated with poorer survival in high grade B-cell non-Hodgkin's lymphomas, though it is not known how this applies across all B-cell lymphoid malignancies. We conducted a retrospective study of immunoglobulin levels and clinical outcomes including survival, hospitalization, and infection rates in patients diagnosed with B-cell non-Hodgkin lymphomas of all grades at our institution. Two-hundred twenty-three adults (aged = 18 years) with available pre-treatment IgG levels were selected, with hypogammaglobulinemia defined as IgG< 500 mg/mL. For this analysis, we grouped DLBCL (n=90), Primary CNS (n=5), and Burkitt lymphoma (n=1) together as high-grade, while CLL (n=52), mantle cell (n=20), marginal zone (n=25), follicular (n=21), and Waldenstrom macroglobulinemia (n=5) were low-grade. The incidence of hypogammaglobulinemia in our cohort of both high and low-grade lymphoma patients was 13.5% (n=30). Across all NHL subtypes, individuals with baseline IgG< 500 mg/dL showed an increased rate of hospitalization (4.453, CI: 1.955-10.54, p= 0.0005) and higher mortality (3.325, CI: 1.258, 8.491, p= 0.013), yet no association in number of infections when compared with those with IgG=500 mg/dL. There was a higher hospitalization rate (3.237, CI: 1.77-6.051, p=0.0017) in those with high-grade lymphoma with hypogammaglobulinemia when compared with low-grade. There was no statistically significant difference in individuals who were alive after three years in those with baseline IgG<500 mg/dL. Our study is the first to analyze incidence of hypogammaglobulinemia at the time of diagnosis of NHL as a potential biomarker of interest for future outcomes including hospitalization and infection.

First-Line Respiratory Support for Children With Hematologic Malignancy and Acute Respiratory Failure.

To characterize trends in noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV) use over time in children with hematologic malignancy admitted to the PICU with acute respiratory failure (ARF), and to identify risk factors associated with NIV failure requiring transition to IMV. Retrospective cohort analysis using the Virtual Pediatric Systems (VPS, LLC) between January 1, 2010 and December 31, 2019. One hundred thirteen North American PICUs participating in VPS. Two thousand four hundred eighty children 0-21 years old with hematologic malignancy admitted to participating PICUs for ARF requiring respiratory support. None. There were 3013 total encounters, of which 868 (28.8%) received first-line NIV alone (NIV only), 1544 (51.2%) received first-line IMV (IMV only), and 601 (19.9%) required IMV after a failed NIV trial (NIV failure). From 2010 to 2019, the NIV only group increased from 9.6% to 43.1% and the IMV only group decreased from 80.1% to 34.2% (p < 0.001). The NIV failure group had the highest mortality compared with NIV only and IMV only (36.6% vs. 8.1%, vs. 30.5%, p < 0.001). However, risk-of-mortality (ROM) was highest in the IMV only group compared with NIV only and NIV failure (median Pediatric Risk of Mortality III ROM 8.1% vs. 2.8% vs. 5.5%, p < 0.001). NIV failure patients also had the longest median PICU length of stay compared with the other two study groups (15.2 d vs. 6.1 and 9.0 d, p < 0.001). Higher age was associated with significantly decreased odds of NIV failure, and diagnosis of non-Hodgkin lymphoma was associated with significantly increased odds of NIV failure compared with acute lymphoid leukemia. For children with hematologic malignancy admitted to the PICU with ARF, NIV has replaced IMV as the most common initial therapy. NIV failure rate remains high with high-observed mortality despite lower PICU admission ROM.

Utility of FDG-PET in predicting the histology of relapsed or refractory lymphoma

Abstract18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) is a valuable prognostic tool in modern lymphoma care. In this study, we explored the use of quantitative FDG-PET parameters in predicting the histology of suspected relapsed or refractory (R/R) lymphoma. We retrospectively analyzed 290 FDG-PET scans performed for suspected R/R lymphoma. FDG-PET parameters measured were maximum and mean standardized uptake value (SUVMax and SUVMean), total metabolic tumor volume, and total lesion glycolysis (TLG). Receiver operating characteristic curve analysis was used to obtain the optimal thresholds that best discriminate (1) benign vs R/R lymphoma, (2) indolent vs aggressive non-Hodgkin lymphoma (NHL), and (3) aggressive transformation of indolent NHL. We found that although all 4 FDG-PET parameters discriminated R/R lymphoma from benign histology, TLG was the best performing parameter (optimal cut-off ≥245, sensitivity 63%, specificity 86%, positive predictive value [PPV] 97%, negative predictive value [NPV] 30%, area under the curve [AUC] 0.798, and P < .001). SUVMax discriminated aggressive from indolent NHL with modest accuracy (optimal threshold ≥15, sensitivity 46%, specificity 79%, PPV 82%, NPV 38%, AUC 0.638, and P < .001). In patients with a prior diagnosis of indolent NHL, SUVMax was a modest predictor of transformation (optimal cut-off ≥12, sensitivity 71%, specificity 61%, PPV 50%, NPV 78%, AUC 0.676, and P .006). Additionally, SUVMax ≥25 and an increase in SUVMax (ΔSUVMax) from baseline ≥150% were highly specific (96% and 94%, respectively). These FDG-PET thresholds can aid in identification of suspected R/R lymphoma cases with higher likelihood of R/R disease and aggressive transformation of indolent NHL, guiding the necessity and urgency of biopsy.

