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1.
Clin Epigenetics ; 16(1): 68, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773655

ABSTRACT

BACKGROUND: Large B-cell lymphoma (LBCL) is the most common lymphoma and is known to be a biologically heterogeneous disease regarding genetic, phenotypic, and clinical features. Although the prognosis is good, one-third has a primary refractory or relapsing disease which underscores the importance of developing predictive biological markers capable of identifying high- and low-risk patients. DNA methylation (DNAm) and telomere maintenance alterations are hallmarks of cancer and aging. Both these alterations may contribute to the heterogeneity of the disease, and potentially influence the prognosis of LBCL. RESULTS: We studied the DNAm profiles (Infinium MethylationEPIC BeadChip) and relative telomere lengths (RTL) with qPCR of 93 LBCL cases: Diffuse large B-cell lymphoma not otherwise specified (DLBCL, n = 66), High-grade B-cell lymphoma (n = 7), Primary CNS lymphoma (n = 8), and transformation of indolent B-cell lymphoma (n = 12). There was a substantial methylation heterogeneity in DLBCL and other LBCL entities compared to normal cells and other B-cell neoplasms. LBCL cases had a particularly aberrant semimethylated pattern (0.15 ≤ ß ≤ 0.8) with large intertumor variation and overall low hypermethylation (ß > 0.8). DNAm patterns could not be used to distinguish between germinal center B-cell-like (GC) and non-GC DLBCL cases. In cases treated with R-CHOP-like regimens, a high percentage of global hypomethylation (ß < 0.15) was in multivariable analysis associated with worse disease-specific survival (DSS) (HR 6.920, 95% CI 1.499-31.943) and progression-free survival (PFS) (HR 4.923, 95% CI 1.286-18.849) in DLBCL and with worse DSS (HR 5.147, 95% CI 1.239-21.388) in LBCL. These cases with a high percentage of global hypomethylation also had a higher degree of CpG island methylation, including islands in promoter-associated regions, than the cases with less hypomethylation. Additionally, telomere length was heterogenous in LBCL, with a subset of the DLBCL-GC cases accounting for the longest RTL. Short RTL was independently associated with worse DSS (HR 6.011, 95% CI 1.319-27.397) and PFS (HR 4.689, 95% CI 1.102-19.963) in LBCL treated with R-CHOP-like regimens. CONCLUSION: We hypothesize that subclones with high global hypomethylation and hypermethylated CpG islands could have advantages in tumor progression, e.g. by inactivating tumor suppressor genes or promoting treatment resistance. Our findings suggest that cases with high global hypomethylation and thus poor prognosis could be candidates for alternative treatment regimens including hypomethylating drugs.


Subject(s)
DNA Methylation , Lymphoma, Large B-Cell, Diffuse , Humans , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/mortality , DNA Methylation/genetics , Female , Male , Prognosis , Middle Aged , Aged , Adult , Rituximab/therapeutic use , Aged, 80 and over , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Vincristine/therapeutic use , Prednisone/therapeutic use , Telomere/genetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Telomere Shortening/genetics , Epigenesis, Genetic/genetics , CpG Islands/genetics
2.
BMC Cancer ; 24(1): 621, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38773392

ABSTRACT

BACKGROUND: Diffuse large B-cell lymphomas (DLBCLs) display high molecular heterogeneity, but the International Prognostic Index (IPI) considers only clinical indicators and has not been updated to include molecular data. Therefore, we developed a widely applicable novel scoring system with molecular indicators screened by artificial intelligence (AI) that achieves accurate prognostic stratification and promotes individualized treatments. METHODS: We retrospectively enrolled a cohort of 401 patients with DLBCL from our hospital, covering the period from January 2015 to January 2019. We included 22 variables in our analysis and assigned them weights using the random survival forest method to establish a new predictive model combining bidirectional long-short term memory (Bi-LSTM) and logistic hazard techniques. We compared the predictive performance of our "molecular-contained prognostic model" (McPM) and the IPI. In addition, we developed a simplified version of the McPM (sMcPM) to enhance its practical applicability in clinical settings. We also demonstrated the improved risk stratification capabilities of the sMcPM. RESULTS: Our McPM showed superior predictive accuracy, as indicated by its high C-index and low integrated Brier score (IBS), for both overall survival (OS) and progression-free survival (PFS). The overall performance of the McPM was also better than that of the IPI based on receiver operating characteristic (ROC) curve fitting. We selected five key indicators, including extranodal involvement sites, lactate dehydrogenase (LDH), MYC gene status, absolute monocyte count (AMC), and platelet count (PLT) to establish the sMcPM, which is more suitable for clinical applications. The sMcPM showed similar OS results (P < 0.0001 for both) to the IPI and significantly better PFS stratification results (P < 0.0001 for sMcPM vs. P = 0.44 for IPI). CONCLUSIONS: Our new McPM, including both clinical and molecular variables, showed superior overall stratification performance to the IPI, rendering it more suitable for the molecular era. Moreover, our sMcPM may become a widely used and effective stratification tool to guide individual precision treatments and drive new drug development.


