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Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of B-cell non-Hodgkin's lymphoma (NHL), up to 30%–40% of patients will relapse and 10%–15% of patients have primary refractory disease, so exploring new treatment options is necessary. Ferroptosis is a non-apoptotic cell death mode discovered in recent years. Its occurrence pathway plays an essential impact on the therapeutic effect of tumors. Numerous studies have shown that modulating critical factors in the ferroptosis pathway can influence the growth of tumor cells in hematological malignancies including DLBCL. This review highlights recent advances in ferroptosis-related genes (FRGs), including STAT3, Nrf2, and ZEB1, and focuses on the clinical potential of ferroptosis inducers such as IKE, α-KG, DMF, and APR-246, which are currently being explored in clinical studies for their therapeutic effects in DLBCL. Correlational studies provide a novel idea for the research and treatment of ferroptosis in DLBCL and other hematological malignancies and lay a solid foundation for future studies. [ABSTRACT FROM AUTHOR]

Objective: Patients with hematological malignancies have an elevated risk of developing pneumonia after contracting COVID-19. Lymphoma is the most prevalent hematologic malignancy. It is critical to identify patients at high risk of contracting COVID-19-associated pneumonia. Methods: From January 11–31, 2023, we distributed questionnaires to patients diagnosed with lymphoma according to 2016 World Health Organization diagnostic and classification criteria. COVID-19 infection was confirmed based on symptoms and laboratory tests. Pneumonia was confirmed using computed tomography scans. Results: In total, 257 patients were included in this study; 221 patients (86.0%) had COVID-19 infection and 61 (27.6%) of these had pneumonia. Patients with B-cell non-Hodgkin lymphoma (B-NHL) had a significantly higher pneumonia incidence than patients with other lymphoma types (31.8% vs. 27.6%, P=0.005). Higher incidence of pneumonia was observed in patients receiving anti-CD20 therapy (30.0% vs. 16.3%, P=0.048) and Bruton's tyrosine kinase (BTK) inhibitor therapy (51.3% vs. 22.5%, P=0.001). B-NHL (hazard ratio [HR]=3.7, 95% confidence interval [CI] 1.4–10.0, P=0.009), anti-CD20 therapy (HR=2.3, 95% CI 1.0–5.2, P=0.050), BTK inhibitor (HR=3.6, 95% CI 1.8–7.4, P<0.001), active therapy (HR=3.0, 95% CI 1.5–5.7, P=0.001), and lack of disease remission (HR=3.7, 95% CI 1.8–7.4, P=0.001) were high-risk factors for developing pneumonia. Anti-PD-1 therapy was a protective factor against pneumonia development (HR=0.2, 95% CI 0.05–0.9, P=0.034). In multivariable analysis, BTK inhibitor (HR=3.5, 95% CI 1.6–8.0, P=0.003), active therapy (HR=3.3, 95% CI 1.6–6.8, P=0.001), and disease non-remission (HR=2.9, 1.3–6.4, P=0.007) were independent risk factors for pneumonia development after COVID-19 infection in patients with lymphoma. Conclusions: Patients with lymphoma receiving BTK inhibitors, undergoing active therapy, and lacking disease remission exhibited a higher risk for pneumonia associated with COVID-19. [ABSTRACT FROM AUTHOR]

This study examines remaining life expectancy (RLE) after a cancer diagnosis, focusing on age, sex, cancer type, and metabolic syndrome (MS) components, using data from the SIDIAP database in Catalonia (2006–2017). RLE was analyzed for 13 cancer types, stratified by sex and MS components. The cohort study includes 183,364 individuals followed from diagnosis until death, transfer, or study end (December 2017). RLE at age 68 (median diagnosis age) was calculated based on MS components (0, 1, 2, and ≥ 3). Men aged 68 with 0 MS components had an RLE of 13.2 years, compared to 8.9 years for those with ≥ 3 MS. Women had an RLE of 15.9 years with 0 MS components versus 11.4 years with ≥ 3 MS. RLE varied by cancer type, with the highest RLE in men seen in prostate cancer and in women in non-Hodgkin lymphoma. The lowest RLE for both sexes was in pancreatic cancer. The largest differences between 0 and ≥ 3 MS components were observed in non-Hodgkin lymphoma and the smallest in pancreatic cancer. Increased MS components were associated with reduced RLE in at least 8 cancer types for men and 9 for women. Prevention strategies targeting MS components could increase RLE in cancer patients. [ABSTRACT FROM AUTHOR]

Background To assess population-based quality of cancer care in sub-Saharan Africa and to identify specific gaps and joint opportunities, we assessed concordance of diagnostics and treatments with National Comprehensive Cancer Network Harmonized Guidelines for leading cancer types in 10 countries. Methods Adult patients with female breast cancer, cervical cancer, colorectal cancer, non-Hodgkin lymphoma, and prostate cancer were randomly drawn from 11 population-based cancer registries. Guideline concordance of diagnostics and treatment was assessed using clinical records. In a subcohort of 906 patients with potentially curable cancer (stage I-III breast cancer, cervical cancer, colorectal cancer, prostate cancer, aggressive non-Hodgkin lymphoma [any stage]) and documentation for more than 1 month after diagnosis, we estimated factors associated with guideline-concordant treatment or minor deviations. Results Diagnostic information based on guidelines was complete for 1030 (31.7%) of a total of 3246 patients included. In the subcohort with curable cancer, guideline-concordant treatment was documented in 374 (41.3%, corresponding to 11.7% of 3246 patients included in the population-based cohort): aggressive non-Hodgkin lymphoma (59.8%/9.1% population based), breast cancer (54.5%/19.0%), prostate cancer (39.0%/6.1%), colorectal cancer (33.9%/9.5%), and cervical cancer (27.8%/11.6%). Guideline-concordant treatment was most frequent in Namibia (73.1% of the curable cancer subcohort/32.8% population based) and lowest in Kampala, Uganda (13.5%/3.1%). Guideline-concordant treatment was negatively associated with poor ECOG-ACRIN performance status, locally advanced disease stage, origin from low Human Development Index countries, and a diagnosis of colorectal cancer or cervical cancer. Conclusions The quality of diagnostic workup and treatment showed major deficits, with considerable disparities among countries and cancer types. Improved diagnostic services are necessary to increase the share of curable cancer in sub-Saharan Africa. Treatment components within National Comprehensive Cancer Network Guidelines for several cancers should be prioritized. [ABSTRACT FROM AUTHOR]

AbstractFollicular lymphoma (FL) represents the second most frequent type of non-Hodgkin lymphoma and the most common indolent histology. The disease course of FL is heterogeneous, likely resulting from diverse molecular and immunological features that drive a broad spectrum of clinical presentations. While some patients with low-volume and asymptomatic disease are suitable for observation, patients with high tumor burden, advanced-stage, or symptomatic disease more often necessitate treatment initiation. The decision to begin therapy is personalized and typically initiated when GELF criteria are met. The introduction of novel agents has modified the treatment landscape for FL, allowing for more personalized strategies based on the specific characteristics of patients and diseases. In this review, we discuss the indications for treatment initiation and optimization, focusing on long-term follow-up of pivotal studies and emerging non-chemotherapy regimens. We further consider effective novel combination regimens and future directions for the evolution of frontline immunotherapy for the treatment of patients with FL. [ABSTRACT FROM AUTHOR]

Primary uterine non-Hodgkin lymphoma (NHL) is rarely reported, as its incidence is extremely low. We describe a 72 year old patient with primary uterine non-Hodgkin's lymphoma stage IV, diffuse B-cell large cells, who responded well to cytotoxic chemotherapy (R-CHOP). Radiological investigations exhibited certain characteristics, including magnetic resonance T2 weighted imaging, enhanced scanning, diffusion weighted imaging and apparent diffusion coefficient values. The lesion in the anterior wall of the uterine body was relatively large, with a size of about 34mm×47mm×43mm. The gold standard for diagnosis is still the pathological examination of a biopsy specimen, which revealed diffuse large cell of B lineage. This article reviews data collected from 141 patients in the literature. [ABSTRACT FROM AUTHOR]

