Hodgkin's Disease Research Articles

Surgical Treatment of Breast Lymphedema: A Distinct Pathology With Unique Challenges.

Supermicrosurgical advances such as lymphovenous bypass (LVB) have enabled effective physiologic treatment of lymphedema affecting the extremities. Reports of surgical treatment for breast lymphedema (BL) are sparse, consisting of case reports and almost exclusively LVB. We report our experience with BL, including a case of mastectomy and breast reconstruction with abdominal free flap and inguinal vascularized lymph node transfer (VLNT) for BL. We compare our series with the surgical literature to discern unique characteristics and treatment limitations inherent to this disease. A database was prospectively maintained from September 2020 to May 2023 including all patients diagnosed with BL who were referred to our institution. Breast lymphedema was diagnosed using clinical criteria, and relevant patient data were recorded. Patients interested in surgical management underwent indocyanine green lymphography to determine candidacy for LVB or other interventions. All patients, including those surgically managed, were treated with complex decongestive therapy. Nine patients with BL were included. Eight had undergone breast-conserving therapy for breast cancer with whole breast irradiation. One patient was treated for Hodgkin lymphoma with axillary lymphadenectomy and axillary radiation. Indocyanine green lymphography was performed in 6 patients, of which 4 patients had diffuse dermal backflow. Two patients had lymphatic targets suitable for LVB, including the patient without breast irradiation. Three patients were managed surgically. One patient without bypass targets underwent breast reduction with partial symptomatic relief, later followed by a mastectomy with abdominal free flap reconstruction and VLNT. Two patients with suitable bypass targets underwent LVB, with resolution of breast swelling and subjective symptoms. The diffuse lymphatic obliteration due to radiation field effect in BL results in a distinct pathophysiology compared with extremity lymphedema. Although published reports of surgical BL treatment almost exclusively describe LVB, other surgical options may be more frequently required. Ablative strategies such as mastectomy and regenerative techniques such as VLNT should be considered potential first-line treatment options for these patients.

Pulmonary Infundibular Stenosis Secondary to a Mediastinal Hodgkin Lymphoma Tumor Invasion in a Young Adult Male: What a Rare Occurrence!

Introduction: Cardiac involvement is a rare unusual localization of Hodgkin lymphoma, as it’s known that primary lymphomas of the heart are rare. They develop primarily in the right atrium, and extend to the pericardium in about one third of the cases. Pulmonary infundibular stenosis secondary to mediastinal mass Hodgkin lymphoma invasion is rare but not impossible especially in relapse cases. Case Report: A rare case of a young adult patient diagnosed with Hodgkin Lymphoma under chemotherapy presents a relapse of his pathology associated with heart failure; predominantly, right heart failure due to extension of the mediastinal mass tumor to the right cavities of the heart causing pulmonary infundibular stenosis which is a rare occurrence. He was put under an intense chemotherapy and symptomatic heart failure treatment with close follow-up after multi-disciplinary discussions including cardiologist, onco-hematologists and cardiothoracic surgeons. Three months later, a significant reduction of the mass was observered. Conclusion : Pulmonary infundibular stenosis secondary to mediastinal Hodgkin lymphoma invasion is a rare entity of secondary tumors of the heart. Multimodal imagery is the key tool for diagnosis. There prognosis depend on multiple factors but generally good in younger adult patients compared to aged individuals.

EBV-Related Lymphoproliferative Diseases: A Review in Light of New Classifications.

Epstein-Barr virus (EBV) is a prevalent virus that can be detected in the vast majority of the population. Most people are asymptomatic and remain chronically infected throughout their lifetimes. However, in some populations, EBV has been linked to a variety of B-cell lymphoproliferative disorders (LPDs), such as Burkitt lymphoma, classic Hodgkin lymphoma, and other LPDs. T-cell LPDs have been linked to EBV in part of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphomas, extranodal nasal natural killer/T-cell lymphomas, and other uncommon histotypes. This article summarizes the current evidence for EBV-associated LPDs in light of the upcoming World Health Organization classification and the 2022 ICC classification.

