Non-Hodgkin lymphoma

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Non-Hodgkin lymphoma
Other namesNon-Hodgkin disease
Mantle cell lymphoma - intermed mag.jpg
Micrograph of mantle cell lymphoma, a type of non-Hodgkin lymphoma. Terminal ileum. H&E stain.
Specialty Hematology and oncology
Symptoms Enlarged lymph nodes, fever, night sweats, weight loss, tiredness, itching [1]
Usual onset65–75 years old [2]
Risk factors Poor immune function, autoimmune diseases, Helicobacter pylori infection, hepatitis C, obesity, Epstein-Barr virus infection [1] [3]
Diagnostic method Bone marrow or lymph node biopsy [1]
Treatment Chemotherapy, radiation, immunotherapy, targeted therapy, stem cell transplantation, surgery, watchful waiting [1]
Prognosis Five-year survival rate 71% (USA) [2]
Frequency4.3 million (affected during 2015) [4]
Deaths231,400 (2015) [5]

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. [1] Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tiredness. [1] Other symptoms may include bone pain, chest pain, or itchiness. [1] Some forms are slow-growing while others are fast-growing. [1]

Contents

Lymphomas are types of cancer that develop from lymphocytes, a type of white blood cell. [2] Risk factors include poor immune function, autoimmune diseases, Helicobacter pylori infection, hepatitis C, obesity, and Epstein–Barr virus infection. [1] [3] The World Health Organization classifies lymphomas into five major groups, including one for Hodgkin lymphoma. [6] Within the four groups for NHL are over 60 specific types of lymphoma. [7] [8] Diagnosis is by examination of a bone marrow or lymph node biopsy. [1] Medical imaging is done to help with cancer staging. [1]

Treatment depends on whether the lymphoma is slow- or fast-growing and if it is in one area or many areas. [1] Treatments may include chemotherapy, radiation, immunotherapy, targeted therapy, stem-cell transplantation, surgery, or watchful waiting. [1] If the blood becomes overly thick due to high numbers of antibodies, plasmapheresis may be used. [1] Radiation and some chemotherapy, however, increase the risk of other cancers, heart disease, or nerve problems over the subsequent decades. [1]

In 2015, about 4.3 million people had non-Hodgkin lymphoma, and 231,400 (5.4%) died. [4] [5] In the United States, 2.1% of people are affected at some point in their life. [2] The most common age of diagnosis is between 65 and 75 years old. [2] The five-year survival rate in the United States is 71%. [2]

Signs and symptoms

The signs and symptoms of non-Hodgkin lymphoma vary depending upon its location within the body. 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. [1] Enlarged lymph nodes may cause lumps to be felt under the skin when they are close to the surface of the body. Lymphomas in the skin may also result in lumps, which are commonly itchy, red, or purple. Lymphomas in the brain can cause weakness, seizures, problems with thinking, and personality changes. [9]

While an association between non-Hodgkin lymphoma and endometriosis has been described, [10] these associations are tentative. [11]

Diagnosis

Tests for non-Hodgkin lymphoma include;

If cancer is found, the following tests may be done to study the cancer cells:

Other tests and procedures may be done depending on the signs and symptoms seen and where the cancer forms in the body. [12] [13]

Causes

The many different forms of lymphoma probably have different causes. These possible causes and associations with at least some forms of NHL include:

Familial component

Familial lymphoid cancer is rare. The familial risk of lymphoma is elevated for multiple lymphoma subtypes, suggesting a shared genetic cause. However, a family history of a specific subtype is most strongly associated with risk for that subtype, indicating that these genetic factors are subtype-specific. Genome-wide association studies have successfully identified 67 single-nucleotide polymorphisms from 41 loci, most of which are subtype specific. [27]

