non-Hodgkin Research Articles

Wells Syndrome: A Rare Skin Manifestation of Non-Hodgkin's Lymphoma

Wells Syndrome: A Rare Skin Manifestation of Non-Hodgkin's Lymphoma

Linfoma não Hodgkin da Zona Marginal Extranodal Tipo MALT com Acometimento da Coluna Torácica: revisão Sistemática da Literatura e Relato de Caso em um Hospital Universitário no Brasil

Background: Primary bone lymphomas are rare, accounting for less than 1% of non-Hodgkin's lymphomas (NHL). Extranodal marginal zone non-Hodgkin lymphoma of mucosa-associated lymphoid tissue (MALT) arising in the vertebral spine is extremely rare, with only seven cases reported. Methodology: A systematic literature review was conducted on cases from 2012 to 2022 of extranodal marginal zone MALT lymphoma involving the vertebral spine and associated with spinal cord compression. Additionally, a case report from a university hospital in Rio de Janeiro is described. The study was approved by the Research Ethics Committee (approval number: 5.818.416). Searches were performed in SciELO, PubMed, and LILACS databases, using the Health Sciences Descriptors: ("Vertebral Body" OR Spine) AND ("Lymphoma B-Cell Marginal Zone" OR "MALT Lymphoma" OR "Lymphoma of Mucosa Associated Lymphoid Tissue" OR "Mucosa Associated Lymphoid Tissue Lymphoma"). Articles with full texts available in English or Portuguese were selected. Case Description: A 56-year-old female presented with right-sided back pain, progressing to right flank irradiation, lower limb weakness (LLLL), and constitutional symptoms. MRI revealed a solid extradural mass occupying two-thirds of the vertebral canal's diameter, displacing and compressing the dorsal cord to the left. A bone marrow biopsy confirmed infiltration. Laminectomy was performed, and histopathology identified stage IVB extranodal marginal zone MALT lymphoma. Adjuvant chemotherapy led to complete remission. Results and Discussion: The literature review uncovered two relevant case reports. The thoracic spine was the most commonly affected region, and LLLL weakness was the most frequent symptom, with normal laboratory results. Treatment typically involved surgical tumor removal combined with radiotherapy or chemotherapy. Recurrence occurred in both cases, but follow-up showed no evidence of disease. The clinical presentation and exam findings of the current patient were similar to those in the literature, though with bone marrow infiltration. Treatment was consistent with cases in the review, with no recurrence to date. Conclusion: This case represents an uncommon manifestation of primary extranodal marginal zone MALT lymphoma with spinal cord compression, distinguished by bone marrow infiltration—a feature not previously reported in the two cases found in the literature. The case may be considered within the same group of cases reviewed.

Non-Hodgkin's Lymphoma of the Testis

Non-Hodgkin's Lymphoma of the Testis

The Importance of Real-World Data in Evaluating the Safety of Biosimilars: A Descriptive Study of Clinical Practice in an Oncohematological Italian Population.

The clinical safety and efficacy of rituximab biosimilars compared to the reference rituximab (Mabthera) have been well established in randomized trials. However, concerns persist regarding the safety of changing from the reference product to biosimilars, and particularly between different biosimilars. This prospective multicenter observational study was conducted in 13 oncohematology units of eight Italian regions. The study included 800 patients with non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) who received rituximab between March 2018 and June 2022. To minimize survivorship bias, only newly diagnosed patients (i.e., those without prior rituximab treatment) were included in the analysis of adverse drug reactions (ADRs). Thus, this study focused on 505 incident cases (79.8% of the initial cohort) from 13 centers. A total of 3681 rituximab infusions were administered, and 16.8% of the patients experienced at least one ADR. These were observed most frequently during the first infusion (44 patients, 52%) and the second infusion (17 patients, 20%). The most frequent reactions were general disorders and administration site conditions (n. 50, 8% serious). These findings support the clinical safety of rituximab biosimilars and suggest that switching between biosimilars does not increase the risk of adverse events. This evidence may alleviate concerns about biosimilar use, potentially leading to broader acceptance and reduced healthcare costs.

