Aggressive Lymphoma | |
---|---|
Diffuse Large B-cell Lymphoma | |
Specialty | Hematology and oncology |
Aggressive lymphoma, also known as high-grade lymphoma, is a group of fast growing non-Hodgkin lymphoma. [1]
Some common symptoms for aggressive lymphoma are weight loss, night sweats, nausea and recurrent fevers.[ citation needed ] Since these tumors are fast to grow and spread, immediate intervention is required after diagnosis.[ citation needed ]
There are several subtypes of aggressive lymphoma. These include AIDS-associated lymphoma, angioimmunoblastic lymphoma, Burkitt lymphoma, central nervous system (CNS) lymphoma, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL) and peripheral T-cell lymphoma. [1] Diffuse large B-cell lymphoma is the most common subtype as well as the most common type of non-Hodgkin lymphoma. [2]
Aggressive lymphoma accounts for approximately 60 percent of all non-Hodgkin cases in the United States. [1]
The most common types of high grade non-Hodgkin lymphoma are: [3]
Diffuse large B-cell lymphoma (DLBCL) is a type of high-grade NHL which is the most common type of NHL worldwide at affecting 30–40 percent of all NHL cases. [4] It is more prevalent in elderly patients with a median age of 70 years. Patients most often present with a rapidly growing tumor mass in single or multiple, nodal or extranodal sites. The most commonly diagnosed versions of DLBCL are germinal center B-cell like (GCB) and activated B-cell like (ABC) subtypes. [5]
Immunohistochemical and flow cytometry analysis is also necessary for the diagnosis of this disease. The DLBCL cells have found to express B-cell antigens such as CD19, CD20, and CD22 as well as the transcription factors PAX5, BOB.1, and OCT2. CD20 is especially relevant in diagnostics as well as therapeutics because it is the target of the Rituximab humanized monoclonal antibody that is used in the most common treatment strategy. [5] In addition to this, the majority of cells also express surface or cytoplasmic immunoglobulins, specifically IgM, IgG and IgA. While these analyses allow for diagnosis by displaying proof of B-cell lineage, they can also be used in treatment strategy and can give insight into prognosis of the specific case being considered.[ citation needed ]
Burkitt lymphoma is named after the British surgeon Denis Burkitt. Burkitt identified this disease in 1956 in children in Africa. [6] In Africa, Burkitt lymphoma is common in children also infected by malaria and Epstein–Barr virus.[ citation needed ]
Outside of Africa, Burkitt lymphoma is less common. In the U.S., about 1,200 people are diagnosed each year, and the disease disproportionately affects those younger than the age of 40. [6] Burkitt lymphoma is especially likely to develop in people infected with HIV, the virus that causes AIDS. Before highly active antiretroviral therapy (HAART) became a widespread treatment for HIV/AIDS, the incidence of Burkitt lymphoma was estimated to be 1,000 times higher in HIV-positive people than in the general population. [6]
Peripheral T-cell lymphomas are less common accounting for approximately 7% of all non-Hodgkin lymphoma cases. [7] It represents a diverse group of diseases that lacks clear definition. These diseases may involve extranodal sites such as the liver, bone, marrow, intestinal tract and the skin. [7] Due to its difficulties in classification, diagnosis and treatment is often regarded as "orphan diseases".[ citation needed ]
Some of the risk factors that increase the risk factor of aggressive lymphoma include: [8]
The symptoms of aggressive lymphoma are similar to that of low-grade lymphomas. Patients may come in with painless swollen lymph nodes in their neck, armpits or groin. They can also describe symptoms such as abdominal pain, chest pain, persistent fatigue, fever, night sweats and unexplained weight loss depending on the stage of their tumor and its location. [8]
Since the presentation of aggressive lymphoma are similar to that of other types of non-Hodgkin lymphoma it is important analyze the tumors morphologically and run immunohistochemical tests to ensure correct diagnosis. For aggressive lymphoma, swift and specific treatment dependent upon correct diagnosis can be the difference between life and death for the patient.[ citation needed ]
For limited high grade lymphoma the typical treatment is chemotherapy and a targeted drug, followed by radiotherapy. While advanced high grade aggressive lymphoma patients receive similar treatments, the duration is extended.[ citation needed ]