Infection Outcomes and Hypogammaglobulinemia in Patients with Non-Hodgkin Lymphoma Treated with Immunoglobulin Replacement Therapy

CONCLUSIONS Patients diagnosed with non-Hodgkin lymphoma (NHL) histologies often develop hypogammaglobulinemia (HGG), a secondary immunodeficiency (SID) that is associated with exposure to NHL-related treatments. Those with HGG frequently experience infections, which represent the leading cause of death in NHL (33% of cases). Patients with HGG who experience recurrent infections may benefit from immunoglobulin replacement therapy (IgRT). We aimed to assess real-world IgRT utilization and associated infection outcomes in patients with NHL. This retrospective, longitudinal, observational study evaluated HGG (immunoglobulin G [IgG] &amp;lt; 500 mg/dL) status and infection outcomes among adult patients diagnosed with NHL after 2010 who had ≥ 12 months of clinical data and ≥ 3 visits/year after NHL diagnosis and received immune globulin infusion (human), 10% (IG10% [ie, Gammagard Liquid]). De-identified clinical data from the Massachusetts General Brigham Research Patient Data Registry was used. IgG testing, infection outcomes, and antimicrobial use were compared 3 months before versus 3 months after initiation of IG10%. Generalized estimating-equation logistic regression models were used to obtain odds ratios (ORs), 95% confidence intervals (CIs), and P values. A total of 13,232 patients with NHL were identified. Among patients with NHL, 623 (4.7%) received ≥ 1 IgRT during the follow-up period, of whom, 563 (90.4%) received IG10%. The majority of patients with NHL treated with IG10% were male (61.3%), White (90.1%), with a median (interquartile range [IQR]) age of 62 (53-69) years, and median (IQR) follow-up of 4.8 (2.3-7.7) years. Median (IQR) administrations of IG10% across recipients were 2 (1-4) and over half of patients (55.6%) received ≥ 2 IG10% administrations. Median (IQR) time from initiation of IG10% to end of follow-up was 25.6 (6.8-55.2) months. Most patients had ≥ 1 IgG test in the follow-up period (n = 532 [94.5%]), median (IQR) number of IgG tests was 10 (4-27), and 84.2% of patients had ≥1 IgG test result available before initiation of IG10%. Of the patients treated with IG10% who had IgG test results available (n = 532), 81.6% were identified with HGG (&amp;lt; 500 mg/dL). Few patients had IgG testing at the time of first NHL diagnosis (13.3%), and median (IQR) time from diagnosis to first IgG test was 4.9 (0.8-17.4) months. Of the patients with ≥ 2 IG10% administrations (n = 313), median (IQR) time from the first administration of IG10% to subsequent IgG testing was 1.0 (0.3-2.8) month. Most patients (91.3%) who received ≥ 2 IG10% administrations and ≥ 1 IgG testing had an IgG test between first and second administrations of IG10%. Median (IQR) serum IgG levels were higher in the 3 months following initiation of IG10% versus 3 months before initiation of IG10% (520.0 mg/dL [413.0-670.0] vs 339.0 mg/dL [228.0-405.0]), and significantly fewer patients had HGG (34.7% vs 83.0%, P &amp;lt; 0.0001). In addition, significantly lower odds of infection (OR 0.60, 95% CI 0.47-0.75), severe infection (OR 0.40, 95% CI 0.32-0.50), and associated antimicrobial use were observed 3 months after IG10% initiation (Figures 1 and 2). In this real-world study of patients with NHL, treatment with IG10% was shown to be associated with significantly lower rates of HGG as well as lower odds of infection, severe infection, and antimicrobial use 3 months after IG10% initiation. Guidelines and consensus-based recommendations are needed to optimize the use of IgG testing, initiation of IgRT, and SID management in patients with NHL.