A rare occurrence of Hodgkin lymphoma in a Xeroderma pigmentosum patient: A case report and literature review

Xeroderma pigmentosum (XP) is a rare genetic disorder characterized by extreme sensitivity to ultraviolet (UV) radiation, resulting in an increased risk of skin cancer and other UV-induced malignancies. Reports of hematological malignancies occurring in patients with XP are found in the literature, but they seem to be quite rare. This report describes a 29-year-old male patient with XP who developed Hodgkin lymphoma. The potential increased risk of lymphoma in XP patients is highlighted in this paper; however, further studies are needed to better understand the underlying mechanisms of lymphomagenesis in XP patients and to develop optimal treatment strategies for hematological and other internal malignancies in this setting.

Pulmonary diseases in patients with classical Hodgkin lymphoma relative to a matched background population: A Danish national cohort study.

Late toxicities can impact survivorship in patients with classical Hodgkin lymphoma (cHL) with pulmonary toxicity after bleomycin-containing chemotherapy being a concern. The incidence of pulmonary diseases was examined in this Danish population-based study. A total of 1474 adult patients with cHL treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or BEACOPP (bleomycin, vincristine, etoposide, doxorubicin, cyclophosphamide, procarbazine and prednisone) between 2000 and 2018 were included along with 7370 age- and sex-matched comparators from the background population. Median follow-up was 8.6 years for the patients. Patients with cHL had increased risk of incident pulmonary diseases (HR 2.91 [95% CI 2.30-3.68]), with a 10-year cumulative risk of 7.4% versus 2.9% for comparators. Excess risks were observed for interstitial lung diseases (HR 15.84 [95% CI 9.35-26.84]) and chronic obstructive pulmonary disease (HR 1.99 [95% CI 1.43-2.76]), with a 10-year cumulative risk of 4.1% and 3.5% respectively for patients. No excess risk was observed for asthma (HR 0.82 [95% CI 0.43-1.56]). Risk factors for interstitial lung diseases were age ≥60 years, the presence of B-symptoms and low albumin. These findings document a significant burden of pulmonary diseases among patients with cHL and emphasize the importance of diagnostic work-up of pulmonary symptoms.

Investigating the safety and feasibility of osteopathic manipulative medicine in hospitalized children and adolescent young adults with cancer.

Children and adolescents young adults (AYAs) undergoing treatment for oncologic diagnoses are frequently hospitalized and experience unwanted therapy-induced side effects that diminish quality of life. Osteopathic manipulative treatment (OMT) is a medical intervention that utilizes manual techniques to diagnose and treat body structures. Few studies have investigated the implementation of OMT in the pediatric oncology outpatient setting. To date, no studies have investigated the safety and feasibility of OMT in the pediatric oncology inpatient setting. The objective of this study is to investigate the safety and feasibility of OMT in the pediatric oncology inpatient setting. This is a prospective, single-institution pilot study evaluating children and AYAs aged≥2 years to≤30 years with a diagnosis of cancer hospitalized at Riley Hospital for Children (RH) from September 2022 to July 2023. Approval was obtained from the Indiana University Institutional Review Board (IRB). Patients were evaluated daily with a history and physical examination as part of routine inpatient management. Patients who reported chemotherapy side effects commonly encountered and managed in the inpatient setting, such as pain, headache, neuropathy, constipation, or nausea, were offered OMT. Patients provided written informed consent/assent prior to receiving OMT. OMT was provided by trained osteopathic medical students under the supervision of a board-certified osteopathic physician and included techniques commonly taught in first- and second-year osteopathic medical school curricula. Safety was assessed by a validated pain (FACES) scale immediately pre/post-OMT and by adverse event grading per Common Terminology Criteria for Adverse Events (CTCAE) 24 h post-OMT. All data were summarized utilizing descriptive statistics. A total of 11 patients were screened for eligibility. All patients met the eligibility criteria and were enrolled in the study. The majority of patients were male (n=7, 63.6 %) with a median age of 18.2 years at time of enrollment (range, 10.2-29.8 years). Patients had a variety of hematologic malignancies including B-cell acute lymphoblastic leukemia (ALL) (n=5, 45.5 %), T-cell ALL (n=1, 9.1 %), acute myeloid leukemia (AML) (n=2, 18.2 %), non-Hodgkin's lymphoma (n=2, 18.2 %), and Hodgkin's lymphoma (n=1, 9.1 %). All patients were actively undergoing cancer-directed therapy at the time of enrollment. There were 40 unique reasons for OMT reported and treated across 37 encounters, including musculoskeletal pain (n=23, 57.5 %), edema (n=7, 17.5 %), headache (n=5, 12.5 %), peripheral neuropathy (n=2, 5.0 %), constipation (n=2, 5.0 %), and epigastric pain not otherwise specified (n=1, 2.5 %). Validated FACES pain scores were reported in 27 encounters. Of the 10 encounters for which FACES pain scores were not reported, 8 encounters addressed lower extremity edema, 1 encounter addressed peripheral neuropathy, and 1 encounter addressed constipation. The total time of OMT was documented for 33 of the 37 encounters and averaged 9.8 min (range, 3-20 min). Hospitalized children and AYAs with cancer received OMT safely with decreased pain in their reported somatic dysfunction(s). These findings support further investigation into the safety, feasibility, and efficacy of implementing OMT in the pediatric oncology inpatient setting and to a broader inpatient pediatric oncology population.