For advanced diffuse large B-cell lymphoma the standard therapy for patients with DLBCL is the combination use of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). [2] While this commonly used regimen results in 60–70 percent of patients with DLBCL to be cured of disease there is also a group of patients that relapse and do not respond well to R-CHOP. For these patients the current treatment strategies are insufficient in treating their cancer. In addition to this, alternative treatments continue to be research due to the highly toxic nature of R-CHOP. [2]
In contrast to mature B-cell neoplasms, therapeutic advances in peripheral T-cell lymphoma have generally lagged behind, particularly with regard to the introduction of immune therapies, which have impacted significantly and favorably on the prognosis of aggressive B cell lymphomas such as diffuse large B-cell lymphoma. As such, it remains a heterogeneous entity with a generally unfavorable prognosis. [9]
While there is no way of definitively predicting the outcome of an individual's diagnosis of aggressive lymphoma, there are ways of best guessing the prognosis of the patient. These prognostic factors can be divided into three categories. The first category depends on the patient and can be their age and overall health. The second category is dependent upon the tumor and includes the stage, tumor burden, and extranodal involvement. Finally, the last category is dependent on aggressiveness indicators. Factors such as LDH serum level and proliferative fraction can give insight into the tumor microenvironment and proliferation potential which may impact the prognosis. [5]
Two promising immunotherapy approaches against diffuse large B-cell lymphoma are chimeric antigen receptor (CAR) T cell therapy and therapeutic blocking of programmed cell death protein 1 pathway (PD-1/PD-L1). [10] While CAR T-cells have shown promising efficacy in patients with DLBCL, there have been some unexpected toxicity related issues that have come up for further research. [10]
One proposal to improve research for treatment in aggressive lymphoma is to use canines as model animals. Canine lymphoma prevalence has been increasing over the years similar to the incidence of human lymphoma cases. Lymphoma represents the most frequent hematopoietic cancer in dogs with canine non-Hodgkin lymphoma (cNHL) having the highest incidence at 83% of all hematopoietic cancers. [11] In addition to this diffuse large B-cell lymphoma is the most commonly seen subtype of NHL in both species. [12] The advantages of using canines as model animals include spontaneous disease occurring without an isogenic background or genetic engineering; chronology of disease adapted to lifespan; shared environmental and societal status that allows dogs to be treated as "patients", while at the same time being able to ethically explore translational innovations that are not possible in human subjects; and organization of dogs into breeds with relatively homogeneous genetic backgrounds and distinct predisposition for lymphomas. [12] In addition to this, there have also been studies that suggest that breed type might influence disease progression and response to therapy which is very promising for human therapeutic research. [12]
Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tiredness. Other symptoms may include bone pain, chest pain, or itchiness. Some forms are slow-growing while others are fast-growing.
Lymphoma is a group of blood and lymph tumors that develop from lymphocytes. The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph nodes, fever, drenching sweats, unintended weight loss, itching, and constantly feeling tired. The enlarged lymph nodes are usually painless. The sweats are most common at night.
Tumors of the hematopoietic and lymphoid tissues or tumours of the haematopoietic and lymphoid tissues are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues are all intimately connected through both the circulatory system and the immune system, a disease affecting one will often affect the others as well, making aplasia, myeloproliferation and lymphoproliferation closely related and often overlapping problems. While uncommon in solid tumors, chromosomal translocations are a common cause of these diseases. This commonly leads to a different approach in diagnosis and treatment of hematological malignancies. Hematological malignancies are malignant neoplasms ("cancer"), and they are generally treated by specialists in hematology and/or oncology. In some centers "hematology/oncology" is a single subspecialty of internal medicine while in others they are considered separate divisions. Not all hematological disorders are malignant ("cancerous"); these other blood conditions may also be managed by a hematologist.