Risk of second primary cancers in nodal non-hodgkin lymphoma patients by primary lymph node location: A retrospective cohort population-based study

Background: Non-Hodgkin lymphoma is a diverse group of blood cancers with increasing incidence and survival rates due to advancements in treatment and early detection. However, NHL survivors are at significant risk of developing second primary cancers, which can adversely impact their long-term survival. Methods: This retrospective population-based cohort study utilized data from the Surveillance, Epidemiology, and End Results database, covering 17 geographic areas in the United States from 2000 to 2021. We included patients diagnosed with nodal NHL as a first primary cancer and excluded those diagnosed at autopsy or via death certificate only. Standardized Incidence Ratios, Absolute Excess Risks, and Person-Years at Risk were calculated to evaluate the risk of developing SPCs according to the primary lymph node site and stratified by latency periods following the initial NHL diagnosis. Results: The cohort included 54,012 NHL patients. Our results showed that for most SPCs, the risk of development was different for different primary NHL lymph node locations. The highest risks were observed for thyroid cancer, acute myeloid leukemia, and Hodgkin lymphoma. Notably, the risk for thyroid cancer was highest in the first-year post-diagnosis, while hematological malignancies such as acute myeloid leukemia and Hodgkin lymphoma showed elevated risks in the intermediate and late latency periods. Conclusion: NHL survivors are at an increased risk of developing SPCs, influenced by the primary lymph node site and latency period. These findings highlight the need for tailored surveillance strategies and preventive measures to mitigate the long-term risks of SPCs in NHL survivors. Further research is necessary to elucidate the underlying mechanisms and to develop targeted interventions for this high-risk population.

Effects of asparaginase-associated pancreatitis in children with haematological tumours.

Asparaginase-associated pancreatitis (AAP) is a major challenge for continuing asparaginase therapy. We aimed to investigate the acute and long-term complications and survival rates related to first and second AAP episodes in Chinese children with haematological malignancies. We retrospectively analysed clinical data of children with pancreatitis who received asparaginase chemotherapy for acute lymphoblastic leukaemia (ALL), acute mixed cell leukaemia, and non-Hodgkin's lymphoma at Shanghai Children's Medical Center from November 2013 to November 2023. Of the 76 children included in the study, 12 had local complications (15.79%), with no deaths recorded. Systemic complications manifested in 28 patients (36.84%), resulting in 3 deaths (3.95%). Four patients (5.26%) developed long-term complications (chronic pancreatitis or insulin-dependent diabetes mellitus). No significant differences in local or long-term complications were recorded between children in the asparaginase re-exposed (n=39) and non-re-exposed (n=45) groups. Among the re-exposed patients, eight (25.81%) experienced a second attack without fatalities or complications. Survival analysis of intermediate- to high-risk patients revealed a significantly higher event-free survival (EFS) rate for the re-exposed group than for the non-re-exposed group. The second AAP episode's occurrence and severity had no relation to the first AAP episode's severity, and the second AAP episode was significantly less severe than the first (p<0.001). The second AAP episode's occurrence is unrelated to the first AAP episode's severity, and the second AAP episode's severity is significantly lower than that of the first. Further, asparaginase therapy could improve EFS in children with intermediate and high-risk ALL.

MYC-rearranged mature B-cell lymphomas in children and young adults are molecularly Burkitt Lymphoma

