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Current Hematologic Malignancy Reports Aug 2019Rituximab-based chemoimmunotherapy has resulted in a marked improvement in the survival of diffuse large B cell lymphoma (DLBCL). We reflect upon the history front-line... (Review)
Review
PURPOSE OF REVIEW
Rituximab-based chemoimmunotherapy has resulted in a marked improvement in the survival of diffuse large B cell lymphoma (DLBCL). We reflect upon the history front-line (1L) therapy and highlight advances in management.
RECENT FINDINGS
Since the introduction of R-CHOP, the majority of randomized studies in the front-line treatment of DLBCL have failed to show a benefit. Such studies have involved treatment intensification, adding novel agents to the R-CHOP backbone and targeting such novel agents to biologically defined subgroups. R-CHOP therefore remains standard-of-care for most but new insights into the molecular biology of these diseases, and the development of active targeted molecules offers promise for the future. Accumulating evidence in the very elderly suggests dose attenuation does not compromise survival. Intensification in primary mediastinal B cell lymphoma may avoid the need for radiotherapy, but must be balanced against the risks. PET-CT- and ctDNA-based response assessment may now enable response adapted therapy and early prognostication, improving patient selection and potentially outcomes. Novel technologies and therapies in combination with novel molecular diagnostics will likely become the standard-of-care approach for the personalized therapy of DLBCL but need to be proven in well-designed and conducted randomized trials.
Topics: Age Factors; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Disease Management; Disease Susceptibility; Doxorubicin; Humans; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neoplasm Grading; Prednisone; Prognosis; Rituximab; Treatment Outcome; Vincristine
PubMed: 31254155
DOI: 10.1007/s11899-019-00518-8 -
BMC Neurology Mar 2023Lymphomas are malignant tumors of the immune system that arise in lymphoid organs and can impact the central nervous system. However, lymphomas with acute myelitis as... (Review)
Review
BACKGROUND
Lymphomas are malignant tumors of the immune system that arise in lymphoid organs and can impact the central nervous system. However, lymphomas with acute myelitis as the first manifestation are exceedingly rare, and most of them are symptoms of spinal cord damage due to the lack of specificity in their clinical manifestations. The rate of early misdiagnosis is exceedingly high, and the prognosis is dire. Here, we report a case of mature B-cell lymphoma with acute myelitis as the first presentation and review the related literature.
CASE PRESENTATION
In this study, We report a case of a 70-year-old male patient with bilateral lower extremity weakness, bowel and bladder dysfunction, and recurrent fever. A paraureteral mass was seen beneath the right kidney on imaging, and the final pathological biopsy revealed: CD20 ( +), mature B-cell tumor, The patient refused to undergo additional tests to ascertain the type of lymphoma and subsequent therapy and asked to be discharged. In mid-November 2020, the patient died.
CONCLUSIONS
This case report shows that patients with lymphoma can present with acute myelitis as the first symptom, especially if they have recurrent fever, that conventional treatment for myelitis is ineffective, and that tumors are considered after other causes of myelitis have been ruled out. Furthermore, a focused search for tumor-related evidence, as well as early identification and therapy, may help patients live longer lives.
Topics: Male; Humans; Aged; Myelitis; Lymphoma, B-Cell; Lymphoma
PubMed: 36932413
DOI: 10.1186/s12883-023-03164-z -
The American Journal of Surgical... Oct 2022Pediatric-type follicular lymphoma (PTFL) and pediatric nodal marginal zone lymphoma (PNMZL) are rare pediatric-type indolent B-cell lymphomas (PedIBCL) that differ...