Maternal immunization is an important tool directed against a variety of infectious maladies in the offspring. A complementary, but less explored area is the use of maternal immunization in the prevention and treatment of childhood cancers. This in part stems from the lack of adequate experimental model systems. Lymphomas of the Central Nervous System (CNS) and ocular involvement pose a therapeutic challenge. Ocular lymphoma is a lethal disease caused mainly by two clinically distinct forms of non-Hodgkin's lymphoma: non-Hodgkin's lymphoma of the central nervous system, or Primary CNS lymphoma (PCNSL), and systemic lymphoma metastatic to the eye. Previously, we developed an experimental model whereby mouse lymphoma cell variants, derived from the S49 T-cell lymphoma, metastasized to the CNS and eyes following Intraperitoneal inoculation at days 7-10 postnatal. Here, we extended the model to study whether maternal immunization can impede CNS/Ocular metastasis in the offspring exposed to the metastatic lymphoma cells. To that effect, female Balb/C mice were vaccinated with either immunogenic, live, S49 lymphoma cell variants, or with a purified protein antigen: the 98 amino acid signal peptide of the envelop precursor protein of Mouse Mammary Tumor Virus (MMTV) endogenously harbored by the S49 lymphoma. The offspring from both vaccination protocols were immunized against a challenge with the CNS/Ocular metastatic lymphoma cells. Immunity was conferred via milk suckling and was prolonged without further challenge for an extended period of at least 3 months. The abovementioned findings constitute a novel experimental model system whereby CNS/Ocular metastasis of malignant lymphoma in the offspring is impeded through maternal vaccination/immunization and thus, can be followed mechanistically as well as for novel therapeutic modalities. [ABSTRACT FROM AUTHOR]

AbstractNodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity accounting for ≈5% of all Hodgkin lymphoma (HL) cases. As some characteristics of NLPHL resemble B-cell non-Hodgkin lymphoma (B-NHL), nodular lymphocyte-predominant B-cell lymphoma has been proposed as alternative name. Unlike classical HL (cHL), NLPHL is mostly diagnosed in early stages. The clinical course is usually indolent. Overall, NLPHL patients have an excellent prognosis and the majority experiences long-term survival. Except for stage IA disease which is sufficiently treated with radiotherapy alone, treatment of newly diagnosed NLPHL is often very similar to cHL. However, activity has also been demonstrated for rituximab-containing protocols applied in B-NHL. Second-line treatment is chosen individually and mostly less intensive than in cHL. Chimeric antigen receptor T-cell therapy and bispecific antibodies may be part of future treatment strategies for NLPHL. This review aims at summarizing recent data on treatment approaches and discussing future perspectives in NLPHL. [ABSTRACT FROM AUTHOR]

Preface and importance: Burkitt's lymphoma (BL) is a relatively rare post-transplant lymphoproliferative disorder (PTLD), and there is currently limited research on the occurrence of BL following adult liver transplantation. Case introduction: We report a 45-year-old male who developed BL that rapidly progressed at seven years after left liver transplantation. The patient eventually abandoned treatment due to severe clinical complications. Clinical discussion: BL is a highly invasive B-cell-derived non-Hodgkin lymphoma (NHL), with fast progression and easy involvement of the central nervous system. The current case had sporadic BL with atypical site of onset. After analysis, the investigators considered the possible development of tumor lysis syndrome (TLS) in the later stage of hospitalization, which is a more serious complication of BL. There is currently no unified treatment plan for adult BL. Conclusion: BL is a relatively rare complication after liver transplantation, and its early detection and treatment are crucial. For advanced BL, attention should be given in preventing the occurrence of TLS. Further research and exploration are needed to determine the optimal treatment plan for adult BL. [ABSTRACT FROM AUTHOR]

Introduction: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of non-Hodgkin lymphoma with a good prognosis, but the optimal treatment for relapsed/refractory (R/R) SPTCL has been rarely discussed. Methods: This study aims to compare the efficacy of conventional chemotherapy and chemo-free immunomodulatory regimen for R/R SPTCL. We retrospectively reviewed the patients with first relapse or primary refractory SPTCL between September 1997 and October 2020. Results: A total of 19 patients with R/R SPTCL with a median age of 34 were included. All patient received the first-line chemotherapy-based treatment with a median PFS of 1.8 months. In these patients, 16 received salvage second-line treatment with an ORR of 31.3% and a median TTNT of 3.0 months. 13 of these 16 patients received chemotherapy-based treatment, resulting in a median TTNT of 2.4 months. 2 of these 16 patients received allogeneic hematopoietic stem cell transplantation and achieved long term complete remission (CR). In third-line treatment, 7 patients received chemotherapy-based regimen and 6 received chemo-free regimen such as VRMP (bortezomib, lenadomide and methylprednisolone) regimen and CsA plus IFNα regimen. The median TTNT of chemotherapy and chemo-free group were 3.2 months and not reached, respectively. Discussion: Chemo-free group had a better TTNT than chemotherapy group (p=0.007). The use of chemotherapy-free regimens for R/R SPTCL appears promising and warrants further validation. [ABSTRACT FROM AUTHOR]

Background: Amulirafusp alfa (IMM0306) is a fusion protein of CD47 binding domain of signal-regulatory protein alpha (SIRPα) with CD20 monoclonal antibody on both heavy chains. This study aimed to evaluate the safety and preliminary efficacy of amulirafusp alfa in relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). Methods: We enrolled patients with CD20 + r/r B-NHL who had previously received at least two lines of therapy to receive a single-dose of amulirafusp alfa in the first 2 weeks, followed by a multiple-dose period, in which the patients received the same intravenous dose every week in 4-week cycles. The primary endpoints were to evaluate the safety, determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of amulirafusp alfa. Results: Between May 22, 2020 and February 10, 2022, 48 patients with r/r B-NHL were enrolled and received amulirafusp alfa at the doses of 40–2000 μg/kg. As of the data cut-off date of April 18, 2024, no dose-limiting toxicity was observed, and the MTD was not reached. The dose of 2000 μg/kg was identified as the RP2D. All grades and ≥ grade 3 treatment-related adverse events (TRAEs) occurred in 48 (100%) and 33 (68.8%) patients, respectively. The most common ≥ grade 3 TRAEs were lymphocyte count decreased (28/48, 58.3%), white blood cell count decreased (10/48, 20.8%), absolute neutrophil count decreased (9/48, 18.8%) and anemia (5/48, 10.4%). At the doses of 800–2000 μg/kg, objective response rate in follicular lymphoma and marginal zone lymphoma was 41.2% (7/17, 95% confidence interval [CI] 18.4–67.1) and 33.3% (2/6, 95% CI 3.7–71.0), respectively. Conclusion: Amulirafusp alfa showed favorable safety profile and preliminary efficacy in patients with r/r B-NHL, meriting further investigation. Trial registration NCT05805943. [ABSTRACT FROM AUTHOR]

The document discusses the challenges pathologists face in diagnosing Burkitt lymphoma (BL) due to its strict criteria and similarities with other lymphomas like diffuse large B-cell lymphoma (DLBCL). A study involving experienced hematopathologists revealed significant variability in BL diagnosis, with shifts in diagnosis based on morphology, immunophenotype, genotype, and clinical context. The study highlights the need for additional techniques to improve the accuracy of BL diagnosis and emphasizes the importance of multidisciplinary approaches in treatment decisions for individual patients. [Extracted from the article]

