Hodgkin's Disease Research Articles

Unusual synchronous and metachronous association of hematologic neoplasms with gynecologic neoplasms: Acaseseries and literature review.

The aim of the present study was to evaluate the occurrence of synchronous or metachronous hematologic and gynecologic malignancies. The medical database of the pathology department at a tertiary center was searched from 2016 to 2024 for cases involving both hematologic and gynecologic tumors. A literature search using Google Scholar and PubMed was also conducted between May and June 2024. Articles reporting surgical pathology data were included, while radiologic studies and those lacking pathology data were excluded. Cases involving one gynecologic cancer and one hematologic malignancy were analyzed. Three cases from our center and 25 cases from 15 English-language articles were identified. The mean age of the cases at diagnosis was 61.4 ± 9.4 years. A total of 19 patients (68%) were diagnosed with synchronous cancers, while the rest had metachronous diagnoses. Endometrial cancer was seen in 20 cases (71.4%): 14 synchronous and five metachronous endometrioid adenocarcinomas, and one unspecified metachronous endometrial cancer. This was followed by five cases of ovarian cancer (17.9%): three synchronous serous ovarian carcinomas, one metachronous serous ovarian carcinoma, and one synchronous ovarian adenocarcinoma. Additionally, there were two cases of cervical cancer (7.1%): one synchronous adenosquamous carcinoma and one metachronous invasive squamous carcinoma, and one case of carcinosarcoma (3.6%). Involvement of more than one site is possible for hematolymphoid cancer, commonly affecting the pelvic or para-aortic lymph nodes in 16 patients (57.1%), with other sites including the cervix (4 cases, 14.3%), ovary (4 cases, 14.3%), uterus (2 cases, 7.1%), iliac/inguinal lymph nodes (2 cases, 7.1%), fallopian tube (1 case, 3.6%), vagina (1 case, 3.6%), liver (1 case, 3.6%), abdomen (1 case, 3.6%), and appendix (1 case, 3.6%). Two cases were unspecified. Non-Hodgkin lymphoma (NHL), primarily of B cell lineage, was the most common hematologic malignancy (25 cases, 89.3%, with 22 cases being B cell lineage). In contrast, Hodgkin lymphoma was observed in two cases (7.1%), and acute leukemia in one case (3.6%). Among 21 patients with available follow-up data, eight died during the follow-up period. The co-occurrence of NHL, Hodgkin lymphoma, and acute leukemia with gynecologic cancers is rare. However, during surgery for gynecologic cancers, the potential of synchronous lymphoma should be considered, particularly in cases with unusual retroperitoneal lymphadenopathy.

Pathobiological Features and Therapeutic Opportunities Linked to TNF Family Member Expression in Classic Hodgkin Lymphoma

Pathobiological Features and Therapeutic Opportunities Linked to TNF Family Member Expression in Classic Hodgkin Lymphoma

Proteomic profiling identifies classic Hodgkin lymphoma patients at risk of bleomycin pulmonary toxicity

Advances in treating classic Hodgkin lymphoma (cHL) have improved cure rates, with overall survival exceeding 80%, resulting in a growing population of survivors at risk of long-term complications, particularly cardiac and pulmonary toxicity. Bleomycin, a key component of combination chemotherapy, is associated with bleomycin-induced pulmonary toxicity (BPT). Using label-free quantification nano liquid chromatography-tandem mass spectrometry, protein expression in diagnostic lymphoma samples from patients with and without BPT was compared. Results showed differential protein expression and disrupted cellular pathways, suggesting biological differences in BPT risk. Immunohistochemical analysis revealed higher expression of JAK3, BID, and MMP9, and lower expression of CD20, TPD52, and PIK3R4 in patients with BPT. High BID and low CD20 expression were associated with inferior overall survival, while high BID and low JAK3 and CD20 expression were linked to poorer progression-free survival. These findings highlight altered protein profiles in pretreatment cHL biopsies associated with BPT development.

Chemotherapy alone versus chemotherapy plus radiotherapy for adults with early-stage Hodgkin's lymphoma.

Chemotherapy alone versus chemotherapy plus radiotherapy for adults with early-stage Hodgkin's lymphoma.

