Search Results (127)

Background: Here, we propose a novel predictive scoring system incorporating age and the systemic inflammation response index (SIRI), which is calculated using neutrophil, monocyte, and lymphocyte counts, for patients with newly diagnosed primary central nervous system lymphoma (PCNSL). Methods: The study included 55 consecutive patients with sufficient blood test data and follow-up at our institution between November 2006 and May 2022. Age and SIRI were identified as prognostic factors and incorporated into a predictive multivariate Cox proportional hazards model. A scoring system of 0–2 points was created, with 1 point each assigned to age ≥ 65 years and high SIRI score (≥1.43 × 10⁹/L). We subsequently validated the predictive scoring system in an independent external validation cohort. Results: Patients with 0, 1, and 2 points were assigned to groups 1, 2, and 3, respectively. The median overall survival (OS) was 35.9 months in the entire training cohort and 57.8, 37.2, and 16.1 months in groups 1, 2, and 3, respectively. The three groups showed significant differences in median OS (p < 0.001), with lower scores corresponding to longer survival times. The performance of our new scoring system was significant in the training cohort and in the external validation cohort. Conclusion: Our new scoring system incorporating age and SIRI may serve as a preliminary prognostic model for predicting OS in patients with PCNSL. This score may be beneficial for disease risk stratification and clinical decision-making in the future. Full article

Epcoritamab, a subcutaneous CD3×CD20 bispecific antibody, has shown substantial activity in relapsed or refractory (R/R) B-cell lymphomas, but the immunological correlates of durable remission and treatment discontinuation remain unclear. We retrospectively analyzed 21 consecutive patients who initiated epcoritamab at our institution between 1 December 2023 and 31 December 2025, including 17 with R/R large B-cell lymphoma (LBCL) and 4 with R/R follicular lymphoma (FL). Clinical follow-up was updated through 18 May 2026. Serial cytotoxic T lymphocyte (CTL) subset and T-cell receptor (TCR) Vβ repertoire analyses were performed in selected cases. Among response-evaluable patients, the overall response rate was 9/14 in LBCL and 4/4 in FL. Median overall survival was 431 days in LBCL and 431.5 days in FL. Progression-free survival was analyzed descriptively because of the small sample size and substantial censoring. A patient with clinically and radiologically suspected central nervous system relapse of LBCL achieved radiological complete remission after epcoritamab treatment. In two LBCL and one FL case in whom epcoritamab was electively discontinued after complete remission, Vβ-skewed CTL populations were observed, and total memory CTLs exceeded total effector CTLs at discontinuation. These exploratory findings suggest that epcoritamab treatment may be associated with longitudinal remodeling of CTL subsets and Vβ-skewed CTL populations in selected responders. The potential relevance of these immunological patterns to durable response and treatment discontinuation should be validated in larger prospective cohorts with functional and sequence-based T-cell analyses. Full article

Post-transplant lymphoproliferative disorder (PTLD) involving the central nervous system (CNS) is a rare but serious life-threatening complication seen in recipients of solid organ transplant. Primary CNS encompasses 5–15% of all types of PTLD diagnoses, and heart transplant recipients represent 3–5% of those reported cases. Diagnosis is often delayed due to the highly variable presentation, with some cases remaining undiagnosed for years. Multidisciplinary collaboration is crucial for early diagnosis and management. A 53-year-old woman patient presented with altered mental status. MRI revealed nodular ventriculitis and bilateral periventricular hyperdense infiltrates. CSF studies demonstrated lymphocytic pleocytosis, elevated protein, and EBV-PCR-positive results. A stereotactic brain needle biopsy confirmed the presence of EBV-positive diffuse large B-cell lymphoma, consistent with primary CNS PTLD, 14 months after her heart transplant. Despite appropriate management, the patient experienced progressive neurological decline and ultimately suffered a fatal intracerebral hemorrhage. We demonstrate the importance of the early diagnosis and variable presentation of post-heart-transplant PTLD. The importance of surveillance regardless of EBV status and close monitoring of disease progression due to potential life-threatening complications, such as fatal hemorrhages. Therefore, primary CNS-PTLD remains a challenging disease and is being increasingly recognized with improved transplant recipient survival and prolonged exposure to chronic immunosuppression. Full article

