Hodgkin's Disease Research Articles

Association between Epstein-Barr virus LMP-1 and Hodgkin lymphoma LMP-1 mechanisms in Hodgkin lymphoma development.

Hodgkin lymphoma is histologically characterised by the presence of Hodgkin (H) and Reed-Sternberg (RS) cells originating from germinal centre B-cells rearranged in the IgV gene. The formation of multinucleated RS cells is a product of telomere organisation in a process initiated by telomere aggregate accumulation in mononuclear H cells and may be mediated by latent membrane protein 1 (LMP-1) expression. LMP-1 is the main oncoprotein of EBV and supports several tumourigenic processes. LMP-1 may rescue proapoptotic B-cells through downregulation of B-cell receptor (BCR) components, mimicking and inducing multiple distinct B-cell signalling pathways to promote proliferation and survival, such as Janus kinase-signal transducer and activator of transcription (JAK-STAT), nuclear factor-kappa b (NF-кB), and cellular MYC (c-MYC), and inducing telomere instability mainly through Telomere repeat binding factor 2 (TRF2) downregulation to promote the formation of multinucleated RS cells. This review presents recent discoveries regarding the influence of LMP-1 on the surviving cellular signalling, genomic instability and mecanical formation of HRS cells.

Challenges of Treating a Patient with Autism and Hodgkin’s Lymphoma

Abstract Hodgkin’s lymphoma (HL) and autism spectrum disorder (ASD) are a rare combination. Diagnosing and treating patients with this combination is challenging. Here, we report the case of a 19-year-old male with ASD and HL. Upon initial presentation to our clinic, the patient was very active with the clinical features of autism. Pathology confirmed stage IVBs HL of the mixed cellularity subtype. He received six cycles of Adriamycin, bleomycin sulfate, vinblastine sulfate, and dacarbazine and has been in remission for the last 4 years. This report presents the challenges in the diagnosis and treatment of a young patient with ASD and cancer and how to overcome them.

Considerations for anti-PD1-based first-line treatment of Hodgkin lymphoma.

Anti-PD1-based first-line treatment holds great promise in classical Hodgkin lymphoma. The management of immune-related adverse events in the context of time-limited combined checkpoint blockade and chemotherapy administered in curative intent is a challenge. Kuczmarski and Lynch provide a case-based approach to key toxicities observed in this setting. Commentary on: Kuczmarski etal. Managing common toxicities associated with checkpoint inhibitor and chemotherapy combinations for untreated classic Hodgkin lymphoma. Br J Haematol 2024;205:100-108.

Breastfeeding Duration Reduces the Risk of Childhood Leukemia and Modifies the Risk of Developing Functional Gastrointestinal Disorders.

Objective: The aim of this study was to test the hypothesis that the duration of breastfeeding in infancy reduces the risk of childhood leukemia or lymphoma, and modifies the risk of developing functional gastrointestinal disorders (FGIDs). Subjects and Methods: This case-control study involved the recruitment of children with lymphoid malignancy and functional gastrointestinal symptoms with healthy children as controls. Focused questionnaires were used to collect data on breastfeeding history and other key risk factors. Univariate and multivariate analyses were undertaken. Results: Of the 334 children with lymphoid malignancy, 65% were male. The control group included 334 age- and sex-matched participants. Most (n = 189; 56.6%) of the children with leukemia were <10 years of age. Differences between cases and controls included the duration of breastfeeding (p < 0.0001), mean birthweight (p < 0.001), maternal age (p < 0.001), paternal age (p < 0.001), birth order (p < 0.001), mean number of children (p < 0.001), BMI percentile (p = 0.042), and maternal smoking (p = 0.012). Breastfeeding duration of up to 6 months' duration, when compared with feeding of longer than 6 months, was associated with increased odds ratios (OR) for acute lymphoblastic leukemia (OR = 3.43, 95% confidence interval [CI] 2.37-4.98; p < 0.001), Hodgkin's lymphoma (OR = 1.58, 95% CI: 0.88-2.84, p = 0.120), Non-Hodgkin's lymphoma (OR = 2.14, 95% CI: 1.25-3.65, p = 0.005), and overall (OR = 1.95, 95% CI: 1.40-2.71, p < 0.001). Cases also differed from controls with regard to FGIDs, such as stomach ache (p < 0.001), dyspepsia (p < 0.001), early satiety (p = 0.017), bowel satisfaction (p < 0.001), bloating (p < 0.001), nausea (p = 0.005), vomiting (p = 0.039), constipation (p = 0.003), diarrhea (p = 0.010), gastrointestinal canal congestion (p =0.039), muscle aches pains (p = 0.008), fecal incontinence (p = 0.021), and indigestion (p = 0.003). A multivariate stepwise regression analysis revealed that maternal smoking (p < 0.001), formula feeding (p < 0.001), duration of breastfeeding (p < 0.001), birth order (p = 0.002), mother's age (p = 0.004) and the child's birthweight (p = 0.009) were predictors for leukemia. Further analysis showed that dyspepsia (p < 0.001), gastrointestinal tract canal congestion (p < 0.001), constipation (p = 0.009), diarrhea (p = 0.013), bowel satisfaction (p = 0.021), bloating (p = 0.022), duration of breastfeeding (p < 0.001), and stomach ache (p = 0.025) were significant predictors for developing FGID symptoms after adjusting for age, gender, and other confounding variables. Conclusion: This study confirmed that breastfeeding has some effect on reducing possible risk of childhood lymphoma and leukemia and FGID symptoms compared with healthy control children.