Rare secondary lymphomas involving the brain

Central nervous system (CNS) involvement is rare in patients with Hodgkin lymphoma (HL). Accordingly, the clinical features and outcomes are not well described. Anaplastic large cell lymphoma (ALCL) is a rare and aggressive type of non-Hodgkin lymphoma that can arise in various parts of the body, including the central nervous system (CNS). Secondary ALCL involving the CNS is more common than primary disease. In general, these rare lymphomas in the CNS present with a predilection for parenchymal lesions with dural extension. Here we report two cases with metastatic/secondary lymphomas involving the CNS, with review of the literature. We believe awareness of these rare entities involving the CNS is beneficial for pathologists and neuropathologists.

Safety and Efficacy of Tinostamustine in a Subpopulation of Patients With Relapsed/Refractory Hodgkin Lymphoma From a Phase I Trial.

A significant unmet need remains for patients with Hodgkin lymphoma (HL) who fail to respond to first-line treatment or experience an early relapse. Tinostamustine, a novel alkylating deacetylase inhibitor, inhibits tumor cell growth and slows disease progression in models of hematological malignancies and solid tumors. This was a Phase I, multicenter, open-label, two-stage trial investigating the safety and efficacy of tinostamustine in patients ≥ 18years with relapsed/refractory (R/R) hematological malignancies, including HL. Stage 1 involved dose-escalation to determine the maximum tolerated dose (MTD) of tinostamustine, optimal infusion time and recommended Phase II dose (RP2D). Stage 2 confirmed the safety and efficacy of the RP2D in expansion cohorts of selected R/R hematological malignancies. Ten patients with heavily pre-treated HL entered dose-escalation, with nine patients experiencing treatment-emergent adverse events (TEAEs) considered to be related to study treatment-primarily hematological toxicities. MTD was 100mg/m2 tinostamustine over 60min and signals of efficacy were observed for patients with HL. In Stage 2, all 20 patients with HL experienced ≥ 1 TEAE, which were principally hematological or gastrointestinal. There were no tinostamustine-related deaths in either stage of the study. Overall response rate in Stage 2 was 37% (2 complete responses, 5 partial responses; 95% confidence interval [CI]: 16%, 62%) and median progression-free survival 3.8months (95% CI: 2.2-9.4months). Tinostamustine is a promising new therapeutic approach for the treatment of patients with R/R classical HL with limited options. This study demonstrates a predictable and manageable safety profile with signals of efficacy. Trial Registration: ClinicalTrials.gov identifier: NCT02576496.

Pitfalls in the Cytological Diagnosis of Nodal Hodgkin Lymphoma.

Hodgkin lymphoma (HL) is a hematopoietic neoplasm characterized by malignant Reed-Sternberg (RS) cells in an inflammatory background. Although the cytological features of HL are well elucidated in literature, yet many postulated factors cause its misdiagnosis. This study aims to assess the diagnostic reliability of fine needle aspiration cytology (FNAC) in HL and evaluate the factors contributing to a false-negative and false-positive diagnosis, taking histopathology as the gold standard. This was a retrospective study in which 47 cases of HL diagnosed on histopathology were compared with their prior cytological diagnosis. The patient's age ranged from 3 to 80 years (median: 36 years) with a M:F ratio of 2.9:1. Lymph node aspirations were performed from multiple anatomical sites, out of which the cervical was the most common (57.8%). FNAC was inconclusive in two cases due to unsatisfactory smears. The false-negative diagnosis of reactive lymphadenitis was given in four cases, and false-positive in four cases, which included three cases of non-HL, and one case of malignant small round blue cell tumor. The overall diagnostic accuracy of FNAC in the diagnosis of HL was 82.2%. The cytological diagnosis of HL can be challenging when classic RS cells are absent. Contributing factors for a false-negative diagnosis include obscuring reactive inflammatory cells, fibrosis of the involved lymph nodes, partial involvement of the lymph node, and misinterpretation. A thorough clinical examination with evaluation of FNAC smears from multiple areas, and ancillary tests help improve the diagnostic accuracy of cytological diagnosis.

Deciphering the Genetic Complexity of Classical Hodgkin Lymphoma: Insights and Effective Strategies.

