Toward a paradigm shift in prognostication and treatment of early-stage Hodgkin lymphoma.

Twenty years after the conceptual revolution that occurred in the millennium turnaround upon the introduction of PET/CT in lymphoma staging, restaging, and prognostication, a number of new parameters for PET reading have been proposed: (1) the shift from a qualitative to a semi-quantitative reading for PET reporting, (2) an international consensus on these novel interpretation keys, (3) a standardized and agreed procedure to measure the total metabolic tumour volume (TMTV), and (4) the proposition of new indexes to portray the tumour spread: (D-Max and Total Lesion Surface -TLS). These proved to be very powerful prognosticators, able to revolutionize the traditional Ann Arbor four-stage lymphoma staging. During the 17° Lugano meeting on lymphoma, one main question was asked to experts attending a closed workshop dedicated to new metrics for lymphoma diagnosis, staging, restaging, and prognostication: "Should the traditional 4-stage anatomic staging system be simplified to a more clinically relevant 2-stage system (e.g., limited vs. extensive disease)?" Early-stage HL is an example of how these new metrics could fit with this proposal.

Long-term cause-specific mortality in adolescent and young adult Hodgkin lymphoma patients treated with contemporary regimens-A nationwide Danish cohort study.

The documented treatment-induced excess mortality in Hodgkin lymphoma (HL) has spurred important treatment changes over recent decades. This study aimed to examine mortality among young HL patients treated with contemporary strategies, including historical data comparison. This nationwide study included 1348 HL patients, diagnosed in 1995-2015 and aged 15-40 at diagnosis. Among the patients, 66.5% had Ann Arbor stage I-II and 33.5% had stage III-IV disease. With a median follow-up of 14.76 years, 139 deaths occurred, yielding a 5-year overall survival of 94.6%. Older age, advanced disease, earlier treatment periods and extensive regimens were associated with higher overall mortality risk. The cumulative risk of HL-related death showed an initial sharp rise, with a plateau at 5.3% 10-year post-diagnosis. Deaths due to cardiovascular or pulmonary diseases and second cancers initially had minimal risk, gradually reaching 1.2% and 2.0% at the 20-year mark respectively. HL cases had a 7.5-fold higher mortality hazard than the background population. This study suggests that contemporary HL treatment still poses excess mortality risk, but recent changes have notably reduced overall and cause-specific mortality compared to earlier eras. Balancing treatment efficacy and toxicity remains crucial, but our findings highlight improved outcomes with modern treatment approaches.

Circulating tumor DNA for monitoring classic Hodgkin lymphoma patients: Correlation with FDG-PET/CT.

The value of circulating tumor DNA (ctDNA) as a biomarker of disease activity in classic Hodgkin lymphoma (cHL) patients has not yet been well established. By profiling primary tumors and ctDNA, we identified common variants between primary tumors and longitudinal plasma samples in most of the cases, confirming high spatial and temporal heterogeneity. Although ctDNA analyses mirrored HRS cell genetics overall, the prevalence of variants shows that none of them can be used as a single biomarker. Conversely, the estimation of hGE/mL, based on measures of total ctDNA, reflects disease activity and is almost perfectly correlated with standard parameters such as PET/CT that are associated with refractoriness.

Improved outcomes of large B-cell lymphoma patients treated with CD19 CAR T in the UK over time.

The success of CD19 Chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL) has been partially offset by toxicity and logistical challenges, which off-the-shelf agents like CD20xCD3 bispecific antibodies might potentially overcome. However, when using CAR T outcomes as the 'standard-of-care comparator̕ for relapsed/refractory (r/r) LBCL, a potential learning curve with implementing a novel, complex therapy like CAR T needs to be considered. To address this, we analysed 726 UK patients intended to be treated with CD19 CAR T for r/r LBCL and compared outcomes between the first year of the national CAR T programme (Era 1; 2019) and the more recent treatment era (Era 2; 2020-2022). We identified significant improvements for Era 2 versus Era 1 in dropout rate (17% vs. 27%, p = 0.001), progression-free survival (1-year PFS 50% vs. 32%, p < 0.001) and overall survival (1-year OS 60% vs. 40%, p < 0.001). We also observed increased use of bridging therapy, improvement in bridging outcomes, more tocilizumab/corticosteroid use, reduced high-grade cytokine release syndrome (4% vs. 9%, p = 0.01) and intensive care unit admissions (20% vs. 32%, p = 0.001). Our results demonstrate significant improvement in CAR T outcomes over time, highlighting the importance of using up-to-date clinical data when comparing CAR T against new treatment options for r/r LBCL.