Neurocognitive Outcomes over the First 3 Months after Chimeric Antigen Receptor T-Cell (CAR T) Therapy: Preliminary Findings from a Longitudinal Study

Introduction People treated with systemic therapies for cancer may exhibit changes in neurocognitive functioning over time, affecting domains such as memory, processing speed, and executive functioning. There is a need for prospective data regarding neurocognitive outcomes among patients treated with Chimeric Antigen Receptor T-Cell (CAR T) therapy. The purpose of this study was to investigate the trajectory of neurocognitive performance and self-reported cognitive functioning over the first 3 months of CAR T therapy. Methods As part of a larger cohort study of patients treated with CAR T, neurocognitive outcomes were assessed prior to starting CAR T and again at 1- and 3- months post-CAR T. Neurocognitive performance was measured using standardized neuropsychological tests including measures of verbal memory (Hopkins Verbal Learning Test-Revised (HVLT-R) - immediate recall, delayed recall, retention), processing speed (Trail-making Test - Part A (TMT-A)) and executive functioning (Trail-making Test Part B (TMT-B), Controlled Oral Word Association Test (COWAT)). Raw test scores were converted to z-scores (Mean 0, SD 1) based on norms adjusted for age, sex, and education, where applicable. Impairment on individual tests was defined by a z score ≤ -1.64. Participants were categorized as showing overall impairment if they had at least two tests with a z-score of ≤ -1.5 or a z-score ≤ -2.0 on one test. Self-reported cognitive functioning was measured using the Functional Assessment of Cancer Therapy - Cognition, Perceived Cognitive Impairment score (FACT-Cog3 PCI) and the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire C-30, Cognitive Functioning scale (EORTC QLQ-C30 CF). Demographic and clinical data were collected through self-report and patient records. Frequencies of impairment were determined at each time point, with clinically significant changes on individual test scores in the first month determined based on z-score changes of ≥1.0 or minimal clinically important differences for self-report questionnaires. Linear mixed models were generated to estimate the trajectory of neurocognitive performance and self-reported cognitive functioning over time from baseline to 3 months. Results Neurocognitive outcomes were available for 37 participants at baseline, with follow-up data available for 29 patients at 1 month and 17 patients at 3 months. Participants were 54% male, had a mean age 58.4 years (sd 11.3) and a mean 15.5 years (sd 3.2) education. All patients had a diagnosis of non-Hodgkin lymphoma (53% diffuse large B-cell lymphoma (DLBCL), 31% transformed DLBCL from follicular lymphoma). Immune effector cell-associated neurotoxicity syndrome (ICANS) affected 32% of patients (5% Grade 4, 3% Grade 3, 8% Grade 2, 16% Grade 1). Cytokine release syndrome (CRS) affected 97% of patients (3% Grade 3, 76% Grade 2, 19% Grade 1). Frequency of overall impairment at each time point was 10/37 (27%) at baseline, 12/29 (41.4%) at 1 month, and 3/17 (17.6%) at 3 months. At each time point, impairment was most common on tests of executive functioning and memory. Based on individual test score changes between baseline and 1 month, rates of decline on individual tests of neurocognitive performance ranged from 11.5% (TMT-A) to 34.6% (COWAT). Decline on self-reported cognitive functioning was observed for 14.3% (FACT-Cog PCI) and 28.6% (EORTC QLQ-C30 CF) of participants. Based on mixed models (Table 1), there was a statistically significant decline in estimated mean z-scores on a test of executive function (COWAT: -0.52, 95% CI -0.89-(-0.16), p=0.007) at 1-month compared to baseline. At three months, there was a statistically significant improvement in estimated mean z-scores on memory (HVLT-R immediate recall: 0.56, 95% CI 0.11-1.01, p=0.017) and executive functioning (TMT-B: 0.87, 95% CI 0.17-1.57, p=0.019; COWAT: 0.68, 95% CI 0.19-1.16, p=0.009) compared to baseline. Conclusions Impairment is present in a subgroup of patients prior to starting CAR T therapy. Patients may demonstrate declines on performance-based measures and report worsening cognitive symptoms in the first month after CAR T therapy, but also improved performance in some domains by three months. Enrollment and long-term follow-up of patients in this study is ongoing. Future analyses will explore differences in trajectories among subgroups, such as those who have experienced ICANS and CRS.

Real-World Impact of Differences in the World Health Organization (WHO) Classification and International Consensus Classification (ICC) Systems on the Diagnosis of Non-Hodgkin Lymphoma: An Analysis from the LEO Cohort Study

