Aggressive non-Hodgkin Lymphoma Research Articles

Impact of the Affordable Care Act and Medicaid Expansion Among Patients With HIV-Associated Aggressive B-Cell Non-Hodgkin Lymphomas.

To study the influence of the Affordable Care Act (ACA) policy and its Medicaid expansion on insurance status and survival in patients with HIV with aggressive lymphoma. We used the National Cancer Database, a hospital-based national registry, to identify adults age 18-64 years with HIV-associated aggressive B-cell non-Hodgkin lymphomas (HIV-a-B-NHLs), diagnosed during 2007 to 2016. Survival analysis was performed on a subset of patients with HIV-a-B-NHL for whom location data were available who resided in Medicaid expansion-adopted and nonadopted states. Using a quasi-experimental difference-in-difference model, the difference in adjusted 2-year survival rates obtained with a flexible parametric Weibull model was compared for states that adopted the Medicaid expansion of ACA against those that did not adopt the expansion. We identified 8,231 patients with HIV-a-B-NHL and 50,650 non-HIV patients with a-B-NHL. We found that a lower proportion of individuals were uninsured at diagnosis in the expansion states compared with nonexpansion states. We also found that the ACA policy adoption led to a reduction in the proportion of uninsured individuals with HIV-a-B-NHL in expansion states of 34.9%, compared with 15.9% in non-expansion-adopted states. There was a statistically significant improvement in the 2-year survival rate among patients with HIV-a-B-NHL in the expansion compared with nonexpansion states with the adoption of ACA (7.17% v 1.58%, P = .02). Using a novel quasi-experimental model, we found that the ACA policy corresponded with a greater survival improvement in patients with HIV-a-B-NHL within Medicaid expansion-adopted states compared with nonexpansion states. We believe that this evidence should be taken into consideration in future policy making.

Utility of clinical, laboratory, and lymph node MYD88 L265P mutation in risk assessment of diffuse large B-cell lymphoma patients

BackgroundDiffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma and is characterized by heterogeneity in biology and clinical behavior. Mutations in the myeloid differentiation primary response 88 (MYD88) are found in different lymphoproliferative disorders and are associated with variable clinical and prognostic impact.AimTo investigate the frequency of MYD88 L265P mutation and its clinical impact in a cohort of Egyptian DLBCL patients.MethodsFFPE lymph node samples from 87 DLBCL patients (46 males / 41 females; median age, 58 years) were included and analyzed for MYD88 L265P by an allele-specific PCR.ResultsMYD88 L265P mutations were found in 52 patients (59.8%) out of 87 DLBCL cases. Patients with L265 mutation were significantly younger than non-mutated patients (p = 0.022). None of the patients with the L265P mutation showed a significant association with the clinical parameters of DLBCL. Interestingly, MYD88 L265 mutated patients were found to be significantly correlated with HCV infection (p = 0.037). The median follow-up time across the entire cohort was 26 months. Univariate analysis showed that overall survival (OS) was affected by gender, LDH level, and CNS-IPI scoring (p = 0.048, 0.008, and 0.046, respectively), while disease-free survival (DFS) was affected by B symptoms and LDH level (p = < 0.000 and 0.02, respectively). However, the MYD88 mutation status and other prognostic factors showed no association with OS or DFS.ConclusionsOur findings indicate a high frequency of MYD88 L265P mutations in our study population and not associated with prognostic markers or the outcome of the disease.

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

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

Effectiveness of fractionated rituximab in preventing tumor lysis syndrome in aggressive B-cell lymphoma: Insights from real-life clinical practice.

