Type Of Lymphoma Research Articles

Tissue Eosinophilia in B-cell Lymphoma: An Underrecognized Phenomenon.

Tissue eosinophilia is seldom reported in B-cell lymphoma. It poses diagnostic challenges and frequently leads to the consideration of other diagnoses, particularly T-cell lymphomas. The scarce literature underscores the need for in-depth studies to enhance awareness and understanding of this phenomenon. We investigated 54 cases of B-cell lymphoma with notable tissue eosinophils, analyzing clinical information, hematoxylin and eosin staining, immunohistochemistry, and PCR-based clonality analysis. Nodal marginal zone lymphoma (NMZL) emerged as the most prevalent type (n=26), followed by B-cell lymphoma, not otherwise specified (n=13), diffuse large B-cell lymphoma (n=10), follicular lymphoma (n=2), chronic lymphocytic leukemia/small lymphocytic lymphoma (n=1), extranodal marginal zone lymphoma (n=1), and primary cutaneous marginal zone lymphoma (n=1). Shared features across different lymphoma types, best exemplified by NMZL, included plasmacytic differentiation (57.7%), increased vascularity (84.6%) with a tendency for perivascular distribution of neoplastic cells, and a tumor microenvironment abundant in T cells and histiocytes; some cases showed increased PD-1-positive cells. These features often raise consideration of angioimmunoblastic T-cell lymphoma. Along with clonality analysis, features supporting the diagnosis of B-cell lymphoma included cytological atypia in B cells rather than T cells, and the lack of follicular dendritic cell meshwork expansion. In addition, diffuse large B-cell lymphoma frequently exhibited interfollicular distribution and monocytoid appearance, indicating the possibility of transformed NMZL. Collectively, tissue eosinophilia can occur in diverse B-cell lymphomas but is most prevalent in tumors with a postgerminal stage of differentiation.

Clinical and imaging features of lymphomatosis cerebri: analysis of 8 cases and systematic review of the literature

Lymphomatosis cerebri (LC) is a rare type of primary central nervous system lymphoma with diffuse, nonenhancing infiltrative lesions and is often misdiagnosed. Our study aimed to investigate the clinical characteristics and prognosis of LC through analyzing patients from the literature and our own center, so as to improve early diagnosis and treatment. PubMed, Web of Science and our hospital databases were reviewed, and information on demographic, clinical, pathological, cerebrospinal fluid (CSF), neuroimaging and treatment options was extracted. Univariate survival analysis was conducted by generating survival curves and comparing them using the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression model to identify the prognostic predictors. A total of 81 patients (median age: 58 years; interquartile range, IQR: 50–66.5 years), 45 males and 36 females, were included. The most common symptoms were cognitive impairment (65.4%) and gait impairment (50.6%). Imaging studies indicated that all 81 patients had supratentorial structure involvement, and 93.8% (76/81) had bilateral hemisphere involvement. There were 53.3% (32/60) patients with CSF pleocytosis and 65% (39/60) patients with increased CSF protein levels. The median time of diagnosis was 4.8 months (IQR: 2.3–6.9 months). Compared with 4 (95% CI: 1.78–6.22) months for all 81 patients, the median OS was 20 (95% CI: 8.24–31.76) months for those who had chemotherapy plus radiotherapy. Multivariate Cox analysis revealed that chemoradiotherapy (HR: 0.12; 95% CI: 0.02–0.68) and higher CSF glucose level (HR: 0.01; 95% CI: 0.00–0.26) were inversely associated with death. The diagnosis of LC should be alerted when neuroimaging with bilateral hemispheric involvement and CSF abnormality with pleocytosis and increased protein. Once the diagnosis is confirmed, the combination of chemotherapy and radiotherapy can be considered if the patient’s physical condition permits.Journal standard instruction requires an unstructured abstract. Kindly check and confirm.We have checked and confirmed that there is no problem.

NCMP-29. THE NATURAL HISTORY OF NEUROLYMPHOMATOSIS

Abstract Neurolymphomatosis is a rare lymphoid malignancy of the peripheral nervous system. Patients suffer from debilitating neurological deficits due to lymphoma invasion into one or more peripheral nerves and the natural history of this disease is still poorly understood. We performed a PubMed search and extracted data on year of publication, age, gender, type of lymphoma, nerves involved, imaging modalities, treatment received, and survival times. Kaplan-Meier statistics were used to determine outcome parameters over time and compare prognostic factors. Multiple comparisons were done to determine differences among groups. Our search identified 559 patients from 286 articles. Median age was 61 years (range 2-92) from 326 males, 222 females, and 11 with unspecified gender. Median overall survival (OS) was 12.0 months (range 10.0-15.0) for the entire cohort. Most frequent histologies were diffuse large B-cell lymphoma, unspecified T-cell lymphoma, and unspecified B-cell lymphoma, involving the brachial plexus, cranial nerves, and sciatic nerve. None had molecular profiling. There was a progressive lengthening of OS in successive decades, from 0.5 (95%CI 0.0-0.8) to 26.4 (95%CI 18.0-34.8) months from 1951-2022 (r2=0.9432, p< 0.001). Time from first treatment to progression also increased from 2.0 (95%CI N/A) to 28.3 (95%CI 23.1-33.5) months (r2=0.6923, p< 0.001). However, time from symptom onset to diagnosis remained unchanged during this period (r2=0.6206, p=0.277). Patients were most frequently treated with methotrexate-based chemotherapies (n=81), rituximab-based chemotherapies (n=176), and/or radiation (n=79). Only 12 received 3 or more regimens. Primary neurolymphomatosis had a better prognosis than secondary neurolymphomatosis, median OS 15.0 (95%CI 11.0-33.0) vs. 10.0 (95%CI 10.0-10.0) months (p=0.016). No OS difference was noted between B- and T-cell disease (p=0.4393), while patients with low-grade B-cell neurolymphomatosis did better than those with Burkitt's lymphoma (p≤0.001). Outcome for patients with neurolymphomatosis has improved over time. But timely diagnosis remains a major problem that needs improvement.

Single-Cell Analysis Reveals Malignant Cells Reshape the Cellular Landscape and Foster an Immunosuppressive Microenvironment of Extranodal NK/T-Cell Lymphoma.

Extranodal natural killer/T-cell lymphoma (NKTCL) is an aggressive type of lymphoma associated with Epstein-Barr virus (EBV) and characterized by heterogeneous tumor behaviors. To better understand the origins of the heterogeneity, this study utilizes single-cell RNA sequencing (scRNA-seq) analysis to profile the tumor microenvironment (TME) of NKTCL at the single-cell level. Together with in vitro and in vivo models, the study identifies a subset of LMP1+ malignant NK cells contributing to the tumorigenesis and development of heterogeneous malignant cells in NKTCL. Furthermore, malignant NK cells interact with various immunocytes via chemokines and their receptors, secrete substantial DPP4 that impairs the chemotaxis of immunocytes and regulates their infiltration. They also exhibit an immunosuppressive effect on T cells, which is further boosted by LMP1. Moreover, high transcription of EBV-encoded genes and low infiltration of tumor-associated macrophages (TAMs) are favorable prognostic indicators for NKTCL in multiple patient cohorts. This study for the first time deciphers the heterogeneous composition of NKTCL TME at single-cell resolution, highlighting the crucial role of malignant NK cells with EBV-encoded LMP1 in reshaping the cellular landscape and fostering an immunosuppressive microenvironment. These findings provide insights into understanding the pathogenic mechanisms of NKTCL and developing novel therapeutic strategies against NKTCL.

Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription.

MYC+ lymphomas are refractory to standard of care and novel treatments that downregulate MYC are needed. The utility of enitociclib, a selective CDK9 inhibitor in this patient population, is demonstrated in preclinical models and patients. Enitociclib inhibits RNA polymerase II function conferring a transcriptional shift and depletion of MYC and MCL1. Enitociclib intermittent dosing downregulates transcription factors including MYC, providing a therapeutic window for durable responses in patients with MYC+ lymphoma.

Expression of PD-1/PD-L1 in peripheral blood and tumor tissues of patients with classical Hodgkin's lymphoma.

Significant biomarkers can predict and estimate the response to chemotherapy for different types of lymphoma. Classical Hodgkin's lymphoma (cHL) and peripheral T-cell lymphoma (PTCL) belong to different types of lymphoma, their prognosis is very different, programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) have been studied in these 2 types of diseases. However, few studies have involved the difference in PD-1/PD-L1 levels between cHL and PTCL. To find out the difference and relevant clinical application value, we collected blood samples of 29 newly diagnosed cHL patients and 11 newly diagnosed PTCL ones. At the same time, tumor tissue paraffin sections of 13 patients with cHL were collected at the initial diagnosis. Flow cytometry, enzyme-linked immunosorbent assay, and immunohistochemical staining were used to detect PD-1/PD-L1 levels in peripheral blood T cells, plasma, and tumor tissues, and the relationship between the above results and clinical data of patients in patients with cHL were investigated. The levels of PD-1 on CD4+ T cells, PD-L1 on CD4+ T cells and PD-1 on CD8+ T cells in peripheral blood of cHL and PTCL patients were higher than those of healthy controls, the level of PD-1 in CD4+ T cells from peripheral blood was higher from cHL patients with stage III-IV (P = .0178), B symptoms (P = .0398), higher lactate dehydrogenase (P = .0056), higher international prognostic index score (P = .0349), and relapsed in later stages (P = .0306). The expression level of soluble PD-L1 (sPD-L1) from cHL (P < .001) and PTCL (P < .0001) patients was higher than that of the healthy control group, and there was higher sPD-L1 level in patients with higher international prognostic index scores (P = .0016). The dynamic detection of sPD-L1 showed that after 2 courses of chemotherapy, the sPD-L1 level in cHL patients with complete remission declined, but the level of sPD-L1 from patients with incomplete remission was not significantly changed (P > .05). In tumor tissues of cHL patients, PD-1(+) was 77%, PD-L1(+) was 69%, PD-1 and PD-L1 expression levels were high. Our results suggest that PD-1 levels in peripheral blood CD4+ T cells are helpful for the stage of disease in patients with cHL, and the dynamic detection of sPD-L1 level is helpful for the judgment of patients with cHL.

Cathepsin W, T-cell receptor-associated transmembrane adapter 1, lymphotactin and killer cell lectin like receptor K1 are sensitive and specific RNA biomarkers of canine epitheliotropic lymphoma.

Cutaneous T-cell lymphoma (CTCL) is an uncommon type of lymphoma involving malignant skin-resident or skin-homing T cells. Canine epitheliotropic lymphoma (EL) is the most common form of CTCL in dogs, and it also spontaneously arises from T lymphocytes in the mucosa and skin. Clinically, it can be difficult to distinguish early-stage CTCLs apart from other forms of benign interface dermatitis (ID) in both dogs and people. Our objective was to identify novel biomarkers that can distinguish EL from other forms of ID, and perform comparative transcriptomics of human CTCL and canine EL. Here, we present a retrospective gene expression study that employed archival tissue from biorepositories. We analyzed a discovery cohort of 6 canines and a validation cohort of 8 canines with EL which occurred spontaneously in client-owned companion dogs. We performed comparative targeted transcriptomics studies using NanoString to assess 160 genes from lesional skin biopsies from the discovery cohort and 800 genes from the validation cohort to identify any significant differences that may reflect oncogenesis and immunopathogenesis. We further sought to determine if gene expression in EL and CTCL are conserved across humans and canines by comparing our data to previously published human datasets. Similar chemokine profiles were observed in dog EL and human CTCL, and analyses were performed to validate potential biomarkers and drivers of disease. In dogs, we found enrichment of T cell gene signatures, with upregulation of IFNG, TNF, PRF1, IL15, CD244, CXCL10, and CCL5 in EL in dogs compared to healthy controls. Importantly, CTSW, TRAT1 and KLRK1 distinguished EL from all other forms of interface dermatitis we studied, providing much-needed biomarkers for the veterinary field. XCL1/XCL2 were also highly specific of EL in our validation cohort. Future studies exploring the oncogenesis of spontaneous lymphomas in companion animals will expand our understanding of these disorders. Biomarkers may be useful for predicting disease prognosis and treatment responses. We plan to use our data to inform future development of targeted therapies, as well as for repurposing drugs for both veterinary and human medicine.