Predictive Performance of Cardiovascular Risk Scores in Cancer Survivors From the UK Biobank

BackgroundCardiovascular preventive strategies are guided by risk scores with unknown validity in cancer cohorts. ObjectivesThis study aimed to evaluate the predictive performance of 7 established cardiovascular risk scores in cancer survivors from the UK Biobank. MethodsThe predictive performance of QRISK3, Systematic Coronary Risk Evaluation 2 (SCORE2)/Systematic Coronary Risk Evaluation for Older Persons (SCORE-OP), Framingham Risk Score, Pooled Cohort equations to Prevent Heart Failure (PCP-HF), CHARGE-AF, QStroke, and CHA2DS2-VASc was calculated in participants with and without a history of cancer. Participants were propensity matched on age, sex, deprivation, health behaviors, family history, and metabolic conditions. Analyses were stratified into any cancer, breast, lung, prostate, brain/central nervous system, hematologic malignancies, Hodgkin lymphoma, and non-Hodgkin lymphoma. Incident cardiovascular events were tracked through health record linkage over 10 years of follow-up. The area under the receiver operating curve, balanced accuracy, and sensitivity were reported. ResultsThe analysis included 31,534 cancer survivors and 126,136 covariate-matched controls. Risk score distributions were near identical in cases and controls. Participants with any cancer had a significantly higher incidence of all cardiovascular outcomes than matched controls. Performance metrics were significantly worse for all risk scores in cancer cases than in matched controls. The most notable differences were among participants with a history of hematologic malignancies who had significantly higher outcome rates and poorer risk score performance than their matched controls. The performance of risk scores for predicting stroke in participants with brain/central nervous system cancer was very poor, with predictive accuracy more than 30% lower than noncancer controls. ConclusionsExisting cardiovascular risk scores have significantly worse predictive accuracy in cancer survivors compared with noncancer comparators, leading to an underestimation of risk in this cohort.

Combination Therapy with Immune Checkpoint Inhibitors and Histone Deacetylase Inhibitors or Alkylating Agents.

Immune checkpoint inhibitors (CPIs) have been widely adopted in a number of early and advanced malignancies. Histone deacetylase inhibitors (HDACis) and alkylating agents (AAs) have been suggested to potentiate the actions of CPIs on tumor cells. We conducted a comprehensive literature review to explore the potential synergistic activity between CPIs, AAs, and HDACis. Clinical and non-clinical studies describing outcomes in patients with cancer receiving CPIs and either concomitant or sequential (pre- or post-CPI) AAs or HDACis were identified in PubMed using pre-defined search strings. Manual searches of key oncology congresses were similarly performed. All relevant articles and abstracts were manually screened for relevance, classified according to the specific anticancer agents used (CPIs, AAs, or HDACis), tumor entity, and whether treatment was concomitant or sequential. Overall, 227 unique clinical studies across a range of tumor types, both solid tumors and hematological malignancies, were identified. One hundred and fifty-nine publications on Phase I and II clinical studies together with 41 publications on Phase III studies were examined. The most commonly investigated tumor types were melanoma, triple-negative breast cancer, non-small cell lung cancer, and Hodgkin lymphoma. The randomized clinical studies identified, all of which reported on the combination of a CPI with an AA, demonstrated superior outcomes in the combination arm compared with CPI or AA monotherapy. Similarly, combination therapy with CPIs and HDACis demonstrated promising activity. Sequential or concomitant administration of a CPI with an AA or an HDACi may improve outcomes for patients with a range of tumor types. There is a rationale to support further investigation into the potential for synergy between CPIs, alkylating agents and/or HDACis in both the non-clinical and clinical settings.