Tumor lysis syndrome (TLS) is a potentially life-threatening condition resulting from the rapid destruction of malignant cells, leading to electrolyte imbalances and severe complications, such as acute kidney injury, arrhythmias, and seizures. TLS can be managed through hyperhydration, urate-lowering treatments, and a steroid prophase strategy. This study aims to explore the impact of fractionated rituximab, an anti-CD20 antibody, on the occurrence and severity of TLS during the initial cycle in patients with aggressive B-cell non-Hodgkin lymphoma (B-NHL). Data was retrospectively collected from 94 of 186 patients. Among the 94 patients included in the analysis, the median age was 70. Histologies were diffuse large B-cell lymphoma (75%), Burkitt lymphoma (13%) and high-grade B-cell lymphoma (8%). The majority were at an advanced stage (93%) with a high IPI score (75%). Most patients received anthracycline-containing regimens (72%) and prophylactic allopurinol (83%) and/or rasburicase (26%). Steroid prophase was administered to 82% of patients. The study identified one clinical TLS case and six laboratory TLS cases. Significant TLS factors included BL histology, elevated baseline LDH (⟩500 U/l), and rasburicase usage. Infusion reactions were rare (3%). Median progression-free survival was 2.6 years, and 2-year overall survival was 33%, irrespective of TLS occurrence. In this real-life study, clinical TLS occurrence was low (1%). TLS appeared more frequent in BL but did not impact overall survival. Fractionated initial rituximab dosing in addition to preventive strategies is a feasible approach in preventing clinical TLS, warranting further prospective investigation.

Maternal and obstetric outcomes in women with pregnancy-associated haematological malignancies: an observational nationwide cohort study.

Pregnancy-associated haematological malignancy is a rare event; therefore, data available to guide the treatment are scarce. We aimed to evaluate the incidence, overall survival, and maternal morbidity and mortality of women with pregnancy-associated haematological malignancies. We conducted a nationwide observational cohort study using the French National Healthcare Data System (SNDS), a health-care administrative database covering up to 99% of the French population. We included all pregnancies in France ending between Jan 1, 2012, and Dec 31, 2022. Pregnancies with terminations or miscarriages managed on an outpatient basis, and women with a history of haematological malignancies before pregnancy were excluded. A Cox proportional hazards model was used to assess overall survival, defined as the date of haematological malignancy diagnosis to either death or the end of the study follow-up, in the haematological malignancy during pregnancy group (pregnancies with a diagnosis of haematological malignancy during pregnancy) compared with the haematological malignancy post-pregnancy group (pregnancies with a diagnosis of haematological malignancy in the year following pregnancy). Severe maternal morbidity was compared in the haematological malignancy during pregnancy group versus the reference group (pregnancies without a history of haematological malignancy or a diagnosis of pregnancy-associated haematological malignancy). Births were classified as very preterm (<32 weeks of pregnancy), preterm (32-36 weeks), and term (≥37 weeks) and compared in the haematological malignancy during pregnancy group versus the reference group. Inverse probability weighting (IPW) was used for confounder adjustment, using maternal age (categorised), comorbidities, socioeconomic status, and year of delivery (as a category). Of 9 996 523 pregnancies in 5 995 235 women, 1366 pregnancy-associated haematological malignancies were identified: 413 during pregnancy (4·13 per 100 000 pregnancies) and 953 (9·53 per 100 000 pregnancies) within 12 months of the end of pregnancy (post-pregnancy). No significant differences in overall survival were observed between the haematological malignancy during and post-pregnancy groups across all types of haematological malignancy (IPW-adjusted hazard ratio 0·91 [95% CI 0·62-1·34], p=0·63), specifically for Hodgkin lymphoma (0·56 [0·07-4·53], p=0·59), aggressive B-cell non-Hodgkin lymphoma (0·52 [0·12-2·38], p=0·40), and acute leukaemia alone (0·84 [0·50-1·41], p=0·51). Severe maternal morbidity was more frequent in the haematological malignancy during pregnancy group than in the reference group (86 [26·2%] of 328 completed pregnancies vs 120 335 [1·5%] of 7 945 909 completed pregnancies; IPW-adjusted odds ratio 22·71 [95% CI 17·72-29·10], p<0·0001). We observed an increase in very preterm birth (32 [9·8%] vs 92 712 [1·2%]; IPW-adjusted odds ratio 11·90 [95% CI 7·91-17·91], p<0·0001) and preterm birth (116 [35·4%] vs 430 472 [5·4%]; 11·76 [9·34-14·81], p<0·0001) in the haematological malignancy during pregnancy group compared with the reference group. This nationwide observational study examines pregnancy-associated haematological malignancies in France, revealing no significant difference in overall survival between women diagnosed during pregnancy and post-pregnancy. Our data highlight an increased frequency of severe maternal morbidity and obstetric complications among women diagnosed during pregnancy. Notably, the study underscores the necessity for specialised care to manage these complex cases effectively. None. For the French translation of the abstract see Supplementary Materials section.