Polygenic HLA-Class I and HLA-Class II Models Define Various Types of Lymphoma

Introduction: Human leukocyte antigen (HLA) plays a major role in the interaction between the immune system and oncogenic process in various types of tumors including lymphoma. Mono-allelic and bi-allelic loss of the HLA-I has been reported in diffuse large B-cell lymphoma (DLBCL) and other types of lymphoma. Poor outcome was also reported with the loss of the HLA-I system in lymphoma. Since HLA-I and HLA-II are both critical for healthy immune response and both can be expressed in the lymphoma cells as well as in the lymphoma responding microenvironment, analyzing both systems is crucial for deciphering the role of the HLA system in lymphoma. Toward this goal, we evaluated the expression level of various HLA-I and HLA-II genes and compared these levels between subtypes of lymphoma. We quantified RNA expression levels of 15 HLA-I and HLA-II genes using next generation sequencing (NGS) and used machine learning algorithm (random forest) to evaluate the depth of the significance in variation of the expression profiles between various types of lymphoma. Methods: RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue from 99 diffuse large B-cell lymphoma (DLBCL), 79 T-cell lymphoma, 40 follicular lymphoma, 28 mantle cell lymphoma, and 14 Hodgkin lymphoma samples. RNA sequencing was performed using a targeted hybrid capture panel. The sequenced HLA-I genes were HLA-A, HLA-B, HLA-C, HLA-E, HLA-F, and HLA-H. The sequenced HLA-II genes were HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB5, and HLA-DRB6. Salmon v1.4.0 software was used for expression quantification (TPM). Random forest machine learning system was used for predicting subtypes. Two thirds of samples were used for training the random forest algorithm and one third was used for testing. Results: RNA levels of individual HLA-I and HLA-II genes varied mildly between various B-cell lymphoma subtypes without specific pattern, especially after adjusting for multiple testing. However, T-cell lymphoma showed overall significantly (P&amp;lt; 0.0001) higher HLA-I (B, C, and F) and lower HLA-II (DRB1 and DRB5) expression levels as compared with B-cell lymphoma. In contrast, using machine learning algorithm to evaluate combination of HLA-I and HLA-II expression profiles showed discrete and significant differences between various types of lymphoma. The levels of expression of HLA-I and HLA-II genes were adequate to distinguish between DLBCL and follicular lymphoma with AUC of 0.778 (95% CI: 0.46-1.00), and between DLBCL and T-cell lymphoma with AUC of 0.833 (95% CI: 0.624-1.00). The number of Hodgkin lymphoma and mantle cell cases was small but the random forest distinguished between DLBCL and Hodgkin lymphoma with AUC of 0.833 (95% CI: 0.294-1.00), and between DLBCL and mantle cell lymphoma with AUC of 0.778 (95% CI: 0.416-1.00). Conclusions: This data confirms the polygenic effects of the HLA-I and HLA-II on various types of lymphoma. The HLA-I and HLA-II combined expression profiles are significantly different between various types of lymphoma. More importantly, this data suggests that immune modulating therapy should consider the polygenic effects of both the HLA-I and HLA-II systems.

Development and External Validation of a Lymphoma-Specific Venous Thromboembolism Risk Assessment Model

Introduction: Venous thromboembolism (VTE) significantly affects cancer patients undergoing systemic therapy. Existing risk models developed in the pan-cancer population, such as the Khorana score, offer limited discrimination in cancer-specific setting. We aimed to develop and validate a risk assessment model (RAM) tailored for lymphoma patients, accounting for the clinical and sociodemographic heterogeneity across three distinct healthcare systems in the United States. Methods: Electronic health records (EHR) linked to cancer registry 2006-2021 from the Veterans Affairs national healthcare system (VA) with a total of 10,313 lymphoma patients were randomly divided into an 80% derivation cohort and a 20% internal validation cohort. Further external validation was carried out using data from two other healthcare systems - Harris Health System (HHS, N= 854, 2011-2020) and MD Anderson Cancer Center (MDACC, N=1,858, 2017-2020). Patients were included if they had newly diagnosed lymphoma requiring first-line systemic therapy within 1 year of diagnosis. Patients were excluded if they had recent diagnosis of acute VTE within the last 6 months or were prescribed anticoagulant within 1 month before index date. The index date was the time of systemic therapy, and all covariates were extracted on or before the index date. Incident VTE was defined using our published computable phenotype algorithm (PMID 36626707; 37067102). For RAM derivation (Figure 1), 32 candidate predictors were initially chosen based on clinical relevance and EHR data availability. Missing values were imputed via chain random forest. Parsimonious variable categories were selected by a combination of Least Absolute Shrinkage and Selection Operator (LASSO), Recursive Feature Elimination (RFE), and random forest to generate the final logistic regression model. For external validation, complete case analysis was performed using the derived beta coefficients without model refitting. Bootstrapped time-dependent c statistics and calibration curves for 6-month VTE were used to assess discrimination and fit. A pre-determined threshold of 8% VTE at 6-month from the predicted probability was used to stratify high vs. low-risk groups. Competing risk models were used to assess cumulative incidence. Results: At 6 months, the VTE incidence were 5.75% (n=469) in VA derivation and 6.12% (n=124), 8.24% (n=69), and 6.55% (n=112) in the VA, HHS, and MDACC validation cohorts, respectively. The three healthcare systems had different baseline characteristics in demographics, lymphoma types, systemic therapies, and comorbidities. Patients from VA were mostly older males with more comorbidities and remote history of VTE, patients from HHS were mostly uninsured minorities who were younger but with more aggressive histology, while those from MDACC were patients treated at a comprehensive cancer center. The variables in the final RAM included lymphoma type (4 groups ranging from very-low to very-high risk), body mass index, indwelling catheter, cytotoxic vs. targeted therapy, history of VTE, recent hospitalization, and paralysis/immobilization. Table 1 shows the variable prevalence in each cohort. As shown in Figure 1, the new RAM showed promising discrimination for VTE with a C-statistic of 0.69 in the derivation cohort and 0.67, 0.70, 0.72 in the internal and two external validation cohorts. By splitting patients using an 8% predicted risk threshold, the high- vs. low-risk group achieved a clear differentiation in risk stratification despite significant differences in baseline characteristics. This represented a noticeable improvement for lymphoma patients over the Khorana Score, which yielded C-statistics of 0.53-0.56. The overall calibration of the RAM appeared adequate. Conclusions: Using multiple cancer-EHR cohorts with heterogeneous patients and a wide range of lymphoma subtypes, we successfully derived and externally validated an improved RAM for VTE specifically in lymphoma patients requiring early initiation of systemic therapy. Along several well-known patient-specific risk factors, lymphoma type was an important predictor of VTE risk. The new RAM could improve VTE risk stratification and prevention efforts in lymphoma patients.

Clinical Course of Adult T-Cell Leukemia-Lymphoma with Central Nervous System Involvement