Introduction: The use of standardized, evidence-based classification systems is crucial for the accurate diagnosis and treatment of diseases. Moreover, standardized classification facilitates research and epidemiologic studies and promotes consistency in communication among healthcare professionals. Since 2016, the revised 4 th edition of the World Health Organization classification (WHO-HAEM4R) has been the global standard for diagnosis of lymphoid malignancies. With the emergence of new data, 2 new classification systems were developed and published in 2022: the 5 th edition of the WHO Classification (WHO-HAEM5) and the International Consensus Classification (ICC). Both WHO-HAEM5 and ICC maintain a shared fundamental concept of disease classification that integrates clinical, pathologic, and molecular data. However, they differ on nomenclature, establishment of new entities, and/or diagnostic criteria for some disease categories. To evaluate the impact of these differences on real-world diagnosis of non-Hodgkin lymphoma (NHL), we examined the diagnostic classification of NHL in the Lymphoma Epidemiology of Outcomes (LEO) Cohort Study (NCT02736357). Methods: Initiated in 2015, LEO is an ongoing prospective observational study of patients aged ≥18 years with newly diagnosed NHL. Patients are enrolled at 8 major U.S. medical centers. Clinical, epidemiologic, pathologic, and treatment data are abstracted at baseline and active follow-up is conducted for all patients. Lymphoma subtype is coded for each case based on expert hematopathology re-review of the diagnostic pathology slides, the pathology report, biomarker data, and clinical data. Of note, NHL subtype distribution is similar to SEER data. We studied all patients enrolled in LEO between 7/1/2016 (the date LEO pathology review started using WHO-HAEM4R diagnostic codes) and 5/31/2020. WHO-HAEM4R diagnoses and additional clinicopathologic data, when relevant, were used to map cases into the corresponding WHO-HAEM5 and ICC diagnoses. Differences between WHO-HAEM5 and ICC were annotated for each case as: None - same disease entity; Minor - difference in nomenclature with similar diagnostic criteria; Major - difference in disease category and/or diagnostic criteria; or Unevaluable - insufficient data to assign WHO-HAEM5 and/or ICC diagnosis. Results: LEO enrolled 6143 patients during the study period. Of these, comparison between WHO-HAEM5 and ICC was evaluable in 5730 (93.3%). Unevaluable cases included those without a specific WHO-HAEM4R diagnosis at enrollment (N=384; e.g., patients with a low-grade B-cell lymphoma that could not be definitively sub-classified) and those with a specific WHO-HAEM4R diagnosis, but with insufficient clinicopathologic data to assign a specific WHO-HAEM5 and/or ICC diagnosis (N=29). Of the 5730 evaluable cases, 5376 (93.8%) showed no difference between WHO-HAEM5 and/or ICC diagnosis, 311 (5.4%) showed minor differences (nomenclature only), and 43 (0.8%) showed major differences (Table 1). The 43 major differences all involved B-cell NHLs; 20 (46.5%) were attributable to different approaches to classifying double-hit lymphomas, 21 (48.9%) to classification of splenic/leukemic B-cell lymphomas, and 2 (4.6%) to classification of B-cell lymphomas occurring at specific anatomic sites (Table 2). Conclusion: In a large, prospective lymphoma cohort reflecting real-world clinical practice at 8 major U.S. medical centers, major diagnostic differences in the classification of NHL using WHO-HAEM5 or ICC classification criteria were seen in 0.8%, whereas the remaining 99.2% of diagnoses were either the same or showed differences in nomenclature only. The existence of 2 concurrent classification systems presents potential for discrepancies in pathologic diagnosis, clinical practice, clinical trials, and other lymphoma research. Furthermore, some of the differences between WHO-HAEM5 and ICC are clinically and potentially therapeutically significant, and their resolution requires further study. Nevertheless, our findings argue that the proportion of patients affected would be small in real-world practice settings. This appears largely related to incidence rates of specific lymphoma subtypes, with major differences between the 2 classifications predominantly affecting rare entities, while there is general concordance on the most common forms of NHL.

Baseline Immunoglobulin G and Immune Function in Lymphoma: A Retrospective Analysis