Background/Objectives: ACE (angiotensin-converting enzyme) is considered a serological marker of sarcoidosis as elevated levels have been reported in 30–80% of patients. However, elevated ACE levels are also encountered in other medical conditions, and the clinical correlation between ACE levels and disease activity in sarcoidosis is disputable as well. To determine the significance of elevated ACE levels in the diagnosis and follow-up of sarcoidosis patients. Methods: All electronic patient records in which an ACE level was recorded in a large tertiary hospital were identified using a computerized algorithm. Medical diagnoses, ACE numerical values, and clinical data were also automatically extracted. Furthermore, all records with a diagnosis of sarcoidosis were manually reviewed for ascertainment of the diagnosis and searched for additional clinical manifestations and treatment responses. Results: A total of 1416 records with a documented ACE level were found in the database, and 146 of the records had a diagnosis of sarcoidosis in the medical record. However, the diagnosis was excluded in 27 of these cases after a manual review of the records. Elevated ACE levels were most commonly encountered among patients with sarcoidosis, non-Hodgkin's lymphoma, cirrhosis, and interstitial lung disease. Elevated ACE levels had a positive predictive value of 12.76% and a negative predictive value of 94.6% for the diagnosis of sarcoidosis in our cohort, with a sensitivity of 63.5% and a specificity of 59.5%. Among patients with sarcoidosis, ACE levels around the time of diagnosis were higher than ACE levels in remission. However, a paired analysis did not find a statistically significant difference in ACE levels between the two timepoints. A positive correlation between lack of cardiac involvement and elevated ACE levels was found on multivariate analysis. Conclusions: ACE levels are a non-specific serological marker with low specificity and sensitivity for sarcoidosis and a poor positive predictive value, but with a negative predictive value of 94.6%. Furthermore, elevated ACE levels correlated poorly with disease activity in our cohort. [ABSTRACT FROM AUTHOR]

Simple Summary: The mantle cell lymphoma field has advanced significantly due to ongoing developments in molecular pathogenesis prediction and novel therapeutic approaches. The area has undergone a revolution with the development of Bruton tyrosine kinase inhibitors, which are now the cornerstone of R/R MCL therapy. Developing and implementing new targeted and combination approaches has already improved therapeutic options, especially for refractory or relapsed diseases. Background/Objectives: Aurora (AK) A/B are oncogenic mitotic kinases that when over-expressed are poor prognostic markers in mantle cell lymphoma (MCL). Methods and Results: Alisertib, an AK-A inhibitor, has anti-tumor activity in relapsed/refractory (r/r) MCL patients. We evaluated alisertib plus ibrutinib in MCL to abrogate ibrutinib resistance. Alisertib plus ibrutinib was therapeutically synergistic on both Granta-519 insensitive to ibrutinib and JeKo-1 cells sensitive to ibrutinib. Alisertib decreased PI-3K, BTK, p38, HCK, and RSK kinases, indicative of its multipotent effect on cellular proliferation and growth. A mouse xenograft model of Granta-519 demonstrated that alisertib plus ibrutinib had a comparable anti-tumor response to ibrutinib plus rituximab. However, alisertib plus ibrutinib plus rituximab demonstrated significantly stronger tumor growth inhibition than the doublets. Conclusions: Both double and triple combinations showed enhanced survival versus ibrutinib alone. Ibrutinib insensitivity can be disrupted by alisertib plus ibrutinib in MCL. [ABSTRACT FROM AUTHOR]

Simple Summary: This research explores the role of different methods for assessing bone marrow infiltration (BMI) in mantle cell lymphoma (MCL) during initial diagnosis. Traditional bone marrow biopsy (BMB) is a standard procedure, but newer imaging techniques like PET/CT scans may offer additional or alternative insights. Our study aims to clarify the diagnostic accuracy and prognostic value of these methods, both individually and in combination, for predicting patient outcomes. We propose a new prognostic model that integrates PET/CT results, which could improve the ability to classify patients by risk. The findings may impact clinical approaches by guiding better-informed decisions in MCL diagnosis and prognosis. Background: Assessment of bone marrow infiltration (BMI) is part of the initial staging of mantle cell lymphoma (MCL), although BMI evaluated by biopsy (BMB) is not considered significant in the MIPI scales, and standardized recommendations remain lacking. Objectives: To evaluate the accuracy and prognostic impact of BMI assessed by PET/CT and BMB in a large series of MCL patients. Methods: We deconstructed the IPI-NCCN, MIPI, and MIPI-c indices and considered BMI as positive if indicated by a BMB, PET/CT scan, or a combination of both. Results: In the total cohort (n = 148), 110 patients had BMI detected by BMB and 33 by PET/CT. The sensitivity of BMB was higher than that of PET/CT (94.8% vs. 28.4%), as were its negative predictive value (84.2% vs. 27.8%) and accuracy (95.9% vs. 43.9%). In the total cohort, BMI detected by PET/CT showed a significant predictive value for PFS (p = 0.027), while BMB demonstrated independent prognostic value only in combination with PET/CT (p = 0.025). Among intensively treated patients (n = 128), PET/CT had significant clinical impact on PFS (p = 0.030), and when combined with BMB, it provided independent prognostic value for both PFS and OS (p = 0.026 and p = 0.033, respectively). Based on these findings, we propose a prognostic model (MCL-PET-I) that incorporates BMI by PET/CT, allowing for the identification of three groups with distinct clinical outcomes (p < 0.0001 for PFS and p = 0.00025 for OS). Conclusions: In the upfront work of MCL, PET/CT-based BMI has greater prognostic impact, while BMB remains essential for staging. We propose the MCL-PET-I prognostic index, which effectively differentiates between clinical risk groups. [ABSTRACT FROM AUTHOR]

Simple Summary: This prospective study evaluated the prognostic value of selected tools from the comprehensive geriatric assessment (CGA) in elderly patients with diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) treated with R-CHOP or R-CHOP-like regimens. A total of 62 patients were included in the analysis. The findings indicated that the Lawton Instrumental Activities of Daily Living (iADL) scale was a significant predictor of adverse events and treatment outcomes in this patient population. Background: The prognostic value of the comprehensive geriatric assessment (CGA) is recognized by many in hematology. However, there is no consensus on the utilization of alternative abbreviated methods to assess disabilities in elderly patients with B-cell non-Hodgkin's lymphomas (B-NHLs). Aim: The aim of this study was to prospectively analyze the prognostic value of selected CGA tools in predicting adverse events (AEs) and outcomes of R-CHOP or R-CHOP-like treatment in elderly patients with diffuse large B-cell lymphomas (DLBCLs) or mantle cell lymphomas (MCLs). Methods: All patients who participated in this study underwent the Katz Index of Independence in Activities of Daily Living (ADL), the Lawton Instrumental Activities of Daily Living (iADL) scale, the Vulnerable Elders Survey-13 (VES-13), the Groningen Frailty Index (GFI), and the Mini Nutritional Assessment Short Form (MNA-SF) before starting anticancer treatment. Selected clinical predictors were also included in the study. Results: A total of 62 patients with newly diagnosed DLBCLs or MCLs, treated with R-CHOP in the Department of Hematology, Blood Neoplasm and Bone Marrow Transplantation of Wroclaw University Hospital between 1 July 2018, and 1 July 2020, were included in the study. The median age upon initiation of the treatment was 72 years (range: 61–68). Multinomial logistic regression and Cox proportional hazard regression analysis demonstrated that the iADL scale was significantly associated with response to treatment (OR = 1.21, 95% CI: 1.02–1.44, p = 0.03), was inversely related to non-hematological AEs (OR = 0.81, 95% CI: 0.71–0.92, p = 0.001), and was a statistically significant predictor of longer overall survival (OS) (HR = 0.83, 95% CI: 0.79–0.89, p < 0.001) and longer progression-free survival (PFS) (HR = 0.91, 95% CI: 0.83–0.99, p = 0.03). Conclusions: These results underscore the effectiveness of the iADL scale as a quick, easy-to-use, and universal CGA tool for evaluating crucial functional status before treatment in elderly hematological patients with DLBCLs or MCLs. [ABSTRACT FROM AUTHOR]

Summary: The clinical and prognostic implications of nodal involvement (NI) in Waldenström macroglobulinaemia (WM) are largely unknown. In this study, we explored the impact of NI on clinical presentation and outcome in a population‐based cohort of 469 patients with WM, consecutively diagnosed between 2000 and 2022. NI was detected in 34% of patients and was associated with symptomatic disease, adverse prognostic factors, an increased risk of transformation, and lymphoma‐related death. Our findings indicate that NI is of prognostic significance in WM, suggesting a need for enhanced surveillance in these patients. [ABSTRACT FROM AUTHOR]