Subject(s)
Artificial Intelligence , Lymphoma, Large B-Cell, Diffuse , Humans , Lymphoma, Large B-Cell, Diffuse/mortality , Female , Male , Middle Aged , Prognosis , Retrospective Studies , China/epidemiology , Aged , Adult , Aged, 80 and over , Young Adult , Adolescent
3.
Kyobu Geka ; 77(5): 389-393, 2024 May.
Article in Japanese | MEDLINE | ID: mdl-38720609

ABSTRACT

Primary pulmonary diffuse large B-cell lymphoma( DLBCL) is rare, accounting for 0.4% to 1.0% of all malignant lymphomas and 0.45% of all lung malignancies. We report a case of primary pulmonary DLBCL caused by methotrexate-associated lymphoproliferative disorder (MTX-LPD). A 73-year-old man was referred to our hospital due to a growing lung nodule. Transbronchoscopic biopsy did not confirm the diagnosis, but positron emission tomography-computed tomography (PET-CT) showed an accumulation of SUVmax 28.7 in the same area and SUVmax 40.5 in the contralateral mediastinum, suggesting an advanced primary lung cancer. A partial thoracoscopic left lower lobe resection was performed in our department. Histopathological examination revealed AE1/AE3 negative, CD20 and 79a positive, bcl-2 positive, and a diagnosis of primary lung DLBCL. MTX-LPD was suspected, and discontinuation of the drug resulted in subsequent shrinkage of the residual tumor. If the diagnosis cannot be made by transbronchoscopic biopsy of an expanding nodule shadow, aggressive surgical diagnosis should be considered.


Subject(s)
Lung Neoplasms , Lymphoma, Large B-Cell, Diffuse , Humans , Male , Aged , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Lung Neoplasms/pathology , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Lymphoma, Large B-Cell, Diffuse/surgery , Diagnosis, Differential , Positron Emission Tomography Computed Tomography
4.
Medicine (Baltimore) ; 103(19): e38013, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728507

ABSTRACT

Colon lymphoma is a rare type of gastrointestinal lymphoma and represents 0.2% to -1.2% of all primary colon cancers. This study aimed to retrospectively examine the general characteristics, treatment methods, and survival characteristics of patients with colon lymphoma who were followed-up at our center. This retrospective study included patients diagnosed with colon lymphoma who were followed up at Ankara Numune Training and Research Hospital and Ankara Bilkent City Hospital between December 2005 and June 2023. Clinicopathological features, radiological findings, treatments, and modalities of patients were obtained from their medical records. Fourteen patients with primary colon lymphoma were included in the study. Thirteen patients (92.9%) were diagnosed with diffuse large B-cell lymphoma. The median age of the patients was 55 (28-84) years. The tumor location was the terminal ileum/cecum in 50% of the patients. At the time of diagnosis, 10 patients (7 with stage 1E-2E disease, 2 with stage 3E disease, and 1 with stage 4E disease due to tumor obstruction) underwent surgery. Twelve patients received chemotherapy (6 patients as adjuvant and 6 patients as first-line treatment). The median overall survival (OS) was 10 years (0.1-21.5) years, the 5-year median OS was 71%, and the 10-year median OS was 53%. Primary colon lymphoma is a rare disease and its optimal treatment is not clearly defined. The primary treatment for primary colon lymphoma is a combination of surgery and chemotherapy. A clear consensus on the treatment can be established through prospective studies.