Stage-adapted treatment of HIV-associated Hodgkin lymphoma: Long-term results of a prospective, multicenter study.

Results of a prospective study of stage-adapted treatment of humanimmunodeficiency virus (HIV)-associated Hodgkin lymphoma (HIV-HL) showed a 2-year overall survival (OS) of 90.7% with no significant difference between early favorable (EF), early unfavorable (EU), and advanced HL. Patients with EF HIV-HL received two to four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) + 30 Gy involved field (IF) radiation, those with EU HIV-HL received four cycles of ABVD or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) baseline + 30 Gy IF, and six to eight cycles of BEACOPP baseline were administered in advanced disease. The objective of the present analysis is to determine long-term outcomes of HIV-HL. Of 108 patients, 23 (21%) had EF HL, 14 (13%) had EU HL, and 71 (66%) had advanced-stage HL. After a median follow-up of 9.14 (range, 0-12.9) years, there were five primary refractory HL patients (5%) and 11 relapses (10%), of which seven were late relapses (>2 years). A second primary malignancy (SPM) occurred in 10 patients after a median of 7.3 years (range, 1.5-10.7) from HL diagnosis. The 10-year OS for patients with EF, EU, and advanced HL was 95.7%, 84.6%, and 76.1%, respectively. By multivariate analysis, Center for Disease Control and Prevention category C (hazard ratio [HR]3.00, 95% confidence interval [CI]:1.16-7.74, p = 0.023) and achievement of complete remission were significant for OS (HR 0.03, 95% CI: 0.01-0.08, p = 2.45 × 10-9). In conclusion, a stage-adapted treatment approach for HIV-HL is highly effective with long-term survival rates similar to those reported in HIV-uninfected HL. However, the risk for late relapse and SPM is significant.

Tumor-Immune Signatures of Treatment Resistance to Brentuximab Vedotin with Ipilimumab and/or Nivolumab in Hodgkin Lymphoma.

Identification of multi-omic immune markers from peripheral blood may help elucidate resistance mechanisms to checkpoint inhibitor and antibody-drug conjugate combinations with potential implications for treatment decisions in relapsed HL.

Life-threatening airway obstruction by Riedel's thyroiditis: a rare presentation and diagnostic dilemma.

Riedel's thyroiditis is the rarest form of thyroiditis, occasionally resulting in rapid thyroid enlargement and potential tracheal obstruction. Here, we detail the case of an 81-year-old woman with a medical history including Hodgkin lymphoma, Hashimoto's thyroiditis, and multinodular goiter. She presented to the emergency room with stridor, cervical swelling, and breathing difficulties for over 2 days. CT scans revealed substantial thyroid enlargement causing significant glottal and tracheal compression, to a minimum tracheal diameter of 7 mm. Due to the severity of the compressive symptoms, orotracheal intubation and mechanical ventilation were deemed necessary. Surprisingly, despite the initial suspicion of malignancy given the rapid growth in the elderly, subsequent cytological and histological evaluations indicated a benign form of invasive fibrous thyroiditis - Riedel's thyroiditis. Although surgical intervention was advised, the patient declined and opted for endobronchial treatment with a prosthetic stent and subsequent treatment with systemic glucocorticoids. Following successful treatment, she was discharged within a week and resumed normal activities without respiratory distress. This case is noteworthy for its rapid benign mass growth, rare emergent presentation, and the patient's advanced age. The rapid enlargement of the thyroid gland in elderly patients poses a diagnostic challenge, stemming from the higher occurrence of aggressive thyroid carcinomas. Despite the clinical presentation, a comprehensive diagnostic workup, including fine-needle aspiration and core-needle biopsy, is crucial for accurately distinguishing between benign and malignant causes of thyroid nodule enlargement. This case report illustrates diverse treatment options for Riedel's thyroiditis, and the importance of individualized treatment plans based on the degree of airway obstruction, patient preferences, and response to initial interventions. Clinicians should contemplate the inclusion of glucocorticoids in the therapeutic regimen for Riedel's thyroiditis, particularly in cases where surgical intervention is not feasible or declined by the patient.