AbstractMantle cell lymphoma (MCL) is a rare, incurable B-cell non-Hodgkin lymphoma and over half of patients affected are older adults (≥65 years of age). New targeted treatments for MCL have emerged over the past two decades. Nonetheless, MCL-specific death rates for older adults remain elevated compared with younger adults, demonstrating the challenge of treating this population. The older adult population is at risk for overtreatment or undertreatment. Clinicians must be mindful of how to optimize the holistic care of older adults receiving treatment for MCL. Evaluating fitness through a geriatric assessment (GA) is an important step when choosing therapy. The treatment armamentarium includes both chemotherapy and non-chemotherapy options and toxicities must be considered in the context of the patient’s GA and proactively managed. Herein, the treatment of MCL in older adults is reviewed and strategies for choosing treatment are offered to assist in treatment decision-making for this challenging population. [ABSTRACT FROM AUTHOR]

Combination antiretroviral therapy (ART) has improved outcomes for human immunodeficiency virus (HIV) associated non-Hodgkin lymphoma. This is an analysis of 127 patients with HIV with Burkitt lymphoma (HIV-BL) and diffuse large B-cell lymphoma (HIV-DLBCL) treated at the Zhongnan Hospital of Wuhan University over a 17-year period during the ART and rituximab era. The median CD4 count for the cohorts was 0.141 × 109/L (range, 0.001-0.861 × 109/L). DA-EPOCH ± R (54%) were most commonly used in HIV-BL. CHOP± R (42%) was most commonly used to treat HIV-DLBCL. The complete response rate after first-line curative therapy was 10/28 (36%) in HIV-BL and 25/57 (44%) in HIV-DLBCL. The 2-year progression-free survival (PFS) and overall survival (OS) for the HIV-BL cohort was 50% and 41% respectively. The 2-year PFS and OS for the HIV-DLBCL cohort was 55% and 47% respectively. Current China practice favours the treatment of HIV-BL and HIV-DLBCL similarly to the HIV-negative population with the use of concurrent ART. However, due to the extremely low percentage of patients receiving ART prior to the lymphoma diagnosis, the high percentage of patients with poor performance status, and the advanced stage at diagnosis, the treatment of HIV-related lymphoma remains the major challenge in China. [ABSTRACT FROM AUTHOR]

RTX was initially used for non-Hodgkin's lymphoma treatment and has been used in the clinical treatment of various autoimmune diseases as well as in antirejection and immune induction therapy for kidney transplant recipients. Following RTX treatment, the time for B cell regeneration varies among patients, but there is no unified recommendation for the frequency of B cell monitoring. This study aimed to investigate the clinical significance of periodic monitoring of peripheral blood B lymphocytes in individualized immunotherapy following rituximab (RTX) treatment in patients with different diseases. This study included 488 patients with different diseases divided in four groups who were hospitalized and followed up from April 2017 to March 2024 (including 77, 161, 120, and 130 cases of neuromyelitis optica, pemphigus, membranous nephropathy, and kidney transplant recipients, respectively). Dynamic changes in percentage and absolute count of peripheral blood B lymphocytes before and after RTX treatment were investigated in the four groups, as well as the number of B cell subsets in 32 patients with optic neuromyelitis after RTX treatment. Although most patients showed high expression of B cells after 24 weeks, less than 6.8% of patients still began to experience B cell regeneration within 4 weeks. Thus, regular B cell monitoring following RTX treatment is helpful to better track the remission and recurrence of the disease and provide effective laboratory support for the selection and implementation of individualized immunotherapy. [ABSTRACT FROM AUTHOR]

Angioimmunoblastic T-cell lymphoma (AITL) presents a wide range of clinical and histopathological features, often resembling various reactive and neoplastic diseases. This similarity poses a challenge in making a definitive diagnosis in many cases. Distinguishing the neoplastic T cells can be particularly difficult since they typically constitute a small proportion of the overall cellular infiltration. The tumour and inflammatory cells exhibit polymorphism and variable proportions. Additionally, the concurrent proliferation of B cells can mimic both reactive and neoplastic conditions. Furthermore, the atypical B cells may resemble Reed-Sternberg cells and show positivity for CD30 and CD15, often leading to misdiagnosis as classical Hodgkin lymphoma. In this case report, we present the case of a 65-year-old man initially diagnosed with classical Hodgkin lymphoma who underwent ABVD chemotherapy. [ABSTRACT FROM AUTHOR]

In English medical terminology, there is a steady tendency for the functioning and even an increase in the number of eponymous terms. The authors focus on the term formation potential of eponyms, ways of their creation, and the semantics of derived units. This paper highlights the main morphological methods of creating eponymous terms in English medical terminology. The suffixation is represented by the suffixes: -ia, -(i)an, -ean, -ella, -(i)al, -ic, -osis, -iasis, -ism, -itis, -oma, -ize. The productivity of this method is provided by derivational suffixes with a semantic burden borrowed from Greek and Latin languages. The semantic range of suffixes contributes to creating new terms with similar meanings. Prefixation in eponymous terms was limited to using prefixes pre- and non-. Only two terms were identified in our investigation: pre-Alzheimer's brain and non-Hodgkin's lymphoma. The majority of eponymous terminological units are found to be formed by affix combination. The components of this type of eponymous term are the prefixes a-, anti-, de-, hemi-, non-, post-, pre-, and the suffixes -ian, -ic, -ism,-ize such as anti-Mullerian hormone or hemiparkinsonism. The prefix performs a word-building role as an affix with a mutational meaning, while the suffix generalizes and specifies the meaning of the term. The methods of the word and stem composition are not prevailing. There are structural models with the morphemes pseudo- in the preposition and -like in the postposition: pseudo-Cushing syndrome and Burkitt-like lymphoma. Morphological methods of creating eponymous terms combine borrowed and native English morphemes where the elucidation of derivatives relies on the meanings of their components. Suffixation occupies a dominant position in the creation of eponymous terminological units. [ABSTRACT FROM AUTHOR]

Anti-CD19 chimeric antigen receptor (CAR) T-cell and anti-CD20 bispecific antibody therapies (BsAbs) are rapidly moving to earlier treatment lines for patients with B-cell non-Hodgkin lymphoma (B-NHL). The rapid pace of the advancement of these T-cell-engaging therapies is juxtaposed by a lack of a comprehensive understanding of the scope and kinetics of immunodeficiency following these treatments. We review emerging studies detailing the safety and efficacy of CD19 CAR-T and CD20 BsAbs in earlier lines for B-NHL, as well as a discussion of the limited knowledge of immune recovery following these treatments. We integrate the limited consensus prevention and management recommendations, advocating that the management of secondary immunodeficiency following these transformative therapies is an urgent unmet need in immune oncology research. A collaboration between hematologists/oncologists and immunologists in the management of these patients is critical to optimize patient care. [ABSTRACT FROM AUTHOR]

The efficacy of statins as anti-cancer drugs has been demonstrated in several malignancies but has been poorly investigated in hematological malignancies (HM). By studying its effect on oncogenic miRNAs, we investigated the effect of statin therapy on HM patients. The data were used to identify enriched pathways that were altered due to statin treatment. The main aim of this study was to identify significantly differentially expressed miRNAs and involved regulatory pathways post-atorvastatin treatment in HM patients. A panel of 95 plasma circulating miRNAs involved in tumorigenesis, apoptosis, and differentiation were relatively quantified using qPCR for blood samples obtained from 12 HM patients, 4 with Chronic Myeloid Leukemia (CML), 4 with Non-Hodgkin Lymphoma (NHL), and 4 with Essential Thrombocythemia. Pre- and post-administration of a 6-week atorvastatin course miRNA expression levels were measured. Significantly differentially expressed miRNAs were those with a fold change >2 or <0.5 using the Livak method with a two-sided p-value < 0.05. To further understand the underlying mechanism of statin regulated miRNA, GO and KEGG pathway enrichment analyses were conducted for identified target genes using the DAVID 6.8 bioinformatics tool. Out of 95 miRNAs, 14 exhibited significant fold changes post-treatment with statins including miR-198, miR-29a+b+c, miR-204, miR-222, miR-224, miR-155, miR-128b, miR-296, miR-199a+b, miR-194, miR-125a, miR-200a, and the let-7-family that were upregulated and miR-150 that was downregulated post-statin treatment. Higher mir-222, mir-194, mir-128b, and mir-199b expressions were significantly associated with better overall survival using the Cancer Genomic Atlas leukemia and lymphoma patient cohorts. Enrichment analysis identified the PI3k-Akt pathway as well as other pathways involved in the epithelial–mesenchymal transition. Atorvastatin upregulated several tumor suppressor genes involved in mediating better prognosis. The data can be used to enhance personalized treatments for patients with hematological malignancies by helping to predict the different pathways that may be targeted and, therefore, result in better survival outcomes in these patients. [ABSTRACT FROM AUTHOR]