Introduction: Non-Hodgkin's lymphoma (NHL) encompasses a diverse group of lymphoma subtypes with a wide range in disease course. Previous studies show that hypogammaglobulinemia in treatment-naïve patients is associated with poorer survival in high grade B-cell non-Hodgkin's lymphomas, though data is lacking on how this applies across all B-cell lymphoid malignancies. We conducted a retrospective study of immunoglobulin levels and clinical outcomes including survival, hospitalization, and infection rates in patients diagnosed with B-cell non-Hodgkin lymphomas of all grades at our institution. Methods: Patient data was collected from January 2010 to June 2022. Two-hundred twenty-three adults (aged &amp;gt; 18 years) with available pre-treatment IgG levels were selected, with hypogammaglobulinemia defined as IgG&amp;lt; 500 mg/mL. For this analysis, DLBCL (n=90), Primary CNS (n=5), and Burkitt's lymphoma (n=1) was classified as high-grade, while CLL (n=52), mantle cell (n=20), marginal zone (n=25), follicular (n=21), and lymphoplasmacytic lymphomas (n=5) as low-grade. Baseline clinical, staging, and laboratory information was collected including hospital admissions, date of death, and number of infections. Preliminary results for overall survival, 3-year survival and 5-year survival were also analyzed. Multivariate logistic models were used to predict outcomes dichotomized for baseline IGG and high/low grade cancers. Kaplan-Meier estimates and Cox model were performed to analyze the overall survival data. Results: The incidence of pre-treatment hypogammaglobulinemia was 47% in the high-grade B-cell lymphoma cohort and 57% the low-grade B-cell lymphoma cohort (p=.9371). Across all NHL subtypes, individuals with baseline IgG&amp;lt; 500 showed an increased rate of hospitalization (4.453, CI: 1.955-10.54, p= 0.0005) and higher mortality (3.325, CI:1.258, 8.491, p= 0.013), yet no association in number of infections when compared with those with IgG&amp;gt;500. There was no statistical difference in patients' hospitalization rate when they were treated with IVIG only, rituximab only, or a combination (p=.141792). Additionally, there was no statistically significant correlation with COVID infections when evaluating grade of lymphoma (p=.8527) or IgG level (p=.6535). There was no statistically significant difference in individuals who were alive after three years and five years in those with baseline IgG&amp;lt;500. Discussion: Our study is the first to analyze incidence of hypogammaglobulinemia at time of diagnosis of NHL as a potential biomarker of interest for future outcomes including hospitalization and infection. These findings demonstrate an association between hypogammaglobulinemia when comparing the rate of hospitalization and mortality across the spectrum of B-cell NHL. This effect was further amplified in patients with aggressive B-cell lymphoma. Given the common use of monoclonal antibodies to treat B cell lymphomas of all subtypes and the known risk of hypogammaglobulinemia from these treatments and the common finding of hypogammaglobulinemia at diagnosis of B cell NHL, pretreatment screening of IgG levels may be important to identify patients at risk for infection, hospitalization and death. Further clinical equipoise exists requiring a randomized clinical trial to indicate the use as a prognostic factor for infection, hospitalization, and mortality.

A label-free sensor based on a carbon nanotube-graphene platform for the detection of non-Hodgkin lymphoma genes

Early diagnosis of non-Hodgkin lymphoma (NHL) is crucial for effective management. We report an ultrasensitive electrochemical genosensor using multi-walled carbon nanotube (MWCNT)-graphene nanocomposite for detection of lymphoma biomarker gene. MWCNTs were dispersed over graphene nanoplatelets to form a conductive nanocomposite platform. The high surface area and π-π stacking ability enabled efficient immobilization of lymphoma probe DNA. Detailed materials characterization was performed using microscopy and spectroscopy techniques. The sensor was fabricated by drop-casting probe-conjugated nanocomposite suspension onto a glassy carbon electrode. The genosensor exhibited a wide dynamic range of 1 fM to 1 nM with a sensitivity of 0.895 kΩ per decade of target concentration. The sensor showed excellent selectivity for fully complementary target sequence over even single base mismatch. Hybridization detection by electrochemical impedance spectroscopy was further validated using differential pulse voltammetry which showed drastic reduction in redox peak current after incubating with target. The nanocomposite genosensor demonstrated good reproducibility with relative standard deviation of 3.72 % among five independently prepared electrodes. Clinical applicability was tested by spiking lymphoma gene biomarker in 10 % serum and recoveries of 93–99 % were obtained. The proposed MWCNT-graphene nanocomposite genosensor provides a simple, specific and ultrasensitive platform for point-of-care diagnosis of NHL.

Standardization of Outpatient Care after CAR-T Therapy across a Large Cell Therapy Network- through Technology and Decentralized Virtual Nurses: Preliminary Results