Neurolymphomatosis as an Initial Presentation of Non Hodgkins Lymphoma: A Case Report.

Neurolymphomatosis (NL) is a rare clinical disease where neoplastic cells invade the cranial nerves, roots, plexus, or other peripheral nerves in patients with hematologic malignancy mainly Non-Hodgkins Lymphoma(NHL). Primary NL occurs as the first manifestation of a hematologic malignancy. We report a 68-year male who presented to us with low backache and burning paraesthesia in the back of both lower limbs followed by a left foot drop. The clinical and electrophysiological examination was suggestive of bilateral lumbosacral radiculopathy involving L2-S1 roots. Plain MRI of the lumbosacral spine was normal. F18FDG PET CT Scan revealed increased uptake in both L5 and left L3 roots. Contrast-enhanced MRI of the lumbosacral spine showed marked fusiform thickening and enhancement of both L5 and left L3 roots CT-guided Biopsy from left L5 root, lymph node, and bone marrow was suggestive of large B cell lymphoma-germinal center cell type. The diagnosis was neurolymphomatosis secondary to NHL.

Biclonal Low-Grade B Cell Lymphoma as Detected by Multiparametric Flow Cytometry in Blood and Marrow.

Biclonal B cell lymphomas (BCL) of two different low-grade components are rare. Multiparametric flow cytometry (MFC) is an integral tool in lymphoma diagnosis and very efficient in picking up BCL cases, especially when the associated second component is small. We studied the incidence of BCL in the routine blood and marrow samples sent for immunophenotyping by MFC. A total of 376 cases were analyzed retrospectively. We studied their clinical, immunophenotypic, molecular, and cytogenetic findings with literature review. We found five cases of BCL with two different clonal low-grade B cell components at an incidence of 1.3%. All cases were males with a median age of 68 years. The chronic lymphocytic leukemia (CLL) clone was present in all 5 cases. The other associated component in cases 1 to 5 were lymphoplasmacytic lymphoma, follicular lymphoma, splenic marginal zone lymphoma, hairy cell leukemia, and monoclonal B cell population of non-CLL type respectively. Diagnosing BCL may be challenging and may also go undiagnosed when the second component is petite and overshadowed by the more significant component. It may be critical if the small, unnoticed lymphoma component is of a more aggressive type. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01625-y.

Primary Testicular Non-Hodgkin's Lymphoma With Bilateral Adrenal Metastasis: A Rare Presentation.

Primary testicular lymphoma is the common testicular neoplasm in patients aged more than 65 years. It accounts for a small number of cases of adult testicular malignancies. Though the metastasis to bone marrow, liver, and central nervous system are well known, metastasis to adrenal glands is a very rare entity. It can be mistaken as a germ cell tumor or a dual malignancy. To rule out other causes, a multidisciplinary approach is required. Here, we present a rare case of primary testicular Non-Hodgkin's lymphoma with bilateral adrenal metastasis.

B-Cell Receptor Signaling Is Thought to Be a Bridge between Primary Sjogren Syndrome and Diffuse Large B-Cell Lymphoma.

Primary Sjogren syndrome (pSS) is the second most common autoimmune disorder worldwide, which, in the worst scenario, progresses to Non-Hodgkin Lymphoma (NHL). Despite extensive studies, there is still a lack of knowledge about developing pSS for NHL. This study focused on cells' signaling in pSS progression to the NHL type of diffuse large B-cell lymphoma (DLBCL). Using bulk RNA and single cell analysis, we found five novel pathologic-independent clusters in DLBCL based on cells' signaling. B-cell receptor (BCR) signaling was identified as the only enriched signal in DLBCL and pSS peripheral naive B-cells or salivary gland-infiltrated cells. The evaluation of the genes in association with BCR has revealed that targeting CD79A, CD79B, and LAMTOR4 as the shared genes can provide novel biomarkers for pSS progression into lymphoma.