Background: B-cell lymphoblastic lymphoma (B-LBL) is an aggressive type of non-Hodgkin lymphoma that usually involves lymph nodes, skin and soft tissue. Bone marrow and peripheral blood are normally spared from involvement in the disease. B-LBL typically forms solid masses that have similar pathologic and immunophenotypic features to their liquid counterpart, B-cell acute lymphoblastic leukemia (B-ALL). The presentation of B-LBL with a solitary epidural mass at the cervical spine is very rare and the optimal treatment of such cases is unknown. Most of the literature on the management of B-LBL comes from small case series, pediatric patients, or as part of retrospective data that combine B-LBL with B-ALL cases. Case presentation: The case presented herein is a unique presentation that was treated using three modalities, namely surgical resection, radiotherapy and consolidation with systemic chemotherapy, adopted from the United Kingdom acute lymphoblastic leukemia (UKALL14) protocol. Conclusions: The patient attained complete remission following the planned treatment and is still in remission for more than four and half years from the time of his initial diagnosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Primary vulvar diffuse large B‐cell lymphoma is a diagnostically challenging malignant tumor due to its low incidence and diverse clinical presentations. It has a good prognosis and is usually radio‐chemotherapy‐responsive. This case report emphasizes considering lymphoma as a differential in vulvar inflammatory conditions. [ABSTRACT FROM AUTHOR]

Background: Blood cancers account for a significant proportion of cancer-related deaths worldwide. In this study, hematological cancer mortality in northern Iran was examined during 2013-2021, along with age-adjusted mortality rates. Methods: In a cross-sectional study, we conducted an analysis of all deaths from hematological neoplasms registered in Babol city between 2013 and 2021. In order to estimate the population, the most recent census data was used. The mortality rates and trends for each hematological malignancy were reported in crude mortality rate (CMR) and age-standardized mortality rate (ASMR). Results: In total, 357 deaths (10.8% of all cancer-related deaths) were attributed to hematological neoplasms, with an average age of 61.9 ± 19.3 years. The crude and age-adjusted mortality rates of hematological neoplasms increased from 3.1 and 2.7 per 100 000 people in 2013 to 8.1 and 6.9 per 100,000 people in 2021, respectively. Mortality trends of hematological cancers increased with age decade for both sexes (P < 0.001). Additionally, when examining the trends of each hematological neoplasm, there was a significant increase in neoplasms including non-Hodgkin lymphoma (P = 0.033), multiple myeloma (P = 0.002), and leukemia (P < 0.001), except for the consistent trend observed in Hodgkin lymphoma (P = 0.247). Conclusion: The trend of hematological malignancies in Babol city is increasing across all age groups and in both sexes. This study emphasizes the need for effective prevention and treatment strategies, including improving access to cancer care, enhancing surveillance in families with blood malignancies and reducing modifiable risk factors. Additionally, further research is warranted to develop targeted interventions. [ABSTRACT FROM AUTHOR]

Odronextamab (Ordspono™), a CD20xCD3 bispecific antibody, is being developed by Regeneron Pharmaceuticals for the treatment of B-cell non-Hodgkin's lymphoma. On 26 August 2024, odronextamab received its first approval in the EU as monotherapy for the treatment of adult patients with relapsed/refractory follicular lymphoma (FL) or relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after ≥ 2 lines of systemic therapy. Clinical trials in various other B-cell non-Hodgkin's lymphoma, including mantle cell lymphoma, marginal zone lymphoma and chronic lymphocytic leukaemia, are underway in multiple countries. This article summarizes the milestones in the development of odronextamab leading to this first approval for the treatment of adult patients with relapsed/refractory FL or relapsed/refractory DLBCL. [ABSTRACT FROM AUTHOR]

Simple Summary: Follicular lymphoma (FL) is an indolent heterogeneous B-cell malignancy with variable clinical presentation and outcomes. Despite previous prognostic clinical scores' validation, unmet medical needs remain in understanding the reason why selected groups of FL patients experience a less or more aggressive clinical course with higher risk of relapse, death or histological transformation (HT). Prognostic refinement by stratification of symptomatic disease and clinical evolution according to staging and tumor burden status are crucial gaps that requires further investigation. Therefore, this study will present advances in clinical subclassification and in the impact of staging and tumor burden on treatment efficacy and survival. Additionally, it will provide new perspectives on characterization of risk factors for HT and early-progression (POD-24). Insights into disease progression patterns may help clinicians to establish personalized treatment strategies for FL patients. Background: Clinical staging (CS) and tumor burden (TB) play a significant role in FL prognosis and direct its up-front therapy. The aim of this study is to report prognostic factors and clinical outcomes in newly-diagnosed FL patients stratified according to CS and TB in early-stage (ES) disease, advanced-stage with low tumor burden (AS-LTB) and advanced-stage with high tumor burden (AS-HTB). Methods: Two hundred fourteen patients with FL grades 1–3A had baseline clinical characteristics and outcomes assessed. Survival according to up-front immunochemotherapeutic (ICT) regimens was assessed in the AS-HTB subgroup. Independent predictors for OS, PFS, POD-24, and Histological Transformation (HT) were identified. Results: Seventy-five percent of cases were categorized as AS-HTB, 13.5% as AS-LTB and 11.5% as ES. With a median follow-up of 8.15 years, the estimated 5-year OS and PFS were 75.4% and 57.2%, respectively. OS, but not PFS was markedly decreased in AS-HTB FL patients compared to ES and AS-LTB cases. POD-24 rate was 21.7% and overall mortality rate was 38.7% during the entire follow-up. The annual cumulative rate of HT to high-grade B-cell lymphoma (HGBCL) was 0.5%, and higher in AS-HTB cases, in comparison to ES and AS-LTB. Considering patients with AS-HTB there were no differences in clinical outcomes among cases submitted to ICT based on R-CHOP, R-CVP and regimens containing purine analogs. Additionally, ECOG ≥ 2, hypoalbuminemia, B-symptoms and HT were independently associated with poor survival. High content of centro-blasts (grade 3A), involvement of ≥3 nodal sites by FL and rituximab omission in up-front therapy predicted POD-24. Conclusions: FL has marked clinical–prognostic heterogeneity, translated into diverse CS and TB subcategories. Here, we demonstrated that FL patients classified as AS-HTB demonstrated decreased survival and higher rates of HT to HGBCL compared to ES and AS-LTB cases. Prognostic factors identified in our analysis may help to identify FL patients with higher-risk of HT and early-progression (POD-24). [ABSTRACT FROM AUTHOR]