Introduction: Shifting Chimeric Antigen Receptor T-cell (CAR-T) therapy to the outpatient setting may increase patient satisfaction and inpatient capacity, and reduce infection risk. Outpatient protocols require resources for patient management outside of clinic hours to be safe and effective. Our Transplant and Cellular Therapy Network (TCTN) leveraged wearable technology and decentralized nurses in four outpatient CAR-T programs. We sought to characterize patient adherence, time spent on patient monitoring, and clinical outcomes. Methods: Patients were deemed eligible for outpatient therapy if they were adults (18+ years), lived within 30-60 minutes of the treating hospital, had a 24/7 caregiver, and received CAR-T with known risks of developing cytokine release syndrome (CRS). The outpatient CAR-T program included enrollment into an FDA-cleared virtual care platform, daily engagement with virtual nurses for the duration of the program, and in-person clinic visits during the highest risk period (Days 1-14). The remote monitoring kit included a wearable device that continuously transmitted vital signs (pulse, respiratory rate, O 2 saturation and skin temperature), a tablet, axillary temperature patch and blood pressure (BP) cuff. Patients were asked to always wear the device outside of clinic visits, take a BP reading 3x/day, and complete surveys via the tablet. A multidisciplinary taskforce established clinical pathways for remote monitoring across sites and developed parameters for alarms, virtual nurse check-ins, and escalation of care to ER/clinic. Virtual nurses contacted patients based on vital sign trends, responded to patient concerns, and triaged in accordance with clinical pathways, escalating as appropriate. The virtual care platform, video and phone call logs with the virtual nurses, and clinical data were extracted for 40 patients between 2/20/23 and 6/15/2023. Inpatient admission, patient adherence, alarms, calls, and clinical metrics were summarized. Non-parametric measures were reported as median (IQR). Metrics for specific windows of time were reported for a subset of variables: wearable adherence (day vs. night) and alarms/calls during clinic hours (weekdays 8 am - 5 pm) vs. non- clinic hours. Adherence was derived from tasks/wear time completed vs. prescribed. Results: Forty patients (66 ± 12 years, 24 male) with diagnoses of Non-Hodgkin Lymphoma (75%), Plasma Cell Disorder (20%), or Acute Lymphoblastic Leukemia (5%) received CAR-T therapy [axi-cel (40%), liso-cel (25%), cilta-cel (20%), brexu-cel (12.5%), tisa-cel (2.5%)] and completed the outpatient CAR-T program. The median length of monitoring on the platform was 14.7 (10.4 - 27.6) days. Overall wearable adherence was 79 (67.7 - 87.9) %; 67 (48.7 - 83.4) % in the day and 89.1 (79.8 - 92.8) % at night. Median survey completion was 50 (7.7 - 80) % and BP compliance was 95 (69.8-100) %. Out of 717 patient days, 68.4% had 100% BP compliance (3 readings/day). There was a total of 780 alarms; 67% operational and 86% clinical alarms occurred during non-clinic hours (Table 1). The operational alarm rate was 0.5 and the clinical alarm rate was 0.6 per patient-day. 75% of patients triggered at least one operational and clinical alarm during their program. The virtual nurses engaged in 1102 calls through the tablet or phone (3.5 ± 3.4 mins). More than half of the calls were during non-clinic hours (63%) and 70% of calls were with a patient/care giver. Calls about a clinical alarm or clinical concern were 3x and 6.8x higher, respectively, during non-clinic hours. Twenty-seven patients required some level of hospital observation service and/or admission to the hospital; 25 patients developed CRS. Median duration from infusion to admission/observation was 5 (1-11) days. Median days to discharge was 5 (1-26). Of those admitted,10 patients were admitted to the ICU with a median stay of 5.5 (1-21) days. Conclusion: Our TCTN established a successful, integrated outpatient management process to ensure patient safety within the first 30 days post CAR T-Cell therapy. The virtual care platform and decentralized virtual nurses have enabled patients to recover safely with more time at home rather than in hospital. Future research will address patient and provider experiences and continue to expand on the safety and resource utilization of this integrated program.

Risk of Therapy-Related Acute Myeloid Leukemia (t-AML) in Adolescent and Young Adults Cancer Patients Treated with Chemotherapy with or without Radiotherapy: A National Population-Based Cohort Study Using SEER Registry

INTRODUCTION The risk of treatment-related acute myeloid leukemia (t-AML) in adolescents and young adults (AYA) with first cancers treated with chemotherapy with or without radiation is not well characterized. We analyzed Surveillance, Epidemiology and End Result (SEER) data for the past 45-years (1975-2020) to identify the overall risk of t-AML in treated AYA cancer patients (pts) and by index cancer sites as well as latency periods. METHOD We analyzed NCI's SEER-8 registries. ICD-O-3/WHO-2008 codes were used to identify pts with index cancer types between the ages of 15-39 years (AYA), treated with either chemotherapy or radiotherapy, and with a subsequent diagnosis of acute myeloid leukemia (AML) at least one year after index cancer, between January 1975 and December 2020. The risk of t-AML was estimated by standardized incidence ratio (SIR), defined as the ratio of observed t-AML-cases in the AYA-with-cancer, to the expected number of AML-cases in the matched general US population. A reference rate file for AML incidence in age, gender, race and calendar-year matched US population is available in SEERStat software. A Poisson distribution of observed t-AML was assumed for the calculation of 95% confidence intervals (CIs). A P-value &amp;lt;.05 was considered statistically significant. We stratified the risk of t-AML for index cancer types with ten or more pts, by attained-calendar-years, and latency at multiple time intervals (Table-1) from index cancer diagnosis. RESULT Among 102,879 AYA cancer pts eligible for analysis, 236 pts developed t-AML with SIR of 6.19 (95%CI: 5.43-7.04, P &amp;lt;.05) with excess risk of 1.46 per-10000 person-years (pyrs). (Table-1). We stratified risk for index cancer types with at least ten patients developing t-AML, these included breast, Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), testicular, thyroid, bone and joint, and soft tissue including heart. As a general trend, risk of t-AML was highest during 1-3 years after index cancer diagnosis compared to subsequent latency periods. However, risk for t-AML was significantly greater than the matched-general US population even after 20-40 years of breast cancer, HL, and NHL (Table-1). When stratified by attained calendar-year periods (1975-1985, 1986-1995, 1996-2005, 2006-2015, 2016-2020), risk for t-AML was higher than general population in all time periods. However, overall SIR was comparatively lower for recent time periods, particularly lowest during 2016-2020 [SIR: 3.49 (2.51-4.72, P &amp;lt;.05)]. Notably, the highest risk for t-AML in 2016-2020 was observed with index cancer of soft tissue including heart [SIR: 10.12 (1.23-36.57), P &amp;lt;.05]. CONCLUSION In this study spanning between 1975-2020, we observed the risk of t-AML trending down among AYA in recent years, albeit higher than the age matched general population. The risk of t-AML remained significantly elevated even after 20-40 from diagnosis of breast cancer, HL and NHL. Since these pts likely received radiation and older (higher intensity) chemotherapy based-regimens, it is essential to analyze the long-term impact of newer therapies for these cancers and assess the risk of t-AML in future studies.