Importance: A comprehensive analysis of childhood cancer and cancer predisposition syndromes (CPSs) incidence can provide insights that lead to improvements and modifications in treatment protocols through personalized therapy, thereby reducing toxicity. Purpose: This study aimed to analyze age-specific hospital-based childhood cancer rates and the distribution of CPSs in a 20-year pediatric cohort from the region. Materials: A total of 2190 patients, aged from birth to 17 years, diagnosed with any type of neoplasm classified by ICD-10 codes at Karol Jonscher’s Clinical Hospital of Poznan University of Medical Sciences (KJCH PUMS) between 1 January 2000, and 31 December 2019, were included, with 193 (8.8%) having an underlying CPS. Results: The pediatric population of the Greater Poland Region has declined over the past two decades. The most common diagnoses can be grouped into three main categories: (1) leukemias, involving 704 patients (32.1%); (2) central nervous system (CNS) tumors, represented by 382 children (17.4%); and (3) lymphomas, including 279 patients (12.7%), together accounting for 1353 cases (61.8%). The age-specific hospital-based case rate for childhood cancer (all types combined) peaked in the 0–28 days age group at 71.8 per 100,000 person-years (95% CI: 52.2–96.4), with a trend to decrease with age and a slight increase among adolescents aged 16–17 years (13.6 per 100,000, 95% CI: 12.0–15.4). The age-specific incidence of CPS-positive cancers declined from 18.0 (95% CI: 8.2–29.4) per 100,000 person-years in the first month of life to 0.7 (95% CI: 0.3–1.2) in 16–17-year-olds. CPS-positive children were diagnosed at significantly younger ages for four cancer types: liver and intrahepatic bile duct tumors (C22: A = 0.097, adjusted p < 0.001), myeloid leukemia (C92: A = 0.179, adjusted p < 0.001), lymphoid leukemia (C91: A = 0.309, adjusted p = 0.007), and renal tumors (C64: A = 0.335, adjusted p = 0.013). Conclusions: CPSs likely play a significant and underestimated role in pediatric cancers, especially during early childhood. Improving access to genetic testing could greatly enhance risk assessment, personalized treatment, and long-term outcomes in pediatric oncology. Full article

Background/Objectives: Radiogenomics integrates quantitative imaging features with genomic and molecular data to better characterize tumor biology and support precision oncology. While extensively investigated in solid tumors, its application to hematologic malignancies remains relatively unexplored despite the widespread use of advanced imaging in lymphoma and multiple myeloma. Methods: A systematic review was conducted following PRISMA 2020 guidelines. PubMed, Scopus, and Web of Science were searched up to December 2025 for studies investigating radiogenomic associations in hematologic malignancies. Study quality was assessed using PROBAST and METRICS. Two reviewers independently screened all records and performed data extraction through consensus. Results: Twelve studies were included, covering multiple myeloma and various lymphoma subtypes (aggressive B-cell lymphoma, classical Hodgkin lymphoma, and primary CNS lymphoma). Imaging modalities included PET/CT, MRI and CT. Across studies, radiomic and imaging-derived features were associated with cytogenetic abnormalities, gene expression profiles, and circulating tumor DNA metrics. In multiple myeloma, MRI and CT-based radiomics showed promising ability to predict high-risk cytogenetic abnormalities. In lymphoma, PET-derived volumetric and dissemination features correlated with molecular risk profiles and tumor microenvironment characteristics. Several studies demonstrated improved prognostic performance when imaging features were combined with genomic or clinical variables. Conclusions: Radiogenomic approaches in hematologic malignancies show promising potential for non-invasive risk stratification and improved prognostic assessment. However, current evidence remains limited by small cohorts, heterogeneous methodologies, and a lack of external validation. Prospective multicenter studies and standardized imaging–genomic pipelines will be essential to enable clinical translation. Full article