Follicular lymphoma (FL) is a cancer that involves certain types of white blood cells known as lymphocytes. The cancer originates from the uncontrolled division of specific types of B-cells known as centrocytes and centroblasts. These cells normally occupy the follicles (nodular swirls of various types of lymphocytes) in the germinal centers of lymphoid tissues such as lymph nodes. The cancerous cells in FL typically form follicular or follicle-like structures (see adjacent Figure) in the tissues they invade. These structures are usually the dominant histological feature of this cancer.
Lymphoma (lymphosarcoma) in animals is a type of cancer defined by a proliferation of malignant lymphocytes within solid organs such as the lymph nodes, bone marrow, liver and spleen. The disease also may occur in the eye, skin, and gastrointestinal tract.
T-cell lymphoma is a rare form of cancerous lymphoma affecting T-cells. Lymphoma arises mainly from the uncontrolled proliferation of T-cells and can become cancerous.
Primary gastric lymphoma is an uncommon condition, accounting for less than 15% of gastric malignancies and about 2% of all lymphomas. However, the stomach is a very common extranodal site for lymphomas. It is also the most common source of lymphomas in the gastrointestinal tract.
Primary central nervous system lymphoma (PCNSL), also termed primary diffuse large B-cell lymphoma of the central nervous system (DLBCL-CNS), is a primary intracranial tumor appearing mostly in patients with severe immunodeficiency. It is a subtype and one of the most aggressive of the diffuse large B-cell lymphomas.
The B-cell lymphomas are types of lymphoma affecting B cells. Lymphomas are "blood cancers" in the lymph nodes. They develop more frequently in older adults and in immunocompromised individuals.
Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibodies. It is the most common form of non-Hodgkin lymphoma among adults, with an annual incidence of 7–8 cases per 100,000 people per year in the US and UK. This cancer occurs primarily in older individuals, with a median age of diagnosis at ~70 years, although it can occur in young adults and, in rare cases, children. DLBCL can arise in virtually any part of the body and, depending on various factors, is often a very aggressive malignancy. The first sign of this illness is typically the observation of a rapidly growing mass or tissue infiltration that is sometimes associated with systemic B symptoms, e.g. fever, weight loss, and night sweats.
Richter's transformation (RT), also known as Richter's syndrome, is the conversion of chronic lymphocytic leukemia (CLL) or its variant, small lymphocytic lymphoma (SLL), into a new and more aggressively malignant disease. CLL is the circulation of malignant B lymphocytes with or without the infiltration of these cells into lymphatic or other tissues while SLL is the infiltration of these malignant B lymphocytes into lymphatic and/or other tissues with little or no circulation of these cells in the blood. CLL along with its SLL variant are grouped together in the term CLL/SLL.
Cancer is a category of disease characterized by uncontrolled cell growth and proliferation. For cancer to develop, genes regulating cell growth and differentiation must be altered; these mutations are then maintained through subsequent cell divisions and are thus present in all cancerous cells. Gene expression profiling is a technique used in molecular biology to query the expression of thousands of genes simultaneously. In the context of cancer, gene expression profiling has been used to more accurately classify tumors. The information derived from gene expression profiling often helps in predicting the patient's clinical outcome.
Copanlisib, sold under the brand name Aliqopa, is a medication used for the treatment of adults experiencing relapsed follicular lymphoma who have received at least two prior systemic therapies.
Loncastuximab tesirine, sold under the brand name Zynlonta, is a monoclonal antibody conjugate medication used to treat large B-cell lymphoma and high-grade B-cell lymphoma. It is an antibody-drug conjugate (ADC) composed of a humanized antibody targeting the protein CD19.