Pediatric-type follicular lymphoma (PTFL) and pediatric nodal marginal zone lymphoma (PNMZL) are rare pediatric-type indolent B-cell lymphomas (PedIBCL) that differ clinicopathologically from their adult counterparts. Accurate diagnosis is important to avoid overtreatment but is often challenging. The mutational landscape of PTFL is known and may aid diagnosis, but the genetic features of PNMZL are not well understood. We analyzed 21 cases of PedIBCL according to their clinicopathologic findings and classified them into PTFL (n=11), PNMZL (n=2), and "mixed type" tumors (n=8) showing ambiguous histology. We also analyzed 2 cases of adult B-cell lymphomas showing features of PedIBCL. Targeted sequencing of 121 lymphoma-related genes was performed. The median age of PedIBCL patients was 16 years (range: 3 to 47), and all but 1 PTFL patient were male. All patients presented with limited-stage disease, and only 1 relapsed. There were no significant differences in clinical features among the 3 PedIBCL groups. The most frequently mutated genes were MAP2K1 , TNFRSF14 , KMT2C , IRF8 , and NOTCH2 . The genetic features of all groups were similar to the established mutational landscape of PTFL. The 2 adult B-cell lymphomas cases also had MAP2K1 , TNFRSF14 , and IRF8 mutations, but the clinical features were not typical of PedIBCL. In summary, this study demonstrated that PTFL and PNMZL are similar diseases with overlapping clinical, pathologic, and genetic features; mixed type tumors can also occur. Atypical adult cases with similar histologic features were also observed. Therefore, the disease spectrum of PedIBCL may be much broader than is currently believed.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Interferon Regulatory Factors; Lymphoma, B-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Follicular; Male; Middle Aged; Mutation; Young Adult
PubMed: 35834399
DOI: 10.1097/PAS.0000000000001932 -
Current Oncology (Toronto, Ont.) Dec 2021Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is a rare disease, representing <1% of all non-Hodgkin lymphomas (NHL). The most common clinical manifestations... (Review)
Review
Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is a rare disease, representing <1% of all non-Hodgkin lymphomas (NHL). The most common clinical manifestations include splenomegaly, lymphocytosis, and hemocytopenia. A diagnosis of SDRPL can be challenging, as it shares multiple clinical and laboratory features with splenic marginal zone lymphoma (SMZL), hairy cell leukemia (HCL), and HCL variant (HCL-v). Obtaining splenic tissue remains the gold standard for diagnosis. In the cases where splenic tissue is not available, diagnosis can be established by a review of peripheral blood and bone marrow studies. SDRPL is characterized by a diffuse involvement of the splenic red pulp by monomorphous small-to-medium sized mature B lymphocytes effacing the white pulp. The characteristic immunophenotype is positive for CD20, DBA.44 (20 to 90%), and IgG, and typically negative for CD5, CD10, CD23, cyclin D1, CD43, annexin A1, CD11c, CD25, CD123, and CD138. The Ki-67 proliferative index is characteristically low. Cyclin D3 is expressed in the majority of SDRPL in contrast with other types of small B-cell lymphomas, thus facilitating the recognition of this disease. There is no standard treatment regimen for SDRPL. Initial treatment options include splenectomy, rituximab monotherapy, or a combination of both. Chemoimmunotherapy should be considered in patients with advanced disease at baseline or progression.
Topics: Humans; Immunophenotyping; Leukemia, Hairy Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell; Splenic Neoplasms
PubMed: 34940070
DOI: 10.3390/curroncol28060431 -
Journal of Internal Medicine Nov 2017B-cell malignancies are a heterogeneous group of lymphoproliferative disorders with different molecular characteristics and clinical course. It is increasingly... (Review)
Review
B-cell malignancies are a heterogeneous group of lymphoproliferative disorders with different molecular characteristics and clinical course. It is increasingly recognized that the group displays considerable heterogeneity also regarding aetiologic factors. Here, we summarize the latest developments in the aetiology of B-cell lymphoid malignancy subtypes focusing on immune perturbation. Severe immune suppression constitutes a strong and well-established risk factor for aggressive subtypes (e.g. diffuse large B-cell and Burkitt lymphoma), but appears unrelated to risk of common low-grade subtypes (e.g. follicular and mantle cell lymphoma). Inflammation and infections are known co-factors amongst the immunosuppressed; however, immune stimulation is now recognized as a crucial determinant of lymphomagenesis also amongst immunocompetent individuals. This is best exemplified in marginal zone lymphomas where local chronic inflammation and infection in the stomach, ocular adnexa and salivary glands have been directly linked with the development of oligoclonal and monoclonal malignant B-cell populations. Aggressive subtypes (e.g. diffuse large B-cell lymphoma) are increasingly linked with features of systemic immune stimulation including autoimmune/inflammatory disease and subclinical cytokine elevations. Lifestyle factors (e.g. high body mass index, cigarette smoking) are associated with risk of diffuse large B-cell and follicular lymphoma, respectively, possibly mediated through inflammation. Recent genome-wide association studies further underline the importance of immune function by linking several subtypes to variations in the human leucocyte antigen (HLA) class genes. In the future, improved knowledge of mechanistic pathways of inflammation/infections in lymphoma development may translate to active measures of prevention or treatment, as is already the case for some low-grade lymphoma subtypes.