Subject(s)
Colonic Neoplasms , Humans , Middle Aged , Male , Aged , Female , Retrospective Studies , Colonic Neoplasms/therapy , Colonic Neoplasms/pathology , Colonic Neoplasms/mortality , Adult , Aged, 80 and over , Lymphoma/therapy , Lymphoma/epidemiology , Lymphoma/diagnosis , Lymphoma/mortality , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Large B-Cell, Diffuse/epidemiology , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/pathology , Neoplasm Staging
5.
Saudi Med J ; 45(5): 490-494, 2024 May.
Article in English | MEDLINE | ID: mdl-38734435

ABSTRACT

OBJECTIVES: To investigate the basic characteristics of patients with diffuse large B-cell lymphoma (DLBCL) and whether hepatitis B surface antigen positive (HBsAg [+]) affects the survival of patients with DLBCL. METHODS: The study was carried out at Affiliated Hospital of Hebei University, Baoding, China, including 602 DLBCL cases from January 2011 to December 2021. We analyzed patients' general clinical data and applied multivariate and univariate Cox analyses to assess the factors influencing their survival times. RESULTS: The HBsAg(+) and HBsAg(-) groups comprised 154 (25.6%) and 448 (74.4%) of the 602 cases, respectively. HBsAg(+) cases tended to be later-stage (III-IV) with higher international prognostic index (IPI) points (3-5) and a greater tendency toward B symptoms, impaired liver function, and recurrence than HBsAg(-) cases (all p<0.05). After follow-up, 194 (32.2%) patients died. The median overall survival (OS) and 5-year OS rates in the HBsAg(+) and HBsAg(-) groups were 16.5 months (42%) and 35 months (63%), respectively. Cox analyses indicated that HBsAg(+) affected the prognosis of DLBCL cases (HR=1.46, 95%CI=1.07-1.99, p=0.017). CONCLUSION: The HBsAg(+) seems to be an independent hazard factor for the worse prognosis of DLBCL patients; hence, a focus on these patients in clinic is required.


Subject(s)
Hepatitis B Surface Antigens , Hepatitis B , Lymphoma, Large B-Cell, Diffuse , Humans , Male , Middle Aged , Female , Hepatitis B Surface Antigens/blood , Hepatitis B/complications , Hepatitis B/epidemiology , Adult , Aged , Prognosis , Survival Rate , China/epidemiology , Young Adult , Proportional Hazards Models , Aged, 80 and over , Neoplasm Staging
6.
Exp Clin Transplant ; 22(4): 307-310, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38742322

ABSTRACT

Posttransplant lymphoproliferative disorder is a life-threatening complication after solid-organ transplants. In adults, recipients of heart transplants have the highest risk, whereas renal transplant recipients have the lowest risk among all solid-organ transplants. The most common site for posttransplant lymphoproliferative disorders are gastrointestinal tract followed by the graft itself. Airway involvement in posttransplant lymphoproliferative disorder is rarely encountered. We report a case of a 26-year-old renal allograft recipient who presented to the emergency room with airway obstruction necessitating an emergency tracheostomy. Imaging revealed a left tonsillar mass extending into the nasopharynx and retropharyngeal space causing complete oropharyngeal occlusion. Endoscopic biopsy from nasopharyngeal mass showed a diffuse large B-cell lymphoma and was Ebstein-Barr virus positive. Reduction in immunosuppression and treatment with posttransplant lymphoproliferative disorder-1 risk-stratified approach resulted in complete remission.


Subject(s)
Airway Obstruction , Immunosuppressive Agents , Kidney Transplantation , Lymphoma, Large B-Cell, Diffuse , Humans , Kidney Transplantation/adverse effects , Adult , Treatment Outcome , Airway Obstruction/etiology , Airway Obstruction/virology , Airway Obstruction/diagnosis , Immunosuppressive Agents/adverse effects , Male , Lymphoma, Large B-Cell, Diffuse/virology , Acute Disease , Biopsy , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/virology , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/immunology , Tracheostomy/adverse effects , Remission Induction , Immunocompromised Host , Nasopharyngeal Neoplasms/virology , Nasopharyngeal Neoplasms/surgery , Nasopharyngeal Neoplasms/diagnosis
8.
Zhonghua Nei Ke Za Zhi ; 63(5): 521-524, 2024 May 01.
Article in Chinese | MEDLINE | ID: mdl-38715494