HIV/AIDS

The Centers for Disease Control and Prevention (CDC) included certain types of non-Hodgkin lymphoma as AIDS-defining cancers in 1987. [28] Immune suppression rather than HIV itself is implicated in the pathogenesis of this malignancy, with a clear correlation between the degree of immune suppression and the risk of developing NHL. Additionally, other retroviruses, such as HTLV, may be spread by the same mechanisms that spread HIV, leading to an increased rate of co-infection. [29] The natural history of HIV infection has greatly changed over time. As a consequence, rates of non-Hodgkin lymphoma (NHL) in people infected with HIV has significantly declined in recent years. [16]

Treatment

The traditional treatment of NHL includes chemotherapy, radiotherapy, and stem-cell transplants. [30] [31] There have also been developments in immunotherapy used in the treatment of NHL. [32]

Chemotherapy

The most common chemotherapy used for B-cell non-Hodgkin lymphoma is R-CHOP, which is a regimen of four drugs (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus rituximab. [33]

R-CHP with polatuzumab vedotin, an antibody-drug conjugate, was included as a category 1 preferred regimen for first-line DLBCL by the National Comprehensive Cancer Network in 2023. [34]

Treatment complications

If participants receive stem-cell transplants, they can develop a graft-versus-host disease. When compared with placebo for treating immune mediated inflammation post transplantation and in autoimmunity, mesenchymal stromal cells (MSCs) may reduce the all-cause mortality if they are used for a therapeutic reason. [35] Moreover, the therapeutic use of MSCs may increase the complete response of acute and chronic GvHD, but the evidence is very uncertain. [35] The evidence suggests that MSCs for prophylactic reason result in little to no difference in the all-cause mortality, in the relapse of malignant diseases, and in the incidence of acute GvHD. [35] The evidence suggests that MSCs for prophylactic reason reduce the incidence of chronic GvHD. [35]

Platelet transfusions may be necessary for those who receive chemotherapy or undergo a stem cell transplantation due to the higher risk for bleeding. When comparing therapeutic/non-prophylactic platelet transfusions to prophylactic platelet transfusions there is little to no difference in the mortality secondary to bleeding and they may result in a slight reduction in the number of days on which a significant bleeding event occurred. [36] The evidence suggests that therapeutic platelet transfusions result in a large increase in the number of people with at least one significant bleeding event and they likely result in a large reduction in the number of platelet transfusions. [36] [37]

Other

It is unclear if including aerobic physical exercise, in addition to the standard treatment for adult patients with haematological malignancies, is effective at reducing anxiety and serious adverse effects. [38] Aerobic physical exercises may result in little to no difference in the mortality, in the quality of life and in the physical functioning. [38] These exercises may result in a slight reduction in depression and most likely reduce fatigue. [38]

Prognosis

Prognosis depends on the subtype, the staging, a person's age, and other factors. Across all subtypes, 5-year survival for NHL is 74%. [39] [40] [41]

Epidemiology

Globally, as of 2010, there were 210,000 deaths, up from 143,000 in 1990. [42]

Rates of non-Hodgkin lymphoma increase steadily with age. [21] Up to 45 years NHL is more common among males than females. [43]

Australia

Around 6600 people are diagnosed with non-Hodgkin lymphoma in Australia each year. [44]

Canada

In Canada NHL is the fifth most common cancer in males and sixth most common cancer in females. The lifetime probability of developing a lymphoid cancer is 1 in 44 for males, and 1 in 51 for females. [45]

United Kingdom

On average, according to data for the 2014–2016 period, around 13,900 people are diagnosed with NHL yearly. It is the sixth most common cancer in the UK, and is the eleventh most common cause of cancer death accounting for around 4,900 deaths per year. [46]

United States

Age adjusted data from 2012 to 2016 shows about 19.6 cases of NHL per 100,000 adults per year, 5.6 deaths per 100,000 adults per year, and around 694,704 people living with non-Hodgkin lymphoma. About 2.2 percent of men and women will be diagnosed with NHL at some point during their lifetime. [47]