Background: The prognostic significance of histological transformation (HT) in treatment-naive diffuse large B-cell lymphoma (DLBCL) remains controversial. This study aimed to evaluate the clinical outcomes and failure patterns of treatment-naive transformed DLBCL (trDLBCL) compared with de novo DLBCL using a large-scale cohort. Methods: We retrospectively analyzed 1735 consecutively enrolled treatment-naive DLBCL patients (118 trDLBCL and 1617 de novo). Propensity score matching (PSM) was performed to balance baseline characteristics. Survival outcomes were assessed using Kaplan–Meier and Cox proportional hazards models. Subgroups were defined by pathology (t-FL vs. t-MZL) and pattern: concurrent (synchronous indolent lymphoma and DLBCL components at diagnosis) vs. pure transformation (DLBCL occurring as the sole histology in patients with a prior history of untreated indolent lymphoma). Results: In the overall cohort, trDLBCL was associated with significantly inferior progression-free survival (PFS) compared with de novo disease and remained an independent adverse prognostic factor in multivariable analysis (HR 1.754, p < 0.001). These findings were confirmed in a 1:1 propensity score-matched cohort (108 pairs), where trDLBCL continued to show worse PFS (p < 0.01), while overall survival (OS) was comparable (p = 0.99). Within trDLBCL patients, the underlying indolent subtype (t-FL vs. t-MZL) did not significantly affect survival (PFS p = 0.17, OS p = 0.35), whereas “pure transformation” was associated with markedly inferior PFS (p = 0.005) and OS (HR 2.56, p = 0.02) compared with concurrent transformation. Failure pattern analysis revealed a higher risk of early progression in trDLBCL (POD24: 30.56% vs. 18.52%; OR 1.94, 95% CI: 1.05–3.56), whereas central nervous system (CNS) involvement was low and comparable between groups (2.78% vs. 0.93%, p = 0.62). Conclusions: Treatment-naive trDLBCL is associated with inferior PFS driven by early progression, whereas OS is comparable due to effective salvage therapies. Pure transformation appeared to define a higher-risk subgroup with inferior disease control, supporting the need for future prospective studies to evaluate risk-adapted frontline, consolidation, or maintenance strategies. Full article

Background: Intraventricular central nervous system (CNS) lymphoma is an atypical presentation of extranodal lymphoma, whether primary or secondary. The most commonly diagnosed subtype of lymphoma is diffuse large B-cell lymphoma (DLBCL). There is a documented relation of HIV, EBV and KSHV infections with lymphomagenesis. AIDS-related lymphomas (ARLs) are described as a defining illness of the acquired immunodeficiency syndrome (AIDS). This study presents a novel case and systematic review of clinical, radiographic and histopathological features of intraventricular lymphomas. Methods: We report on a 27-year-old woman with a left lateral ventricle DLBCL with surrounding edema treated with steroids. A systematic review of 147 additional cases (1977–2025) was conducted, analyzing patient demographics, tumor characteristics, clinical features, imaging, treatment, and outcomes. The tumor locations were divided into three groups depending on the extent of ventricular involvement. Descriptive statistics summarized findings. Findings: 147 cases (mean age, 54.2 years; range, 3–87; 63.3% male) were analyzed. Immunodeficiency in patients was unusual (6.1%). Fully intraventricular lesions were the most common presentation (52.4%), with systemic involvement solely in 10 cases (6.8%). The lesions were predominantly located in the lateral ventricles or fourth ventricles (46 times each), and bilateral involvement was noted 37 additional times. DLBCL was diagnosed in 101 cases (78.9%). Interpretation: Intraventricular involvement in central nervous system lymphoma poses a diagnostic and therapeutic challenge due to non-specific symptoms and atypical locations. Adding to the diagnostic difficulty of intraventricular masses in young patients, we wish to highlight that immunocompromised patients are a notably insignificant subgroup of patients in our study. Full article

Epstein–Barr virus (EBV)-positive primary central nervous system lymphoma (PCNSL) is a rare entity typically associated with profound immunosuppression, most commonly in transplant recipients or individuals with HIV. We report a case of EBV-positive PCNSL arising in a 75-year-old male with myasthenia gravis receiving chronic mycophenolate mofetil (MMF) therapy outside the transplant setting. The patient presented with progressive neurological deficits, and brain magnetic resonance imaging demonstrated multiple enhancing lesions. Stereotactic biopsy revealed diffuse large B-cell lymphoma of non–germinal center subtype with immunoblastic features and EBV-encoded RNA (EBER) positivity, confirming EBV-positive PCNSL. MMF was discontinued, and the patient was treated with rituximab and high-dose methotrexate, resulting in stable disease. This case highlights that prolonged MMF therapy may confer sufficient immunosuppression to permit EBV-driven lymphoproliferative disease even in non-transplant patients. Early recognition, withdrawal of immunosuppression, and initiation of methotrexate-based chemotherapy can lead to favorable outcomes. Full article