Beyond Chemotherapy: Present and Future Perspectives in the Treatment of Lymphoproliferative Disorders.

Over the past three decades, the treatment of lymphoproliferative disorders has undergone profound changes, notably due to the increasing availability of innovative therapies with the potential to redefine clinical management paradigms. A major impact is related to the development of monoclonal antibodies, checkpoint inhibitors, bispecific antibodies, and chimeric antigen receptor T (CAR-T) cell therapies. This review discusses the current landscape of clinical trials targeting various hematological malignancies, highlighting promising early-phase results and strategies to overcome resistance. Lymphoproliferative disorders encompass a range of conditions: while in Hodgkin lymphoma (HL) the goal is to reduce chemotherapy-related toxicity by integrating immunotherapy into the frontline setting, peripheral T cell lymphoma (PTCL) lacks effective targeted therapies. The review emphasizes a shifting therapeutic landscape towards precision medicine and treatment modalities that are less toxic yet more effective.

Germinal center cytokine driven epigenetic control of Epstein-Barr virus latency gene expression.

Epstein-Barr virus (EBV) persistently infects 95% of adults worldwide and is associated with multiple human lymphomas that express characteristic EBV latency programs used by the virus to navigate the B-cell compartment. Upon primary infection, the EBV latency III program, comprised of six Epstein-Barr Nuclear Antigens (EBNA) and two Latent Membrane Protein (LMP) antigens, drives infected B-cells into germinal center (GC). By incompletely understood mechanisms, GC microenvironmental cues trigger the EBV genome to switch to the latency II program, comprised of EBNA1, LMP1 and LMP2A and observed in GC-derived Hodgkin lymphoma. To gain insights into pathways and epigenetic mechanisms that control EBV latency reprogramming as EBV-infected B-cells encounter microenvironmental cues, we characterized GC cytokine effects on EBV latency protein expression and on the EBV epigenome. We confirmed and extended prior studies highlighting GC cytokine effects in support of the latency II transition. The T-follicular helper cytokine interleukin 21 (IL-21), which is a major regulator of GC responses, and to a lesser extent IL-4 and IL-10, hyper-induced LMP1 expression, while repressing EBNA expression. However, follicular dendritic cell cytokines including IL-15 and IL-27 downmodulate EBNA but not LMP1 expression. CRISPR editing highlighted that STAT3 and STAT5 were necessary for cytokine mediated EBNA silencing via epigenetic effects at the EBV genomic C promoter. By contrast, STAT3 was instead necessary for LMP1 promoter epigenetic remodeling, including gain of activating histone chromatin marks and loss of repressive polycomb repressive complex silencing marks. Thus, EBV has evolved to coopt STAT signaling to oppositely regulate the epigenetic status of key viral genomic promoters in response to GC cytokine cues.