Background: Adult T-cell leukemia-lymphoma (ATL) is a peripheral T-cell lymphoma with a highly diverse clinical presentation. Although central nervous system (CNS) involvement is common, the detailed clinical presentation of CNS-ATL needs to be clarified. Objective: This study aims to clarify the clinical course of ATL with CNS involvement. CNS involvement was classified according to the criteria of JALSG202 for acute lymphocytic leukemia as follows: Grade I: no symptoms and cerebrospinal fluid (CSF)cell count less than 5/μl and presence of abnormal lymphocytes; Grade II: asymptomatic and CSF cell count 5-50/μl and presence of abnormal lymphocytes; Grade III: symptomatic or CSF cell counts &amp;gt; 50 cells/μl and presence of abnormal lymphocytes. Results: The analysis included 213 cases of ATL treated at Kagoshima University Hospital from 2002 to 2021. Of these aggressive ATL cases, the clinical subtypes at initial presentation were as follows: acute type 109, lymphoma type 54, chronic type 30, smoldering type 18, and 2 cases were unclassifiable. The median age of the patients was 63 years, and 96 cases (45.1%) were women. Sixty patients had received allogeneic hematopoietic stem cell transplants. During the clinical course, 28 patients (13.1%) with a median age of 61 years and 13 women（46.4%）had CNS involvement. Two cases were classified as Grade I, six as Grade II, and 20 as Grade III. Among them, nine patients (4.2%) showed neurological symptoms at the initial ATL diagnosis, and 1 patient presented with neurological findings at the time of chronic to acute transformation. Of the remaining 203 patients, prophylactic intrathecal chemotherapy was administered in 101 cases, at which time CNS involvement was diagnosed in 9 cases (8.9%). Three patients developed symptomatic involvement while responding to chemotherapy. One patient developed symptomatic involvement when refractory to chemotherapy. Four cases were CNS recurrence with systemic disease progression after remission. Two cases were identified as primary CNS-ATL. The simplified ATL-PI (Prognostic Index) at initial ATL diagnosis for the 28 patients with CNS involvement revealed four cases with high-risk, thirteen with intermediate-risk, two with low-risk, six not eligible due to indolent ATL subtypes, and three cases with unknown risk. The incidence of CNS involvement by ATL subtype was 17.8% (19/107) for acute type, 1.8% (1/54) for lymphoma type, 16.7% (5/30) for chronic type, and 0% for smoldering type (excluding 1 case of unknown subtype and 2 cases of primary CNS-ATL) at ATL diagnosis. At the diagnosis of CNS involvement, 15 (53.6％) patients showed at least 5% of ATL cells in the peripheral blood. During a median observation period of 429 days, the 1-year cumulative incidence of CNS involvement was 12.3% (95% CI 8.3-17.1%). High-dose methotrexate-based therapy was administered to 5 patients with CNS involvement, which had a certain effect on CNS lesions but had limited efficacy for other lesions. All of these cases were treated with concomitant intrathecal chemotherapy. The 2-year overall survival rate after diagnosis of CNS involvement was 16.9% (95% CI 4.9-35.2%). The CNS-IPI (International Prognostic Index) did not predict CNS involvement in ATL. Conclusions: This is the largest study to examine the clinical course of CNS involvement of ATL. The 1-year cumulative incidence of CNS involvement was 12.3%, indicating that CNS involvement is an early complication after diagnosis of aggressive ATL, especially in leukemic subtypes. The prognosis after the diagnosis of CNS involvement was also clarified. The high frequency of CNS involvement during prophylactic intrathecal chemotherapy in patients with ATL without neurological symptoms suggests that it is an important clinical question that needs to be addressed.

Favorable Outcome of Abbreviated R-CHOP in Patients with Primary Testicular Lymphoma

Background Primary testicular lymphoma (PTL) is a rare type of extranodal large B-cell lymphoma with an increased risk of relapse mostly involving the contralateral testis or central nervous system (CNS). To minimize the risk of relapse, Vitolo et al. (2011) introduced a multimodality approach in limited stage PTL including radical orchiectomy, 6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) with 4 intrathecal methotrexate (MTX IT) administrations and radiotherapy of the contralateral testis. In limited stage diffuse large B-cell lymphoma, without involvement of the testis, 4 cycles of R-CHOP proved non-inferior to 6 cycles of R-CHOP (Poeschel et al. 2019; Persky et al. 2020). However, it is unknown whether the number of cycles of R-CHOP can be reduced in PTL. Therefore, we aimed to evaluate the impact of the number of R-CHOP cycles on outcome in PTL patients in the Netherlands. Methods PTL patients ≥18 years, Ann Arbor stage I-II, diagnosed in 2014-2021, who received at least 3 cycles of R-CHOP were identified in the Netherlands Cancer Registry, with survival follow-up through 2022. Patients with CNS involvement at diagnosis were excluded. Treatment modalities were categorized as 3 cycles R-CHOP or 6 cycles R-CHOP. Patients who received 4, 5 or more than 6 cycles of R-CHOP were included in the 6 cycles modality. The primary endpoints were progression-free survival (PFS), and overall survival (OS). PFS was defined as the time between end of primary treatment and relapse, or death from any cause, whichever came first, and OS was defined as the time between end of primary treatment and death from any cause. The secondary endpoint was cumulative incidence function (CIF) of CNS relapse, defined as the number of CNS relapses divided by the total number of patients in the study population at risk for a specific time. Uni- and multivariable analyses were conducted to establish independent predictors of risk of relapse and mortality among patients who received 3 cycles of R-CHOP versus 6 cycles of R-CHOP. Uni- and multivariable analysis to calculate risk of relapse and mortality after adjustment for the baseline and treatment characteristics was performed using Cox regression. Results A total of 139 patients were identified: median age, 68 years (range, 37-86 years); stage I, 68%; IPI 0, 87%. Of these patients, 43 received 3 cycles R-CHOP and 96 received 6 cycles R-CHOP (number of cycles 4:4%; 5:6%; 6 or more: 90%). Patients with stage I disease more commonly received 3 cycles of R-CHOP compared to patients with stage II ( p&amp;lt;0.01; Table 1). In combination with R-CHOP, most patients received MTX IT (93%), high-dose MTX (4%) or did not receive prophylaxis (4%). The median number of MTX IT cycles was 5 in patients who received 3 cycles R-CHOP and 6 in patients who received 6 cycles R-CHOP ( p=0.08). Of the patients who received 3 cycles R-CHOP, 29% received &amp;lt;4 MTX IT cycles, compared to 11% in patients who received 6 cycles R-CHOP ( p=0.02). Overall, 82% received radiotherapy, 5% orchidectomy and 13% no consolidation. The median follow-up from end of treatment was 42 months (inter quartile range [IQR], 22-70 months). Overall response rate (ORR; partial remission or greater) for patients who received 3 cycles R-CHOP and 6 cycles R-CHOP were similar (79% versus 86%, respectively, p=0.27). The 5-year PFS and OS were 66% and 75%, respectively. Regarding 3 versus 6 R-CHOP, the 5-year PFS and OS were similar, i.e. 65% versus 67% ( p=0.81) and 73% versus 76% ( p=0.69), respectively (Figure 1). In univariable analysis, risk of relapse and mortality were similar for patients who received 3 cycles of R-CHOP or 6 cycles R-CHOP. In multivariable analysis, none of the covariables influenced the risk of relapse or mortality. The 5-year CIF of CNS was 6.7%, with a median time from end of treatment to CNS relapse of 25 months. 6 (14%) out of 43 PTL patients with 3 cycles R-CHOP relapsed to CNS, and 1 (1%) out of 96 patients with 6 cycles R-CHOP ( p&amp;lt;0.01). The number of MTX cycles was not related on developing a CNS relapse (p=0.81). Conclusion In this nationwide population of PTL patients, nearly one-third of patients received 3 cycles of R-CHOP instead of 6 cycles. No difference in survival was observed between the two groups. These data support investigating reduction of systemic treatment from 6 cycles of R-CHOP in this patient group.