ABSTRACT

A 48-year-old male was admitted to Peking Union Medical College Hospital presented with intermittent fever for two years. The maximum body temperature was 39 ℃, and could spontaneously relieve. The efficacy of antibacterial treatment was poor. He had no other symptoms and positive signs. He had a significant weight loss, and the serum lactate dehydrogenase increased significantly. It was highly alert to be lymphoma, but bone marrow smear and pathology, and PET-CT had not shown obvious abnormalities. Considering high inflammatory indicators, increased ferritin and large spleen, the patient had high inflammatory status, and was treated with methylprednisolone. Then the patient's body temperature was normal, but the platelet decreased to 33×109/L. During hospitalization, he had suddenly hemoperitoneum and hemorrhagic shock. He was found spontaneous spleen rupture without obvious triggers, and underwent emergency splenectomy. The pathological diagnosis of spleen was diffuse large B-cell lymphoma.


Subject(s)
Fever of Unknown Origin , Hemoperitoneum , Positron Emission Tomography Computed Tomography , Humans , Male , Middle Aged , Fever of Unknown Origin/etiology , Fever of Unknown Origin/diagnosis , Positron Emission Tomography Computed Tomography/methods , Hemoperitoneum/etiology , Hemoperitoneum/diagnosis , Lymphoma, Large B-Cell, Diffuse/diagnosis , Splenectomy , Spleen/diagnostic imaging , Splenic Rupture/diagnosis , Splenic Rupture/etiology
9.
Zhonghua Xue Ye Xue Za Zhi ; 45(3): 209-214, 2024 Mar 14.
Article in Chinese | MEDLINE | ID: mdl-38716591

ABSTRACT

Primary mediastinal large B-cell lymphoma (PMBL) is an aggressive B-cell lymphoma that is thought to arise from thymic (medullary) B cells and has unique clinicopathologic and molecular features. In recent years, the understanding of the pathogenesis and treatment of PMBL has been updated to varying degrees, particularly in the area of new drug therapy. In order to improve the diagnosis and treatment of PMBL in China, the Lymphocyte Disease Group of the Chinese Medical Association (CMA) and the Anti-Lymphoma Alliance of the Chinese Society of Clinical Oncology (CSCO) commissioned a group of experts to formulate this consensus.


Subject(s)
Consensus , Lymphoma, Large B-Cell, Diffuse , Mediastinal Neoplasms , Humans , Mediastinal Neoplasms/diagnosis , Mediastinal Neoplasms/therapy , China , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/therapy
10.
Zhonghua Xue Ye Xue Za Zhi ; 45(3): 308-312, 2024 Mar 14.
Article in Chinese | MEDLINE | ID: mdl-38716606

ABSTRACT

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non Hodgkin's lymphoma. The current treatment plan can significantly improve the prognosis of patients, but about 30%-40% of DLBCL patients still experience drug resistance and relapse after treatment. For patients with refractory/relapse DLBCL, clinical treatment remains difficult and their prognosis is poor. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains one of the most important curative methods for refractory/relapse DLBCL patients. This article will review the role and progress of allo-HSCT in the treatment of refractory/relapse DLBCL.


Subject(s)
Hematopoietic Stem Cell Transplantation , Lymphoma, Large B-Cell, Diffuse , Transplantation, Homologous , Humans , Lymphoma, Large B-Cell, Diffuse/therapy , Hematopoietic Stem Cell Transplantation/methods
11.
J Cancer Res Clin Oncol ; 150(5): 224, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693452

ABSTRACT

BACKGROUND: Incorporating chimeric antigen receptor (CAR)-T cell therapy into relapsed or refractory large B-cell lymphoma (rr LBCL) treatment algorithms has yielded remarkable response rates and durable remissions, yet a substantial portion of patients experience progression or relapse. Variations in outcomes across treatment centers may be attributed to different bridging strategies and remission statuses preceding CAR-T cell therapy. PATIENTS: Twenty-nine consecutive adult patients receiving tisagenlecleucel (tisa-cel) for rr LBCL from December 2019 to February 2023 at Jena University Hospital were analyzed. RESULTS: The median age was 63, with a median of 3 prior treatments. Twenty patients (69%) were refractory to any systemic therapy before CAR-T cell treatment. Following leukapheresis, 25 patients (86%) received bridging therapy with the majority undergoing chemotherapy (52%) or combined modality therapy (32%). Radiotherapy (RT) was part of the bridging strategy in 44%, with moderately hypofractionated involved site RT (30.0 Gy/2.5 Gy) being applied most frequently (64%). Post-CAR-T infusion, the objective response rate at 30 days was 83%, with 55% achieving complete response. Twelve-month progression-free (PFS) and overall survival (OS) were 60% and 74%, respectively, with a median follow up of 11.1 months for PFS and 17.9 months for OS. Factors significantly associated with PFS were chemotherapy sensitivity pre-leukapheresis and response to bridging. CONCLUSION: The study underscores the importance of minimal tumor burden at CAR-T initiation, emphasizing the need for suitable bridging regimens. The findings advocate for clinical trials and further real-world analyses to optimize CAR-T cell therapy outcomes by identifying the most effective bridging strategies.