Understanding the genetics of susceptibility to classical Hodgkin lymphoma (cHL) is considerably limited compared to other cancers due to the rare Hodgkin and Reed-Sternberg (HRS) tumor cells, which coexist with the predominant non-malignant microenvironment. This article offers insights into genetic abnormalities in cHL, as well as nucleotide variants and their associated target genes, elucidated through recent technological advancements. Oncogenomes in HRS cells highlight the survival and proliferation of these cells through hyperactive signaling in specific pathways (e.g., NF-kB) and their interplay with microenvironmental cells (e.g., CD4+ T cells). In contrast, the susceptibility genes identified from genome-wide association studies and expression quantitative trait locus analyses only vaguely implicate their potential roles in susceptibility to more general cancers. To pave the way for the era of precision oncology, more intensive efforts are imperative, employing the following strategies: exploring genetic heterogeneity by gender and cHL subtype, investigating colocalization with various types of expression quantitative trait loci, and leveraging single-cell analysis. These approaches provide valuable perspectives for unraveling the genetic complexities of cHL.

A case report of chondroblastic osteosarcoma following treatment for Hodgkin lymphoma

Patients diagnosed with Hodgkin lymphoma (HL) have improved survival because of the early use of effective therapies and positron emission tomography (PET) – adapted strategies. However, long-term observational studies have shown that HL survivors have an increased risk of secondary cancers and other complications, which include cardiovascular disease, infertility and endocrinopathies. Therefore, long-term follow-up and screening of HL survivors is important.Contribution: We report a case of a 22-year-old female with chondroblastic osteosarcoma following treatment of HL. We have devised a simple screening algorithm to ensure comprehensive long-term surveillance of HL survivors.

Improved prognosis with radiotherapy in early-stage Hodgkin lymphoma: acritical analysis of the long-term data from the EORTC/LYSA/FIL H10trial

Improved prognosis with radiotherapy in early-stage Hodgkin lymphoma: acritical analysis of the long-term data from the EORTC/LYSA/FIL H10trial

Temporal changes in the burden of leukaemia and lymphoma in the Australasia and Oceania regions, 2010–2019: an analysis of the Global Burden of Disease Study 2019

ObjectivesLeukaemias and lymphomas are among the most prevalent and significant cancers in Australasia and Oceania. This study aims to examine the burden of leukaemias/lymphomas and its temporal trend in Australasia...

Hodgkin lymphoma: the role of EBV plasma viral load testing in an HIV-endemic setting

South Africa has a high burden of human immune deficiency virus (HIV)-associated Hodgkin lymphoma (HL) which is typically Epstein–Barr virus (EBV) infected, detected by histological stains. Circulating plasma EBV derived from apoptotic EBV infected tumour cells is a potential biomarker. This study aimed to evaluate the role of plasma EBV load testing in newly diagnosed HL patients and correlate pretreatment plasma EBV levels, HIV status and EBV tumour status with overall survival (OS). Untreated HL patients were prospectively included. Polymerase chain reaction measured EBV plasma viral loads. Kaplan–Meier curves with log-rank tests estimated the impact of HIV, EBV tumour status and plasma EBV viral loads on OS. Multivariable analysis was performed using a Cox proportional hazards model. Receiver operative characteristic curve analysis determined cutoff plasma EBV DNA levels with optimal sensitivity, specificity and concordance with tumour EBV status. The 68 patients included 21 (31%) HIV +ve and 33 (49%) EBV tumour +ve. EBV plasma ≥ 10 000 IU/ml (P = 0.008), EBV +ve tumour (P = 0.014), HIV +ve status (P = 0.009) and age ≥ 45 years (P = 0.018) predicted poorer OS on univariate analysis. Plasma EBV levels > 762 IU/ml had 89.29% sensitivity and 96.77% specificity for detecting EBV +ve HL. High plasma EBV levels ≥ 10 000 IU/ml, HIV +ve status and EBV tumour +ve status predicted poorer OS. Plasma EBV levels > 762 IU/ml predicted EBV +ve tumour status with high sensitivity and specificity. Plasma EBV viral DNA testing is a promising biomarker for EBV +ve HL.

Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Special Type of (Follicular) B-Cell Lymphoma?

The clinicopathologic spectrum of nodular lymphocyte-predominant Hodgkin lymphoma, now termed “nodular lymphocyte-predominant B-cell lymphoma” (NLPBCL), may include incipient, typical and transformed forms. On the basis of its clinicopathologic spectrum, NLPBCL is very similar to follicular lymphoma not associated with BCL2 translocation. In addition, NLPBCL, based on biopathologic features (gene profiling signature, and phenotypic and morphotypic characteristics), is a germinal center-derived B-cell neoplasm; therefore, it could be included in the follicular lymphoma group of non-Hodgkin lymphoma.