The Role of Radiation in Primary Mediastinal Large B-Cell Lymphoma

Introduction Primary mediastinal large B-cell lymphoma (PMLBCL) is a rare and aggressive type of non-Hodgkin B-cell lymphoma, accounting for about 3% of all non-Hodgkin lymphomas. The role of radiation therapy following immunochemotherapy is controversial and lately there has been more studies suggesting there is less benefit of adding radiation therapy. Large-scale studies describing and evaluating the effect of radiation therapy on survival outcome are lacking. Materials and Methods The National Cancer Database (NCDB) was queried for patients diagnosed with PMLBCL between 2004 and 2019. All patients aged ³18 years diagnosed with PMLBCL were included. We excluded patients with unknown chemotherapy and radiation therapy status, or received radiation prior to chemotherapy, or received radiation 6 months after chemotherapy or lost to follow-up (unknown vital status of last contact). Kaplan-Meier and multivariate Cox regression were used in the analyses. Results The total cohort consisted of 1,899 patients with PMLBCL. Out of whom 1,177 (62%) were females, 1,560 (76%) were White non-Hispanic, 113 (6%) were White Hispanic and 205 (11%) were African Americans. Among patients with known disease stage, 1,164 (61%) had early-stage disease (stage I and II) and 351 (19%) had advanced stage disease (stage III and IV). 1,443 (76%) received chemotherapy only and 456 (24%) received chemotherapy followed by radiation therapy. The median age at diagnosis was 35 years (range 18-90), 1,215 (64%) were diagnosed at younger age (40 years or less). The median follow-up time was 60 months (95% CI 57-62), the median overall survival (OS) for the whole cohort was not reached, and the 5-year OS was 91%. The 5-year OS for early and advanced stage were 93% and 83%, respectively. In patients with early-stage disease, there was no statistically significant difference in the median OS between patients who received chemotherapy only (N=824) compared to patients who received chemotherapy followed by radiation therapy (N=340) (not reached in both groups, P=0.130) with 5-year OS of 92% and 93%, respectively. In patients with advanced stage disease, there was no statistically significant difference in the median OS between patients who received chemotherapy only (N=294) and patients who received chemotherapy followed by radiation therapy (N=57) (median OS not reached in both groups, P=0.067) with 5-year OS of 82% and 88%, respectively. On multivariate analysis, older age and Charlson-Deyo score ≥3 were associated with worse OS (HR 1.062 95% CI 1.047-1.078; P&amp;lt;0.001 and HR 6.032 95% CI 1.853-19.634; P=0.003, respectively), early stage was associated with better OS (HR 0.508 95% CI 0.364-0.708; P&amp;lt;0.001), whereas adding radiation to chemotherapy did not affect the OS (HR 0.713 95% CI 0.491-1.035; P=0.075). Over the years, there was a significant down trend in using radiation therapy (Figure 1). Using univariate and multivariate logistic regression analysis, we found early-stage disease was associated with increased use of radiation therapy after chemotherapy. Whereas patients who were treated at academic/research programs were less likely to receive radiation therapy (Table 1). Conclusion This large real-world analysis shows a practice change in PMLBCL treatment with a trend in omitting radiation therapy. In our analysis, we found that adding radiation therapy to systemic therapy did not affect the survival outcome in both early and advanced stage disease.

Epidemiology and Survival of Patients with Marginal Zone Lymphoma Treated at the National Cancer Institute of Peru. a Retrospective Analysis of 187 Cases

Background Marginal zone lymphoma (MZL) represents a heterogeneous subgroup, classified as extranodal, splenic and nodal lymphoma. Extranodal cases, also termed mucosa-associated lymphoid tissue (MALT), account for 70% of MZLs. Splenic marginal zone B-cell lymphoma (SMZL) accounts for &amp;lt;2% of all NHL. There is no data about marginal zone lymphoma in Latin American patients. Methods We evaluated retrospectively all patients diagnosed with marginal zone lymphoma at the National Cancer Institute from 2010 to 2019. Baseline characteristics, treatments and survival were retrieved from medical records. Kaplan Meier method was used to analyze the overall survival. The estimate of the survival curves was performed by the Kaplan-Meier method, and the differences were computed by the log-rank test. The Cox proportional hazard models were used to identify predictors of survival of MZL. A level of p &amp;lt;0.05 was considered for a statistical significance. Results During the study period 2010-2019, 4437 patients with B-cell non-Hodgkin lymphoma were evaluated at the INEN, 187 of them were marginal zone lymphomas, representing 4.2% of all cases. The most frequent marginal zone lymphoma was MALT, followed by nodal and splenic lymphoma with 89.8%, 5.3% and 4.8% of cases, respectively. The median age for the entire cohort was 59 years (range 17-89). The median age for the MALT, nodal and splenic MZL cohort were 58.5 years (range 17-89), 75 years (range 52-88), 68 years (range 43-87), respectively. 37.4% were male for the entire cohort, and 37%, 40%, 44% for the MALT, nodal and splenic MZL group. Elevated LDH was seen in 13% of the entire cohort and in 11% and 24% of the MALT and splenic MZL group. Transformed lymphoma was reported in 6.4% of the entire cohort, but in the 20% of nodal MZL and no one case of the splenic MZL. More data you can see in the table 1. The most frequent primary site locations for MALT lymphoma were gastric, ocular adnexal, parotid gland, cutaneous, intestinal and CNS with 36%, 30%, 7%, 5%, 5% and 5%, respectively. The median overall survival was 114 months (IQR 76-133) for the entire cohort and 133 months, 59 and 59 months for the MALT, nodal MZL, and splenic MZL, respectively (p=0.0011), see the figure 1. The 5-year OS was 81.4% (95% CI, 71.6-88.1) for the entire cohort and 85.7% (95% CI, 76.5-91.5) for the MALT lymphoma group. No one patients were alive at 5 years in both nodal and splenic lymphoma groups. Conclusion Marginal zone lymphoma is a relatively rare type of B-cell lymphoma. The most frequent type is MALT lymphoma, followed by nodal MZL. The median age for the entire group was 59 years, however patients with nodal MZL were older with a median age of 75 years. Transformed lymphoma was present in 6% of the entire cohort and in the 20% of the nodal MZL. Gastric, ocular adnexal and parotid gland were the most common primary site of MALT lymphoma. MALT lymphoma had long survival, but nodal and splenic MZL had shorter survival with no one surviving 5 years from diagnosis.

Survival Patterns of Non-Randomized Patients in the IELSG37 Study: Deauville Score 4 Is Not Necessarily Associated with Poor Outcome in Primary Mediastinal Lymphoma

