Nodular Lymphocyte Predominant Hodgkin Lymphoma Research Articles

Management of children and adults with all stages of nodular lymphocyte predominant Hodgkin lymphoma-All StAGEs: Aconsensus-based position paper from the Hodgkin lymphoma subgroup of the UK National Cancer Research Institute.

A consensus statement for the management for patients of all ages with all stages of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)-All StAGEs-is proposed by representatives of the UK National Cancer Research Institute (NCRI) Hodgkin lymphoma study group and the Children's Cancer & Leukaemia Group. Based on current practices and published evidence, a consensus has been reached regarding diagnosis, staging and risk-ik7 stratified management which includes active surveillance, low- and standard-dose immunochemotherapy and radiotherapy.

NCCN Guidelines® Insights: Hodgkin Lymphoma, Version 2.2022.

Hodgkin lymphoma (HL) is an uncommon malignancy of B-cell origin. Classical HL (cHL) and nodular lymphocyte-predominant HL are the 2 main types of HL. The cure rates for HL have increased so markedly with the advent of modern treatment options that overriding treatment considerations often relate to long-term toxicity. These NCCN Guidelines Insights discuss the recent updates to the NCCN Guidelines for HL focusing on (1) radiation therapy dose constraints in the management of patients with HL, and (2) the management of advanced-stage and relapsed or refractory cHL.

Macrophage Infiltration Correlates with Genomic Instability in Classic Hodgkin Lymphoma.

Hodgkin lymphoma (HL) is a biologically diverse group of lymphoid tumors, which accounts for 1% of all de novo neoplasms in the world’s population. It is divided into two main groups: the more common classic Hodgkin lymphoma (cHL) and the less common nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). cHL is further divided into four subtypes, which differ in morphology and the contents of tumor microenvironment. Macrophages are one of the components of tumor microenvironment known to contribute to creating an immunosuppressive microenvironment, which inhibits the activity of cells expressing granzyme B against tumor cells, even when tumor cells are infected with Epstein–Barr virus (EBV). Our research aimed to explore the association between the specific contents of tumor microenvironment and the genetic anomalies in tumor cells. The presence and the relative percentage of cytotoxic T lymphocytes and macrophages was detected by immunohistochemical staining of the antigens specific for certain cell populations. Fluorescent in situ hybridization was used to detect anomalies in the genome of tumor cells and in situ hybridization was used to detect the presence of EBV. Our results show an association between the number of CD163+ macrophages and the number of TP53 copies or BCL6 gene translocation. Patients who had a higher number of CD163+ macrophages infiltrating tumor tissue and three or higher number of copies of TP53 showed poorer survival. We conclude that the presence of macrophages may contribute to genetic instability in cHL, which drives the progression of cHL and decreases survival of the patients.

Ultrasensitive RNA In Situ Hybridization for Kappa and Lambda Light Chains Assists in the Differential Diagnosis of Nodular Lymphocyte-predominant Hodgkin Lymphoma.

Establishing a diagnosis of nodular lymphocyte-predominant Hodgkin lymphoma (nLPHL) is often challenging as the differential diagnosis is broad, including classic Hodgkin lymphoma (cHL), progressive transformation of germinal centers (PTGC), and other lymphoproliferative disorders. In this study, we investigate the utility of a recently described ultrasensitive in situ hybridization assay for kappa and lambda immunoglobulin light chains in distinguishing nLPHL, cHL, and PTGC. A total of 72 cases were examined (21 nLPHL, 33 cHL, and 18 PTGC). In nLPHL, the large neoplastic cells were light chain restricted in 21/21 (100%) cases (16 kappa, 5 lambda). In contrast, Reed-Sternberg cells of cHL were negative for kappa and lambda in all cases (0/33, 0%; P <0.001). In PTGC, polytypic B cells were noted in mantle zones and germinal centers in all cases, with 1 case (5%) also showing focal collections of light chain restricted large B cells. Background monotypic small B cells were identified in 3 cases, including 1 nLPHL and 2 cHL (1 of which arose in chronic lymphocytic leukemia). Ultrasensitive in situ hybridization for kappa and lambda is a useful addition to a standard immunophenotyping panel for the evaluation of suspected nLPHL.