Background/Objectives: Central Nervous System (CNS) relapse represents a severe and often fatal complication of Diffuse Large B-Cell Lymphoma (DLBCL). This study aimed to evaluate clinical, biological, and treatment-related factors associated with progression-free survival (PFS) until CNS relapse in patients with DLBCL. Methods: A retrospective cohort study was conducted using clinical data from adult DLBCL patients evaluated and treated at the Regional Institute of Oncology, Iași, Romania, between 2015 and 2023. Associations between clinical, biological, and treatment-related variables and CNS relapse were evaluated using univariate and multivariable Cox proportional hazards models, Fine–Gray competing-risk analyses, and propensity score-based methods to address confounding by indication for CNS prophylaxis. Results: Twenty-six CNS relapse events (6.3%) and 72 deaths without prior CNS relapse occurred over a median follow-up of 12 months. In the prespecified reduced multivariable Cox model, non-R-CHOP regimens (HR 4.57, 95% CI 1.67–12.52; p = 0.003) and high CNS-IPI scores (HR 4.70, 95% CI 1.14–19.46; p = 0.033) were independently associated with CNS relapse. The 20-month cumulative incidence of CNS relapse was 7.0% in the R-CHOP-like group versus 35.2% in the non-R-CHOP group (Gray’s test p < 0.001). Fine–Gray modeling confirmed the association for non-R-CHOP regimens (SHR 3.38, 95% CI 1.21–9.45; p = 0.02). Cell-of-origin subtype, double-expressor phenotype, and Ki-67 were not significantly associated with CNS relapse. Conclusions: High CNS-IPI and treatment with non-R-CHOP regimens independently predicted earlier CNS relapse. Future multicenter studies with molecular profiling are needed to refine CNS risk stratification. Full article

Background/Objectives: To study the hypothesis that cognitive functions and learning skills are impaired in child/adolescent childhood cancer survivors (CCS). Secondary outcomes included psychosocial parameters and quality of life. Methods: This case–control study was conducted over four years (2017–2021) at the largest pediatric Aghia Sophia Children’s Hospital, in Greece. Eligible participants were children and adolescents in Greece. For CCS, ≥1 year should have elapsed from completion of cancer treatment. Assessments of neurocognitive function, learning and psychosocial skills and health-related quality of life (HRQoL) were performed with validated instruments (WISC-III, LAMDA software, Achenbach CBCL/6-18 and YSR, KIDSCREEN-52, respectively). Results: In total, 219 participants (47.49% males, mean age ± SD 11.72 ± 2.32 years), 70 CCS and 149 controls (matched for age, sex, family income), were included. Cases were CCS of acute lymphoblastic leukemia (n = 25)/brain tumors (n = 19)/lymphoma (n = 17)/nephroblastoma (n = 5)/Ewing sarcoma (n = 3)/rhabdomyosarcoma (n = 1). CCS had worse scores in full-scale Intelligence Quotient (FSIQ) (p = 0.004), verbal IQ (VIQ) (p = 0.005) and all its subscales, performance IQ (PIQ) (p = 0.021), and almost all learning parameters than controls. Attention, working memory, writing/visual–motor coordination, processing accuracy/speed, language acquisition/expression, all psychosocial scales, and HRQoL domains of mood and emotions, were negatively affected in CCS. Female CCS demonstrated lower FSIQ (p = 0.019) and VIQ (p = 0.014) than control females, whereas male CCS retained their total IQ unaffected. Among CCS, those with non-central nervous system (CNS) tumors, higher parental educational level or higher family income had significantly higher IQ than those with CNS tumors, lower parental educational level or lower family income, respectively. Conclusions: CCS in Greece carry a significant burden of cognitive and psychological morbidity. Cognitive/educational and psychosocial support to CCS is imperative. Full article

