Hodgkin's Disease Research Articles

Changes in essential cancer medicines and association with cancer outcomes: an observational study of 158 countries

BackgroundCancer is a major cause of mortality worldwide, and differences in cancer mortality rates between countries are, in part, due to differences in access to cancer care, including medicines. National essential medicines lists (NEMLs) play a role in prioritization of healthcare expenditure and access to medicines. We examined the association between amenable cancer mortality and listing medicines used in the management of eight cancers (non-melanoma skin, uterine, breast, Hodgkin lymphoma, colon, leukemia, cervical, and testicular) in national essential medicines lists of 158 countries and summarized changes to the inclusion of cancer treatments in NEMLs.MethodsWe conducted a cross-sectional examination of NEMLs for 158 countries, which were obtained in May 2023. We identified medicines used to treat each of the eight cancers and determined the number of medicines listed by NEMLs for each cancer. We conducted multiple linear regressions to examine the association between the number of medicines listed on the NEMLs and cancer mortality.ResultsWe found associations between cancer medicine listing and outcomes for six of the eight examined cancers (non-melanoma skin cancer (p = 0.001), uterine cancer (p = 0.006), breast cancer (p = 0.001), Hodgkin lymphoma (p = 0.021), colon cancer (p = 0.006), and leukemia (p = 0.002)), when adjusting for healthcare expenditure and population size.ConclusionThere was an association between listing cancer medicines on NEMLs and cancer mortality. Further research is required to explore how cancer mortality may be impacted by other cancer interventions, as well as policies to improve equitable access to cancer care.

Improved Overall Survival with Checkpoint Inhibition and Allogeneic Transplantation in Relapsed Hodgkin Lymphoma.

Patients with relapsed classic Hodgkin lymphomas receive salvage therapy with immune checkpoint inhibitors (ICI) or chemotherapy (no-ICI). Patients responding to therapy often undergo consolidation with allogeneic blood or marrow transplantations (alloBMT). We previously reported that relapsed cHL patients treated with ICI followed by alloBMT experienced improved 3-year progression-free survival (PFS) compared to patients treated with salvage chemotherapy without ICI, followed by alloBMT. In this retrospective analysis, we report the 5-year OS, PFS, and GVHD incidence in cHL patients treated with ICI before alloBMT with post-transplantation cyclophosphamide (PTCy) GVHD prophylaxis. Among the 147 relapsed/refractory patients with cHL, 71 (48.3%) received ICIs and 76 (51.7%) received chemotherapy without ICIs (no-ICI) before alloBMT. We observed an improved 5-year estimated OS of 91% (ICI) versus 66% (no-ICI), (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.16 to 0.98; P = 0.046) and a 5-year estimated PFS of 84% (ICI) versus 53% (no-ICI) (HR, 0.4; 95% CI, 0.2 to 0.81; P = 0.011). The 12-month cumulative incidence of grade III-IV GVHD was 20% (ICI) and 7% (no-ICI) (SDHR 3.16; 95% CI, 1.13 to 8.81 p = 0.03. More frequent grade III-IV acute GVHD was likely due to the higher incidence of grade III-IV acute GVHD in the subset of patients with pre-transplant exposure to ICI and shortened duration (60 days) of immunosuppression versus patients with long immunosuppression (day 180). These data suggest that cHL patients treated with ICI and alloBMT experience improved OS and the GVHD risk can be mitigated by immunosuppression until day 180.