52 (PB040): FGF signaling blockade hampers the growth of c-Myc-driven aggressive B-cell non-Hodgkin lymphoma

52 (PB040): FGF signaling blockade hampers the growth of c-Myc-driven aggressive B-cell non-Hodgkin lymphoma

A novel murine syngeneic CD8 peripheral T-cell lymphoma model with preclinical applications

Peripheral T-cell Lymphoma (PTCL) represents a heterogenous group of aggressive non-Hodgkin Lymphomas with poor prognostic outcomes and limited treatment options. The development and refinement of therapeutic strategies for PTCL are impeded by a paucity of reliable preclinical models that accurately mimic the disease’s pathophysiology. There is a dire need for more physiologically relevant models for PTCL. Here we describe a spontaneousCD8+ peripheral T-cell lymphoma cell line (LM-23) derived from a 12-week-old female Balb/cJ mouse. Both intravenous and subcutaneous administration of this cell line to syngeneic Balb/cJ mice resulted in rapid establishment of tumor growth. CHOP and anti-PD1 treatment both displayed no benefit to mice in regulating tumor growth. Such results along with its phenotypic characteristics, rapid growth, and metastatic behavior in syngeneic mice highlight its value in studying the elusive disease and discovery of novel therapeutics.

NCCN guideline-concordant cancer care in Sub-Saharan Africa A population-based multi-country study of five cancers.

To assess population-based quality of cancer care in Sub-Saharan Africa and to identify specific gaps and joint opportunities, we assessed concordance of diagnostic and treatment with NCCN harmonized guidelines for leading cancer types in 10 countries. Adult patients with female breast cancer (BC), cervical cancer (CC), colorectal cancer (CRC), Non-Hodgkin lymphoma (NHL) and prostate cancer (PC) were randomly drawn from 11 population-based cancer registries. Guideline concordance of diagnostics and treatment was assessed using clinical records. In a sub-cohort of 906 patients with potentially curable cancer (stage I-III BC, CC, CRC, PC, aggressive NHL (any stage)) and documentation for >1 month after diagnosis, we estimated factors associated with guideline-concordant treatment or minor deviations (GCT). Diagnostic information as per guidelines was complete for 1030 (31.7%)of 3246 patients included. In the sub-cohort with curable cancer, GCT was documented in 374 (41.3%, corresponding to 11.7% of 3246 included in the population-based cohort): aggressive NHL (59.8%/9.1% population-based), BC (54.5%/19.0%), PC (39.0%/6.1%), CRC (33.9%/9.5%), and CC (27.8%/11.6%). GCT was most frequent in Namibia (73.1% of curable cancer subset/32.8% population-based) and lowest in Kampala, Uganda (13.5%/3.1%). GCT was negatively associated with poor ECOG status, locally advanced stage, origin from low HDI countries, and a diagnosis of CRC or CC. 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 SSA. Treatment components within NCCN guidelines synergetic for several cancers should be prioritized.

Impact of critical illness on continuation of anticancer treatment and prognosis of patients with aggressive hematological malignancies