Aggressive B-cell non-Hodgkin lymphomas (NHL) in children, adolescents, and young adults (CAYA) include Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and a subset of high-grade tumors with features intermediate between these entities whose genetic and molecular profiles have not been completely elucidated. In this study, we have characterized 37 aggressive B-NHL in CAYA, 33 with high-grade morphology, and 4 DLBCL with MYC rearrangement (MYC-R), using targeted next-generation sequencing and the aggressive lymphoma gene expression germinal center B-cell-like (GCB), activated B-cell-like (ABC), and dark zone signatures (DZsig). Twenty-two tumors had MYC-R without BCL2 breaks, and two MYC-non-R cases had BCL6 translocations. MYC-R cases, including DLBCL, carried BL-related mutations and copy number alterations. Conversely, MYC-non-R lymphomas had alterations in the B-cell receptor signaling/NF-κB pathway (71%). DZsig was expressed in 12/13 of MYC-R tumors but only in 2/10 of MYC-non-R GCB tumors (P < 0.001). The 3-year event-free survival (EFS) of the whole cohort was 79.6%. TP53 and KMT2C mutations conferred inferior outcome (3-year EFS P < 0.05). Overall, MYC-R lymphomas in CAYA have a molecular profile similar to BL regardless of their high-grade or DLBCL morphology, whereas MYC-non-R has more heterogeneous genetic alterations closer to that of DLBCL.

Non-cryopreserved autologous peripheral blood stem cell transplantation for multiple myeloma and lymphoma in countries with limited resources: practice considerations from the Worldwide Network for Blood and Marrow Transplantation.

Autologous peripheral blood stem cell (PBSC) transplantation is a standard treatment of multiple myeloma (MM), Hodgkin lymphoma and various subtypes of non-Hodgkin lymphoma. Cryopreservation of hematopoietic stem cells is standard practice that allows time for delivery of conditioning regimen prior to cell infusion. The aim of this Worldwide Network for Blood & Marrow Transplantation (WBMT) work was to assess existing evidence on non-cryopreserved autologous transplants through a systematic review/meta-analysis, to study feasibility and safety of this approach. We searched PubMed, Web of Science and SCOPUS for studies that utilized non-cryopreserved autologous PBSC transplantation. Identified literature was reviewed for information on mobilization, apheresis, preservation and viability, conditioning regimen, engraftment, response, and survival. Results highlight collective experience from 19 transplant centers (1686 patients), that performed autologous transplants using non-cryopreserved PBSCs. The mean of infused CD34+ was 5.6 × 106/kg. Stem cell viability at transplantation was >90% in MM and >75% in lymphomas, after a storage time of 24-144 h at +4 °C. Mean time-to-neutrophil engraftment was 12 days and 15.3 days for platelets. Pooled proportion estimates of day 100 transplant-related mortality and graft failure were 1% and 0%, respectively. Non-cryopreservation of apheresed autologous PBSCs appears feasible and safe.

Quality of life and late therapy effects in pediatric non-Hodgkin lymphoma survivors: Insights from a single-institution study.

The survival outcomes of pediatric patients with mature B-non-Hodgkin lymphoma (NHL) have improved due to advances in treatment. We aimed to assess the frequency and severity of late effects and their impact on quality of life among pediatric NHL survivors. This retrospective study included patients diagnosed with mature B-NHL at Children's Cancer Hospital of Egypt (CCHE) 57357 from January 2012 through December 2015. Patients received treatment according to the modified LMB 96 protocol. The minimum follow-up period was 5years. Assessments for toxicity and quality of life were conducted at regular intervals during and after treatment. Patients were assessed for toxicity including pulmonary dysfunction, cardiac dysfunction, lipid profile abnormalities, endocrine dysfunction (thyroid function, vitamin D levels, growth curves), and cognitive function (intelligence quotient [IQ] level using Stanford-Binet Intelligence Scales-5th Edition, and quality of life (QoL) assessment (PedsQoL). A total of 273 patients were eligible, and 206 were evaluable. Median age was 5.45 (range: 2.4-18), with a male-to-female ratio 4:1. Pulmonary function abnormalities were detected in 119/203 (58.6%); most had mild dysfunction (72/119, 60.5%), while 17% had severe dysfunction. Cardiac toxicity occurred in 10% of the patients (n=20). IQ testing showed that 52 patients had a low average IQ score, while 151 patients had either average or above average scores. The total mean QoL score was 99±0.058 classified as "satisfactory." However, significant impairment of the physical domain of quality of life was observed among group C patients compared to A/B (p=.033), older age at diagnosis (p=.042), and those with pulmonary dysfunction (p<.001). Total score of quality of life was significantly impaired among patients with pulmonary dysfunction (p=.009), likewise older age at diagnosis (p=.017) and those with low average IQ scores (p=.033). Childhood mature B-NHL survivors are at significant risk for late effects; pulmonary dysfunction and low average IQ that can subsequently impact QoL.