Nodular lymphocyte predominant Hodgkin lymphoma with T-cell/histiocyte - rich large B-cell lymphoma pathohistological characteristics and extranodal presentation: Case report and literature review

Nodular lymphocyte predominant Hodgkin lymphoma appears in 5% of Hodgkin lymphoma. Because of major biological and clinical differences with classical Hodgkin lymphoma and close relationship to T-cell/histiocyte-rich large B-cell lymphoma, lately the term nodular lymphocyte predominant B-cell lymphoma is accepted. The presence of lymphocyte predominant cells with preserved B-cell phenotype and a lack of CD30 is the prerequisite for the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma. Lymphocyte predominant cells are typically embedded in large nodules of B lymphocytes (growth patterns A and B), but variants that are characterized by lymphocyte predominant cells located outside the nodules, a Tcell- rich nodular growth pattern and T-cell-rich or B-cell-rich diffuse growth patterns, respectively, have also been described (growth patterns C, D, E, and F). Variant growth patterns are associated with the recurrence and progression of disease and should be recognized and specified in pathology reports. Broad B-cell immunohistochemical panel, including PAX5, CD79a, Bob.1, and Oct-2 is indicated in these cases to distinguish between nodular lymphocyte predominant Hodgkin lymphoma, classical Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma, which have significant differences in clinical behavior and treatment. There are different treatment approaches in patients with nodular lymphocyte predominant Hodgkin lymphoma depending on pathohistological type, clinical presentation and stage of the disease. Treatment may include active surveillance, radiation therapy, immunotherapy or chemotherapy. A multidisciplinary approach is beneficial to optimize the diagnosis and management of patients with nodular lymphocyte predominant Hodgkin lymphoma.

Nodular Lymphocyte-Predominant Hodgkin Lymphoma: Review of Current Literature and Case Discussion.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subset of Hodgkin lymphoma (HL). It has a distinct clinical and pathological presentation. Unlike classic HL, where the predominant malignant cells are Reed Sternberg cells, the malignant cells in NLPHL are known as lymphocyte predominant (LP) cells, with their own unique immunohistochemistry antigen expression and staining pattern. Based on risk stratification and staging of the disease, treatment can range from active surveillance in asymptomatic patients with no organ compromise or bulky disease, to aggressive chemotherapeutic agents in advanced disease. Guidelines on which of these chemotherapy regimens would offer the most benefit to our patients are limited due to lack of randomized-controlled studies. Majority of the current prospective data on treatment were inclusive of both HL and NLPHL. Thus, the regimens employed in treatment of NLPHL are similar to the ones used in HL, though NLPHL is often viewed as its own distinct entity. This article aims to review the current literature and future advances on treatment of this rare disease.

Nodular Lymphocyte Predominant Hodgkin Lymphoma: A Rare Subtype with Distinct Clinicopathological Features

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma (HL) characterized by a distinct morphology, an older median age at onset, less incidence of mediastinal involvement, more frequent relapse and better prognosis as compared to Classical-HL (CHL). In contrast to CHL, the tumor cell (LP cell) of NLPHL almost always retains its B cell phenotype and is a CD30 non-expresser. Due to its rarity, only a handful of studies on this entity are available in the lit

Sarcoid like reaction in a child with nodular lymphocytic predominant Hodgkin lymphoma following chemotherapy: A case report

Sarcoid like reaction in a child with nodular lymphocytic predominant Hodgkin lymphoma following chemotherapy: A case report

A comparison and review of the flow cytometric findings in classic Hodgkin lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, T cell/histiocyte rich large B cell lymphoma, and primary mediastinal large B cell lymphoma.