BackgroundMaintaining the dose-intensity of cancer treatment is an important prognostic factor of aggressive hematological malignancies. The objective of this study was to assess the long-term outcomes of intensive care unit (ICU) survivors with acute myeloid leukemia (AML) or aggressive B-cell non-Hodgkin lymphoma (B-NHL) with emphasis on the resumption of the intended optimal regimen of cancer treatment.Patients and methodsWe conducted a retrospective (2013–2021) single-center observational study where we included patients with AML and B-NHL discharged alive from the ICU after an unplanned admission. The primary endpoint was the change in the intended optimal cancer treatment following ICU discharge. Secondary endpoints were 1-year progression-free survival and overall survival rates. Determinants associated with modifications in cancer treatment were assessed through multivariate logistic regression.ResultsOver the study period, 366 patients with AML or B-NHL were admitted to the ICU, of whom 170 survivors with AML (n = 92) and B-NHL (n = 78) formed the cohort of interest. The hematological malignancy was recently diagnosed in 68% of patients. The admission Sequential Organ Failure Assessment (SOFA) score was 5 (interquartile range 4–8). During the ICU stay, 30 patients (17.6%) required invasive mechanical ventilation, 29 (17.0%) vasopressor support, and 16 (9.4%) renal replacement therapy. The one-year survival rate following ICU discharge was 59.5%. Further modifications in hematologic treatment regimens were required in 72 patients (42%). In multivariate analysis, age > 65 years (odds ratio (OR) 3.54 [95%-confidence interval 1.67–7.50], p < 0.001), ICU-discharge hyperbilirubinemia > 20 µmol/L (OR 3.01 [1.10–8.15], p = 0.031), and therapeutic limitations (OR 16.5 [1.83–149.7], p = 0.012) were independently associated with modifications in cancer treatment. Post-ICU modifications of cancer treatment had significant impact on in-hospital, 1-year overall survival and progression-free survival.ConclusionThe intended cancer treatment could be resumed in 58% of ICU survivors with aggressive hematological malignancies. At the time of ICU discharge, advanced age, persistent liver dysfunction and decisions to limit further life-support therapies were independent determinants of cancer treatment modifications. These modifications were associated with worsened one-year outcomes.

An inherited genetic variant of the CEP72 gene is associated with the development of vincristine-induced peripheral neuropathy in female patients with aggressive B-cell lymphoma.

Vincristine-induced peripheral neuropathy (VIPN) is an adverse effect of regimens used for the treatment of aggressive B-cell non-Hodgkin lymphoma (B-NHL). A single-nucleotide polymorphism (SNP) in the promotor region of the CEP72 gene has been identified as risk factor for the development of VIPN in children. To validate these results in adults we aimed to determine the association of the high-risk CEP72 (rs924607 TT genotype) with the occurrence and severity of VIPN. Analysis of SNP rs924607 (TT, CC or CT) was performed in all enrolled patients with available blood samples with a TaqMan genotyping assay. Rates and grades of VIPN were assessed prospectively as part of the RICOVER-60 trial. CEP72 genotype could be assessed in 519 patients. VIPN data was available for 499/519 patients who were included in the final analysis. 286 (57%) patients developed VIPN of any grade during treatment. Grade 2-4 VIPN occurred in 33% (166/499) of patients. The high-risk CEP72 TT genotype at rs924607 was identified in 97/499 (19%) patients. The TT genotype was not correlated with VIPN in the overall study population compared to patients with either CC or CT genotypes (p = 0.748). However, in the subgroup of female patients, the TT genotype was associated with increased occurrence of any-grade VIPN as well as grade 2-4 VIPN as compared to patients with either CC or CT genotypes (p = 0.016 and p = 0.020, respectively). Thus, the SNP rs924607 in the CEP72 gene is associated with increased VIPN incidence in female patients with aggressive B-NHL treated with CHOP chemotherapy. Trial registration ClinicalTrials.gov identifier: NCT00052936, submission date: 2005-06-23, EudraCT Number: 2010-019587-36.

Prognostic significance of diffuse increased fluorine-18-fluorodeoxyglucose (18F-FDG) uptake within the reticuloendothelial system in lymphoma patients.