Performance Metrics Comparison of CT with PET/CT Reports in Lymphoma Patient Follow-Up

The incidence of Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL) is rising annually, necessitating effective monitoring strategies. Computed Tomography (CT) and Positron Emission Tomography/Computed Tomography (PET/CT) are pivotal in this regard but differ in diagnostic accuracy due to their distinct imaging capabilities. This retrospective study evaluates 56 lymphoma patients using both modalities at Al-Ahli Hospital, Hebron, Palestine, from 2020 to 2023. Demographic and clinical data, alongside imaging findings, were analyzed. Results indicate PET/CT's superiority over CT alone, with higher sensitivity, specificity, precision, Accuracy where CT findings were 20%, 30.61%, 0.72%, and 30.34% retrospectively compared with PET/CT findings. Gender-specific analysis revealed marginal associations, highlighting the need for tailored imaging strategies. The study underscores PET/CT's enhanced diagnostic performance in lymphoma surveillance, advocating its use for improved patient management and outcomes. Further research could refine these findings, addressing the evolving landscape of lymphoma imaging.

Fever of unknown origin: A 12-year case series in Colombia.

Fever of unknown origin (FUO) is a diagnostic challenge with highly heterogeneous causes. Its etiology can change according to the studied regions, and the chance of reaching a diagnosis depends on available resources. The aim of this study is to describe the clinical characteristics, etiology and the usefulness of diagnostic aids in cases of FUO managed over 12 years in a Colombian reference center. Single-institution retrospective case series. All cases of FUO between 2006 and 2017 were identified with the help of an electronic medical record search software. Cases of adults with fever for more than three weeks who remained undiagnosed after three days of hospitalization are described. Of 1,009 cases evaluated, 112 cases met the inclusion criteria (median age 43 years, 66% men). The etiologies identified were infectious (31.2%), inflammatory (20.5%), neoplastic (14.3%), and miscellaneous (2.7%) diseases. 31.2% remained without etiological diagnosis. The most frequent conditions were tuberculosis (17%), Hodgkin's lymphoma (7.1%), systemic lupus erythematosus (6.3%), disseminated histoplasmosis, and adult Still's disease. Contrast tomography and biopsies were the studies that most frequently supported or confirmed the final diagnosis. This series of contemporary Latin American cases suggests that the categories of FUO etiologies are similar to those reported in studies from developed countries, with tuberculosis being the most frequent cause in our setting. Our results highlight the importance of tomography-guided invasive studies in the diagnostic approach to FUO.

Hodgkin Lymphoma in Children: A 16-year Experience at the Children's Welfare Teaching Hospital of Baghdad, Iraq.

Childhood Hodgkin lymphoma (HL) is an eminently curable disease. Good outcomes can be achieved even in resource-limited settings, and the focus is increasingly on limiting long-term toxicity. Contemporary treatment incorporates a risk-stratified, response-adapted approach using multiagent chemotherapy with/without low-dose radiotherapy. Many developing countries continue to use ABVD-based regimens due to limited acute toxicity, cost, and ease of delivery. We herein report the outcomes of childhood HL diagnosed and treated in an Iraqi single centre over 16 years. Children ≤14 years old with biopsy-proven HL were enrolled. Most patients received ABVD chemotherapy or COPP/ABV when Dacarbazine was unavailable. Radiotherapy was not available. Three hundred-three children were consecutively newly diagnosed with HL; 284 were considered eligible for the retrospective analysis (treatment refusals 9; deaths before therapy 5; initially diagnosed of non-Hodgkin lymphoma 5). ABVD scheme was administered to 184 children (65%), COPP/ABV to 83 (29%), and other schemes to the remaining 17 patients. Complete response (CR) was achieved in 277 (98%); 4 (1.4%) showed disease progression, and 1 had stable disease. Four patients in CR abandoned therapy and were in CR at the time of analysis, 2 died from infection. Relapse occurred in 42 patients (15%). The 15-year OS and EFS are 89.7% and 70.3%, respectively. In this single Centre, over 16 years, almost 90% of children suffering from HL survive, despite the numerous limitations in diagnostic procedures, shortage of chemotherapy, no radiotherapy facilities, absence of effective second-line treatments, and finally, therapy abandonment for social and financial reasons.