Active Tuberculosis Risk Associated with Malignancies: A 4-Year Retrospective Study in a Tertiary Care Hospital

Background Tuberculosis (TB) remains an important public health problem worldwide. Risk of acquiring TB in patients diagnosed with cancers remains high and can result due to reactivation or reinfection. We share the experience in a large tertiary care hospital. Materials and Methods Clinical samples from presumptive TB patients while on cancer therapy were tested by smear Ziehl–Neelsen (ZN) staining, GeneXpert MTB/RIF (Gx), TB polymerase chain reaction (PCR), and liquid culture (MGIT 960) from January 1, 2019, to December 31, 2022. Statistical Analysis Stata 14.0 software was used for statistical analysis. The p-value calculation was done by Pearson's chi-square test. Results Of 906 patients investigated, 42 (4.64%) tested positive for TB. Seven (1.37%) tested positive by ZN staining, 10 patients (6%) had culture positive by MGIT, 20 (10.53%) and 5 (13.51%) samples were positive by Gx and PCR, respectively. Maximum number of TB-positive patients were found to be suffering from carcinoma lung (28%) followed by leukemia (25%), gastrointestinal cancer (13%), and genitourinary cancer (13%), respectively. Seven of the 42 patients succumbed to the disease; the cases belonged to Hodgkin's lymphoma (75% mortality), leukemia (30% mortality), and genitourinary cancer (20% mortality). Conclusion The incidence of active TB is high in cancer patients, especially lung cancer, leukemia, gastrointestinal, and genitourinary cancers. Mortality was high in Hodgkin's lymphoma patients who developed TB. Screening for TB at the time of diagnosis of a high TB risk cancer would help initiate early treatment. We recommend targeted screening for TB in patients with these high-risk cancers, at the time of diagnosis and periodically through cancer treatment.

Stage at diagnosis and survival by stage for the leading childhood cancers in Rwanda.

The lack of accurate population-based information on childhood cancer stage and survival in low-income countries is a barrier to improving childhood cancer outcomes. In this study, data from the Rwanda National Cancer Registry (RNCR) were examined for children aged 0-14 diagnosed in 2013-2017 for the eight most commonly occurring childhood cancers: acute lymphoblastic leukaemia, Hodgkin lymphoma (HL), Burkitt lymphoma (BL), non-Hodgkin lymphoma excluding BL, retinoblastoma, Wilms tumour, osteosarcoma and rhabdomyosarcoma. Utilising the Toronto Childhood Cancer Stage Guidelines Tier 1, the study assigned stage at diagnosis to all, except HL, and conducted active follow-ups to calculate 1-, 3- and 5-year observed and relative survival by cancer type and stage at diagnosis. The cohort comprised 412 children, of whom 49% (n=202) died within 5years of diagnosis. Five-year survival ranged from 28% (95% confidence interval [CI]: 12.5%-45.6%) for BL to 68% (CI: 55%-78%) for retinoblastoma. For the cancers for which staging was carried out, it was assigned for 83% patients (n=301 of 362), with over half (58%) having limited or localised stage at diagnosis. Stage was a strong predictor of survival; for example, 3-year survival was 70% (95% CI: 45.1%-85.3%) and 11.8% (2.0%-31.2%) for limited and advanced non-HL, respectively (p<.001). This study is only the second to report on stage distribution and stage-specific survival for childhood cancers in sub-Saharan Africa. It demonstrates the feasibility of the Toronto Stage Guidelines in a low-resource setting, and highlights the value of population-based cancer registries in aiding our understanding of the poor outcomes experienced by this population.

Unusual Presentation of Non-Hodgkin Lymphoma of Two Cases: Case Report.