As constituents of the reticuloendothelial system, the spleen and bone marrow (BM) have been recognized as integral components of the systemic inflammatory response in cancer contexts, thereby serving as predictive indicators for assessing cancer prognosis. Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) has attained widespread utilization for staging, assessing treatment response, and prognostication in lymphoma patients. Several investigations have proposed that focal increased 18F-FDG uptake in the BM or spleen may correlate with malignant involvement in lymphoma. However, scant data exist regarding the implications of diffuse BM and splenic uptake. This study aimed to explore the relationships between metabolic parameters of the spleen and BM on 18F-FDG PET/CT and inflammatory markers, and to assess their prognostic value in patients with lymphoma. A retrospective analysis was conducted on 118 patients newly diagnosed with malignant lymphoma, who underwent 18F-FDG PET/CT and exhibited diffuse increased splenic or BM uptake in 18F-FDG PET/CT imaging. The mean standardized uptake value (SUV) of the spleen, BM, and liver was calculated. The association between metabolic variables and systemic inflammatory markers was investigated, and the prognostic significance of clinicopathological and PET parameters was assessed using overall survival (OS) and progression-free survival (PFS). A statistically significant correlation was found between the spleen-to-liver SUV ratio (SLR) and inflammatory markers such as C-reactive protein (r=0.264, P=0.007) and platelet-to-lymphocyte ratio (r=0.227, P=0.021). No significant correlation was observed between BM-to-liver SUV ratio (BLR) and hematologic parameters, while concordance analysis revealed a fair agreement between BLR and bone marrow biopsy (BMB) (Cohen's Kappa-κ =0.271, P=0.002). In patients with aggressive non-Hodgkin lymphoma, both SLR [P=0.017, HR 2.715, 95% confidence interval (CI): 0.875-8.428] and BLR (P=0.044, HR 0.795, 95% CI: 0.348-1.813) were significantly linked to OS, while SLR (P=0.019, HR 2.223, 95% CI: 1.139-4.342) emerged as a significant prognostic factor for PFS. This study highlighted that diffuse increased splenic 18F-FDG uptake in lymphoma patients was closely associated with inflammation, whereas diffuse BM uptake was likely attributable to BM infiltration rather than inflammatory changes. Furthermore, both parameters held promise as prognostic indicators for patients with aggressive lymphoma.

833P Latest results of GVM±R regimen for the salvage therapy of patients with relapsed or refractory aggressive non-Hodgkin's lymphoma

833P Latest results of GVM±R regimen for the salvage therapy of patients with relapsed or refractory aggressive non-Hodgkin's lymphoma

Development of New Diffuse Large B Cell Lymphoma Mouse Models.

Diffuse large B cell lymphoma (DLBCL) is the most diagnosed, aggressive non-Hodgkin lymphoma, with ~40% of patients experiencing refractory or relapsed disease. Given the low response rates to current therapy, alternative treatment strategies are necessary to improve patient outcomes. Here, we sought to develop an easily accessible new xenograft mouse model that better recapitulates the human disease for preclinical studies. We generated two Luciferase (Luc)-EGFP-expressing human DLBCL cell lines representing the different DLBCL cell-of-origin subtypes. After intravenous injection of these cells into humanized NSG mice, we monitored the tumor growth and evaluated the organ-specific engraftment/progression period. Our results showed that human IL6-expressing NSG (NSG-IL6) mice were highly permissive for DLBCL cell growth. In NSG-IL6 mice, systemic engraftments of both U2932 activated B cell-like- and VAL germinal B cell-like-DLBCL (engraftment rate; 75% and 82%, respectively) were detected within 2nd-week post-injection. In the organ-specific ex vivo evaluation, both U2932-Luc and VAL-Luc cells were initially engrafted and expanded in the spleen, liver, and lung and subsequently in the skeleton, ovary, and brain. Consistent with the dual BCL2/MYC translocation association with poor patient outcomes, VAL cells showed heightened proliferation in human IL6-conditioned media and caused rapid tumor expansion and early death in the engrafted mice. We concluded that the U2932 and VAL cell-derived human IL6-expressing mouse models reproduced the clinical features of an aggressive DLBCL with a highly consistent pattern of tumor development. Based on these findings, NSG mice expressing human IL6 have the potential to serve as a new tool to develop DLBCL xenograft models to overcome the limitations of standard subcutaneous DLBCL xenografts.