Topics: Autoimmune Diseases; Chronic Disease; Humans; Infections; Inflammation; Lymphoma, B-Cell; Risk Factors
PubMed: 28875507
DOI: 10.1111/joim.12684 -
Journal of Veterinary Internal Medicine Sep 2022Nodal small cell B-cell lymphoma subtypes in dogs cannot be distinguished by flow cytometry and information regarding treatment, prognosis, and outcome are limited.
BACKGROUND
Nodal small cell B-cell lymphoma subtypes in dogs cannot be distinguished by flow cytometry and information regarding treatment, prognosis, and outcome are limited.
HYPOTHESIS/OBJECTIVES
Objectives were to describe outcome in dogs with nodal small cell B-cell lymphoma diagnosed by flow cytometry and correlate clinical and laboratory data with survival. We hypothesized that B-cell Ki67 expression measured by flow cytometry is associated with shorter progression free survival (PFS) and overall survival (OS).
ANIMALS
Forty-nine dogs with nodal small cell B-cell lymphoma, defined by >80% CD21+ B-cells by flow cytometry and small-sized B-cells by forward scatter.
METHODS
Retrospective study reviewing treatment and outcome data extracted from medical records. Percentage of Ki67-expressing B-cells was measured by flow cytometry. Clinical, laboratory, and flow cytometry data were assessed for association with outcome.
RESULTS
Median percentage of B-cell Ki67 was 41% (range, 3%-97%). Median PFS was 119 days and median OS was 222 days (n = 49). Among cases treated with CHOP-based chemotherapy (n = 32), median PFS was 70 days, median OS was 267 days, and 50% of cases achieved complete response. Low percentage of B-cell Ki67 (≤11%) was associated with prolonged OS by univariable analysis. Greater age, substage B, high B-cell CD25 expression and low B-cell CD21 and class II major histocompatibility complex expression by flow cytometry were independently associated with shorter OS.
CONCLUSIONS AND CLINICAL IMPORTANCE
Most nodal small cell B-cell lymphoma cases had aggressive disease. Low Ki67 expression can help identify cases with better prognosis. Age, substage, and flow cytometry variables are useful prognostic factors.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Dog Diseases; Dogs; Flow Cytometry; Ki-67 Antigen; Lymphoma, B-Cell; Neoplasms; Prognosis; Retrospective Studies
PubMed: 35996942
DOI: 10.1111/jvim.16515 -
Journal of Clinical and Experimental... 2014Indolent B-cell lymphomas include follicular lymphoma (FL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and marginal zone lymphomas (MZLs). They... (Review)
Review
Indolent B-cell lymphomas include follicular lymphoma (FL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and marginal zone lymphomas (MZLs). They are a diverse group of disorders with different clinical, morphological, immunophenotypic and genetic features. However, because of several histological similarities, such as in cell size and nodular structure, it may sometimes be difficult to differentiate them and to make a definitive diagnosis. In this review article, we summarize the histopathology of indolent B-cell neoplasms excluding FL and including hairy cell leukemia, and briefly mention recent genetic findings useful for their differential diagnosis. In addition, a provisional subtype of low-grade B-cell lymphoma, "prolymphocytic/paraimmunoblastic lymphoma", is described.