Background:Primary mediastinal B-cell lymphoma (PMBCL) is clinically and biologically distinct from other types of aggressive lymphoma, it is characterized by a bulky mediastinal mass and most commonly occurs in women between 30 and 40 years of age. Although consolidation radiotherapy (RT) has yielded extremely positive outcomes in PMBCL, it carries a higher risk of long-term complications. Consequently, there has been an ongoing debate regarding the necessity of RT in patients responding to frontline immunochemotherapy. Methods:In the IELSG37 study, PMBCL 530 patients were treated with rituximab- and doxorubicin-containing regimens; 98% had stage I-II. Their response was assessed by positron emission computed tomography (PET/CT); 268 achieved a complete metabolic remission (CMR) defined as Deauville score (DS) 1 to 3 according to the Lugano classification and were randomly allocated to observation or mediastinal RT. The primary analysis [Zucca et al. J Clin Oncol 2023; 41 (suppl 17): abs. LBA7505] has shown that patients in CMR can safely forgo RT. The 3-year overall survival (OS) rate was 99% irrespective of irradiation. RT provided only minimal benefit on progression-free survival (PFS), which was over 96% at 3 years in both arms. Here we present the outcome of the 262 patients who were not randomized and were managed according to the preference of their treating physician. Results:Median follow-up was 64 months (interquartile range [IQR], 49-69). Besides 230 patients failing frontline treatment (174 DS4 and 56 DS5), the non-randomized cohort also included 1 patient with DS2 (who refused randomization and received RT) and 31 patients with DS3 who were initially considered as partial responders before a protocol amendment that changed the definition of CMR from DS 1-2 to DS 1-3. Among these non-randomized patients with DS3, 27 had RT consolidation, 1 was only observed, 2 had salvage chemotherapy ± RT, and 1 had missing data due to consent withdrawal; their 3-year PFS was very close to the one of the randomized patients with DS3 (90 vs 92%, p=0.99). In the DS4 group, 12 patients were observed, 149 had only RT, and 13 had second-line chemotherapy, with (12) or without (1) autologous stem cell rescue, 8 of 13 also had RT. Among the patients with DS5, only 2 were observed, 32 had only RT, and 22 had second-line chemotherapy, with (15) or without (7) autologous stem cell rescue; 12 of them also had RT. The outcome of patients with DS4 was overlapping the one of the patients achieving a CMR, with 3-year PFS of 97.1% (95%CI 93-99) and 97.4% (95%CI 95-99), respectively, while patients with DS5 had a significantly poorer 3-year PFS (62.4%, 95%CI 48-74) [Figure1A]. The 3-year OS showed a similar trend (98% in patients with DS4, 99% in those randomized, and 78% in the DS5 group). Notably, compared to patients receiving consolidation RT alone or only observed, the residual lesions on post-immunochemotherapy PET/CT scans of patients with DS4 and DS5 who were treated more aggressively (with salvage chemotherapy ± autologous transplant and/or RT) displayed significantly higher tracer maximum standardized uptake value (SUVmax, median: 8.2, IQR 4.6-16.5 vs. 3.8, IQR 3.1-4.9; p&amp;lt;0.0001) and larger residual metabolic tumor volume (MTV, median: 18 ml, IQR 3-95 vs. 3.6, ml, IQR 1-10; p&amp;lt;0.0001). These patients had significantly worse outcomes compared to those who received consolidation RT or were observed only [Figure 1B]. Conclusions:Patients with DS4 had outcomes similar to those of patients achieving a CMR, indicating that this group may either include a significant number of “false-positive” cases with inflammatory uptake or that their residual disease is limited and can potentially be cured with consolidation RT. Patients with DS5 had a significantly poorer outcome, although nearly half of them did well with RT alone. It seems plausible that clinical condition of the patient and/or imaging features of the residual disease have influenced treatment choices in patients without CMR after frontline immunochemotherapy. Further studies are needed to investigate whether PET metrics and/or liquid biopsies can aid in personalizing treatment and identifying patients who could potentially avoid irradiation.

Lymphoplasmacytic Lymphoma: An Atypical Presentation with IgG Monoclonal Gammopathy

Introduction Lymphocytic lymphoma (LPL) is a rare type of low-grade mature B-cell non-Hodgkin lymphoma, characterized by a monoclonal population of B lymphocytes, lymphoplasmacytic cells, and plasma cells. In around 95% of LPL cases, the serum immunoglobulin M (IgM) paraprotein is increased, which is correlated to Waldenstrom's Macroglobulinemia (WM), a clinicopathological disease. Only around 5% of LPL cases are associated with the serum paraproteins immunoglobulin G (IgG) or immunoglobulin A (IgA), or light chains alone, or are not linked to a paraprotein. Non-IgM LPLs have a wide range of clinical and pathological features, and MYD88 L265P mutations can occur, though at a lower frequency than WM. Hence, MYD88 testing is advised for prospective therapeutic purposes. Case Presentation A 69-year-old male was referred to a hematologist for uncontrolled epistaxis and periorbital edema. On initial workup, he had high total protein, elevated globulin, hypoalbuminemia, anemia, and proteinuria. Further investigation revealed a high IgG level with low IgM, IgA, and complement levels. Serum Protein Electrophoresis (SPEP): Increased total protein, decreased alpha two and beta globulins with a large monoclonal protein peak migrating in the gamma region, which accounts for 4.77 g/dl of the total 5.38g/dl gamma. Elevated Kappa Quantitative Free Light Chains of 355.39 (3.30 - 19.40mg/L), Decreased Lambda Quantitative Free Light Chains of 1.51 (5.71 - 26.30mg/L), Elevated Kappa Lambda Free Light Chains Ratio of 235.36 (0.26 - 1.65). Serum ImmunoFixation Electrophoresis demonstrated IgG-type kappa monoclonal protein with an additional faint band in IgG kappa. X-Ray skeletal survey showed a possible small lytic area in the inferior aspect of the C2 vertebral body, prompting him to have a cervical spine MRI which revealed no lytic lesions but an 18 mm vertebral body hemangioma inside T2. Molecular testing was positive for MYD88 Mutation c.794T&amp;gt;C (p. L265P) and negative for CXCR4 mutation. Plasma cell myeloma prognostic panel and chromosome analysis were normal. Flow cytometry of bone marrow aspirate showed a kappa light chain restricted plasma cell population (1.6% of total cells) with the following immunophenotype: positive for CD138, CD38, CD45, and negative for CD19, CD20, CD56, CD 117, and lambda light chains. The B-cell population showed kappa light chain restriction with the following immunophenotype: positive for CD19, CD20, and kappa light chains and negative for CD5, CD10, CD11c, CD23, and lambda light chains (Image 2). PET-CT of the whole body was negative for the extension of the disease. Transfusion with the two least incompatible PRBCs had little effect. However, plasmapheresis significantly improved his hemoglobin level by less than 7g/dl. A bone marrow biopsy revealed he had LPL with IgG Monoclonal Gammopathy (Image 1). He received one cycle of CyBorD (Cyclophosphamide, Bortezomib, Dexamethasone), followed by seven cycles of KCD (Carfilzomib, Cyclophosphamide, Dexamethasone) and Rituximab. The patient was diagnosed with low-grade B cell lymphoma with plasmocytic differentiation/lymphoplasmacytic lymphoma, with MYD88 mutation c.794T&amp;gt;C (p. L265P) positivity and CXCR4 mutation negativity. After plasmapheresis, the IgG level dropped to 1958. Follow-up SPEP revealed decreased alpha2 and beta globulins, decreased free lambda light chains, and increased K/L ratio. The patient was treated with Acalabrutinib, and his anemia, epistaxis, and coagulopathy resolved. Repeat PET-CT scan revealed no evidence of illness progression. Discussion LPL is not always linked with IgM monoclonal gammopathy; it can also be associated with IgG or IgA monoclonal gammopathy, light chains alone, or no monoclonal paraprotein. Non-IgM LPL has a high prevalence of extramedullary involvement, a lower rate of MYD88 mutation, and few hyper viscosity symptoms. The MYD88 mutation does not allow WM and Non-IgM LPL to be distinguished from other lymphoproliferative disorders with similar clinical and immunophenotypic features. The case described is unique as the patient has high levels of IgG (11,200) at presentation. In contrast to our patient, who has LPL with IgG Monoclonal gammopathy, approximately 95 percent of LPL patients have IgM Monoclonal gammopathy, which corresponds with WM. As a result, clinicians should be on the lookout for LPL that lacks an IgM Monoclonal Paraprotein.