Final results of a phase II study of CHOEP plus lenalidomide as initial therapy for patients with stage II-IV peripheral T-cell lymphoma.

There remains no one standard induction for nodal-based peripheral T-cell lymphoma (PTCL). We conducted a phase II study of lenalidomide plus CHOEP as a novel induction strategy. Patients received CHOEP at standard doses in combination with 10 mg of lenalidomide on days 1-10 of a 21-day cycle for six cycles of therapy followed by observation, high-dose therapy with autologous stem cell rescue, or maintenance lenalidomide per provider preference. Among 39 patients evaluable for efficacy, the objective response rate after six cycles was 69%, with complete response in 49%, partial response in 21%, stable disease in 0% and progressive disease in 13%. Thirty-two patients (82%) completed full induction, and seven patients (18%) discontinued for toxicity, primarily hematologic. Any grade hematologic toxicity occurred in over 50% of patients, with grade 3 or 4 febrile neutropenia occurring in 35% of patients despite mandated growth factors. With a median followup of surviving patients of 21.3 months, the estimated 2-year progression-free and overall survival were 55% (95% CI 37%-70%) and 78% (95% CI 59%-89%), respectively. In sum, six cycles of lenalidomide plus CHOEP resulted in a modest response rate primarily due to hematologic toxicity, which prevented all patients from completing planned induction.

Traumatic Rupture of Cystic Left Retroperitoneal Mass: An Atypical Presentation of Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Though the presentation is diverse, patients typically have a history of "B" symptoms and lymphadenopathy in areas such as the neck, mediastinum, or abdomen. However, a growing body of evidence suggests DLBCL can present as a cystic mass in diverse tissues. We present the case of a large cystic left retroperitoneal mass of unknown origin in a patient subsequently diagnosed with DLBCL. The diagnosis was obtained via percutaneous biopsy of the cystic mass in preparation for surgical excision. Upon diagnosis, surgical intervention was aborted, and the patient was started on chemotherapy treatment. However, four weeks into her treatment, she slipped and fell while in the bathroom and presented to the emergency department in shock with a computed tomography (CT) scan suggestive of splenic rupture. She underwent emergent splenectomy and resection of the cystic mass. She was discharged on postoperative day 7 and is currently continuing with outpatient chemotherapy. The presentation of DLBCL is notoriously diverse, however, this patient represents a unique presentation that adds to a growing body of literature suggesting DLBCL can present as a cystic mass. Pathological diagnosis should be obtained in all patients with cystic lesions of unknown origin before any surgical intervention to avoid unnecessary surgery and provide an optimal management plan.

Health-related quality of life in early-stage Hodgkin lymphoma: a longitudinal analysis of the ABVD arm in the randomized controlled trial HD.6.

Early-stage Hodgkin lymphoma has become one of the most curable hematologic malignancies. Depending upon the disease location, possible toxicities, and patient preference, chemotherapy alone with ABVD remains an accepted treatment modality for this disease. There remains a paucity of data regarding the longitudinal trajectory of health-related quality of life (HRQoL) in patients treated for HL. The impact of disease and treatment on HRQoL is increasingly important to understand as the number of long-term survivors increases. We report the longitudinal HRQoL using data prospectively collected from diagnosis up to 10 years post-treatment in the ABVD arm of the HD.6 randomized controlled trial for early-stage HL patients (N=169). We analyzed HRQoL using the EORTC QLQ-C30 collected at baseline, 3 months, 6 months, and 12 months after completion of chemotherapy and yearly up to year 10. Clinically and statistically significant improvements were noted for specific domains including emotional (3 months post-treatment), social (12 months post-treatment) and financial functioning (2 years post-treatment), and the specific symptom of fatigue (6 months post-treatment) during the follow-up period. To our knowledge, this is the first prospective, longitudinal analysis of HRQoL specifically among patients with early-stage HL treated with ABVD therapy alone. Although improvements were noted, sustained clinically and statistically significant improvements were noted only in select symptoms emphasizing the need to better understand and optimize HRQoL among this patient group.