Lymphomas are a diverse group of neoplastic disorders arising primarily in lymph nodes. They have been majorly classified into Hodgkin and Non-Hodgkin lymphomas(NHL). NHL can be of B, T and Null cell categories having further subtypes based on their histological characteristics. Lymphomas can be nodal and extra nodal. The head and neck area are the second most common site of extra nodal lymphoma, with tonsils being the most common site of involvement; other sites include the nasopharynx and tongue base. B- Cell type being the most common type. Predominantly occurs in elderly. Presentations depends on the site involved. Various modalities like surgical treatment, chemotherapy (or) radiotherapy is available. Each stage has varied survival rates and prognosis and responses to the treat depending on the patient factors. In this paper, we report two cases of patients with non-Hodgkin lymphoma of tonsil, where the preoperative clinical diagnosis and radiological diagnosis was inconclusive and final diagnosis was established based on histopathological examination.

Real-life study on the use of response adapted therapy in patients with Hodgkin Lymphoma: Results from a multicenter experience.

Few data are known regarding the use of interim positron emission tomography (iPET) after the first two cycles (iPET2) of chemotherapy in treatment-naïve classical Hodgkin lymphoma (cHL) in routine clinical practice, and about the real-life adoption of intensification strategies for iPET positive patients. We conducted a multicenter retrospective study on cHL to investigate the use of iPET in the real-life setting, its prognostic role and outcomes of patients early shifted to intensification. Six hundreds and forty-one patients were enrolled (62% had advanced stage). iPET2 was positive in 89 patients (14%) including 8.7% and 17% early and advanced stage patients, respectively (p=0.003). Among iPET 2 positive cases treatment was immediately modified in 19 cases; in 14 cases treatment was modified after an additional positive iPET4. Overall 56 iPET2 positive patients never received intensified therapies. Most frequently used intensified therapy was autologous stem cell transplantation followed by BEACOPP. After a median follow-up of 72months, the 5-year progression-free survival (PFS) was 82% with iPET2 positive patients showing a worse PFS compared with iPET2 negative cases: 31% versus 85%. Focusing on advanced stage patients with a positive iPET2, the 5-year PFS was 59% for patients shifted to intensified therapy at any time point versus 61% for patients who never received intensified therapy. Our study confirmed the higher curability of naïve cHL patients in a real-world setting, and the prognostic role of iPET2 in this setting. A poor adherence to response-adapted strategy which however did not translate into a difference in patient outcomes.

Breast Cancer Induced by Radiotherapy Following Hodgkin's Disease: A Study of Four Cases and Literature Review

Radiotherapy is a cornerstone in the treatment of Hodgkin's disease but can have long-term consequences, notably the development of secondary malignant tumors. This case study and literature review highlight the imaging characteristics, diagnostic challenges, and clinical outcomes of this late complication. The aim of this article is to underscore the role of imaging modalities in the diagnosis, characterization, and management of this rare and complex condition. We discuss the radiological findings, clinical diagnosis, and therapeutic considerations, thereby providing valuable insights into radio-induced breast cancer in Hodgkin's disease and emphasizing the importance of personalized surveillance in these high-risk patients.

The Class I Histone Deacetylase Inhibitor as a Potent Therapeutic Target for Treating Glioblastoma and Mocetinostat as a Novel Inhibitor in the Induction Death of Cancer Cells

Epigenetic abnormality is one of the hallmarks of glioblastoma cancer cells. Histone deacetylase (HDAC) modification has a crucial role in epigenetic abnormality, which results in the initiation and progression of glioblastoma cancer cells. The selective HDAC inhibitors are well-known epigenetic regulators and promising anti-cancer agents that target specific HDAC enzymes and inhibit the proliferation of many cancer cells. Selective HDAC inhibitors isoform provides a high efficacy as chemotherapy in inhibiting cancer confirmation compared to non-selective HDAC inhibitors. Additionally, selective HDAC inhibitors suppress Class -I HDAC1, HDAC2, HDAC3, and HDAC11. HDAC class I inhibitors induce apoptosis, differentiation, autophagic death cells, and reactive oxygen species (ROS)- induced cell death, inhibit cell migration, invasion, and angiogenesis in cancer cells, while the normal cells showed more resistance to HDAC class I inhibitors. Mocetinostat (MGCD0103), a benzamide histone deacetylase, is a potent anti-cancer therapy for the treatment of several cancer cell lines and induction of autophagy. It has been approved by The Food and Drug Administration (FDA) for the treatment of Hodgkin lymphoma (HL) cell lines. MGCD0103 is a synthesized and selective HDAC inhibitor that has vigorous inhibitory activity against Class-I and IV HDAC. MGCD0103 is well tolerated and has favorable pharmacokinetic properties, pharmacodynamic profile, and fast absorption within 1 hour after oral administration, long elimination half-life, and sustained HDAC inhibition. Therefore, MGCD0103 is expected to be a promising anti-cancer drug for treating several types of human cancer cells. Keywords: MGCD0103; Apoptosis; Differentiation; Gliblastoma; HDAC; inhibitors.