Epstein–Barr virus–associated lymphoproliferative diseases are a group of disorders in which one or more types of lymphoid cells, i.e. B cells, T cells, NK cells, and histiocytic-dendritic cells, are infected with the Epstein–Barr virus (EBV). This causes the infected cells to divide excessively, and is associated with the development of various non-cancerous, pre-cancerous, and cancerous lymphoproliferative disorders (LPDs). These LPDs include the well-known disorder occurring during the initial infection with the EBV, infectious mononucleosis, and the large number of subsequent disorders that may occur thereafter. The virus is usually involved in the development and/or progression of these LPDs although in some cases it may be an "innocent" bystander, i.e. present in, but not contributing to, the disease.
T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a malignancy of B cells. B-cells are lymphocytes that normally function in the humoral immunity component of the adaptive immune system by secreting antibodies that, for example, bind to and neutralize invasive pathogens. Among the various forms of B-cell lymphomas, THRLBCL is a rarely occurring subtype of the diffuse large B-cell lymphomas (DLBCL). DLBCL are a large group of lymphomas that account for ~25% of all non-Hodgkin lymphomas worldwide. THRLBCL is distinguished from the other DLBCL subtypes by the predominance of non-malignant T-cell lymphocytes and histiocytes over malignant B-cells in its tumors and tissue infiltrates.
Primary testicular diffuse large B-cell lymphoma (PT-DLBCL), also termed testicular diffuse large B-cell lymphoma and diffuse large B-cell lymphoma of the testes, is a variant of the diffuse large B-cell lymphomas (DLBCL). DLBCL are a large and diverse group of B-cell malignancies with the great majority (-85%) being typed as diffuse large B-cell lymphoma, not otherwise specified. PT-DLBCL is a variant of DLBCL, NOS that involves one or, in uncommon cases, both testicles. Other variants and subtypes of DLBCL may involve the testes by spreading to them from their primary sites of origin in other tissues. PT-DLBCL differs from these other DLBCL in that it begins in the testes and then may spread to other sites.
Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a cutaneous lymphoma skin disease that occurs mostly in elderly females. In this disease, B cells become malignant, accumulate in the dermis and subcutaneous tissue below the dermis to form red and violaceous skin nodules and tumors. These lesions typically occur on the lower extremities but in uncommon cases may develop on the skin at virtually any other site. In ~10% of cases, the disease presents with one or more skin lesions none of which are on the lower extremities; the disease in these cases is sometimes regarded as a variant of PCDLBL, LT termed primary cutaneous diffuse large B-cell lymphoma, other (PCDLBC-O). PCDLBCL, LT is a subtype of the diffuse large B-cell lymphomas (DLBCL) and has been thought of as a cutaneous counterpart to them. Like most variants and subtypes of the DLBCL, PCDLBCL, LT is an aggressive malignancy. It has a 5-year overall survival rate of 40–55%, although the PCDLBCL-O variant has a better prognosis than cases in which the legs are involved.
Indolent lymphoma, also known as low-grade lymphoma, is a group of slow-growing non-Hodgkin lymphomas (NHLs). Because they spread slowly, they tend to have fewer signs and symptoms when first diagnosed and may not require immediate treatment. Symptoms can include swollen but painless lymph nodes, unexplained fever, and unintended weight loss.
Diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI) is a subtype of the Diffuse large B-cell lymphomas and a rare form of the Epstein–Barr virus-associated lymphoproliferative diseases, i.e. conditions in which lymphocytes infected with the Epstein-Barr virus (EBV) proliferate excessively in one or more tissues. EBV infects ~95% of the world's population to cause no symptoms, minor non-specific symptoms, or infectious mononucleosis. The virus then enters a latency phase in which the infected individual becomes a lifetime asymptomatic carrier of the virus. Some weeks, months, years, or decades thereafter, a very small fraction of these carriers, particularly those with an immunodeficiency, develop any one of various EBV-associated benign or malignant diseases.
This article incorporates public domain material from Dictionary of Cancer Terms. U.S. National Cancer Institute.