Low B-cell content is associated with a CD73-low tumour microenvironment and unfavourable prognosis in classic Hodgkin lymphoma.

B-cell content in the tumour microenvironment (TME) of classic Hodgkin lymphoma (HL) is known to be associated with prognosis. Here we demonstrate that whole slide image analysis using routinely available slides predicts outcomes in patients treated with ABVD in a prospective trial with a high B-cell content being associated with a favourable prognosis. B cells in the TME did not correlate with B cells in peripheral blood. In the TME maturation, stages of B cells (naive and memory) were consistent. However, we detected down-regulation of CD73 in HL with low B cells suggestive of an antibody-independent function of B cells in the TME of HL.

B-cell lymphocytosis in relatives of Colombian patients with chronic B-cell lymphoproliferative disorders / Linfocitosis monoclonal de células B en familiares de pacientes colombianos con síndromes linfoproliferativos crónicos B.

Introduction. Monoclonal B-cell lymphocytosis generally precedes chronic lymphocytic leukemia, affecting about 12% of the healthy adult population. This frequency increases in relatives of patients with chronic B-cell lymphoproliferative disorders. Objective. To determine the frequency of monoclonal B-cell lymphocytosis in relatives of patients with chronic B-cell lymphoproliferative disorders, their immunophenotypic/cytogenetic characteristics, a possible relationship with infectious agents, and short-term follow-up in the Colombian population. Materials and methods. Fifty healthy adults with a family history of chronic B-cell lymphoproliferative disorders were studied using multiparametric flow cytometry, cytogenetic/serological testing, lifestyle survey, and 2-year follow-up. Results. The frequency of monoclonal B-cell lymphocytosis found was 8%, with a predominance of female gender and advanced age, increasing to 12.5% for individuals with a family history of chronic lymphocytic leukemia. Three out of four individuals presented chronic lymphocytic leukemia-type immunophenotype, all with low counts. In turn, a significantly higher number of cells/µl is observed in these individuals in T lymphocyte subpopulations, together with a greater predisposition to the disease. The described clonal populations increase over time in a non-significant manner. Conclusions. The frequency and behavior of monoclonal B-cell lymphocytosis in patients with family history of chronic B-cell lymphoproliferative disorders are like those found in related studies, which suggests that there is no involvement of more relevant genes that can trigger uncontrolled clonal proliferation, but that generates immunological deregulation that could justify a greater risk of serious infection in these individuals.

Introducción. La linfocitosis monoclonal de células B, generalmente, precede la leucemia linfocítica crónica y afecta alrededor del 12 % de la población adulta sana. Esta frecuencia se incrementa en familiares de pacientes con síndromes linfoproliferativos crónicos de células B.Objetivo. Determinar la frecuencia de linfocitosis monoclonal B en familiares de pacientes con síndromes linfoproliferativos crónicos B, sus características inmunofenotípicas y citogenéticas, posible relación con agentes infecciosos, y seguimiento a corto plazo de población colombiana.Materiales y métodos. Se estudiaron 50 adultos sanos con antecedentes familiares de síndromes linfoproliferativos crónicos de célula B, empleando citometría de flujo multiparamétrica, pruebas citogenéticas y serológicas, encuesta de hábitos de vida y seguimiento a dos años.Resultados. La frecuencia encontrada de linfocitosis monoclonal B fue del 8 %, con predominio del sexo femenino y edad avanzada, incrementándose al 12,5 % en individuos con antecedentes familiares de leucemia linfocítica crónica. Tres de cuatro individuos presentaron inmunofenotipo de tipo leucemia linfocítica crónica, todas con bajo recuento. A su vez, en estos individuos se observa de manera significativa un mayor número de células/µl en subpoblaciones linfocitarias T, junto con mayor predisposición a la enfermedad. Las poblaciones clonales descritas aumentan a lo largo del tiempo de manera no significativa.Conclusiones. La frecuencia y comportamiento de la linfocitosis monoclonal de célula B en pacientes con antecedentes familiares de síndromes linfoproliferativos crónicos B es similar a lo encontrado en estudios relacionados,lo que sugiere que no existe afectación degenes de mayor relevancia que puedan desencadenar una proliferación clonal descontrolada, pero que generan desregulación inmunológica que podría indicar un mayor riesgo de infección grave en estos individuos.