8079 PPI Breaks a Leg! An Unusual Case of Atypical Femur Fracture

Abstract Disclosure: M. Sedghian: None. M. Flanagan: None. D. Pinkhasova: None. K. Selk: None. G. Moloney: None. Background: Atypical femur fractures (AFF) occur along the shaft of the femur extending from the subtrochanteric region proximally to the distal femoral metaphysis. These fractures have an increased incidence in patients taking bisphosphonates and denosumab for osteoporosis and develop as stress reactions in the lateral cortex of the femoral shaft (beaking). However, few cases that meet the characteristics of these fractures have occurred in patients who have never used antiresorptive drugs. We present a case with a history of long-term proton pump inhibitor (PPI) use and possible association with AFF. Clinical Case: The patient is a 68-year-old female with a past medical history of hypothyroidism who presented to the emergency department (ED) after an atraumatic femur fracture and consequently ground level fall. The patient reported experiencing a distinctive cracking sound in her femur while leaning over to wash her feet, resulting in a fall that prompted her to seek immediate care in the ED. Upon initial evaluation, radiographic imaging was significant for displaced left mid-femoral diaphyseal fracture and right femur lateral cortex thickening consistent with AFF. Labs were consistent with elevated PTH to 100.7 [18.4-80.1], Vit D2 1,25 (OH)2 &amp;lt;8 pg/mL, Vit D 25OH 34 ng/ml [30-100], and Calcium level of 9.5. Upon further history taking, the patient stated that she has been taking PPIs intermittently for more than 10 years. She denied a history of bisphosphonate and denosumab exposure, non-Hodgkin's lymphoma, rheumatoid arthritis, and COL1A2 variant mutations as main predisposing factors for atypical femur fractures. She had potential steroid exposure for less than a year before hospitalization as she was on "adrenal complex" from her functional medicine provider. The patient underwent open reduction and internal fixation of the left femur with placement of intramedullary nail and prophylactic fixation with placement of intramedullary nail of the right femur as there was radiographic evidence of beaking. Discussion/Conclusion: Several studies suggested a possible association between PPIs and fracture risk, especially hip fractures, but the relationship remains contentious. Overall, PPIs are positively associated with elevated fracture risk in multiple studies. Increased gastrin production and hypochlorhydria are the two main mechanisms that affect bone remodeling, decreasing bone turnover, impairing calcium absorption, and altering homocysteine levels through impairment of folate and vitamin B12 absorption.This case supports a potential association between long-term PPI use and atypical femur fractures. There have been other case reports that also highlight this potential risk of PPI use. This shows the importance of more comprehensive research on this topic as the number of patients on long-term PPIs is growing in outpatient settings. Presentation: 6/2/2024

Non-Hodgkin Lymphoma Presenting as an Ulcerated Soft Tissue Mass on Left Thigh: A Rare Case Report

Non-Hodgkin Lymphoma Presenting as an Ulcerated Soft Tissue Mass on Left Thigh: A Rare Case Report

Real-World Efficacy and Safety of the Combination of Rituximab, Lenalidomide, and Ibrutinib in Patients with Relapsed and/or Refractory Non-Hodgkin Lymphoma

Real-World Efficacy and Safety of the Combination of Rituximab, Lenalidomide, and Ibrutinib in Patients with Relapsed and/or Refractory Non-Hodgkin Lymphoma

The Landscape of Cutaneous T-Cell Lymphoma (CTCL) in the Middle East and North Africa (MENA) and the Establishment of the MENA CTCL Working Group