Background/Objectives: The high risk of CNS dissemination poses a significant challenge in the management of primary vitreoretinal lymphoma (PVRL). We evaluated the clinical value of our institutional protocol for PVRL, which combines targeted vitreous sampling with routine central nervous system (CNS) surveillance using magnetic resonance imaging (MRI) every 4–6 months. Methods: We retrospectively reviewed 34 consecutive patients who underwent vitreous biopsies at Niigata University Hospital between January 2010 and December 2021; 12 patients were initially diagnosed with PVRL without CNS involvement. The protocol mandates submission of both undiluted vitreous samples and the entire vitreous cassette contents, including perfusion fluid, for cytologic evaluation. Patients with PVRL underwent MRI surveillance every 4–6 months. Results: Among 12 patients with PVRL, vitreous cytology classified as Class IV or higher demonstrated a positivity rate of 75% (9/12) using undiluted samples alone, which increased to 92% (11/12) when cassette contents were included. Ancillary test results revealed an interleukin (IL)-10/IL-6 ratio > 1 in 75% (9/12) and immunoglobulin heavy chain gene rearrangement in 92% (11/12). Extraocular relapse occurred in 92% of patients (11/12), including 10 cases of CNS involvement and one systemic relapse, with a mean time to CNS progression of 11.8 months. The 5-year overall survival was 58%. Conclusions: Comprehensive vitreous sampling incorporating perfusion fluid may improve cytologic detection in PVRL within a single-center setting. Routine MRI surveillance facilitates early detection of CNS relapse in patients with PVRL; however, a survival benefit cannot be established from this retrospective analysis. Full article

Introduction: Central nervous system (CNS) involvement is reported to represent 5% of extranodal diffuse large B cell lymphoma (DLBCL) at diagnosis. To stratify patients’ risk of CNS involvement, the CNS-International Prognostic Index (CNS-IPI) score was developed. Serum uric acid level has not been incorporated into IPI or CNS-IPI score and its correlation with CNS-IPI risk groups and the CNS relapse has not been studied to date. Therefore, we aimed to retrospectively analyze the relationship between uric acid levels and CNS relapse risk in patients with newly diagnosed adult DLBCL. Methods: Ninety-four adult newly diagnosed DLBCL patients were retrospectively assessed via electronic records and patient files. Demographic data, IPI and CNS-IPI scores, hematologic parameters, serum lactate dehydrogenase, beta-2 microglobulin, serum uric acid and creatinine levels at diagnosis were recorded for analysis. Uric acid levels were compared between CNS-IPI low-intermediate and high groups and cumulative incidence of CNS relapses were analyzed between normal and elevated uric acid levels. Results: Uric acid levels were found to be significantly higher in CNS-IPI high-risk patients (p = 0.008). Elevated serum uric acid levels at diagnosis were significantly associated with high CNS-IPI risk in the logistic regression analysis (OR 1.34, 95% CI 1.05–1.78, p = 0.047). Uric acid also higher than 5.39 mg/dL showed a discriminatory ability in ROC analyses (AUC 0.633, 95% CI 0.495–0.771, p = 0.05). In the competing risks regression analysis, accounting for non-CNS-related death and progression as the competing events, CNS-IPI subgroups and uric acid levels were not significantly associated with the cumulative incidence of CNS relapse (SHR 0.81, 95% CI 0.12–5.59; Fine–Gray, p = 0.834), (SHR 0.55, 95% CI 0.09–3.47; Fine–Gray, p = 0.526), respectively. Conclusions: Even though uric acid levels are significantly higher and showed a discriminatory ability to detect the CNS-IPI high subgroup, elevated uric acid levels could not predict the CNS relapses. Full article