The "Hodgkin-like" lymphomas including classic Hodgkin lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, T cell/histiocyte rich large B cell lymphoma, and primary mediastinal large B cell lymphoma have been shown to be pathobiologically related. With the exception of primary mediastinal large B cell lymphoma, these lymphomas have similar morphologic growth patterns with occasional neoplastic cells within a prominent reactive cell background. Historically, distinguishing these entities was difficult by flow cytometry; however, over the past 15 years, our laboratory has developed antibody-fluorochrome combinations capable of accurately distinguishing these entities by their immunoprofile. Additionally, an algorithmic approach based on characterization of the background reactive B-cell and T-cell populations can aid in narrowing the differential diagnosis. This review summarizes both the morphologic and immunophenotypic features and the current flow cytometric insights of the neoplastic and reactive populations found in this unique subset of lymphomas.

The characterization and frequency of diagnosis of EBV-positive variants with a lymphoid predominance in the structure of Hodgkin lymphoma

Introduction. Epstein — Barr virus (EBV) plays an important role in the pathogenesis of lymphoid tumors, in particular Hodgkin lymphoma. The frequency of expression of the EBV varies in different histological variants of classical Hodgkin lymphoma and is rarely observed in nodular lymphocyte predominant Hodgkin lymphoma.Aim — to study the pathomorphological features of the histological variants of Hodgkin lymphoma with lymphoid predominance associated with the EBV, as well as the frequency of their diagnosis in the structure of Hodgkin lymphoma.Materials and methods. The retrospective study included 794 patients with a verified diagnosis of Hodgkin lymphoma using histological and immunohistochemical methods on biopsy material for the period 2018–2019 (age range — 18–91 years old; median — 34 years old; men : women — 1.1 : 1). The presence of EBV in biopsies was assessed by immunohistochemical reaction with antibodies to EBV (clone LMP1), or by chromogenic in situ hybridization with probes for EBV-encoded small RNAs.Results. Classical Hodgkin lymphoma was diagnosed in 91 % (725/794) cases, nodular lymphocyte predominant Hodgkin lymphoma — in 9 % (69/794) cases. EBV-positive Hodgkin lymphoma accounted for 11 % (82/725) of all cases of classical Hodgkin lymphoma, (age range — 18–81 years old, median — 45 years old; men : women — 2.5 : 1). All cases of nodular lymphocyte predominant Hodgkin lymphoma were EBV-negative. Lymphocyte-rich classical Hodgkin lymphoma was found in 14 patients (14/725, 2 %), 4 patients showed intermediate morphoimmunohistochemical features with nodular lymphocyte predominant Hodgkin lymphoma, which were statistically significantly different from classical Hodgkin lymphoma by the presence of B-zones in the form of large nodules (p = 0.0157) and expression CD20 by tumor cells (p = 0.0404).Conclusion. Nodular lymphocyte predominant Hodgkin lymphoma is not characterized by a connection with EBV infection, unlike classical variant — lymphocyte-rich classical Hodgkin lymphoma. The obtained data support the concept of the existence of a transient form of Hodgkin lymphoma, which has the features of nodular lymphocyte predominant Hodgkin lymphoma and classical Hodgkin lymphoma, in the pathogenesis of which the Epstein — Barr virus likely plays a role.

Transformation and outcome of nodular lymphocyte predominant Hodgkin lymphoma: a Finnish Nationwide population-based study

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare B-cell malignancy associated with excellent survival. However, some patients experience histological transformation into aggressive large B-cell lymphoma. Population-based data on transformation in patients with NLPHL is limited. We conducted a nationwide population-based study to estimate the risk of transformation and relative survival in patients diagnosed with NLPHL in Finland between 1995 and 2018. We identified a total of 453 patients (median age, 48 years; 76% males) with the incident NLPHL from the Finnish Cancer Registry. The cumulative incidence of transformation was 6.3% (95% CI, 4.2-9.6) at 10 years. After adjusting for sex, age and year of diagnosis, transformation was associated with a substantially increased risk of death (HR 8.55, 95% CI 4.49−16.3). Ten-year relative survival was 94% (95% CI, 89%‒100%). The patients diagnosed at a later calendar year had lower excess risk of death (HR, 0.38 per 10-year increase; 95% CI, 0.15‒0.98). We conclude that while the 10-year relative survival for the patients with NLPHL was excellent in this large population-based cohort for the entire study period, transformation resulted in a substantially increased mortality compared with the patients without transformation. Our results also suggest a reduction in excess mortality over time.