The Functional Interaction Between Epstein–Barr Virus and MYC in the Pathogenesis of Burkitt Lymphoma

The Epstein–Barr virus (EBV) is associated with a wide range of diseases, malignant and non-malignant. EBV was, in fact, the first virus described with cell transformation capacity, discovered by Epstein in 1964 in lymphoma samples from African children. Since then, EBV has been associated with several human tumors including nasopharyngeal carcinoma, gastric carcinoma, T-cell lymphoma, Hodgkin lymphoma, diffuse large B cell lymphoma, and Burkitt lymphoma among others. The molecular hallmark of Burkitt lymphoma (BL) is a chromosomal translocation that involves the MYC gene and immunoglobulin loci, resulting in the deregulated expression of MYC, an oncogenic transcription factor that appears deregulated in about half of human tumors. The role of MYC in lymphoma is well established, as MYC overexpression drives B cell proliferation through multiple mechanisms, foremost, the stimulation of the cell cycle. Indeed, MYC is found overexpressed or deregulated in several non-Hodgkin lymphomas. Most endemic and many sporadic BLs are associated with EBV infection. While some mechanisms by which EBV can contribute to BL have been reported, the mechanism that links MYC translocation and EBV infection in BL is still under debate. Here, we review the main EBV-associated diseases, with a special focus on BL, and we discuss the interaction of EBV and MYC translocation during B cell malignant transformation in BL.

T-cell diversity and exclusion of blood-derived T-cells in the tumor microenvironment of classical Hodgkin Lymphoma

Abstract The Tumor Microenvironment (TME) in classical Hodgkin Lymphoma (HL) contains abundant immune cells and only few neoplastic Hodgkin and Reed-Sternberg cells (HRSC). We analyzed the T-cell receptor (TCR) repertoire to detect T-cell expansion in the TME and blood. In contrast to solid cancer tissue, T-cells in the TME of HL are highly polyclonal at first diagnosis and show only minor clonal expansion during anti-PD1 immune checkpoint blockade (ICB). At relapse and during ICB, pre-amplified T-cell populations increase in the TME of solid cancers but to a much lesser extent in HL. In contrast, T-cell populations in the peripheral blood of HL patients display higher clonality than healthy controls reaching clonality levels comparable to solid cancer. However, pre-amplified blood T-cells in HL patients show only minor additional clonal expansion during ICB. Moreover, blood-derived T-cells do not repopulate the TME of HL to the same extent as observed in solid cancers. Thus, the T-cell repertoire in the TME of HL appears unique by a relatively low clonal T-cell content and the exclusion of clonally expanded T-cells from the peripheral blood. Exclusion of clonally expanded tumor-specific T-cells from the TME may present a novel mechanism of immune evasion in HL.

Brentuximab Vedotin (Adcetris)

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform nonbinding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec. This review assesses brentuximab vedotin for injection (Adcetris), 50 mg per vial, lyophilized powder for reconstitution, IV infusion. Indication: For the treatment of previously untreated patients with stage IV Hodgkin lymphoma, in combination with doxorubicin, vinblastine, and dacarbazine.

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.

Stevens-Johnson Syndrome secondary to nivolumab in a patient with mixed cell variety classical Hodgkin Lymphoma

The immune checkpoint inhibitors (ICIs) nivolumab and pembrolizumab are some of the principal treatment options for relapsed or refractory classic Hodgkin lymphoma. However, immunotherapy has been related to dermatological adverse events (DAEs) and could lead to discontinuation of cancer treatment in severe cases. DAEs encompass entities such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS/TEN-like reactions, drug reaction with eosinophilia and systemic symptoms (DRESS). We reported a case of a 46-year-old- female with classic mixed cellularity Hodgkin lymphoma, Lugano IV, who underwent a hematopoietic cell transplant and subsequent relapse, currently with Stevens-Johnson Syndrome secondary to nivolumab.

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.

Correlation Between Progression-Free and Overall Survival in Patients with Hodgkin Lymphoma: A Comprehensive Analysis of Individual Patient Data from Randomized GHSG Trials

Correlation Between Progression-Free and Overall Survival in Patients with Hodgkin Lymphoma: A Comprehensive Analysis of Individual Patient Data from Randomized GHSG Trials

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.

Evolution of Breast Cancer Management after Mediastinal Hodgkin Lymphoma: Towards a Breast- Conserving Approach

Evolution of Breast Cancer Management after Mediastinal Hodgkin Lymphoma: Towards a Breast- Conserving Approach

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.