The high cancer burden in the Middle East and North Africa (MENA region) is coupled with an increasing cancer incidence. While the MENA region constitutes 6% of the world’s population, it remains underrepresented in clinical trials. Cutaneous T-cell lymphomas (CTCLs) represent a heterogeneous group of rare extranodal non-Hodgkin lymphomas with variable clinical presentation. In the MENA region, where darker skin colors are more common than in the West, CTCL generally presents at a younger age and with distinct clinical features that necessitate special expertise and management across disciplines: rare forms of CTCL are more common (hypo- and hyperpigmented MF) and a higher prevalence of pediatric MF is noticed. The multidisciplinary approach to cancer management is growing worldwide and is necessary for the comprehensive management of CTCL. The MENA CTCL group was established with the aim of creating a collaborative environment for the diagnosis and treatment of CTCL in the region. Its first meeting was held in May 2023. The group plans to increase the global representation of the MENA region and establish CTCL registries and patient advocacy groups in the region.

Serum concentrations of per- and polyfluorinated substances and risk of B-cell non-Hodgkin lymphoma

Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants that are detectable in the serum of most U.S. adults. Some studies of highly-exposed individuals have suggested positive associations between PFAS and B-cell non-Hodgkin lymphoma (B-NHL). To investigate whether associations exist at lower exposure levels, we conducted a nested case-control study investigating serum PFAS concentrations and B-NHL within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We measured pre-diagnostic serum concentrations of five PFAS among 706 cases (age at diagnosis = 55–93 years, median 73 years) and 706 controls individually matched on age at blood draw, sex, self-reported race and ethnicity, study center, and year of blood collection (the median follow-up years = 10). We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for PFAS concentrations in relation to B-NHL, both overall and for selected histologic subtypes [diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), and marginal zone lymphoma (MZL)] using conditional logistic regression. We found no evidence of a positive association with B-NHL for any of the five PFAS. In analyses of histologic subtypes, perfluorohexane sulfonate (PFHxS) was significantly associated with DLBCL in a model adjusting for all other PFAS (OR for highest vs. lowest quintile = 2.19, 95 % CI = 1.21, 3.95; Ptrend = 0.02), but not in a model without mutual adjustment (OR = 1.37, 95 % CI = 0.82, 2.29; Ptrend = 0.26). We also observed an inverse association between perfluorononanoate and DLBCL (mutually-adjusted OR = 0.83, 95 % CI = 0.69, 0.99 per doubling in concentration), although the association was null among participants with blood drawn prior to 1997 (OR<1997 = 1.00, 95 % CI = 0.82, 1.21; OR≥1997 = 0.65, 95 % CI = 0.53, 0.79; Pinteraction = 0.0003). In conclusion, our findings from a prospective cohort study with PFAS serum concentrations comparable to that of the general population do not support an association with increased risk of B-NHL overall. The suggestive evidence of a positive association between PFHxS and DLBCL warrants further investigation.

Unraveling the role of hepatitis B virus DNA integration in B-cell lymphomagenesis.

Studies have shown that hepatitis B virus (HBV)-associated B-cell non-Hodgkin lymphoma (NHL) constitutes a unique subgroup with distinct clinical features. It still leaves open the question of whether the integration of HBV DNA into the B-cell genome is a causal mechanism in the development of lymphoma. Using the hybridisation capture-based next generation sequencing and RNA sequencing, we characterised the HBV integration pattern in 45 HBV-associated B-cell NHL tumour tissues. A total of 354 HBV integration sites were identified in 13 (28.9%) samples, indicating the relatively low integration frequency in B-cell NHLs. High plasma HBV DNA loads were not associated with the existence of HBV integration. The insertion sites distributed randomly across all the lymphoma genome without any preferential hotspot neither at the chromosomal level nor at the genetic level. Intriguingly, most HBV integrations were nonclonal in B-cell NHLs, implying that they did not confer a survival advantage. Analysis of the paired diagnosis-relapse samples showed the unstable status of HBV integrations during disease progression. Furthermore, transcriptomic analysis revealed the limited biological impact of HBV integration. Our study provides an unbiased HBV integration map in B-cell NHLs, revealing the insignificant role of HBV DNA integration in B-cell lymphomagenesis.