Spectrum of B-cell neoplasms associated with immunoglobulin G4-related disease.

Immunoglobulin G4-related disease (IgG4-RD) has rarely been associated with lymphoid neoplasms, the spectrum of which remains unclear. B-cell lymphoid neoplasms (LN) associated with IgG4-RD diagnosed in a 4-year period were analysed. There were five men and three women at a median age of 76.5 (52-90) years; three with synchronous IgG4-RD and LN; three with IgG4-RD preceding LN by 2, 3, and 22years; and two with LN preceding IgG4-RD by 2.5 and 7years. All patients presented with disseminated lymphadenopathy. Monoclonal gammopathy of undetermined significance (MGUS)/smouldering multiple myeloma (SMM) was found in three patients, all with an IgGκ paraprotein. Levels of IgGκ and IgG4 correlated. Diffuse large B-cell lymphoma (DLBCL) was found in three patients, with one case showing co-existing lymphoma and IgG4-RD in the same lymph node biopsy. The remaining two cases were marginal zone lymphoma (MZL) developing in a lacrimal gland previously involved by IgG4-RD; and nodular lymphocyte predominant Hodgkin lymphoma (NLP-HL) diagnosed in a lymph node with concomitant IgG4-RD. Low-dose continuous prednisolone was given for MGUS/SMM, with both monoclonal IgGκ and IgG4 responding. Combination chemotherapy was given for DLBCL, with two patients achieving complete response and one patient dying from refractory lymphoma. The patient with MZL refused treatment, whereas the case of NLP-HL responded completely to chemotherapy. Our findings together with previous observations suggest that IgG4-RD has an increased risk of B-cell neoplasms. Patients with IgG4-RD presenting with lymphadenopathy require vigorous investigations to exclude lymphoid neoplasms.

The NLPHL Tumor Microenvironment Is Markedly Enriched in the Tigit and PD-1 Signalling Axes Compared to Classical Hodgkin Lymphoma

The NLPHL Tumor Microenvironment Is Markedly Enriched in the Tigit and PD-1 Signalling Axes Compared to Classical Hodgkin Lymphoma

Outcomes of Histological Variants of Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL): A Single-Center Retrospective Study

BackgroundNodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma that typically presents with early-stage favorable disease and exhibits an indolent clinical course with long-term remissions and eventual relapse. Histopathologic variants of NLPHL have recently been described and may have poorer outcomes compared to typical NLPHL. Risk of transformation of variant NLPHL has not been previously described.MethodsWe retrieved patients with NLPHL diagnosed between 2001 and 2016 whose cases had been reviewed at the University of Chicago and who had available clinical information. Patient characteristics, initial histology, treatment history, history of progression and histologically-verified transformation, and survival status were obtained from the electronic medical record. Patients were grouped into three cohorts: NLPHL, variant NLPHL, and transformed NLPHL (t-NLPHL) at diagnosis. t-NLPHL included diffuse large B-cell lymphoma (t-NLPHL/DLBCL) and T-cell/histiocyte-rich large B-cell lymphoma (t-NLPHL/THRBCL) histologies. Standard descriptive statistical analyses were performed. Relapse-free survival (RFS), transformation-free survival (TFS), and overall survival (OS) were estimated by the Kaplan-Meier method. All statistical analyses were performed using STATA, version 15.1.ResultsThere were 48 patients with newly-diagnosed NLPHL: 34 with NLPHL (71%), 8 with variant NLPHL (17%), and 6 with t-NLPHL (13%) at diagnosis. Patient, disease and frontline treatment characteristics are displayed in Table 1. There was no significant difference in age, male predominance, initial disease stage, or presence of extranodal disease between the three cohorts. B symptoms were more likely in t-NLPHL, and patients with t-NLPHL at diagnosis were more likely to receive frontline R-CHOP. Patients with variant NLPHL were significantly more likely to have progressive disease after frontline therapy.A total of 26 patients (54%) developed relapsed disease and 6 (13%) developed subsequent t-NLPHL (Table 2). The majority of histologically-confirmed relapses were NLPHL (N = 12, 71%), and the majority of subsequent transformations were t-NLPHL/THRBCL (N = 4, 66%). Nearly all of the patients with subsequent transformations developed t-NLPHL at the time of first relapse (N = 5, 83%). There was no significant difference in incidence of relapse or histology at relapse, nor was there any difference in incidence of transformation or histology at transformation, between the three cohorts.RFS, TFS and OS for each cohort are displayed in Figure 1, with a median follow-up of 8.5 years (range 1.5-34.5 years). Between the three cohorts, there was no significant difference in RFS (p = 0.46) or OS (p = 0.29). There was a significant difference in TFS between the typical and variant NLPHL cohorts (p = 0.048), although the number of transformation events was low. A total of 6 patients (13%) died, with no significant difference in incidence of death or cause of death between the three cohorts (Table 2). Only 1 patient in the entire cohort died from lymphoma, a patient with variant NLPHL who died of transformed lymphoma. There were three deaths secondary to treatment (myelodysplastic syndrome, acute lymphocytic leukemia, and cardiomyopathy).ConclusionsThis single-center retrospective study suggests that variant NLPHL was less likely to respond to frontline therapy and had a shorter transformation-free survival compared to typical NLPHL, but without compromise in terms of PFS and OS. This suggests that current salvage therapies are effective for relapsed and transformed variant NLPHL. Investigation of transformation risk in variant NLPHL with larger datasets is warranted. [Display omitted] DisclosuresSmith: Alexion, AstraZeneca Rare Disease: Other: Study investigator; Celgene, Genetech, AbbVie: Consultancy. Venkataraman: EUSA Pharma: Consultancy.

Treatment of Early-Stage Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Subgroup Analysis of the Randomized German Hodgkin Study Group HD16 Study