Background: Primary pulmonary diffuse large B-cell lymphoma (PP-DLBCL) is a rare extranodal non-Hodgkin's lymphoma (EN-NHL). Its prognosis as an aggressive lymphoma is abysmal, and predictive models are still lacking. Methods: We screened patients diagnosed with PP-DLBCL between 2010 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. Then, univariate and multivariate COX regression analyses were used to identify independent risk factors affecting patient prognosis. Finally, a novel nomogram was constructed and the model was evaluated by looking at three dimensions. Results: A total of 831 patients were included in this study. Most of the patients were elderly (526 (63.8%)) and female (428 (51.9%)). The included patients were randomized in a 7:3 ratio into a training group (577 (70%)) and a validation group (248 (30%)). We concluded that the independent risk factors of prognosis were age, extrapulmonary metastasis, radiotherapy, chemotherapy, and surgical intervention. The results of receiver operating characteristic curves, calibration curves, and decision curve analysis in the training and validation groups confirmed that the risk prediction nomogram could accurately predict the survival of PP-DLBCL. Conclusion: This study is the first large population-based clinical data study on PP-DLBCL. A novel predictive model about prognosis has been developed to help clinical decision-making. PLAIN LANGUAGE SUMMARY: Primary pulmonary diffuse large B-cell lymphoma (PP-DLBCL), a rare extranodal non-Hodgkin's lymphoma (EN-NHL), has a very poor prognosis as an aggressive lymphoma. We screened individuals from the Surveillance, Epidemiology, and End Results (SEER) database who were diagnosed with PP-DLBCL between 2010 and 2019. Then, univariate and multivariate COX regression analyses were used to identify independent risk factors affecting patient prognosis. Finally, we built a new predictive model to aid in clinical decision making. [ABSTRACT FROM AUTHOR]

Background: Peripheral T-cell lymphomas (PTCL) are an aggressive group of mature T-cell neoplasms, often associated with poor outcomes, in part, due to frequent relapsed/refractory disease. The objective of this study was to assess the prognostic impact of disease progression within 24 months (POD24) on overall survival (OS) for patients diagnosed with PTCL. Methods: A retrospective analysis was conducted on a cohort of patients with newly diagnosed PTCL who underwent chemotherapy at the Affiliated Hospital of Xuzhou Medical University between January 2010 and September 2021. Prognostic assessment was limited to patients who were evaluable for POD24. Results: Records were reviewed for 106 patients with PTCL, of whom 66 patients experienced POD24 (referred to as the POD24 group) and 40 patients did not experience POD24 (referred to as the no POD24 group). Significant differences were observed between the POD24 group and the no POD24 group in regard to clinical stage, Eastern Cooperative Oncology Group (ECOG) performance status (PS), International Prognostic Index (IPI) score, lactate dehydrogenase (LDH) levels, β2-microglobulin (β2-MG) levels, prealbumin and albumin levels. Patients in the POD24 group had a significant shorter median OS compared to the no POD24 group (11.9 months vs not reached, respectively; P < 0.001). Non response (NR) to treatment and POD24 were identified as independent negative prognostic factors for survival in patients with PTCL. Conclusion: POD24 is a prognostic factor associated with unfavorable outcomes in patients with PTCL and can be used to identify high-risk patients and guide treatment decisions. [ABSTRACT FROM AUTHOR]

Purpose:In vitro maturation (IVM) of oocytes obtained from ovarian tissue during ovarian tissue cryopreservation (OTC) is a technique for fertility preservation in patients with cancer obviating the need to postpone chemotherapy initiation. Little is known about IVM outcomes in hematological malignancies, especially post-chemotherapy. The purpose of this study was to evaluate the effect of cytotoxic treatment on the potential to retrieve immature oocytes and mature them in vitro and examine the association between serum inflammatory markers and these results. Methods: In this retrospective study, we evaluated inflammation markers, including B symptoms and IVM outcomes of 78 chemotherapy-naive and exposed patients diagnosed with Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), or acute myeloid leukemia (AML). Results: The mean number of oocytes found was 7.2 ± 7.2. The average number of oocytes matured by IVM was 2.8 ± 3.5, and a mean IVM rate was 32.1 ± 27.7%. All patients in the ALL and AML groups had previous exposure to chemotherapy before OTC, compared with 50.0% (7/14) and 31.9% (15/47) in the NHL and HL groups, respectively. Among patients with lymphoma, chemotherapy exposure was associated with the reduced number of retrieved oocytes (9.8 ± 7.7 vs. 5.3 ± 5.7 oocytes, p = 0.049) in the HL group but not with the number of mature oocytes or IVM rate. B symptoms were not associated with IVM outcomes. Lymphocyte count (ß = 1.584; p = 0.038) and lactate dehydrogenase (ß = 0.009; p = 0.043) were the only significant parameters associated with the number of matured oocytes in a linear regression model. Conclusion: IVM is a promising assisted reproductive technology, which holds great potential for patients in need of urgent fertility preservation or those who cannot receive hormonal stimulation. Our results demonstrate the feasibility of the technique even in the presence of B symptoms and elevated inflammation markers and in patients with previous exposure to chemotherapy. [ABSTRACT FROM AUTHOR]

Follicular lymphoma (FL), the second most common subtype of non-Hodgkin lymphoma, relies on interactions with immune elements in the tumor microenvironment, including T-follicular helper cells and follicular dendritic cells, for its survival and progression. Despite its initial responsiveness to chemoimmunotherapy, FL is generally considered incurable. Strategies to improve immune-mediated control of FL could significantly benefit this population, particularly as it includes many elderly and comorbid patients. Immune cell engagers, especially bispecific antibodies (BsAbs), are crucial in targeting FL by bridging tumor and effector cells, thereby triggering T-cell activation and cytotoxic killing. CD3 × CD20 BsAbs have shown the most promise in clinical development for B-NHL patients, with structural variations affecting their target affinity and potency. This review summarizes the current clinical trials of BsAbs for relapsed/refractory FL, highlighting the approval of some agents, their role in first-line treatment or combination therapies, their toxicity profiles, and the future of this therapeutic approach compared to other immune cell therapies. [ABSTRACT FROM AUTHOR]

Immunotherapy has shaped the treatment approach to diffuse large B-cell lymphoma (DLBCL), with rituximab leading to remarkable improvements in outcomes for both relapsed and treatment-naïve patients. Recently, groundbreaking immunotherapies like chimeric antigen receptor T-cells have entered the treatment arena for relapsed/refractory (R/R) DLBCL and gained regulatory approval in several countries. The concept of harnessing a patient's own T-cells to combat cancer has been further explored through the development of bispecific antibodies (BsAbs), a class of engineered antibody products designed to simultaneously target two different antigens. These novel drugs have demonstrated impressive single-agent activity and manageable toxicity in patients with heavily pretreated B-cell non-Hodgkin lymphoma. In this review, we provide an up-to-date overview of recently completed or ongoing BsAbs trials in patients with R/R DLBCL, including single-agent results, emerging combination data, and novel constructs. [ABSTRACT FROM AUTHOR]

Few treatment options exist for patients with non-Hodgkin lymphoma, and outcomes remain poor for relapsed or refractory disease. We evaluated the safety and preliminary clinical activity of valemetostat, a novel inhibitor of EZH2 and EZH1, in patients with relapsed or refractory non-Hodgkin lymphomas. This first-in-human, multicentre, open-label, single-arm, phase 1, dose-escalation and dose-expansion trial was done in 19 hospitals across Japan and the USA. Patients were included if they were aged 18 years or older in the USA or 20 years or older in Japan with a primary diagnosis of relapsed or refractory non-Hodgkin lymphoma and an Eastern Cooperative Oncology Group performance status of 0 or 1. In the dose-escalation part, patients received oral valemetostat at doses of 150 mg per day, 200 mg per day, 250 mg per day, and 300 mg per day continuously in 28-day cycles until progressive disease or unacceptable toxicities. All patients received 200 mg per day in the dose-expansion part. The primary endpoints were safety, pharmacokinetics, and the recommended phase 2 dose; the secondary endpoints were the maximum tolerated dose and the antitumour activity of valemetostat. Responses were assessed in patients who received at least one dose, with measurable lesions at baseline according to the International Working Group 2007 revised criteria for malignant lymphoma (peripheral T-cell lymphoma and B-cell non-Hodgkin lymphoma) and the modified 2009 criteria for adult T-cell leukaemia/lymphoma. The trial is registered with ClinicalTrials.gov , NCT02732275 , and is currently active, but not recruiting. Between April 7, 2016, and June 10, 2021, 90 patients (53 [59%] males and 37 [41%] females; 49 [54%] Asian, 33 [37%] White, and eight [9%] Black) were enrolled and treated with valemetostat and included in the safety analysis set. 57 (63%) patients had peripheral T-cell lymphoma, 14 (16%) had adult T-cell leukaemia/lymphoma, and 19 (21%) had B-cell non-Hodgkin lymphoma. Seven (8%) patients received valemetostat 150 mg per day, 74 (82%) received 200 mg per day, seven received 250 mg per day, and two received 300 mg per day. Median follow-up was 7·4 months (IQR 3·4–17·6). All patients had at least one treatment-emergent adverse event; the most common treatment-emergent adverse events of any grade were decreased platelet count (52 [58%] of 90 patients), dysgeusia (45 [50%]), and anaemia (38 [42%]). The most common grade 3–4 adverse events were decreased neutrophil count (21 [23%]), decreased platelet count (18 [20%]), and decreased lymphocyte count (17 [19%]). The most common serious adverse event of any grade was Pneumocystis jirovecii pneumonia (four [4%]). No treatment-related deaths occurred. The overall response rate was 54·5% (48 of 88; 95% CI 43·6–65·2) for patients in the efficacy analysis set. The maximum tolerated dose was not reached; the recommended phase 2 dose of 200 mg per day was determined. Valemetostat exposure was variable between patients and was overlapped over the dose range of 150–250 mg per day. The safety profile of valemetostat monotherapy was acceptable in these patients with relapsed or refractory non-Hodgkin lymphoma. Favourable clinical activity was observed. These findings support a new indication for valemetostat in this setting. Daiichi Sankyo. [ABSTRACT FROM AUTHOR]