Aberrant CD45 Immunoreactivity in Neuroendocrine Neoplasms: A Diagnostic Pitfall-Report of 10 Specimens and Clinical Recommendations.

Leukocyte common antigen (LCA), or CD45, is classically thought of as a leukocyte-exclusive protein, and as such, CD45 immunohistochemistry (IHC) is often used as a key differentiator between non-Hodgkin lymphomas (NHLs) and morphologically similar neuroendocrine neoplasms (NENs). Herein, we report our experience regarding aberrant CD45 immunoreactivity in a series of NENs. A natural language search was used to retrieve desired archival patient files. All prior NENs which had a positive neuroendocrine diagnosis or IHC results (synaptophysin, chromogranin, CD56, and/or neuron-specific enolase), as well as CD45 staining performed, were reviewed for possible CD45 positivity (n = 686). Among these 686 NENs, 10 were aberrantly positive for CD45 staining. CD45 showed nuclear, cytoplasmic, and/or membranous staining in tumor cells. The significance of such staining is unclear. Albeit for a minority of patients, pathologists should be aware that NENs may aberrantly stain with CD45 and thereby pose a diagnostic pitfall. Therefore, broadening routine IHC panels is recommended to differentiate NENs more clearly from NHLs.

Tattoos and Risk of Hematologic Cancer: A Population-Based Case-Control Study in Utah.

Approximately one-third of US adults have a tattoo, and the prevalence is increasing. Tattooing can result in long-term exposure to carcinogens and inflammatory and immune responses. We examined tattooing and risk of hematologic cancers in a population-based case-control study with 820 cases diagnosed 2019-2021 and 8200 frequency-matched controls, ages 18-79 years. We calculated odds ratios (OR) and 95% confidence intervals (CI) using multivariable-adjusted logistic regression models. The prevalence of tattooing was 22% among Hodgkin lymphoma (HL) cases, 11% among non-Hodgkin lymphoma (NHL) cases, 16% among myeloid neoplasm cases, and 15% among controls. Though there were no clear patterns of associations between ever receiving a tattoo and risk of HL, NHL, or myeloid neoplasms overall, in analyses restricted to ages 20-60 years, ever receiving a tattoo (OR 2.06 [95% CI 1.01, 4.20]) and receiving a tattoo 10+ years prior (OR 2.64 [95% CI 1.23, 5.68]) were associated with an aggregated group of rarer mature B-cell NHLs. We also observed elevated risks for a 10+ year latency for myelodysplastic syndromes and chronic myeloid leukemia (OR 1.48 [95% CI 0.40, 5.41], and OR 1.24 [95% CI 0.45, 3.43], respectively). Though estimates were imprecise, we found some suggestive evidence that tattooing may be associated with an increased risk of certain hematologic cancer subtypes. With an estimated 46% prevalence of tattooing in US individuals ages 30-49, additional studies are needed to understand the degree to which these exposures may be associated with hematologic cancer risk.

459 (PB447): Fibrinogen-like protein 2 (FGL2) is a multifaceted immune checkpoint with potential therapeutic application in B-cell non-Hodgkin Lymphomas

459 (PB447): Fibrinogen-like protein 2 (FGL2) is a multifaceted immune checkpoint with potential therapeutic application in B-cell non-Hodgkin Lymphomas

368 (PB356): Design and functional characterization of a first-in-class irreversible inhibitor of HOIL-1-interacting protein (HOIP) with selective antitumor activity against B-cell non-Hodgkin lymphoma

368 (PB356): Design and functional characterization of a first-in-class irreversible inhibitor of HOIL-1-interacting protein (HOIP) with selective antitumor activity against B-cell non-Hodgkin lymphoma

201 (PB189): Different expression of CDK4 and CDK6 among B-cell non-Hodgkin lymphomas as a marker of sensitivity to CDK4/6 inhibitors

201 (PB189): Different expression of CDK4 and CDK6 among B-cell non-Hodgkin lymphomas as a marker of sensitivity to CDK4/6 inhibitors