Pediatric-type follicular lymphoma: a short review.

Pediatric-type follicular lymphoma is an uncommon and newly recognized entity of lymphoid neoplasm commonly encountered in the young population. Despite its indolent clinical course and localized nodal involvement, it has been characterized by its high-grade histopathological features. The overlapping features between this disease and several entities have made approaching this unique entity significantly challenging, with all such features being reflected in the strict diagnostic criteria highlighted by the WHO 2016 lymphoid malignancy classification. Despite its characteristic high-grade histology, its cure rates have remained high, with relapse and transformation rarely occurring. Interestingly, several cases have achieved remission following nodal disease resection, possibly eliminating the need for chemotherapy and radiation and preventing long-term morbidities from later approaches in disease survivors.

Rapid Progression of Large B-cell Lymphoma in Behçet's Disease on Immunosuppressive Therapy: A Case Report with Literature Review.

Behçet's disease (BD) is a systemic vasculitis characterized by various symptoms, including orogenital ulcers, uveitis, arthritis, skin lesions, and the involvement of the gastrointestinal tract and central nervous system. BD has been associated with malignancies such as leukemia, myelodysplastic syndrome, lymphoma, multiple myeloma, Hodgkin's disease, and lymphosarcoma. The rarity of association with B-cell lymphoma may also be added to the list, given our findings in this case report. Patients with vasculitides benefit from immunosuppressive therapy that can minimize disease and may prevent disease manifestations and exacerbations. However, there may be an increased risk of cancer development, which calls for consideration while starting and maintaining this population of patients on immunosuppressive therapy.

The Association of Epstein-Barr Virus With Cancer.

Epstein-Barr virus (EBV) is classified as a herpesvirus and is known for being one of the few viruses that can lead to the development of cancer. This study has gathered several studies to provide evidence as to this association as well as some of the mechanisms specific to EBV that allow this to happen. The development of EBV into cancer as well as the proteins involved in this oncogenesis play a crucial role in understanding this problem as well as creating a solution for mitigating this disease process in the future. This study summarized three of the most common malignancies caused by EBV in order to consolidate information about each of them. Additional emphasis was placed on finding which EBV serum markers were seen to be most indicative of prognosis and likelihood of developing malignancy. Higher serum EBV viral DNA loads were seen to be a useful indicator in assessing the risk of various cancers and should be studied further in relation to cancers that were not mentioned in this review.

A Comparative Study on Clinico-radiological Differentiation of Sino-nasal Squamous Cell Carcinoma (SCC) and Sino-nasal Non-Hodgkins Lymphoma (NHL).

(1) To compare clinical presentations between sinonasal non-Hodgkins Lymphoma (NHL) and sino-nasal Squamous cell carcinoma (SCC). (2) To compare computed tomographic (CT) scan findings between sino-nasal NHL and sino-nasal SCC. (1) Design: Retrospective Comparative study. (2) Setting: tertiary care hospital. (3) Subjects: patients with histologically proven primary maxillary tumors (NHL and SCC). (4) Method: (a) Patients: medical records between March 2013 to March 2018 were examined and patients with histologically proven primary maxillary tumors (NHL and SCC) were included in the study. (b) CT imaging: unenhanced and contrast enhanced images were obtained for all patients. Unenhanced CT images were reconstructed using bone and soft tissue algorithm. (c) Image Assessment: Predominant growth patterns of the tumors were noted from the CT images. Sino-nasal NHL: 8 men and 3 women; Sino-nasal SCC: 19 men and 5 women. Mean age of the NHL and SCC patients were 66.18 y and 64.88 y respectively. Nasal obstruction, diplopia/blurred vision, nasal/cheek pain and cranial nerve palsies were significantly more common presentation among sino-nasal NHL patients (p values of 0.0053, 0.0014, 0.0089 and 0.0089 respectively). Permeative growth pattern was significantly higher among NHL patients (54.54%) (p value = 0.026) whereas SCCs showed significant destructive growth pattern (83.33%) (p value = 0.0009). Intra-tumoral necrosis was significantly higher in SCC patients (87.5%) (p value = < 0.0001). Nasal obstruction, diplopia/blurred vision, nasal/cheek pain and cranial nerve palsies were the predominant presenting features in sino-nasal NHL patients. In CT imaging, Sino-nasal SCCs showed predominantly destructive growth pattern and intra-tumoral necrosis whereas permeative growth was predominant feature of sino-nasal NHL.