E033 Beyond the surface: artful imitation of Hodgkin’s lymphoma as axial spondyloarthritis

Abstract Background/Aims Rheumatic conditions may be associated with different neoplastic-diseases. Sacroiliitis is not defined as a paraneoplastic syndrome in the literature and considered as the direct involvement of the sacral/iliac bones or sacroiliac joints. There are only few reported cases of back pain and sacroiliac bones/joint involvement as an initial presentation of Hodgkin’s lymphoma. Methods An 18 year boy presented with low back pain of 18 months duration. He had significant morning stiffness and reported good response with non-steroidal anti-inflammatory drugs. He also complained of intermittent fever, insignificant weight loss and occasional dry cough. He denied peripheral joint pain, skin lesions, urethritis, conjunctivitis, uveitis and gastrointestinal disease. The family history was negative for spondyloarthritis (SpA) and neoplastic diseases. He was given empirical anti-tubercular drugs for 6 months with no significant improvement. He was evaluated by physician and rheumatologist elsewhere and treated as SpA in view of inflammatory low back pain, very high inflammatory markers and sacroiliac bones/joint involvement on MRI. The patient tested negative for HLA-B27 (PCR). He was initially started on sulfasalazine, however there was no induction of remission and later switched to tofacitinib since last 4 months. General examination was unremarkable. Bilateral sacroiliac compression and FABER tests were the only positive findings on systemic examination. Results There was leukocytosis (14,100/mm3) with predominant polymorphs, hemoglobin was 9.8g/dl, thrombocytosis (5.4 lakhs/mm3), serum CRP was markedly raised (123mg/L) and ESR was 57mm/hr. His workup for infectious diseases and rheumatic diseases were unremarkable. Repeat MRI according to SpA protocol showed altered marrow signal intensity in lumbar and sacral vertebral bodies and enhancing lytic lesion in right iliac bone till sacroiliac joint. PET-CT revealed multifocal FDG avid mixed lytic sclerotic lesions disseminated in the axial as well as appendicular skeleton with FDG avid sub-centimetric bilateral neck, supraclavicular, axillary, mediastinal and bilateral external/internal iliac and inguinal lymph nodes. Excision biopsy of right supra-clavicular node showed classical Hodgkin lymphoma (CD15 and CD30+ve). He was referred to the haematology clinic for further management. Bone marrow examination was suggestive of tumour infiltration. He received chemotherapy according to the protocol. He is under haematologist care and on a regular follow up with significant improvement in symptoms along with normal inflammatory markers. Conclusion There may be involvement of sacral/ iliac bones and sacroiliac joints by various malignancies including Hodgkin’s lymphoma. Morning stiffness, good response to NSAIDs and MRI findings may delay the diagnosis of primary malignancy, however we should keep a differential of lymphoproliferative disorders as in the aforementioned case and perform other diagnostic modalities. When the expected clinical response is not achieved, the physician must think of a malignancy in cases with persistently high inflammatory markers and marked constitutional symptoms. Disclosure P. Khatri: None. J. Yadavalli: None. K. Shivam: None. R. Gupta: None.

Recent updates in the therapeutic uses of Pembrolizumab: a brief narrative review.