ABCL-309 Survival Disparities Among Indolent and Aggressive Non-Hodgkin Lymphomas in Armenia

ABCL-309 Survival Disparities Among Indolent and Aggressive Non-Hodgkin Lymphomas in Armenia

Survival Disparities Among Indolent and Aggressive Non-Hodgkin Lymphomas in Armenia

Survival Disparities Among Indolent and Aggressive Non-Hodgkin Lymphomas in Armenia

Evaluation of the incidence, predictors, risk assessment scores and outcomes of thromboembolism in a cohort of Egyptian NHL patients - Real World Experience

Non-Hodgkin’s Lymphoma (NHL) is the most common subtype of lymphoma. The incidence of venous thromboembolism (VTE) in aggressive NHL was estimated recently to be 11%. Several risk assessment scores and factors are available to help identify cancer patients at risk for developing VTE. Patients with a pathologically confirmed diagnosis of NHL were identified at the Oncology Center of Mansoura University. The study included 777 patients: 719 with DLBCL-NOS, 26 with Anaplastic-B-cell, and 32 with T-cell-rich-NHL. Data were retrospectively collected from electronic medical records, including clinical, radiological, and laboratory information related to VTE and NHL. The median age at NHL diagnosis was 53 years, (range: 18–98). There was a male predominance, 51.4% of the cases. At initial lymphoma diagnosis, VTE was identified in 46 (5.9%) patients, and 61 (7.9%) patients experienced VTE while undergoing chemotherapy. According to logistic regression analysis, a PS (performance status) ≥ 2, bulky lesions, and mediastinal masses were significant predictors of VTE at presentation, with P-values of 0.022, 0.002, and < 0.001, respectively. Meanwhile, NHL patients who developed VTE during chemotherapy had significantly poorer PS, higher absolute neutrophilic counts (ANC), neutrophil/lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lactate dehydrogenase (LDH) levels than lymphoma patients without VTE, with P-values of 0.003, 0.034, 0.049, 0.01 and 0.007, respectively, as determined by multivariate analysis. The ROC curve identified the cut-off values of 4.875 × 109/L for ANC, 2.985 for NLR, 144.85 for PLR, and 417.5 U/L for LDH as potential markers for predicting VTE in NHL patients. Patients with a PS ≥ 2 and values exceeding these cut-offs for ANC, NLR, and PLR experienced significantly higher incidences of VTE than other groups, with P-values of 0.003, < 0.001, < 0.001, and < 0.001, respectively. At the end of the follow-up, the overall survival was significantly shortened by VTE occurring during chemotherapy, hypoalbuminemia, intermediate-high and high international prognostic index (IPI) scores (intermediate-high and high), responses other than CR and relapse, all with P-values < 0.05. ECOG PS and Inflammatory markers such as NLR, PLR, and neutrophilic count could serve as predictors of the development of thrombotic events in patients with NHL-DLBCL. Additionally, the occurrence of VTE during chemotherapy is an independent poor prognostic marker for overall survival (OS).

BCL6 confers resistance to HDAC inhibitors in DLBCL

Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with limited response to chemotherapy. Histone acetylation is reduced in DLBCL. Chidamide, a histone deacetylase inhibitor, shows promise in lymphomas but needs further investigation for DLBCL. Our study indicated that chidamide effectively suppresses DLBCL both in vitro and in vivo. High-throughput RNA sequencing analysis provided comprehensive evidence that chidamide markedly influences crucial signaling pathways in DLBCL, including the MAPK, MYC and p53 pathway. Additionally, we observed substantial variability in the sensitivity of DLBCL cells to chidamide, and identified that elevated expression of BCL6 might confer resistance to chidamide in DLBCL. Moreover, our investigations revealed that BCL6 inhibited chidamide-induced histone acetylation by recruiting histone deacetylase (HDACs), leading to drug resistance in DLBCL cells. Furthermore, we found that lenalidomide targeted BCL6 degradation through the ubiquitination pathway and restore the sensitivity of drug-resistant DLBCL to chidamide. Collectively, these findings provided valuable insights into the global impact of chidamide on DLBCL and highlight the potential of targeting HDACs as a therapeutic strategy for DLBCL. Identifying BCL6 as a biomarker for predicting the response to chidamide and the combination therapy with BCL6 inhibition has the potential to lead to more personalized and effective treatments for DLBCL patients.