Subject(s)
Immunotherapy, Adoptive , Lymphoma, Large B-Cell, Diffuse , Humans , Male , Middle Aged , Female , Aged , Immunotherapy, Adoptive/methods , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Adult , Remission Induction , Neoplasm Recurrence, Local/therapy , Neoplasm Recurrence, Local/pathology , Germany , Receptors, Antigen, T-Cell/therapeutic use , Retrospective Studies , Combined Modality Therapy
12.
J Transl Med ; 22(1): 414, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693538

ABSTRACT

Primary testicular lymphoma (PTL) is a rare lymphoma predominantly occurring in the elderly male population. It is characterized by a limited response to treatment and a heightened tendency towards relapse. Histologically, approximately 90% of PTL cases are classified as diffuse large B-cell lymphomas (DLBCL). Genetic features of PTL were delineated in a limited scope within several independent studies. Some of the articles which analyzed the genetic characterization of DLBCL have incorporated PTL samples, but these have been constrained by small sample sizes. In addition, there have been an absence of independent molecular typing studies of PTL. This report summarizes the common mutational features, copy number variations (CNVs) and molecular typing of PTL patients, based on whole-exome sequencing (WES) conducted on a cohort of 25 PTL patients. Among them, HLA, CDKN2A and MYD88 had a high mutation frequency. In addition, we found two core mutational characteristics in PTL including mutation in genes linked to genomic instability (TP53 and CDKN2A) and mutation in immune-related genes (HLA, MYD88, CD79B). We performed molecular typing of 25 PTL patients into C1 subtype with predominantly TP53 mutations and C2 subtype with predominantly HLA mutations. Notably, mutations in the TP53 gene predicted a poor outcome in most types of lymphomas. However, the C1 subtype, dominated by TP53 mutations, had a better prognosis compared to the C2 subtype in PTL. C2 subtype exhibited a worse prognosis, aligning with our finding that the mechanism of immune escape in PTL was primarily the deletions of HLA rather than PD-L1/PD-L2 alterations, a contrast to other DLBCLs. Moreover, we calculated the tumor mutation burden (TMB) and identified that TMB can predict prognosis and recurrence rate in PTL. Our study underscores the significance of molecular typing in PTL based on mutational characteristics, which plays a crucial role in prognostication and guiding therapeutic strategies for patients.


Subject(s)
DNA Copy Number Variations , Genomics , Mutation , Testicular Neoplasms , Humans , Male , Testicular Neoplasms/genetics , Testicular Neoplasms/pathology , Testicular Neoplasms/classification , Mutation/genetics , DNA Copy Number Variations/genetics , Aged , Middle Aged , Lymphoma/genetics , Lymphoma/pathology , Lymphoma/classification , Exome Sequencing , Aged, 80 and over , Adult , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Large B-Cell, Diffuse/classification
14.
Cancer Cell ; 42(5): 833-849.e12, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38701792

ABSTRACT

Glucocorticoids have been used for decades to treat lymphomas without an established mechanism of action. Using functional genomic, proteomic, and chemical screens, we discover that glucocorticoids inhibit oncogenic signaling by the B cell receptor (BCR), a recurrent feature of aggressive B cell malignancies, including diffuse large B cell lymphoma and Burkitt lymphoma. Glucocorticoids induce the glucocorticoid receptor (GR) to directly transactivate genes encoding negative regulators of BCR stability (LAPTM5; KLHL14) and the PI3 kinase pathway (INPP5D; DDIT4). GR directly represses transcription of CSK, a kinase that limits the activity of BCR-proximal Src-family kinases. CSK inhibition attenuates the constitutive BCR signaling of lymphomas by hyperactivating Src-family kinases, triggering their ubiquitination and degradation. With the knowledge that glucocorticoids disable oncogenic BCR signaling, they can now be deployed rationally to treat BCR-dependent aggressive lymphomas and used to construct mechanistically sound combination regimens with inhibitors of BTK, PI3 kinase, BCL2, and CSK.