Indolent lymphomas are rare in children and mostly consist of pediatric type follicular (PTFL) and pediatric marginal zone lymphomas (PMZL) and extranodal marginal zone lymphoma (ENMZL). Twenty children with indolent lymphoma (10 PTFL, 6 PMZL, 3 ENMZL, 1 mixed type) among 307 Non-Hodgkin Lymphoma (NHL) were retrospectively evaluated. The mean age of the entire group was 10.4 ± 4.4 and was significantly lower in PTFL than in PMZL. Seven patients (35%) had an associated inborn error of immunity (IEI) which was higher than that seen in aggressive lymphomas (5.9%) (p < 0.0001). Seventeen patients (85%) had stage I/II disease. Two patients received no treatment after surgery. Eleven patients were treated only with 3-6 courses of rituximab. Four patients received 3-6 courses of R-CHOP protocol. The prognosis was excellent Five years overall and event-free survivals were 100% and 85%, respectively. [ABSTRACT FROM AUTHOR]

PURPOSE: Compare the association of individual comorbidities, comorbidity indices, and survival in older adults with non-Hodgkin lymphoma (NHL), including in specific NHL subtypes. METHODS: Data source was SEER-Medicare, a population-based registry of adults age 65 years and older with cancer. We included all incident cases of NHL diagnosed during 2008-2017 who met study inclusion criteria. Comorbidities were classified using the three-factor risk estimate scale (TRES), Charlson comorbidity index (CCI), and National Cancer Institute (NCI) comorbidity index categories and weights. Overall survival (OS) and lymphoma-specific survival, with death from other causes treated as a competing risk, were estimated using the Kaplan-Meier method from time of diagnosis. Multivariable Cox models were constructed, and Harrel C-statistics were used to compare comorbidity models. A two-sided P value of <.05 was considered significant. RESULTS: A total of 40,486 patients with newly diagnosed NHL were included. Patients with aggressive NHL had higher rates of baseline comorbidity. Despite differences in baseline comorbidity between NHL subtypes, cardiovascular, pulmonary, diabetes, and renal comorbidities were frequent and consistently associated with OS in most NHL subtypes. These categories were used to construct a candidate comorbidity score, the non-Hodgkin lymphoma 5 (NHL-5). Comparing three validated comorbidity scores, TRES, CCI, NCI, and the novel NHL-5 score, we found similar associations with OS and lymphoma-specific survival, which was confirmed in sensitivity analyses by NHL subtypes. CONCLUSION: The optimal measure of comorbidity in NHL is unknown. Here, we demonstrate that the three-category TRES and five-category NHL-5 scores perform as well as the 14-16 category CCI and NCI scores in terms of association with OS and lymphoma-specific survival. These simple scores could be more easily used in clinical practice without prognostic loss. [ABSTRACT FROM AUTHOR]

The association of AA with malignancies has been a scope of controversy as the current literature is highly inconsistent in this regard. To evaluate the association between AA and hematological malignancies (HMs) and solid malignancies (SMs) using a large-scale, real-life computerized database. A cross-sectional study was conducted to compare the prevalence of HMs and SMs among patients with AA relative to age-, sex-, and ethnicity-matched control subjects. Chi-square and t-tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The study included 51,561 patients with AA and 51,410 controls. AA was significantly associated with HMs (adjusted OR, 1.27; 95% CI, 1.07–1.51; P = 0.006). This association was more robust among patients with late-onset AA (≥ 50 years; OR, 1.33; 95% CI, 1.04–1.71; P = 0.025). On the other hand, AA was not found to be significantly associated with SM (adjusted OR, 0.97; 95% CI, 0.88–1.06; P = 0.487), excluding among patients with alopecia totalis and universalis (OR, 2.10; 95% CI, 1.03–4.27; P = 0.036). In a granular analysis including 5 HMs and 18 SMs, non-Hodgkin lymphoma was the only malignancy that proved positively associated with AA (adjusted OR, 1.32; 95% CI, 1.03–1.69; P = 0.028). AA is associated with HMs but not SMs. Further research is warranted to validate our observations in other study cohorts. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma, characterized by its aggressive nature and heterogeneity. Despite significant advances in understanding DLBCL pathogenesis, there is still a need to elucidate the intricate mechanisms involved in disease progression and identify novel therapeutic targets. Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as crucial mediators of intercellular communication in various physiological and pathological processes, including cancer. In recent years, evidence has suggested that EVs play a vital role in DLBCL biology by facilitating the exchange of genetic material, especially miRNAs, and proteins and lipids between tumor cells, immune cells, and the tumor microenvironment. We summarize and discuss the biological functions of EVs in DLBCL and their effects on the tumor microenvironment, highlighting their influence on DLBCL pathobiology, immune evasion, angiogenesis, and drug resistance. We also investigated EVs' diagnostic and prognostic potential as circulating biomarkers in DLBCL, emphasizing their utility in the non-invasive monitoring of the disease status and treatment response. Understanding the complex interplay between EVs and DLBCL may open up new avenues for personalized medicine, improve patient stratification, and facilitate the development of innovative therapeutic interventions in this devastating hematological malignancy. [ABSTRACT FROM AUTHOR]

Diffuse Large B-cell Lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL). Despite the use of newer agents, such as polatuzumab vedotin, more than one-third of patients have ultimately relapsed or experienced refractory disease. MiRNAs are single-stranded, ~22-nucleotide-long RNAs that interact with their target RNA. They are significant regulators of post-transcriptional gene expression. One significant miRNA, miR-155, is involved in the pathophysiology of DLBCL and it is a critical modulator of hematopoiesis, inflammation, and immune responses. Targets of miR-155, such as histone deacetylase 4 (HDAC4), suppressor of cytokine signaling-1 (SOCS1) and immune cells, play a crucial role in DLBCL pathogenesis, since miR-155 regulates key pathways, transcription factors and cytokine expression and shapes the tumor microenvironment in DLBCL. In this review, we examine the role of miR-155 in DLBCL and its potential as a future diagnostic, prognostic, or predictive biomarker. [ABSTRACT FROM AUTHOR]