Background:Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity accounting for approximately 5% of all Hodgkin lymphoma (HL) cases. Pathological and clinical characteristics differ from classical HL (cHL). In contrast to cHL, the malignant cells in NLPHL are consistently positive for CD20 but stain negative for CD30. The clinical course of NLPHL is usually indolent and patients present with early-stage disease more frequently than in cHL.Patients and Methods:We investigated characteristics and outcomes of 85 patients with NLPHL (stage IB and stage II without risk factors) who had treatment within the randomized German Hodgkin Study Group HD16 study for early-stage HL. Results were compared to those from 495 cHL patients (stage IB and stage II without risk factors) treated within the same study. Patients were randomized between standard treatment consisting of 2 cycles of ABVD followed by consolidation radiotherapy and treatment guided by interim positron emission tomography after 2 cycles of ABVD (PET-2). PET-2-guided treatment consisted of 2 cycles of ABVD alone for patients with a negative PET-2 and 2 cycles of ABVD followed by consolidation radiotherapy for patients with a positive PET-2 (defined as a Deauville score ≥ 3). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method including 95%-confidence intervals (95%-CI) and hazard ratios (HR) obtained from Cox regression models. Analyses were performed descriptively.Results:Overall, 62/85 NLPHL patients (73%) were male as compared to 254/495 cHL patients (51%) (p=0.0002). The median age was 37 years (range: 19-71 years) among patients with NLPHL and 36 years (range: 18-75 years) among patients with cHL (p=0.4380). Information on the histopathological growth pattern was available for 67/85 NLPHL patients of which 44 (66%) had a typical growth pattern. The PET-2 was positive in 39/85 NLPHL patients (46%) and in 171/495 cHL patients (35%) (p=0.0507). After a median observation time of 64 months, the 5-year PFS was 90.3% (95%-CI: 83.8-96.7%) for all 85 NLPHL patients and 90.8% (95%-CI: 88.1-93.5%) for all 495 cHL patients (HR=1.1; 95%-CI: 0.5-2.1). The 5-year PFS rates for PET-2-positive NLPHL (n=39) and cHL (n=171) patients were 89.3% (95%-CI: 79.4-99.2%) and 91.6% (95%-CI: 87.2-96%) (HR= 1.3; 95%-CI: 0.5-3.5), respectively. The 5-year PFS rates for PET-2-negative NLPHL (n=46) and cHL (n=324) patients were 91% (95%-CI: 82.7-99.4%) and 90.4% (95%-CI: 87-99.4%) (HR=0.85; 95%-CI: 0.3-2.4), respectively. PET-2-negative NLPHL (n=25) and cHL (n=152) patients treated with 2 cycles of ABVD alone had 5-year PFS rates of 83% (95%-CI: 67.8-98.2%) and 88.2% (95%-CI: 82.7-93.6%) (HR=1.5, 95%-CI: 0.5-4.5), respectively. In contrast, PET-2-negative NLPHL (n=21) and cHL (n=172) patients treated with 2 cycles of ABVD followed by consolidation radiotherapy had 5-year PFS rates of 100% and 92.3% (95%-CI: 88.1-96.5%) (HR=0; 95%-CI: 0), respectively. NLPHL patients with a typical growth pattern (n=44) had a 5-year PFS of 95.2% (95%-CI: 88.8-100%) whereas patients with an atypical growth pattern (n=23) had a 5-year PFS of 82.2% (95%-CI: 66.3-98%) (HR=2.5; 95%-CI: 0.5-11.2). A total of 9 NLPHL patients experienced disease progression or relapse during follow-up. The median time to NLPHL recurrence was 14 months (range: 1-89 months). There were 2 cases of second primary malignancies (1 case of malignant melanoma, 1 case of stomach cancer) among patients with NLPHL. No patient developed histological transformation into aggressive B-cell non-Hodgkin lymphoma. The 5-year OS rates were 100% and 98.6% (95%-CI: 97.5-99.7%) (HR=0; 95%-CI: 0) for patients with NLPHL and cHL, respectively.Conclusion:Taken together, the 5-year outcomes for patients with newly diagnosed early-stage NLPHL were similar to their counterparts with cHL. Thus, the current standard of care for early-stage cHL consisting of 2 cycles of ABVD followed by consolidation radiotherapy represents a highly active option also for the treatment of patients with the initial diagnosis of stage IB and stage II NLPHL without risk factors. DisclosuresFuchs: Takeda: Consultancy, Honoraria; Lukon: Honoraria; Celgene: Honoraria; BMS: Honoraria; MSD: Honoraria. von Tresckow: AstraZeneca: Honoraria, Other: congress and travel support; Kite-Gilead: Consultancy, Honoraria; BMS-Celgene: Consultancy, Honoraria, Other: congress and travel support; Amgen: Consultancy, Honoraria; AbbVie: Other: congress and travel support; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: congress and travel support, Research Funding; Pentixafarm: Consultancy, Honoraria; MSD: Consultancy, Honoraria, Other: congress and travel support, Research Funding; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other, Research Funding. Engert: Takeda: Consultancy, Honoraria, Research Funding; BMS: Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria; Tessa Therapeutics: Consultancy; Amgen: Honoraria; ADC Therapeutics: Consultancy; MSD: Honoraria; Hexal: Honoraria.