Odronextamab Monotherapy for the Treatment of Relapsed/Refractory (R/R) Follicular Lymphoma (FL) and Diffuse Large B-Cell Lymphoma (DLBCL): Focus on Clinical Pharmacology and Pharmacometrics in the ELM-1 and ELM-2 Studies

Background Odronextamab is a CD20×CD3 bispecific antibody that binds CD20 on B-cells and CD3 on T-cells, triggering T-cell-mediated cytotoxicity of malignant B-cells. Odronextamab demonstrated clinically meaningful efficacy and generally manageable safety in patients (pts) with R/R FL and DLBCL in the Ph 1 ELM-1 (NCT02290951; Bannerji R, et al . Lancet Haematol. 2022) and Ph 2 ELM-2 (NCT03888105) studies (Kim TM. ASH. 2022; Kim WS. ASH. 2022). Here, assessments of pharmacokinetics (PK), pharmacodynamics (PD), and exposure-response (E-R) analyses for efficacy and safety are presented, to support posology for the treatment of R/R FL and DLBCL. Methods Pts enrolled in ELM-1 and ELM-2 received IV odronextamab step-up doses of 0.7, 4, and 20 mg in Weeks (Wks) 1-3 of Cycle (C) 1 (21-day/cycle), odronextamab QW (FL: 80 mg; DLBCL: 160 mg) during C2-4, then odronextamab Q2W (FL: 160 mg; DLBCL: 320 mg) until disease progression or unacceptable toxicity. Pts who achieved a durable complete response for ≥9 months transitioned to Q4W dosing. After odronextamab infusion, serum samples were collected over time, odronextamab serum concentrations measured, and data analyzed using descriptive and population PK methods. Blood samples were collected to measure T-cells, T-cell activation and proliferation markers (e.g. HLA-DR, Ki67), peripheral CD19 + B-cells, and cytokines. E-R for efficacy was assessed with trough concentration at time of first efficacy assessment (C trough at Wk 12) and best overall response using logistic regressions. E-R for safety was assessed with odronextamab concentrations at the time of a safety event and safety events including any grade (Gr) and Gr ≥3 treatment-emergent AEs (TEAEs) via multivariate analyses. Results The PK of odronextamab were characterized in 507 pts and were similar between different ethnic populations across B-cell non-Hodgkin lymphoma types. Concentration-time profiles were similar with step-up doses in pts with FL and DLBCL. Exposure in pts with DLBCL was 2-fold higher than in FL during C2-4, in line with the 2× higher dose. PD profiles were similar in pts with FL and DLBCL. Rapid, pronounced, and prolonged B-cell depletion in blood was observed following infusion. Early T-cell activation and proliferation was observed, with T-cell expansion higher in clinical responders vs. nonresponders. Transient cytokine release was mainly observed in C1 and was infrequent in subsequent cycles. In pts with FL, the probability of clinical response increased with odronextamab exposure and the largest response (89%) was achieved at exposures consistent with the median C trough of 80 mg QW at Wk 12, supporting use of 80 mg QW for FL. Exposures associated with 80 mg QW in C2-4 were maintained or exceeded with subsequent 160 mg Q2W maintenance doses. In pts with DLBCL, the probability of clinical response increased with odronextamab exposure, but less steeply than for FL. The largest response (57%) was achieved at exposures consistent with the median C trough of 160 mg QW at Wk 12, supporting use of 160 mg QW for DLBCL. Exposures associated with 160 mg QW were maintained or exceeded with subsequent 320 mg Q2W maintenance doses. Exposure-safety analysis showed consistent results in FL and DLBCL. Among multiple factors evaluated that had potential to be associated with TEAEs, odronextamab exposure was not associated with any Gr or Gr ≥3 TEAEs, including cytokine release syndrome and infections, over time. Conclusions PK analyses showed predictable concentration-time profiles through step-up dosing, at treatment doses, and during maintenance. PD analyses showed durable and complete depletion of B-cells; T-cell activation, proliferation, and expansion; and transient cytokine release, consistent with the mechanism of action of odronextamab. In comparison with DLBCL, clinical response increased with odronextamab exposure faster for FL and can reach a higher response at 80 mg QW. Therefore, a higher odronextamab dose of 160 mg QW is needed to achieve maximal response for DLBCL. The studied regimens showed clinically meaningful activity and acceptable tolerability, and the risk of any Gr or Gr ≥3 TEAEs is not increased from low to high odronextamab exposures. Comprehensive PK, PD, exposure-efficacy, and exposure-safety analyses demonstrated that the selected odronextamab dose regimens have favorable efficacy and generally manageable safety profiles for the treatment of R/R FL and DLBCL.

Clinical Outcomes of Tucidinostat Therapy for Relapsed/Refractory Adult T-Cell Leukemia-Lymphoma (ATL) in Clinical Practice

【Objective】 Tucidinostat, approved for relapsed/refractory adult T-cell leukemia-lymphoma (ATL) treatment in June 2021 in Japan, demonstrated an objective response rate (ORR) of 30.4%, progression-free survival (PFS) of 1.7 months (95% CI: 0.8-7.4), and overall survival (OS) of 7.9 months (95% CI: 2.3-18.0) in a phase IIb trial for 23 cases of relapsed/refractory adult T-cell leukemia-lymphoma (ATL) in Japan. We report the treatment results of this agent in Miyazaki Prefecture. 【Methods】 We retrospectively analyzed the treatment results of relapsed/refractory ATL patients who received Tucidinostat at 6 facilities within the Miyazaki prefecture, and HTLV-1 endemic area in southwest Japan, after its approval. All clinical procedures for patients were part of routine care, and the requirement for written patient consent was waived by the committee in view of the retrospective nature of this study. Approved study protocols were presented on the web site in an opt-out format, ensuring patients had the right to refuse participation in the study. In accordance with these protocols, clinical information was then collected. 【Results】 From October 2021 to July 2023, Tucidinostat was administered to 24 cases of relapsed/refractory ATL. The median age at the start of administration was 72.5 (41-85), with 13 cases of the acute type, 7 cases of the lymphoma type, and 4 cases of poor-prognosis chronic type. The median number of prior treatment regimens was 2 (1-4), with 19 cases of multi-drug combination chemotherapy, 18 cases of mogamulizumab, and 5 cases of oral chemotherapy. There were no cases of transplantation. The period from prior treatment to Tucidinostat administration was 3.2 months (0-27.5 months), and the disease stage at the start of Tucidinostat administration was relapse in 7 cases and refractory in 17 cases. The starting dose was 40mg/day (twice a week) in 19 cases and 20mg/day (twice a week) in 4 cases, with a median number of total treatment courses of 3 (1-20). Of the 24 cases,19 had their dose reduced or treatment suspended because of myelosuppression. The best treatment response was complete response(CR) in 5 cases, parcial response (PR) in 8 cases, Stable Disease(SD) in 8 cases, with an efficacy rate (CR/PR) of 54.2%. The PFS after the start of treatment was 3.7 months (1.8-7.8), and the OS after the start of treatment was 8.6 months. The reason for discontinuation of administration were progression disease in 15 cases, intolerance in 1 case (skin rash in 1 case), and severe complications in 1 case (cryptococcal meningitis). In the Cox proportional hazards model analysis, considering the clinical characteristics at the initiation of Tucidinostat, the initial sIL-2R level negatively impacted PFS. PFS was then stratified using an sIL-2R cutoff of 5000 U/mL, showing a Median Survival Time (MST) of PFS: 0.65 months for those below the cutoff versus 0.15 months for those above it, p=0.006 (log-rank).“A similar trend was observed for OS (Median OS: not reached vs. 0.53 months, p=0.032 (log-rank)). 【Conclusion】 In relapsed/refractory ATL, Tucidinostat achieved treatment results similar to those in the phase IIb trial in clinical practice. In particular, for cases with an sIL2-R value of less than 5000, it was suggested that Tucidinostat may be a meaningful treatment option.