Predicting Toxicities in Older Adults with Non-Hodgkin Lymphoma (NHL) Receiving Systemic Chemotherapy: A Prospective Geriatric Assessment (GA) Study

Background Sixty percent of newly diagnosed NHL patients (pts) are ≥60 years (yrs) old and have significantly worse relapse-free and overall survival (OS) than their younger counterparts. Toxicity (tox) is more common in older adults (OA), and those who experience it derive less benefit from treatment. Use of reduced intensity treatment regimens can minimize tox but might also lead to poorer outcomes due to reduced disease control. Prospective identification of pts at greatest risk of toxic events may allow tailored dose reductions in those vulnerable individuals and mark them for closer monitoring during therapy. Currently, no validated instrument exists to predict tox in OA with NHL. We conducted a prospective study to determine if a geriatric assessment (GA) or its component measures predict tox in OA with NHL and determine if changes in GA during and after treatment correlate with tox. Methods Pts ≥ 60 yrs with confirmed diagnoses of NHL starting a new chemotherapy regimen (chemo) were included. GA was performed: 1) prior to pre-phase therapy in those who received it, 2) prior to initiation of the new chemo, 3) within 7 days prior to each cycle (up to 6), 4) 1 month (+/- 10 days) after completing therapy. GA instruments included MOS physical health subscale for ADLs, OARS subscale for IADLs, self-reported KPS, no. of falls, Timed up and go (TUG) test, Physical Health Section (subscale of OARS) for comorbidities, Mental Health Inventory-17 for psychological state, Blessed Orientation Memory Concentration Test for cognition, MOS social activity survey, MOS social support survey, % weight loss and Mini Nutritional Assessment (MNA) for nutrition and polypharmacy. Data regarding: 1) hematologic Tox ≥ Grade 4, and non-hematologic tox ≥ Grade 3, 2) hospitalization, 3) dose delay or reduction due to tox, and 4) discontinuation of chemo due to tox were collected at each visit. Therapeutic regimens were at the discretion of the physician, characterized as curative intent or palliative. The primary outcome events were severe tox (STox) defined as any of the following: 1) Hospitalization during or within 30 days following chemotherapy, 2) Dose delay or reduction to a dose intensity ≤80% of the planned dose intensity, 3) Discontinuation of chemo due to tox, 4) Death. Secondary tox endpoints were Grade 3 or higher non-hematologic tox and Grade 4 or higher hematologic tox. Results A total of 194 pts were enrolled, one pt was missing baseline data, but was included in endpoint analysis. Median age was 75 yrs (IQR 68-81 yrs), 42% were women, majority had diffuse large B cell lymphoma (72%), and majority had advanced stage disease (75%). All pts with DLBCL were treated with curative intent. The most common regimen was R-CHOP (71%). Median ADL score was 85 (IQR 46-95) and median IADL score was 14 (IQR 13-14). The median TUG time was 10 seconds (sec) (IQR 8-14 sec), and 29% pts had an abnormal TUG test (defined as ≥ 12 sec). Majority of pts (56%) had a normal nutritional status based on MNA score ≥ 24 (Table 1). STox occurred in 57% pts, 25% had grade 3+ non-hematologic tox and 38% had grade 4+ hematologic tox. The 2-year OS was 83% (CI 78%, 89%) and 5-year OS was 78% (CI 71%, 84%) (Figure 1). Pts experiencing STox were older (76 vs 72 yrs, p=0.007), had a lower ADL score (80 vs 90, p=0.014), and lower patient reported KPS (80 vs 90, p&amp;lt;0.001). Pts with an abnormal TUG at baseline had higher incidence of STox vs those with normal TUG (72% vs 51%, p=0.01). Pts with aggressive lymphoma and high aaIPI were more likely to experience STox than those with indolent lymphoma (80% vs 69%, p=0.07) and low aaIPI (58% vs 43%, p=0.09) though these differences did not reach statistical significance. 18 out of the 22 pts on R-EPOCH had STox events (82% vs 54% of patients on other treatments, p = 0.012). Conversely, 52% of the 137 patients on R-CHOP had STox events vs 70% of patients on other treatments (p=0.023). Analyses evaluating the correlation between dynamic changes in GA prior to each cycle and toxicities are currently underway. Conclusions Several components of GA such as low ADL score, self-reported KPS and abnormal TUG are associated with severe treatment related toxicity in OA with NHL receiving systemic chemo. In particular, the TUG test is objective and easy to administer, and an abnormal TUG time should be routinely incorporated in treatment decision making for these pts.