Treatment of cancer has been improved with the discovery of biological drugs that act as immune checkpoint inhibitors. In 2017, FDA designated pembrolizumab, an immune checkpoint inhibitor employed in immunotherapy, as the first tissue-agnostic cancer treatment. To review pembrolizumab's use in oncology, gather and examine the latest discoveries regarding the effectiveness of pembrolizumab in cancer treatment. A literature review was conducted through PubMed(Medline) from January 2015 to December 2023 using "pembrolizumab", "cancer" and "treatment" as search terms. Pembrolizumab demonstrated effectiveness as primary treatment for metastatic nonsmall cell lung cancer, unresectable esophageal cancer, head and neck squamous cell carcinoma and alternative treatment for notable triple-negative breast cancer, biliary, colorectal, endometrial, renal cell, cervical carcinoma, and high microsatellite instability or mismatch repair deficiencies tumors. Pediatric applications include treatment for refractory Hodgkin lymphoma. Evolving research on pembrolizumab allows a deeper clinical understanding, despite challenges as variable patient responses. Pembrolizumab has emerged as a pivotal breakthrough in cancer treatment, improving patient outcomes and safety.

E032 Low dose methotextrate induced leukoencephalopathy: a case report

Abstract Background/Aims Methotextrate is a widely used disease modifying anti-rheumatic drug (DMARD) used to treat connective tissue disorder and inflammatory arthritis. Methotextrate induced neurological toxicity includes vomiting, headaches, blurred vision, mood alteration, somolescence, brain fog, hyperosmia, leukoencephalopathy and pseudo-stroke like syndrome. Here we report a case of methotextrate induced headache with leptomeningeal enhancement, which reversed after stopping the methotextrate. Methods A 66 year old male with known diagnosis of sero-positive rheumatoid arthritis with past medical history of Hodgkins lymphoma in remission. He started on dual DMARD combination of 15 mg methotextrate subcutaneously once a week and 200 mg hydroxychlroquin twice daily. Thereafter he reported history of headaches, which needed hospital admission. He underwent a CT-head scan on admission which did not show any acute concerns. The case was then discussed with the haematology team and later he underwent a PET scan of the whole body which was reviewed in Lymphoma MDT which showed non-specific uptake in hilar nodes, which does not significantly increase the suspicion of lymphoma relapse. On discharge he had MRI head contrast and MRV cerebral veins, which showed a few areas of irregular nodular curvilinear foci of predominantly meningeal enhancement noted in occipital lobes and adjacent T2 /flair hypertense signal noted in relation to these. These changes were discussed in neurology MDT, given the history of lymphomas a possibility, though rare in the absence of systemic relapse. The differential included low dose (oral) methotextrate related neurotoxicity. Patient was advised to stop methotextrate, they repeated MRI scan 3 weeks later which showed disappearance of the curvilinear lesions with leptomeningeal enhancement and patient reported headaches improved. Results List of investigations 1. CSF- profile, no protein, no growth 2. CSF PCR panel for Adeno/Paracheo/Entero/Varicella Zoster/HSV type 1&amp;2-negative 3. Histology report of CSF- No evidence of lymphoma 4. Neuronal Ab: Purkinje cell/ Hu Ab/Ri Ab amd Anti-amphiphysin Ab-negative 5. Myeloma screen- no paraprotein detected 6. Virus panel- EBV- IgM-, HIV /Hep B and C, Cytomegalovirus IgM-not detected. Conclusion Methotextrate is a potent anti-metabolite preventing the formation of tetrahydrofolate, and used as immunosuppressant and anti-neoplastic medication. Though the exact mechanism of the neurotoxicity is not known, the common hypothesis include; interference with myelin synthesis or maintenance and/or interference with neurotransmitter synthesis. The case reported here reiterates the importance of recognizing the neurological side effects in patients on methotextrate even on low dose of methotextrate. It also emphasizes the fact that the neurological changes are reversible on stopping methotextrate. Headaches can still be a side effect and might mimic stroke like episode in patients treated with low dose of subcutaneous methotextrate and hence stopping the medication should be considered in such cases. Disclosure P. Doddamani: None. A. Kinder: None.

Cardiovascular screening outcomes in the Dutch survivorship care program for Hodgkin lymphoma survivors.