Risk Factors of Venous Thromboembolism in Lymphoma Patients: A Meta-Analysis

Background: The prevalence and risk factors of venous thromboembolism (VTE) in lymphoma patients have been extensively studied, but with varying degrees of research quality and inconsistent findings. The primary objective of our study was to investigate the prevalence and identify risk factors associated with VTE in lymphoma patients. Methods: We conducted a systematic search of PubMed, EMBASE, Web of Science, and Cochrane Library databases up to February 2023 to identify relevant studies investigating VTE in lymphoma patients. We calculated the pooled odds ratio using a fixed- or random-effect model and evaluated the quality of each study using the Newcastle-Ottawa Scale. To evaluate the robustness of our findings, we conducted sensitivity analysis. We also identified any potential publication bias using funnel plots and Egger's test. Two researchers independently assessed eligibility and extracted data to ensure accuracy. Results: Our analysis included a total of 17 studies with a combined sample size of 4,983 lymphoma patients (Figure 1). The pooled prevalence of VTE among these patients was 12% (with a confidence interval of 0.09-0.15). Sensitivity analyses were performed, and the results were consistent with the overall pooled estimate. Our meta-analysis revealed that several factors were significant risk factors for VTE in lymphoma patients, including female sex, older age, history of VTE, DLBCL lymphoma type, Ann Arbor stage III~IV, higher ECOG-PS, bulky disease, central nervous system involvement, WBC count &amp;gt;11×10 9/L, D-dimer level &amp;gt;0.5mg/L, central venous catheterization, and treatments with doxorubicin ( P&amp;lt;0.05) (Table 1). However, the funnel plot suggested that there may be some potential publication bias, which was further confirmed by statistical tests. Nevertheless, the results of the trim-and-fill method demonstrated that the pooled estimate remained stable after the addition of nine “missing” studies. Conclusions: Our study revealed that the pooled prevalence of VTE in OC was approximately 12% across lymphoma patients. Risk factors for VTE were identified which may aid in preventative measures for VTE in lymphoma patients.

High-throughput quantitation of amino acids and acylcarnitine in cerebrospinal fluid: identification of PCNSL biomarkers and potential metabolic messengers.

Background: Due to the poor prognosis and rising occurrence, there is a crucial need to improve the diagnosis of Primary Central Nervous System Lymphoma (PCNSL), which is a rare type of non-Hodgkin's lymphoma. This study utilized targeted metabolomics of cerebrospinal fluid (CSF) to identify biomarker panels for the improved diagnosis or differential diagnosis of primary central nervous system lymphoma (PCNSL). Methods: In this study, a cohort of 68 individuals, including patients with primary central nervous system lymphoma (PCNSL), non-malignant disease controls, and patients with other brain tumors, was recruited. Their cerebrospinal fluid samples were analyzed using the Ultra-high performance liquid chromatography - tandem mass spectrometer (UHPLC-MS/MS) technique for targeted metabolomics analysis. Multivariate statistical analysis and logistic regression modeling were employed to identify biomarkers for both diagnosis (Dx) and differential diagnosis (Diff) purposes. The Dx and Diff models were further validated using a separate cohort of 34 subjects through logistic regression modeling. Results: A targeted analysis of 45 metabolites was conducted using UHPLC-MS/MS on cerebrospinal fluid (CSF) samples from a cohort of 68 individuals, including PCNSL patients, non-malignant disease controls, and patients with other brain tumors. Five metabolic features were identified as biomarkers for PCNSL diagnosis, while nine metabolic features were found to be biomarkers for differential diagnosis. Logistic regression modeling was employed to validate the Dx and Diff models using an independent cohort of 34 subjects. The logistic model demonstrated excellent performance, with an AUC of 0.83 for PCNSL vs. non-malignant disease controls and 0.86 for PCNSL vs. other brain tumor patients. Conclusion: Our study has successfully developed two logistic regression models utilizing metabolic markers in cerebrospinal fluid (CSF) for the diagnosis and differential diagnosis of PCNSL. These models provide valuable insights and hold promise for the future development of a non-invasive and reliable diagnostic tool for PCNSL.

Clinicopathological profile of Non-Hodgkin and Hodgkin Lymphoma at the Anatomical Pathology Laboratory of Saiful Anwar General Hospital Malang from January 2018 until May 2023

Lymphomas are a lymphocyte-driven malignancy that comprise up to 10% of cancers diagnosed in individuals &lt; 20 years of age globally. Malignant lymphomas are divided into Hodgkin Lymphoma (HL) and Non Hodgkin Lymphoma (NHL). In 2019 at United States, more than 82.000 new patients diagnosed with lymphoma. Since the epidemiology of Lymphoma is different across regions and may have change over time, its global distribution pattern, risk factors, and temporal trends need to be assessed for developing preventive measures. The purpose of this study was to determine the frequency of NHL and HL based on histopathological type, age, and gender. This research is a descriptive analytic study. Data were obtained from patients who underwent histopathological and immunohistochemistry examinations at the Anatomical Pathology laboratory of Saiful Anwar General Hospital Malang from January 2018 until May 2023. There are 408 cases of Lymphoma consisting of 56 HL and 352 NHL. In HL, the percentage higher in men, and occurred mostly during 21 – 30 years old age group. The most common histopathological type of HL is Classical Hodgkin Lymphoma, with mostly Nodular Sclerosis subtype. In NHL, the percentage higher in men, and occurred mostly during 51 – 60 years old age group. The most common histopathological type of Non Hodgkin Lymphoma is B cell type.