Her Legacy Lives On: Celebrating the Women Behind Head and Neck Eponyms.

This article profiles 6 notable female scientists who have had eponyms named after them, highlighting their significant contributions to various medical fields and whose scientific endeavors have influenced our practice and understanding of otolaryngology. We discuss Łucja Frey Gottesman and her description of Frey's syndrome; Margaret Dix and the Dix-Hallpike test; Lotte Strauss and her work defining Churg-Strauss disease; Dorothy Reed Mendenhall's discovery of Reed-Sternberg cells in Hodgkin's lymphoma; Edith Louise Potter defining Potter sequence in utero; Denise Louis-Bar originally characterizing the condition now known as ataxia-telangiectasia or Louis-Bar syndrome. Despite the challenges these women faced as pioneering female physicians as well as personal and political turmoil, their contributions greatly advanced the fields of otolaryngology, neurology, neuropathology, perinatology, and pediatric pathology. We aim to honor their stories and medical legacies.

Towards IVDR-compliance by implementing quality control steps in a quantitative extracellular vesicle-miRNA liquid biopsy assay for response monitoring in patients with classic Hodgkin lymphoma.

Previously, we showed that quantification of lymphoma-associated miRNAs miR-155-5p, -127-3p and let-7a-5p levels in plasma extracellular vesicles (EVs) report treatment response in patients with classic Hodgkin lymphoma (cHL). Prior to clinical implementation, quality control (QC) steps and validation are required to meet international regulatory standards. Most published EV-based diagnostic assays have yet to meet these requirements. In order to advance the assay towards regulatory compliance (e.g., IVDR 2017/746), we incorporated three QC steps in our experimental EV-miRNA quantitative real-time reverse-transcription PCR (q-RT-PCR) assay in an ISO-13485 certified quality-management system (QMS). Liposomes encapsulated with a synthetic (nematode-derived) miRNA spike-in controlled for EV isolation by automated size-exclusion chromatography (SEC). Additional miRNA spike-ins controlled for RNA isolation and cDNA conversion efficiency. After deciding on quality criteria, in total 107 out of 120 samples from 46 patients passed QC. Generalized linear mixed-effect modelling with bootstrapping determined the diagnostic performance of the quality-controlled data at an area under the curve (AUC) of 0.84 (confidence interval [CI]: 0.76-0.92) compared to an AUC of 0.87 (CI: 0.80-0.94) of the experimental assay. After the inclusion of QC steps, the accuracy of the assay was determined to be 78.5% in predicting active disease status in cHL patients during treatment. We demonstrate that a quality-controlled plasma EV-miRNA assay is technically robust, taking EV-miRNA as liquid biopsy assay an important step closer to clinical evaluation.

The role of autologous stem-cell transplantation in classical Hodgkin lymphoma in the modern era

Despite excellent cure rates with modern front-line regimens, up to 20% of patients with Hodgkin lymphoma will progress through front-line therapy or experience disease relapse. Worldwide, salvage chemotherapy followed by high-dose chemotherapy with autologous stem cell transplantation (HDT/ASCT) is considered the standard of care for these patients and can cure approximately 50% of relapsed or refractory (R/R) patients in the second line. Brentuximab vedotin (BV), an anti-CD30 antibody drug conjugate, and PD1 inhibitors like nivolumab and pembrolizumab, have high response rates in patients who recur after HDT/ASCT. When used prior to HDT/ASCT, BV and PD1 inhibitors appear to dramatically increase the effectiveness of salvage therapies with complete response rates often double those seen with historic chemotherapy-based regimens and durable progression free survival (PFS) post-HDT/ASCT. Emerging data in adults and from pediatric trials showing a durable PFS in a subset of relapsed patients raises the question of whether HDT/ASCT is essential for cure in R/R patients after PD1 based salvage. Future studies will help clarify if ASCT can omitted PD1 based salvage to avoid the potential toxicity of HDT/ASCT without compromising cure.