Topics: Biomarkers; Diagnosis, Differential; Humans; Immunohistochemistry; Immunophenotyping; Lymphoma, B-Cell; Lymphoma, Follicular; Neoplasm Grading
PubMed: 24942942
DOI: 10.3960/jslrt.54.11 -
Impact and Intricacies of Bone Marrow Microenvironment in B-cell Lymphomas: From Biology to Therapy.International Journal of Molecular... Jan 2020Lymphoma, a group of widely prevalent hematological malignancies of lymphocyte origin, has become the focus of significant clinical research due to their high propensity... (Review)
Review
Lymphoma, a group of widely prevalent hematological malignancies of lymphocyte origin, has become the focus of significant clinical research due to their high propensity for refractory/relapsed (R/R) disease, leading to poor prognostic outcomes. The complex molecular circuitry in lymphomas, especially in the aggressive phenotypes, has made it difficult to find a therapeutic option that can salvage R/R disease. Furthermore, the association of lymphomas with the Bone Marrow (BM) microenvironment has been found to portend worse outcomes in terms of heightened chances of relapse and acquired resistance to chemotherapy. This review assesses the current therapy options in three distinct types of lymphomas: diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma. It also explores the role of the BM tumor microenvironment as a secure 'niche' for lymphoma cells to grow, proliferate and survive. It further evaluates potential mechanisms through which the tumor cells can establish molecular connections with the BM cells to provide pro-tumor benefits, and discusses putative therapeutic strategies for disrupting the BM-lymphoma cell communication.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Drug Resistance, Neoplasm; Humans; Lymphoma, B-Cell; Tumor Microenvironment
PubMed: 32019190
DOI: 10.3390/ijms21030904 -
International Journal of Molecular... Aug 2019Tumor metabolism and its specific alterations have become an integral part of understanding functional alterations leading to malignant transformation and maintaining... (Review)
Review
Tumor metabolism and its specific alterations have become an integral part of understanding functional alterations leading to malignant transformation and maintaining cancer progression. Here, we review the metabolic changes in B-cell neoplasia, focusing on the effects of tumor metabolism on the tumor microenvironment (TME). Particularly, innate and adaptive immune responses are regulated by metabolites in the TME such as lactate. With steadily increasing therapeutic options implicating or utilizing the TME, it has become essential to address the metabolic alterations in B-cell malignancy for therapeutic approaches. In this review, we discuss metabolic alterations of B-cell lymphoma, consequences for currently used therapy regimens, and novel approaches specifically targeting metabolism in the TME.
Topics: Animals; Disease Progression; Energy Metabolism; Humans; Immunomodulation; Lymphoma, B-Cell; Molecular Targeted Therapy; Signal Transduction; Tumor Microenvironment
PubMed: 31454887
DOI: 10.3390/ijms20174158 -
International Journal of Cancer Sep 2013In most underdeveloped countries, the initial contact with Epstein Barr virus (EBV) usually happens in the first decade of life and results in an asymptomatic infection,... (Review)
Review
In most underdeveloped countries, the initial contact with Epstein Barr virus (EBV) usually happens in the first decade of life and results in an asymptomatic infection, whereas in developed areas, primary infection in adolescence or adulthood is accompanied by infectious mononucleosis in 50% cases. Although it is generally a harmless passenger, in some individuals, it is associated with B-cell lymphoma. In Argentina, EBV primary infection shows the classical pattern observed in developing populations, given that nearly 70% of patients are seropositive by the age of 2 years. However, EBV association with pediatric Hodgkin and Burkitt lymphoma resembles that observed in developed regions. Concerning diffuse large B-cell lymphoma, our series demonstrated higher EBV association than other adult ones from either developed or underdeveloped countries. Interestingly, the early EBV primary infection observed, characteristic of an underdeveloped population, together with the statistically significant EBV association with patients ≤ 10 years old demonstrated in all types of lymphoma studied, suggest a relationship between low age of EBV seroconversion and B-cell lymphoma development risk.
Topics: Adolescent; Argentina; Child; Child, Preschool; Epstein-Barr Virus Infections; Humans; Infant; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
PubMed: 23001576
DOI: 10.1002/ijc.27858