Antinuclear Antibodies Are Associated with an Increased Risk of Diffuse Large B-Cell Lymphoma.

Immune dysregulation is thought to increase the risk of non-Hodgkin lymphoma (NHL), but the evidence varies by subtype. We evaluated whether antinuclear antibodies (ANA), double-stranded DNA antibodies (anti-dsDNA), and extractable nuclear antigen antibodies (anti-ENA) were associated with the risk of common NHL subtypes in a nested case-control study. The autoantibodies were tested in serum collected years prior to NHL diagnosis in 832 cases and 809 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Logistic regression was used to determine odds ratios (ORs) and 95% confidence intervals (95% CI) for the association with NHL risk. No association was observed between ANA positivity and NHL risk overall (OR: 1.18, 95% CI: 0.88-1.58); however, ANA positivity was associated with an increased risk of diffuse large B-cell lymphoma (DLBCL) (OR: 1.83, 95% CI: 1.15-2.91), with 19.7% of cases and 12.2% of controls testing positive. The presence of either anti-ENA or anti-dsDNA was associated with an increased risk of NHL (OR: 2.93, 95% CI: 1.18-7.28), particularly DLBCL (OR: 3.51, 95% CI: 1.02-12.0) and marginal zone lymphoma (OR: 8.86, 95% CI: 1.26-62.0). Our study demonstrates that autoantibodies are associated with an elevated risk of DLBCL, providing support for autoimmunity as a risk factor.

Increasing incidence of non-Hodgkin lymphoma in England, 1985–2019

Abstract Background In the UK, non-Hodgkin lymphoma (NHL) is the most common hematological malignancy and 6th most common cancer overall - accounting for about 14,200 new cases and 4,900 deaths each year. After rising rapidly from the 1980s onwards, the incidence rates of NHL have broadly stabilised in several European and North American countries since the late 1990s. We conducted a retrospective population-based cohort study to examine whether similar changes in the incidence of NHL have also occurred in England from 1985-2019. Methods Individual-level data for patients diagnosed with NHL, and the corresponding national population (denominator) data were obtained from ONS/PHE. Average annual incidence rates (AAIR) were calculated by sex, three age categories (0-34, 35-64 and 65+ years) and seven five-year time periods (1985-89 to 2015-19). Results During the 35-year study period, a total of 304,994 new cases of NHL were registered in England (54% males, 46% females). In young people aged 0-34 years, the AAIRs increased by 33% in males and 60% in females (from 1.8/100,000 in 1985-89 to 2.4/100,000 in 2015-19 in males, and from 1.0/100,000 in 1985-89 to 1.6/100,000 in 2015-19 in females). In middle age (35-64 years), the AAIRs increased by 54% in males and 57% in females (from 13.3 to 20.5 in males, and from 9.6 to 15.1 in females). At older ages (65+ years), the AAIRs increased by 108% in males and 102% in females (from 47.6 to 99.1 in males, and from 34.1 to 68.7 in females). In both sexes and all age categories, the disease was most frequently diagnosed at the advanced Stage 4. With regards to the socioeconomic status, the disease was relatively more commonly diagnosed in the most deprived groups. Conclusions In contrast with many European and North American countries, there has been a steady and substantial increase in the incidence of NHL in England over the past four decades. Overall, the highest increase was observed in males (115%) and those aged 65+ years (109%). Key messages • The reasons behind this continued increase in incidence in England, which is in contrast with most European/North American populations, remain elusive and need further etiological investigation. • Considering that the large majority of cases were diagnosed at the advanced Stage 4, there is an urgent need for clinical guidance to facilitate early diagnosis of NHL.

Personalised therapy in follicular lymphoma - is the dial turning?

Follicular lymphoma is the most common indolent lymphoma accounting for approximately 20%-25% of all new non-Hodgkin lymphoma diagnoses in western countries. Whilst outcomes are mostly favorable, the spectrum of clinical phenotypes includes high-risk groups with significantly inferior outcomes. This review discusses recent updates in risk stratification and treatment approaches from upfront treatment for limited and advanced stage follicular lymphoma to the growing options for relapsed, refractory disease with perspectives on how to approach this from a personalized lens. Notable gaps remain on how one can precisely and prospectively select optimal treatment for patients based on varying risks, with an anticipation that an increased understanding of the biology of these different phenotypes and increasing refinement of imaging- and biomarker-based tools will, in time, allow these gaps to be closed.