Intracranial lymphoma in human immunodeficiency virus-infected patients: A diagnostic dilemma?

Primary central nervous system (CNS) lymphoma is an aggressive malignancy which constitutes one of the acquired immunodeficiency syndrome -defining illnesses. Early diagnosis and timely management can increase the chances of cure. Although many times the diagnosis is straightforward, we present a case of primary CNS lymphoma in a human immunodeficiency virus--positive individual which posed as a major diagnostic dilemma with initially normal imaging findings. A 42-year-old male presented with unremitting fever and a perianal ulcer for 3 months. A battery of diagnostic tests were negative, including a positron emission tomography-computed tomography scan and a magnetic resonance imaging brain. With unresolving symptoms and a high index of suspicion as he developed dizziness and loss of balance, the same were repeated which confirmed a space-occupying lesion in the cerebellum. Although treatment was instituted, the patient did not recover and died in the 4th month of treatment.

Steroid-Induced Tumor Lysis Syndrome Accompanied by Diabetic Ketoacidosis and Acute Renal Failure in a Non-Hodgkin Lymphoma Patient.

We present a case of a 66-year-old male with a past history of newly diagnosed non-Hodgkin lymphoma, diabetes, and recent surgical splenectomy secondary to splenic infarct who presented to the Emergency Department (ED) with several nonspecific symptoms that were consistent with tumor lysis syndrome. This case report discusses the clinical presentation, diagnosis, and management of spontaneous tumor lysis syndrome.

The Impact of Obesity on Hodgkin's Lymphoma Patients Treated With Uniform Chemotherapy Protocol at Princess Noorah Oncology Center, National Guard Health Affairs, Jeddah, Saudi Arabia: Retrospective Matched Cohort.

Background Hodgkin's lymphoma (HL) is a disease that affects lymphocytes, mostly B cells, and it is commonly diagnosed by the presence of Reed-Sternberg cells. The influence of obesity on the disease course of HL is still controversial. This study's aim was to investigate the treatment outcomes in obese patients suffering from HL and compare them to the outcomes of non-obese patients. Methods This study is a single-center retrospective cohort study that included 280 patients admitted between 2009 and 2020 with different subtypes of HL who received the chemotherapy regimen of Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) at Princess Norah Oncology Center, National Guard Hospital, Jeddah, Saudi Arabia. Based on WHO criteria, the participants were divided into two groups (obese with a BMI that exceeds 30 kg/m2 versus non-obese with any BMI less than 29,9 kg/m2). All demographic data including age, gender, BMI, body surface area (BSA), and HL subtype (nodular sclerosis, mixed cellularity, lymphocyte depletion) were recorded. In addition, the presence of diabetes mellitus (DM), previous cancer, smoking, staging of HL, number of cycles of ABVD, dose intensity of ABVD, and outcomes (emergency visits, death during therapy, primary resistance, relapse) were collected from the participant files. Results Regarding therapy outcomes, 24.1% of obese patients were admitted to the hospital after receiving the first cycle of ABVD as compared to 75.9% of non-obese patients. However, there was no significant statistical difference between obese and non-obese patients in their hospital admission (p value=0.500). In addition, non-obese patients had a higher chance of being admitted to the hospital after receiving the chemotherapy dose with an odds ratio of 1.22 compared to obese patients. For the emergency visits, 20.8% of obese patients were admitted to ER as a complication of the chemotherapy regimen, whereas 79.3% of non-obese patients were admitted to ER after receiving the chemotherapy. The P-value was statistically not significant (0.396), but the odds of ER admissions after ABVD cycles were 1.28 times higher in non-obese patients compared to obese. Conclusion The study outcomes showed a higher odds of hospital admission and ER admission as complications of the chemotherapy regimen in non-obese HL patients as compared to obese patients.