Subject(s)
Glucocorticoids , Receptors, Antigen, B-Cell , Humans , Glucocorticoids/pharmacology , Receptors, Antigen, B-Cell/metabolism , Animals , Signal Transduction/drug effects , Receptors, Glucocorticoid/metabolism , Mice , Cell Line, Tumor , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/metabolism , Burkitt Lymphoma/drug therapy , Burkitt Lymphoma/genetics , Burkitt Lymphoma/metabolism , Burkitt Lymphoma/pathology , Molecular Targeted Therapy/methods , Phosphatidylinositol 3-Kinases/metabolism , src-Family Kinases/metabolism , Gene Expression Regulation, Neoplastic/drug effects
15.
J Hematol Oncol ; 17(1): 34, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38764055

ABSTRACT

Disseminated adenovirus infection is a complication with a relatively high mortality rate among patients undergoing hematopoietic stem cell transplantation. The low efficacy and poor availability of current treatment options are of major concern. Programmed cell death 1 (PD-1) blockade has been used to treat several chronic viral infections. Herein, we report a case of disseminated adenovirus infection in the early posttransplant period. The patient was diagnosed with diffuse large B-cell lymphoma at first and underwent 8 cycles of chemotherapy, including rituximab. She was subsequently diagnosed with acute myeloid leukemia and received haploidentical transplantation. She was diagnosed with Epstein‒Barr virus (EBV)-positive posttransplant lymphoproliferative disorder (PTLD) 2 months after the transplant, and 3 doses of rituximab were administered. The patient was diagnosed with disseminated adenovirus infection with upper respiratory tract, gastrointestinal tract and blood involved at 3 months after transplantation. She was first treated with a reduction in immunosuppression, cidofovir and ribavirin. Then, the patient received salvage treatment with the PD-1 inhibitor sintilimab (200 mg) after achieving no response to conventional therapy. The adenovirus was cleared 3 weeks later, and concomitant EBV was also cleared. Although the patient developed graft-versus-host disease of the liver after the administration of the PD-1 inhibitor, she was cured with steroid-free therapy. Therefore, PD-1 blockade immunotherapy can be considered a promising treatment option for patients with disseminated adenovirus infection after transplantation, with fully weighing the hazards of infection and the side effects of this therapy.


Subject(s)
Hematopoietic Stem Cell Transplantation , Programmed Cell Death 1 Receptor , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Female , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Immune Checkpoint Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Immunotherapy/methods , Middle Aged , Transplantation, Homologous , Adenoviridae Infections/drug therapy , Adenovirus Infections, Human/drug therapy , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy
16.
Clin Exp Med ; 24(1): 105, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38771501

ABSTRACT

Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for B cell malignancies. A certain fraction of patients, however, experience post-CAR-T relapse, and due to the difficulty of precise relapse prediction, biomarkers that can predict the strength and duration of CAR-T efficacy are needed before CAR-T infusion. Therefore, we performed a single-center cohort study including 91 diffuse large B cell lymphoma (DLBCL) patients treated with CAR-T in order to identify such a new prognostic biomarker. After confirming that each of the already reported prognostic parameters (disease status at leukapheresis, primary refractoriness, number of treatment lines, CD3+ cell counts at leukapheresis) has only limited predictive performance, we established a new composite parameter by integrating these four variables, and found that it predicts progression-free survival (PFS) after CAR-T infusion with statistical significance. Moreover, after comprehensive correlation analyses of this new composite parameter with all individual laboratory variables, we determined that the standard deviation of red blood cell distribution width (RDW-SD) at leukapheresis shows significant correlation with the composite parameter and may be a prognostic biomarker (R2 = 0.76, p = 0.02). Validation analysis indicated that a higher RDW-SD is significantly associated with poorer PFS after CAR-T cell therapy (HR, 3.46, P = 0.03). Thus, this study suggests that a single parameter, RDW-SD at leukapheresis, is a novel, useful biomarker that can be obtained early to predict therapeutic effects of CAR-T cell therapy. Post-CAR-T maintenance or re-induction therapies should be adopted for higher risk patients, who may relapse after CAR-T therapy.