Aim: The combination of granulocyte-colony stimulating factor (G-CSF) and plerixafor is one of the approaches for hematopoietic stem cell mobilization in patients with multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), and Hodgkin's lymphoma (HL). This systematic review and meta-analysis aimed to determine the ability of G-CSF+plerixafor to mobilize peripheral blood (PB) CD34+ cells and examine its safety profile. Methods: We performed a database search using the terms 'granulocyte colony stimulating factor', 'G-CSF', 'AMD3100', and 'plerixafor', published up to May 1, 2023. The methodology is described in further detail in the PROSPERO database (CRD42023425760). Results: Twenty-three studies were included in this systematic review and meta-analysis. G-CSF+plerixafor resulted in more patients achieving the predetermined apheresis yield of CD34+ cells than G-CSF alone (OR, 5.33; 95%, 4.34-6.55). It was further discovered that G-CSF+plerixafor could mobilize more CD34+ cells into PB, which was beneficial for the next transplantation in both randomized controlled (MD, 18.30; 95%, 8.74-27.85) and single-arm (MD, 20.67; 95%, 14.34-27.00) trials. Furthermore, G-CSF+plerixafor did not cause more treatment emergent adverse events than G-CSF alone (OR, 1.25; 95%, 0.87-1.80). Conclusions: This study suggests that the combination of G-CSF and plerixafor, resulted in more patients with MM, NHL, and HL, achieving the predetermined apheresis yield of CD34+ cells, which is related to the more effective mobilization of CD34+ cells into PB. [ABSTRACT FROM AUTHOR]

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Introduction: Squamous cell carcinoma (SCC) is a skin malignancy typically treated with surgical resection. Non-Hodgkin lymphoma (NHL) is a group of lymphoid tissue malignancies treated with various strategies, including chemotherapy and radiotherapy. Case Presentation: A 64-year-old male with prior SCC presented with a new scalp lesion. Examination revealed an elevated, irregular, non-tender lesion with mild yellow discoloration. Imaging showed a scalp lesion, cervical lymphadenopathies, and a well-defined mass. Ultrasonography uncovered lymph node involvement and splenomegaly. Fine needle aspiration, biopsy, and immune stains of the lymph node confirmed NHL. Wide local excision of the scalp lesion, reconstruction, and lymph node biopsies were performed, confirming SCC and NHL. The patient received radiotherapy and chemotherapy. Conclusion: This unique rare case emphasizes the complex interplay of SCC and NHL, necessitating vigilant SCC patient follow-up. [ABSTRACT FROM AUTHOR]

Activation of immune receptors, such as Toll-like (TLR), NOD-like (NLR) and Stimulator of Interferon Genes (STING) is critical for efficient innate and adaptive immunity. Gram-negative bacteria (G-NB) contain multiple TLR, NOD and STING agonists. Potential utility of G-NB for cancer immunotherapy is supported by observations of tumor regression in the setting of infection and Coley's Toxins. Coley reported that intravenous (i.v.) administration was likely most effective but produced uncontrollable toxicity. The discovery of TLRs and their agonists, particularly the potent TLR4 agonist lipopolysaccharide (LPS)-endotoxin, comprising ~75% of the outer membrane of G-NB, suggests that LPS may be both a critical active ingredient and responsible for dose-limiting i.v. toxicity of G-NB. This communication reports the production of killed, stabilized, intact bacteria products from non-pathogenic G-NB with ~96% reduction of LPS-endotoxin activity. One resulting product candidate, Decoy10, was resistant to standard methods of cell disruption and contained TLR2,4,8,9, NOD2 and STING agonist activity. Decoy10 also exhibited reduced i.v. toxicity in mice and rabbits, and a largely uncompromised ability to induce cytokine and chemokine secretion by human immune cells in vitro , all relative to unprocessed, parental bacterial cells. Decoy10 and a closely related product, Decoy20, produced single agent anti-tumor activity or combination-mediated durable regression of established subcutaneous, metastatic or orthotopic colorectal, hepatocellular (HCC), pancreatic, and non-Hodgkin's lymphoma (NHL) tumors in mice, with induction of both innate and adaptive immunological memory (syngeneic and human tumor xenograft models). Decoy bacteria combination-mediated regressions were observed with a low-dose, oral non-steroidal anti-inflammatory drug (NSAID), anti-PD-1 checkpoint therapy, low-dose cyclophosphamide (LDC), and/or a targeted antibody (rituximab). Efficient tumor eradication was associated with plasma expression of 15-23 cytokines and chemokines, broad induction of cytokine, chemokine, innate and adaptive immune pathway genes in tumors, cold to hot tumor inflammation signature transition, and required NK, CD4+ and CD8+ T cells, collectively demonstrating a role for both innate and adaptive immune activation in the anti-tumor immune response. [ABSTRACT FROM AUTHOR]

Histologic transformation (HT) of indolent non-Hodgkin lymphoma (iNHL) to diffuse large B-cell lymphoma (DLBCL) carries a poor prognosis. Using the Surveillance, Epidemiology, and End Results-17 database, we conducted a population-based study of adult patients with transformed follicular lymphoma (t-FL), marginal zone lymphoma (t-MZL), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (t-LPL/WM), and de novo DLBCL. Primary outcome was relative survival (RS), and secondary outcomes included overall survival (OS) and lymphoma-specific survival (LSS). Outcomes were modeled using flexible parametric survival models, while multivariable modeling was used to compare RS, OS, and LSS. The incidence of HT was highest in splenic MZL (SMZL, 6.78%) and lowest in extranodal MZL (EMZL, 1.62%). Median follow-up times were similar for patients with de novo DLBCL and transformed indolent lymphomas. The 5-year RS and OS were longer in de novo DLBCL compared to all other transformed iNHL subtypes (68 versus 59%, respectively). For t-FL, early transformation (within 2 years of diagnosis, Hazard ratio [HR] = 1.34) and prior treatment (HR = 1.89) were associated with inferior survival. This association was not observed in other transformed lymphoma subtypes. This is the first comparative study to show that the outcomes of t-LPL/WM were inferior compared to de novo DLBCL and highlights the need to incorporate early experimental therapies in patients with t-FL with early transformation and receipt of prior chemotherapy. [ABSTRACT FROM AUTHOR]

Introduction: Amdizalisib (HMPL-689) is an ATP-competitive PI3Kδ inhibitor currently under investigation for treating Hodgkin's lymphoma. This study aimed to evaluate the metabolism, excretion, pharmacokinetics, and safety profile of amdizalisib in healthy human subjects to support its clinical application. Methods: This Phase I clinical trial included six healthy Chinese male volunteers who received a single oral dose of 30 mg/100 µCi [14C]amdizalisib suspension. Blood, urine, and fecal samples were collected to analyze pharmacokinetics, metabolic pathways, and excretion patterns. Results: Amdizalisib was rapidly absorbed, with a median Tmax of 2.5 h. The Cmax of 244 ± 48.9 ng/mL, and AUC0-t was 1870 ± 474 h ng/mL after a single oral dose. The blood-to-plasma total radioactivity ratio ranged from 0.561 to 0.645, indicating no significant affinity of [14C]amdizalisib and its metabolites to blood cells and the radioactive material is mainly distributed in plasma. Excretion was primarily via feces and urine, with 62.08% ± 3.00% and 37.15% ± 2.84% of the dose recovered, respectively, and over 94% of the drug excreted within 96 h. The parent drug was the main radioactive component in plasma (51.45% of total radioactivity). Additionally, 11 metabolites were identified, and the metabolic pathways include oxidation on the benzene or pyrimidine rings and conjugation with cysteine or glucuronic acid. The major metabolites in plasma were the di-oxidized and hydrogenated product (M424) and the mono-oxidized product (M406-2), accounting for 16.67% and 20.91%, respectively. Both of them are also the major radioactive components in urine and feces, among of which M424 accounted for 21.01% and 14.26%, M406-2 accounted for 8.08% and 11.30%, of the administered dose in urine and feces, respectively. In addition, the di-oxidized and methylated product (M436) was one of the major metabolites in feces accounting for 17.7% of the administered dose. Few of the parent drug was found in urine and feces, suggesting primary metabolized in the liver. No serious adverse events or drug-related deaths occured, with diarrhea as the most common adverse event. Discussion: These findings demonstrate that amdizalisib is rapidly absorbed, extensively metabolized, and primarily excreted via feces and urine, supporting its continued development as a potential therapeutic for Hodgkin's lymphoma. Systematic Review Registration: https://www.chinadrugtrials.org.cn/, identifier CTR20212448. [ABSTRACT FROM AUTHOR]