Outcome of Patients with T- Cell Histiocyte Rich B Cell Lymphoma: Single Institution Series

Outcome of Patients with T- Cell Histiocyte Rich B Cell Lymphoma: Single Institution Series

Sex Differences in Lymphoma Incidence and Excess Mortality By Subtype: A Comprehensive National Study

IntroductionFor most cancer types, cancer incidence as well as cancer-specific mortality is higher in men compared to women. The underlying reasons for this remain unclear but hypotheses include sex differences in environmental exposure to carcinogens, health-seeking behavior and biology, such as hormonal, anatomical, and molecular disparities. For lymphomas, the impact of sex seems to differ by subtype, treatment, and calendar time. For example, in Hodgkin lymphoma (HL), male sex has historically been considered an established negative prognostic factor but in contemporary studies, therapeutic advances appear to have attenuated the prognostic value of sex. In contrast, a negative impact of male sex on prognosis has become manifest during the last decades in patients with diffuse large B-cell lymphoma and follicular lymphoma, with sex differences in rituximab clearance in elderly proposed as one explanation. Previous studies have not considered the longer life expectancy of women when predicting incidence and prognosis, and comprehensive studies on the impact of sex on incidence and excess mortality in lymphomas are lacking. Therefore, we aimed to quantify and outline sex differences in lymphoma incidence and lymphoma excess mortality by subtype in a large, population-based cohort.MethodsAdult patients diagnosed with lymphoma 2000-2019 were identified via the Swedish lymphoma register (>95% national coverage). Sex-specific incidence rates were computed as the number of new cancer cases per 100,000 person-years/year and age-standardized to the Swedish population in 2019 (using population counts from Statistics Sweden). Male-to-female incidence rate ratios (IRRs) with 95% confidence intervals (CIs), adjusted for age and year of diagnosis, were estimated using Poisson regression models. Sex-specific 5-year relative survival was calculated as the ratio of the observed lymphoma patient and the matched (sex, age, and calendar year) population 5-year survival and age-standardized according to the International Cancer Survival Standards. Male-to-female 5-year excess mortality rate ratios (EMRR) including 95% CIs were estimated including age and calendar year in the Poisson regression models.ResultsA total of 36 859 patients with lymphoma were identified during the study period. Median age for all patients was 69 (range 16-99) years. In the whole cohort there was a male predominance of 56%. Distribution of patients by sex, and male-to-female IRR and EMRR adjusted for age and year of diagnosis by major lymphoma subtype are presented in Table 1, and graphically in Figure 1. Overall, significantly higher incidence rates among men were observed for all lymphoma subtypes except marginal zone lymphoma and primary mediastinal B-cell lymphoma. The higher male-to-female IRRs remained largely stable over calendar time. For some subtypes, male-to-female IRR differed by age. For example, in HL, male and female IRs were similar up to 35 years, whereafter the male-to-female IRR increased. For both Burkitt lymphoma and Nodular lymphocyte predominant Hodgkin lymphoma the higher male-to-female IRR was most pronounced among patients under the age of 50, although incidence was higher among men of all ages for both subtypes. Regarding survival, there was a trend for higher excess mortality among men for several subtypes (Table 1, Fig 1). Significantly higher EMRRs among male patients were seen in HL, aggressive lymphomas not otherwise specified, and small lymphocytic lymphoma.ConclusionIn this large population-based study we observe a significantly higher incidence rate among men for all but two lymphoma subtypes. Further, there was a trend for worse survival among male lymphoma patients for most lymphomas although only significantly worse for three subtypes, potentially due to small numbers for rare subtypes and limited adjustment. As of yet, reasons for sex differences in incidence and excess mortality of lymphoma are unknown. Better understanding of underlying factors to these differences may improve management of lymphomas and increase knowledge of lymphoma biology and etiology. Thus, further studies on sex differences in lymphoma with detailed data regarding disease-specific patient characteristics, treatment and patient-related factors such as comorbidity and socioeconomic status are warranted. [Display omitted] DisclosuresWeibull: Jansen-Cilag: Other: part of a research collaboration between Karolinska Institutet and Janssen Pharmaceutica NV for which Karolinska Institutet has received grant support. El-Galaly: Abbvie: Other: Speakers fee; ROCHE Ltd: Ended employment in the past 24 months. Smedby: Jansen-Cilag: Other: part of a research collaboration between Karolinska Institutet and Janssen Pharmaceutica NV for which Karolinska Institutet has received grant support.