Subject(s)
Erythrocyte Indices , Immunotherapy, Adoptive , Lymphoma, Large B-Cell, Diffuse , Humans , Male , Female , Middle Aged , Immunotherapy, Adoptive/methods , Adult , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Large B-Cell, Diffuse/blood , Aged , Prognosis , Treatment Outcome , Biomarkers/blood , Receptors, Chimeric Antigen , Cohort Studies , Young Adult , Leukapheresis
17.
Oncol Rep ; 51(6)2024 06.
Article in English | MEDLINE | ID: mdl-38757403

ABSTRACT

Diffuse large B­cell lymphoma (DLBCL) is the most common pathological type of non­Hodgkin's lymphoma. Although the development of monoclonal antibodies, small­molecule­targeted drugs and novel chemotherapeutic agents, and the increased use of immunotherapy have markedly improved the outcomes of DLBCL, ~40% of patients cannot be cured following the use of standardized first­line treatment. In addition, the specific mechanisms of drug resistance and potential factors associated with a poor prognosis in these patients remain unclear. Proteomics research is used to determine potential associations between changes in DLBCL protein expression levels and different stages of disease occurrence and development. Proteomics may aid in the identification of novel molecular mechanisms and drug resistance mechanisms, through identifying multiple associated proteins and monitoring changes in expression levels. Thus, proteomics research may exhibit potential in the development of therapeutic targets and in improving prognostic evaluation in patients with DLBCL. The present study aimed to review the use of proteomic methods for the investigation of DLBCL, including the mechanisms underlying disease progression and drug resistance in DLBCL, and the function of the tumor microenvironment in lymphoma growth. The present review also demonstrated the potential of proteomic­guided therapeutic strategies for DLBCL and discussed the synergistic benefits of using proteomic methods in DLBCL research.


Subject(s)
Drug Resistance, Neoplasm , Lymphoma, Large B-Cell, Diffuse , Proteomics , Tumor Microenvironment , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Large B-Cell, Diffuse/metabolism , Lymphoma, Large B-Cell, Diffuse/genetics , Proteomics/methods , Prognosis , Biomarkers, Tumor/metabolism , Disease Progression
18.
Expert Rev Mol Diagn ; 24(5): 439-457, 2024 May.
Article in English | MEDLINE | ID: mdl-38709202

ABSTRACT

BACKGROUND: Although anoikis plays a role in cancer metastasis and aggressiveness, it has rarely been reported in diffuse large B cell lymphoma (DLBCL). METHODS: We obtained RNA sequencing data and matched clinical data from the GEO database. An anoikis-related genes (ARGs)-based risk signature was developed in GSE10846 training cohort and validated in three other cohorts. Additionally, we predicted half-maximal inhibitory concentration (IC50) of drugs based on bioinformatics method and obtained the actual IC50 to some chemotherapy drugs via cytotoxicity assay. RESULTS: The high-risk group, as determined by our signature, was associated with worse prognosis and an immunosuppressive environment in DLBCL. Meanwhile, the nomogram based on eight variables had more accurate ability in forecasting the prognosis than the international prognostic index in DLBCL. The prediction of IC50 indicated that DLBCL patients in the high-risk group were more sensitive to doxorubicin, IPA-3, lenalidomide, gemcitabine, and CEP.701, while patients in the low-risk group were sensitive to cisplatin and dasatinib. Consistent with the prediction, cytotoxicity assay suggested the higher sensitivity to doxorubicin and gemcitabine and the lower sensitivity to dasatinib in the high-risk group in DLBCL. CONCLUSION: The ARG-based signature may provide a promising direction for prognosis prediction and treatment optimization for DLBCL patients.