When to use stem cell transplantation for classical Hodgkin lymphoma.

Hodgkin lymphoma (HL) is a rare hematologic malignancy with a bimodal distribution of incidence, with most patients diagnosed between the ages of 15 and 30 years and another peak in patients older than 55 years. It is estimated that in 2023, almost 9000 people were diagnosed with HL in the United States. Most patients will be cured using conventional chemotherapy and radiotherapy. The treatment of HL has changed significantly over the past decade following the approval of highly effective novel therapies, including brentuximab vedotin and the checkpoint inhibitors (CPIs) nivolumab and pembrolizumab. The increasing use of these novel therapies has resulted in decreased utilization of both autologous and allogeneic hematopoietic cell transplantation (HCT) in patients with HL. In this review, we discuss the role of stem cell transplantation in patients with HL, with a particular focus on recent data supporting allogeneic HCT as a curative option in patients who progress on or are intolerant to CPI treatment.

When should we use it? The role of brentuximab vedotin in 2024.

The CD30-directed antibody-drug conjugate brentuximab vedotin (BV) was FDA approved in 2011 for the treatment of relapsed classic Hodgkin lymphoma (cHL), in 2015 for maintenance after autologous transplantation in high-risk patients, and in 2018 for frontline therapy with doxorubicin, vinblastine, and dacarbazine for advanced stage cHL. Although the role of BV in cHL had been reasonably well-established, it is currently being challenged by the changing landscape of other highly effective novel agents, such as checkpoint inhibitor immunotherapies. In this review, we discuss the evolving role of BV in the management of cHL and ongoing studies attempting to define the optimal usage of this effective agent.

Successful Treatment of a Patient Presenting with Simultaneous Diffuse Large B-Cell Lymphoma and Hodgkin Lymphoma: A Case Report

Successful Treatment of a Patient Presenting with Simultaneous Diffuse Large B-Cell Lymphoma and Hodgkin Lymphoma: A Case Report

Causal association of physical activity with lymphoma risk: a Mendelian randomization analysis.

Controversial relationship of physical activity with lower lymphoma risk has been reported in observational studies. The purpose of this study was to explore the causal correlation of physical activity with lymphoma risk using two-sample Mendelian randomization (MR). Genetic variants associated with physical activity (moderate-to-vigorous physical activity (MVPA), average acceleration physical activity, number of days/week of moderate physical activity 10+ min, and number of days/week of vigorous physical activity 10+ min) and lymphoma [overall lymphoma, Hodgkin lymphoma, mature T/NK-cell lymphomas, diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma] were obtained from published genome-wide association studies (GWAS) and the FinnGen database and used as instrumental variables. Primary results were based on inverse variance-weighted (IVW) analysis and were described as odds ratio (OR) and 95% confidence interval (CI). Higher levels of genetically predicted MVPA (OR = 0.079, 95% CI: 0.021-0.300, P = 0.0002) and number of days/week of vigorous physical activity 10+ min (OR = 0.237, 95% CI: 0.098-0.573, P = 0.0014) were negatively associated with Hodgkin lymphoma risk. There was a weak negative association between high levels of genetically predicted MVPA (OR = 0.114, 95% CI: 0.015-0.856, P = 0.0348) and average acceleration physical activity (OR = 0.830, 95% CI: 0.705-0.976, P = 0.0243) and risk of DLBCL. No causal relationship was observed between physical activity and the risk of overall lymphoma, mature T/NK-cell lymphomas, and follicular lymphoma (P > 0.05). This study supported the causal relationship between higher physical activity levels and lower risks of Hodgkin lymphoma and DLBCL.