A Molecular Classifier Increased the Accuracy of Lymphoma Diagnosis By Expert Pathologists in the Diffuse Large B-Cell Lymphoma Gained Trial from the Lysa

A Molecular Classifier Increased the Accuracy of Lymphoma Diagnosis By Expert Pathologists in the Diffuse Large B-Cell Lymphoma Gained Trial from the Lysa

Brentuximab Vedotin in Combination with Nivolumab, Doxorubicin, and Dacarbazine in Newly Diagnosed Patients with Advanced Stage Hodgkin Lymphoma (SGN35-027, Trial in Progress)

Brentuximab Vedotin in Combination with Nivolumab, Doxorubicin, and Dacarbazine in Newly Diagnosed Patients with Advanced Stage Hodgkin Lymphoma (SGN35-027, Trial in Progress)

Investigating Factors Predictive of Large Cell Transformation and Outcomes From Low Grade Lymphomas

<h3>Purpose/Objective(s)</h3> Relapses of low grade (indolent) lymphomas typically remain low grade, but there is a 1-3% annual risk of transformation to large B-cell lymphoma. Predictive factors at time of initial lymphoma diagnosis and clinical outcomes after transformation remain poorly characterized. In this study we aim to characterize clinical and positron emission tomography (PET) features of a cohort with transformed disease. <h3>Materials/Methods</h3> We performed a retrospective review of patients diagnosed with large cell transformation from initial low-grade lymphoma. Patients who did not experience transformation during follow up were referenced as a control. Standardized uptake unit (SUV) parameters from initial staging or low-grade disease follow up diagnostic PET scans were analyzed. Statistical analyses included t-test and Fisher's exact test for significance (SS) using alpha level of 0.05. Statistical analysis was performed using Python (version 3). <h3>Results</h3> We identified 50 patients with a mean age at initial diagnosis of 53 years (range: 16-73). The most common lymphoma types were follicular lymphoma (FL) in 40 (80%) patients, marginal zone (MZL) in 4 (8%), nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) in 3 (6%), 2 (4%) with Waldenstrom's (WM) and one (2%) with primary cutaneous follicle center (PCFCL). Initial lymphoma (non-WM) stages were 23% stage I, 8% stage II, 36% stage III and 33% stage IV. Mean time to transformation was 105 months (range: 5-373). Predominant transformed histology was diffuse large B-cell lymphoma (DLBCL) in 42 (84%) patients. Stage at transformation was 30% stage I-II and 70% stage III-IV. Median follow up from time of transformation was 52 months (range: 2-207). 1-year OS from transformation was 85%. 21 (42%) patients had PET-CT scans 7 months to 13 years prior to transformation with mean SUV-max of 12.2 (range: 3.8-30.0). Compared to 21 (1:1) non-transformed control patients with PET scans, a significant difference was found between the mean SUV-max values of 12.2 vs 6.3 (<i>P</i> < 0.001). Further, as an exploratory analysis, we generated a prognostic scoring model for post-transformation outcomes directly proportional to SUV-max squared and inverse to the time to transformation (in months). Among the 21 patients with pre-transformation PET imaging, the 17 who were alive at last follow up had a mean score of 2.4 vs. 64.2 among the 4 patients who died (<i>P</i> = 0.005). <h3>Conclusion</h3> We demonstrate the utility of PET-CT to identify patients with low grade lymphoma at high risk of transformation to large cell lymphoma. Specifically, we observe an increased risk of poor outcomes with increasing SUV-max and shorter time to transformation. If validated, our study may serve to risk stratify patients initially diagnosed with low grade lymphoma.