Subject(s)
Anoikis , Lymphoma, Large B-Cell, Diffuse , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/diagnosis , Prognosis , Anoikis/drug effects , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/genetics , Transcriptome , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Nomograms
19.
PeerJ ; 12: e17363, 2024.
Article in English | MEDLINE | ID: mdl-38766487

ABSTRACT

Background: Promoter hypermethylation of the tumor suppressor gene is one of the well-studied causes of cancer development. The drugs that reverse the process by driving demethylation could be a candidate for anticancer therapy. This study was designed to investigate the effects of arsenic disulfide on PTPL1 methylation in diffuse large B cell lymphoma (DLBCL). Methods: We knocked down the expression of PTPL1 in two DLBCL cell lines (i.e., DB and SU-DHL-4 cells) using siRNA. Then the DLBCL proliferation was determined in the presence of PTPL1 knockdown. The methylation of PTPL1 in DLBCL cells was analyzed by methylation specific PCR (MSPCR). The effect of arsenic disulfide on the PTPL1 methylation was determined in DLBCL cell lines in the presence of different concentrations of arsenic disulfide (5 µM, 10 µM and 20 µM), respectively. To investigate the potential mechanism on the arsenic disulfide-mediated methylation, the mRNA expression of DNMT1, DNMT3B and MBD2 was determined. Results: PTPL1 functioned as a tumor suppressor gene in DLBCL cells, which was featured by the fact that PTPL1 knockdown promoted the proliferation of DLBCL cells. PTPL1 was found hypermethylated in DLBCL cells. Arsenic disulfide promoted the PTPL1 demethylation in a dose-dependent manner, which was related to the inhibition of DNMTs and the increase of MBD2. Conclusion: Experimental evidence shows that PTPL1 functions as a tumor suppressor gene in DLBCL progression. PTPL1 hyper-methylation could be reversed by arsenic disulfide in a dose-dependent manner.


Subject(s)
Cell Proliferation , DNA Methylation , Lymphoma, Large B-Cell, Diffuse , Humans , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Large B-Cell, Diffuse/metabolism , Cell Line, Tumor , DNA Methylation/drug effects , Cell Proliferation/drug effects , Arsenicals/pharmacology , DNA Methyltransferase 3B , Disulfides/pharmacology , DNA (Cytosine-5-)-Methyltransferases/genetics , DNA (Cytosine-5-)-Methyltransferases/metabolism , DNA (Cytosine-5-)-Methyltransferase 1/metabolism , DNA (Cytosine-5-)-Methyltransferase 1/genetics , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Gene Knockdown Techniques , Promoter Regions, Genetic/drug effects , Gene Expression Regulation, Neoplastic/drug effects
20.
J Investig Med High Impact Case Rep ; 12: 23247096241253334, 2024.
Article in English | MEDLINE | ID: mdl-38747509

ABSTRACT

Primary cardiac lymphoma is an exceedingly rare malignant tumor, with diffuse large B-cell lymphoma (DLBCL) being the most prevalent histological subtype. This disease has non-specific clinical manifestations, making early diagnosis crucial. However, DLBCL diagnosis is commonly delayed, and its prognosis is typically poor. Herein, we report the case of a 51-year-old male patient with DLBCL who presented with recurrent chest tightness for 4 months as the primary clinical symptom. The patient was admitted to the hospital and diagnosed with acute myocardial infarction and left ventricular hypertrophy with heart failure. Echocardiography revealed a progression from left ventricular thickening to local pericardial thickening and adhesion in the inferior and lateral walls of the left ventricle. Finally, pathological analysis of myocardial biopsy confirmed the diagnosis of DLBCL. After treatment with the R-CHOP chemotherapy regimen, the patient's chest tightness improved, and he was discharged. After 2 months, the patient succumbed to death owing to sudden ventricular tachycardia, ventricular fibrillation, and decreased blood pressure despite rescue efforts. Transthoracic echocardiography is inevitable for the early diagnosis of DLBCL, as it can narrow the differential and guide further investigations and interventions, thereby improving the survival of these patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Echocardiography , Heart Neoplasms , Hypertrophy, Left Ventricular , Lymphoma, Large B-Cell, Diffuse , Myocardial Infarction , Vincristine , Humans , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Large B-Cell, Diffuse/complications , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/drug therapy , Male , Middle Aged , Heart Neoplasms/complications , Heart Neoplasms/pathology , Heart Neoplasms/diagnosis , Myocardial Infarction/etiology , Myocardial Infarction/diagnosis , Fatal Outcome , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hypertrophy, Left Ventricular/etiology , Vincristine/administration & dosage , Vincristine/therapeutic use , Doxorubicin/administration & dosage , Doxorubicin/therapeutic use , Rituximab/therapeutic use , Rituximab/administration & dosage , Cyclophosphamide/therapeutic use , Cyclophosphamide/administration & dosage , Prednisone/therapeutic use , Prednisone/administration & dosage
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