Cerebrospinal fluid (CSF) liquid biopsy has been recently recommended by the National Comprehensive Cancer Network (NCCN) as a molecular diagnostic tool for central nervous system (CNS) lymphoma that offers a minimally invasive method to detect key biomarkers when traditional diagnostics are limited by sensitivity or feasibility. This brief report describes the clinical use of two novel CLIA/CAP-approved CSF liquid biopsy tests from Belay Diagnostics, Summit™ and Vantage™, to aid in the diagnosis and management of CNS lymphoma. Results from both tests were reviewed for 50 CSF samples in the context of clinical information provided with the test order. Summit™ and Vantage™ detected clinically significant alterations in CNS lymphoma-associated genes such as MYD88, CD79B, and TP53 as well as MGMT methylation when other modalities (e.g., CSF cytology, MRI, or brain biopsy) were inconclusive. In several cases of suspected secondary CNS lymphoma, Summit™ detected pathogenic genomic variants as well as mild to high levels of aneuploidy, suggesting CNS involvement. Belay testing impacted management in 41 of 50 (82%) cases by informing CNS lymphoma diagnosis, stratification, or progression as well as therapeutic response with an overall false negative rate of 18% (2/11). This report contributes to the growing body of literature that demonstrates how comprehensive molecular profiling of CSF enhances detection and characterization of CNS lymphoma and offers a promising adjunct to conventional diagnostics. Full article

Introduction: The existence of primary adrenal gland lymphoma (PAGL) has been debated due to lack of lymphoid tissue in the adrenal glands. PAGL is extremely rare, accounting for less than 1% of all types of lymphomas. The aim of this study was to analyze patients with PAGL in Polish population. Material and Methods: We retrospectively reviewed 13 adult patients with PAGL diagnosed in Polish Hematological Centers. Results: A total of 13 patients (5 women and 8 men) with PAGL were included into the study. The median age at the diagnosis was 69.1 years (range: 31–85). The most common histological type was diffuse large B-cell lymphoma (DLBCL)-12 patients, the remaining one was diagnosed with Hodgkin lymphoma (HL). In 7 patients (54%), the left adrenal gland was involved; in 3 patients (23.5%), the right adrenal gland was involved; and 3 patients (23.5%) had bilateral lymphoma. Systemic symptoms (B symptoms) were observed in 11 out of 13 patients (85%). Two patients (15%) were treated with chemotherapy alone and the remaining eleven patients (85%) with immune and chemotherapy together (85%). During the follow-up period, 11 patients died, 8 had relapsed or refractory disease (62%), and 3 patients (23%) had relapse in central nervous system (CNS). The median progression-free survival (PFS) was 14.63 months, while the median overall survival (OS) was 20.30 months. Adrenalectomy of the involved adrenal gland was associated with shorter PFS (p = 0.0165), with trend of shorter OS. Achieving complete remission (CR) after front line treatment was associated with significantly longer OS (p = 0.0239) and PFS (p = 0.0152). Conclusions: Adrenal glands are extremely rare as primary locations of extranodal lymphoma. The prognosis of PAGL is generally poor. In this study, we described demographic, clinical, and pathological characteristics as well as factors that may affect survival among these groups. So far, it is the largest polish multicenter experience describing patients with PAGL. Full article

Background/Objectives: Relapsed and refractory (rr) primary large B-cell lymphoma of the central nervous system (PCNSL) has a dismal prognosis, and the standard of care is not established. The most common genetic imbalance includes the B-cell lymphoma 2 (BCL-2) locus. Methods: We planned a bi-centric phase Ib dose-escalation study with the chemotherapy-free combination of the BCL-2 inhibitor venetoclax and CD20 antibody obinutuzumab for rrPCNSL patients in Germany. The intended treatment consisted of 6 cycles of fixed-dose obinutuzumab at 1000 mg intravenously every 3 weeks, and an oral daily dose of 600, 800, or 1000 mg venetoclax, depending on the planned dosing group, followed by a 12-month venetoclax maintenance period. The primary endpoint was the pharmacokinetics of venetoclax and obinutuzumab in cerebrospinal fluid (CSF). Results: This study was prematurely terminated after registration of 5/15 (33%) patients in dosing group 1 (600 mg oral daily dose of venetoclax) between May 2020 and November 2021. The mean ratio of the concentration of venetoclax in CSF over peripheral blood was 0.55% (±0.28 standard deviation (SD)) and 0.25% (±0.23 SD) for obinutuzumab. Two of five patients achieved complete remission, and each one patient achieved partial remission and stable disease as best response. The median duration of response was 6.5 months (range 0.7–47). Conclusions: Venetoclax and obinutuzumab can penetrate into the central nervous system, but the CSF concentration did not correlate with the outcome. The combination is feasible, tolerable, and may lead to durable responses in selected rrPCNSL patients. Full article