Macrophage activation syndrome revealing Hodgkin lymphoma

Macrophage activation syndrome revealing Hodgkin lymphoma

ATM germ line pathogenic variants affect outcomes in children with ataxia-telangiectasia and hematological malignancies

AbstractAtaxia-telangiectasia (A-T) is an autosomal-recessive disorder caused by pathogenic variants (PVs) of the ATM gene, predisposing children to hematological malignancies. We investigated their characteristics and outcomes to generate data-based treatment recommendations. In this multinational, observational study we report 202 patients aged ≤25 years with A-T and hematological malignancies from 25 countries. Ninety-one patients (45%) presented with mature B-cell lymphomas, 82 (41%) with acute lymphoblastic leukemia/lymphoma, 21 (10%) with Hodgkin lymphoma and 8 (4%) with other hematological malignancies. Four-year overall survival and event-free survival (EFS) were 50.8% (95% confidence interval [CI], 43.6-59.1) and 47.9% (95% CI 40.8-56.2), respectively. Cure rates have not significantly improved over the last four decades (P = .76). The major cause of treatment failure was treatment-related mortality (TRM) with a four-year cumulative incidence of 25.9% (95% CI, 19.5-32.4). Germ line ATM PVs were categorized as null or hypomorphic and patients with available genetic data (n = 110) were classified as having absent (n = 81) or residual (n = 29) ATM kinase activity. Four-year EFS was 39.4% (95% CI, 29-53.3) vs 78.7% (95% CI, 63.7-97.2), (P < .001), and TRM rates were 37.6% (95% CI, 26.4-48.7) vs 4.0% (95% CI, 0-11.8), (P = .017), for those with absent and residual ATM kinase activity, respectively. Absence of ATM kinase activity was independently associated with decreased EFS (HR = 0.362, 95% CI, 0.16-0.82; P = .009) and increased TRM (hazard ratio [HR] = 14.11, 95% CI, 1.36-146.31; P = .029). Patients with A-T and leukemia/lymphoma may benefit from deescalated therapy for patients with absent ATM kinase activity and near-standard therapy regimens for those with residual kinase activity.

Autologous Peripheral Blood Stem Cell Transplantation and Timing of Local Radiation Therapy in Patients With Malignant Lymphoma: Results of the Japanese Radiation Oncology Study Group Questionnaire Survey.

Malignant lymphoma (ML) including Hodgkin's lymphoma and non-Hodgkin's lymphoma is often treated with local radiation therapy (RT) in combination with autologous hematopoietic stem cell transplantation (ASCT) to prevent relapse; however, the efficacy and optimal timing of this approach is unclear. In this study, a national survey conducted by the Japanese Radiation Oncology Study Group reviewed ML cases from 2011 to 2019 to determine whether RT should be added to ASCT, focusing on the use of autologous peripheral blood stem cell transplantation (auto-PBSCT), a predominant form of ASCT. The survey encompassed 92 patients from 11 institutes, and assessed histological ML types, treatment regimens, timing of RT relative to auto-PBSCT, and associated adverse events. The results indicated no significant differences in adverse events, including myelosuppression, based on the timing of RT in relation to auto-PBSCT. However, anemia was more prevalent when RT was administered before auto-PBSCT, and there was a higher incidence of neutropenia recovery delay in patients receiving RT after auto-PBSCT. This study provides valuable insights into the variable practices of auto-PBSCT and local RT in ML treatment, emphasizing the need for optimized timing of these therapies to improve patient outcomes and reduce complications.

Transient synovitis of hip joint following COVID-19 infection in a child with Hodgkins lymphoma

Transient synovitis of hip joint following COVID-19 infection in a child with Hodgkins lymphoma

Asteatotic eczema, a cutaneous manifestation of Hodgkin lymphoma in older patients.

Asteatotic eczema, a cutaneous manifestation of Hodgkin lymphoma in older patients.