Incidence of Central Nervous System Relapse in Primary Mediastinal Large B-Cell Lymphoma: Implications for Central Nervous System Prophylaxis

BackgroundPrimary mediastinal large B-cell lymphoma (PMBCL) is an uncommon type of aggressive B-cell non-Hodgkin lymphoma. PMBCL shares some clinical and biologic features with nodular sclerosis classic Hodgkin lymphoma (cHL). Central nervous system (CNS) relapse is exceedingly rare in cHL. Therefore, it may be expected that CNS relapse in PMBCL is also uncommon. Herein, we examined the incidence of CNS relapse in patients with PMBCL treated with standard chemoimmunotherapy. Patients and MethodsThis retrospective single center analysis included 154 patients with newly diagnosed PMBCL seen at Mayo Clinic. The CNS relapse rate was calculated using a competing risk model, with death considered as a competing risk. ResultsWith a median follow-up of 39 months, 3 patients experienced CNS relapse, all associated with systemic relapse. The cumulative incidence of CNS relapse for the entire cohort was 1.43% (95% CI, 0.3%-4.6%) at 1 year and 2.21% (95% CI, 0.6%-5.8%) at both 2 and 5 years. For those who did not receive CNS prophylaxis (n = 131), the incidence was 0.85% (95% CI, 0.1%-4.2%) at 1 year and 1.80% (95% CI, 0.3%-5.8%) at both 2 and 5 years. All 3 patients who experienced CNS relapse had R-CHOP as frontline therapy; 2 patients did not receive any CNS prophylaxis, while 1 patient received intrathecal CNS prophylaxis. ConclusionThe risk of CNS relapse in PMBCL appears to be very low after treatment with standard chemoimmunotherapy, suggesting routine CNS prophylaxis is not necessary.

The Experience of Timisoara Hematology Clinic on the Management of Aggressive Non-Hodgkin Lymphoma Patients

Objectives. One of the most prevalent types of malignant lymphoproliferative disorders is non-Hodgkin lymphoma (NHL), which has shown an increased frequency worldwide of roughly 168% since 1975, coinciding with a decline in the age at diagnosis. Despite a ten-year improvement in overall survival, NHL accounts for approximately 3% of all cancer-related deaths. Delays in diagnosis and the emergence of related comorbidities are caused by the diverse symptomatology and symptoms associated with NHL. Thus, the purpose of this study was to assess patients treated at Timisoara's Clinical Emergency Municipal Hospital who had been diagnosed with aggressive HNL. Material and methods. This cross-sectional study comprised 76 patients diagnosed with aggressive NHL between January 2020 and June 2023 who were admitted to Timisoara's Clinical Emergency Municipal Hospital. Biopsy along with histopathologic examination served as the basis for the diagnosis. As part of the first assessment, bone marrow biopsy and imaging studies (PET/CT) were carried out in addition to laboratory tests. The NHL was staged using the Ann Arbour classification. The present protocols were followed in the establishment of the treatment. PET/CT was used to assess the response to treatment. Results. In this study cohort 72% were stage 4 of NHL at the diagnosis, 16% were stage 3, 5% were stage 2, while only 2% were stage 1. B symptoms were present in 69% of cases. In patients with 4th stage of NHL, bone marrow represents the most frequent extranodal site. 57 patients finished minimum a complete chemotherapy line, from which 90% of the patients had complete (63%) or partial (24%) remission after first-line treatment. Conclusion. The importance of this study was to emphasize the heterogeneity of NHL and to evaluate the treatment response and survivance of aggressive NHL patients.

Development and testing of a lymphoma clinical trial-specific frailty index: a secondary analysis of the NCIC-CTG LY.12 clinical trial

The prevalence of frailty in clinical trials of lymphoma is unknown. We conducted a secondary analysis of the phase III LY.12 trial in which patients with relapsed aggressive non-Hodgkin lymphoma were randomized to different salvage regimens before autologous stem cell transplant. The primary objective was to construct a lymphoma clinical trials-specific frailty index (LyFI) using previously described methods. The secondary objective was to describe the association of frailty withover all and event-free survival (OS, EFS). The LyFI was constructed using 619 patients, and11% (N = 70) were classified as frail. Frailty was associated with EFS (HR 1.94, 95%CI 1.53–2.46) and OS (HR 2.01, 95%CI 1.57–2.58) in univariable analysis, but was only significant as a continuous (not binary) variable in multivariable analysis controlling for prognostic score, suggesting limitations of a FI in this trial population. Future work could validate the FI using clinical assessments and/or apply it to an older trial population.