Risk factors for decreased bone mineral density in patients with Hodgkin’s lymphoma

BACKGROUND: Osteoporosis is a disease characterized by a decrease in bone mineral density that leads to low-energy fractures. Hodgkin’s lymphoma, which occurs mainly in young people (16–35 years), may be one of the causes of impaired bone remodeling. Given the high prevalence of osteoporosis in young patients with Hodgkin’s lymphoma, it is important to identify early predictors of the development of osteoporosis. AIM: To evaluate risk factors for decreased bone mineral density in patients with Hodgkin’s lymphoma receiving pathogenetic therapy. MATERIALS AND METHOD: The study included 63 patients with Hodgkin’s lymphoma and 30 healthy volunteers who served as controls. All participants completed a questionnaire to identify common and specific risk factors for osteoporosis. Common risk factors included sex, age, body mass index, history of fractures in the patient and immediate family, use of hormone replacement therapy, proton pump inhibitors, corticosteroids, comorbidities, amenorrhea in women, level of physical activity, and calcium intake. Specific risk factors for osteoporosis included polychemotherapy as a pathogenetic therapy for Hodgkin’s lymphoma. RESULTS: The study identified four main risk factors for the development of osteopenia/osteoporosis in young patients with Hodgkin lymphoma following pathogenetic therapy such as use of proton pump inhibitors, corticosteroids, chemotherapy-induced amenorrhea in women, and low physical activity. CONCLUSION: Methods for predicting and preventing osteoporosis have not yet been developed for young patients, as this disease is considered to be associated with old age. However, some groups of young patients are at high risk for disruption of bone microarchitecture with low-energy fractures, significantly reducing quality of life. All these factors make early detection of osteoporosis predictors important.

Optimizing resources: low-dose nivolumab combinations in the management of relapsed/refractory Hodgkin lymphoma.

Up to one-third of patients with classical Hodgkin lymphoma (cHL) are not responsive to first-line therapy or eventually relapse. Immune checkpoint inhibitors (ICIs) have been successfully employed to treat relapsed/refractory cHL (r/r cHL) but place patients at risk of financial toxicity. Early-phase trials and observational data suggest that low doses of ICIs may achieve similar results to those obtained with high doses. In this study, we report a single-center experience using low-dose nivolumab (LD-Nivo) in different combinations for r/r cHL, including monotherapy, LD-Nivo plus brentuximab vedotin (BV), and LD-Nivo plus chemotherapy. The primary outcome was to assess the efficacy of LD-nivo in patients with r/r cHL. We included 23 consecutive patients (median age 27years; 57% female). LD-Nivo was prescribed in 40, 100, and 140mg fixed doses Q2W. Survival analysis was performed employing the Kaplan-Meier method. 73% of patients achieved an overall response, 43% complete response, and 30% partial response. One-year overall survival was 94.4% (95% CI, 0.84-1), and the 1-year progression-free survival was 89.4% (95% CI, 0.77-1). OS and PFS were similar accross combinations. The median dose of nivolumab was 0.78mg/kg (range, 0.62-1.11), and the median number of cycles until a response was documented was 6 (range, 2-9). During follow-up, 18 patients received transplantation (11 autologous, 6 allogeneic). No statistically significant differences in survival or response were detected between nivolumab combinations or doses. Adverse events were observed in 61% of the patients, with none grade 3-4. LD-Nivo demonstrated promising results in relapsed/refractory HL, highlighting its potential as a cost-effective treatment option. Further research is needed to validate these findings and guide clinical practice.

Prognosis of patients with Hodgkin lymphoma and indeterminate response to PD-1 inhibitor therapy: considerations for application of LYRIC criteria in real clinical practice.

PD-1 inhibitors have shown unconventional response patterns in classic Hodgkin lymphoma (cHL). These include the phenomenon of pseudoprogression, highlighting the need for specialized response criteria such as the LyRIC, which stringened definitions for disease progression with introduction of indeterminate response category. Despite their potential utility, these provisional criteria are currently underutilized and require further refinement through clinical practice data collection. In this retrospective study LyRIC criteria were systematically used for response assessments in 180 patients with refractory cHL treated with nivolumab. Median follow-up was 60months. Indeterminate response (IR) was a frequent phenomenon in study population: at 3months of therapy 63 (35%) patients had an indeterminate response (IR1 7%, IR2 23%, IR3 6%). Among them 18 (29%) achieved an objective response with continued monotherapy. There were no differences in OS or TTNT depending on the type of IR. IR was the best achieved response in 45 (25%) patients. Patients with IR had favorable prognosis with no difference in OS, PFS and TTNT comparing to patients with PR when subsequent therapy was initiated due to disease progression. Patients with IR may achieve prolonged disease control or a deeper response upon continuing treatment. These findings support the broader implementation and adjustment of LyRIC criteria in clinical practice to enhance decision-making in cHL patients treated with immunotherapy.