Hodgkin lymphoma (HL) survivors are at increased risk of cardiovascular disease (CVD) due to former lymphoma treatment. In 2013, cardiovascular screening for 5-year HL survivors according to national guidelines was implemented in Dutch survivorship clinics. We aim to assess the following: (1) adherence to screening guidelines and (2) the yield of (risk factors for) CVD in the screening program. The study population consisted of 5-year HL survivors who received survivorship care at three University Medical Centers from 2013 to 2016 through 2021. Patient characteristics, cardiovascular screening procedures, and outcomes were collected from the medical records. In 186 survivors eligible for cardiovascular screening (mean age 47.8years, 60.8% female), the following diagnostics were performed: complete blood tests (81.0%, median frequency: yearly instead of advised 5-yearly evaluation), electrocardiogram (93.0%), echocardiography (94.6%). Fifty-five percent of survivors had at least one modifiable cardiovascular risk factor (i.e., current smoking, overweight, new/insufficiently controlled hypertension, dyslipidemia, or diabetes). Screening detected ≥ 1 CVD in 31.1% of survivors. Among survivors with available echocardiography report (n = 106), screening detected new aortic and/or mitral valve dysfunction(s) in 51.0% (with grades 3-4 in 4.9%) and impaired left ventricular ejection fraction in 10.3%. Adherence to the screening guidelines in the Dutch HL survivorship care program was reasonable to good and a substantial number of actionable (risk factors for) CVD were diagnosed. Our findings inform HL survivors at high risk of late cardiotoxicity about cardiovascular screening findings and demonstrate appropriate therapeutic actions after diagnosis of (risk factors for) CVD.

Future perspectives of radiation therapy for Hodgkin Lymphoma: Risk-adapted, response-adapted, and safer than before.

Classical Hodgkin lymphoma is a lymphoproliferative disease with a good prognosis mainly seen in young people. Nevertheless secondary malignancy, cardiac disease and infertility may affect the long survivors with significant impact on quality of life, morbidity and overall survival. In the last decades several treatment strategies were evaluated to reduce the toxicity of first line treatment such as avoiding radiotherapy or its reduction in terms of dosage and extension. Many trials including interim Positron Emission Tomography evaluation fail to compare efficacy between combined modality treatment versus chemotherapy alone in particular in early stage disease. In this review we analyze which subset of patients could take advantage from proton therapy in terms of toxicity and cost effectiveness.

Cotargeting EBV lytic as well as latent cycle antigens increases T-cell potency against lymphoma

AbstractThe remarkable efficacy of Epstein-Barr virus (EBV)-specific T cells for the treatment of posttransplant lymphomas has not been reproduced for EBV-positive (EBV+) malignancies outside the transplant setting. This is because of, in part, the heterogeneous expression and poor immunogenicity of the viral antigens expressed, namely latent membrane proteins 1 and 2, EBV nuclear antigen 1, and BamHI A rightward reading frame 1 (type-2 [T2] latency). However, EBV lytic cycle proteins are also expressed in certain EBV+ malignancies and, because several EBV lytic cycle proteins are abundantly expressed, have oncogenic activity, and likely contribute to malignancy, we sought and identified viral lytic-cycle transcripts in EBV+ Hodgkin lymphoma biopsies. This provided the rationale for broadening the target antigen–specific repertoire of EBV-specific T cells (EBVSTs) for therapy. We stimulated, peripheral blood mononuclear cells from healthy donors and patients with EBV+ lymphoma with both lytic and latent cycle proteins to produce broad repertoire (BR) EBVSTs. Compared with T2 antigen-specific EBVSTs, BR-EBVSTs more rapidly cleared autologous EBV+ tumors in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice and produced higher levels of proinflammatory cytokines that should reactivate the immunosuppressive tumor microenvironment leading to epitope spreading. Our results confirm that lytic cycle antigens are clinically relevant targets for EBV+ lymphoma and underpin the rationale for integrating BR-EBVSTs as a therapeutic approach for relapsed/refractory EBV+ lymphoma (www.clinicaltrials.gov identifiers: #NCT01555892 and #NCT04664179), as well as for other EBV-associated malignancies.