The American Cancer Society lists non-Hodgkin lymphoma as one of the most common cancers in the United States, accounting for about 4% of all cancers. [48]

History

While consensus was rapidly reached on the classification of Hodgkin lymphoma, there remained a large group of very different diseases requiring further classification. The Rappaport classification, proposed by Henry Rappaport in 1956 and 1966, became the first widely accepted classification of lymphomas other than Hodgkin. Following its publication in 1982, the Working Formulation became the standard classification for this group of diseases. It introduced the term non-Hodgkin lymphoma or NHL and defined three grades of lymphoma.[ citation needed ]

NHL consists of many different conditions that have little in common with each other. They are grouped by their aggressiveness. Less aggressive non-Hodgkin lymphomas are compatible with a long survival while more aggressive non-Hodgkin lymphomas can be rapidly fatal without treatment. Without further narrowing, the label is of limited usefulness for people or doctors. The subtypes of lymphoma are listed there.[ citation needed ]

Nevertheless the Working Formulation and the NHL category continue to be used by many. To this day, lymphoma statistics are compiled as Hodgkin's versus non-Hodgkin lymphomas by major cancer agencies, including the US National Cancer Institute in its SEER program, the Canadian Cancer Society and the IARC.[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Lymphoma</span> Hematologic cancer that affects lymphocytes

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.

<span class="mw-page-title-main">Myelodysplastic syndrome</span> Diverse collection of blood-related cancers

A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may include fatigue, shortness of breath, bleeding disorders, anemia, or frequent infections. Some types may develop into acute myeloid leukemia.

<span class="mw-page-title-main">Multiple myeloma</span> Cancer of plasma cells

Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, anemia, kidney dysfunction, and infections may occur. Complications may include hypercalcemia and amyloidosis.

<span class="mw-page-title-main">Chronic lymphocytic leukemia</span> Medical condition

Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes. Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, night sweats, or weight loss for no clear reason may occur. Enlargement of the spleen and low red blood cells (anemia) may also occur. It typically worsens gradually over years.

<span class="mw-page-title-main">Hematopoietic stem cell transplantation</span> Medical procedure to replace blood or immune stem cells

Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce additional normal blood cells. It may be autologous, allogeneic or syngeneic.

<span class="mw-page-title-main">Tumors of the hematopoietic and lymphoid tissues</span> Tumors that affect the blood, bone marrow, lymph, and lymphatic system

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.

<span class="mw-page-title-main">Acute lymphoblastic leukemia</span> Blood cancer characterised by overproduction of lymphoblasts

Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruising, enlarged lymph nodes, or bone pain. As an acute leukemia, ALL progresses rapidly and is typically fatal within weeks or months if left untreated.

<span class="mw-page-title-main">Adult T-cell leukemia/lymphoma</span> Human disease

Adult T-cell leukemia/lymphoma is a rare cancer of the immune system's T-cells caused by human T cell leukemia/lymphotropic virus type 1 (HTLV-1). All ATL cells contain integrated HTLV-1 provirus further supporting that causal role of the virus in the cause of the neoplasm. A small amount of HTLV-1 individuals progress to develop ATL with a long latency period between infection and ATL development. ATL is categorized into 4 subtypes: acute, smoldering, lymphoma-type, chronic. Acute and Lymphoma-type are known to particularity be aggressive with poorer prognosis.

<span class="mw-page-title-main">History of cancer chemotherapy</span>

The era of cancer chemotherapy began in the 1940s with the first use of nitrogen mustards and folic acid antagonist drugs. The targeted therapy revolution has arrived, but many of the principles and limitations of chemotherapy discovered by the early researchers still apply.

<span class="mw-page-title-main">Primary effusion lymphoma</span> Medical condition

Primary effusion lymphoma (PEL) is classified as a diffuse large B cell lymphoma. It is a rare malignancy of plasmablastic cells that occurs in individuals that are infected with the Kaposi's sarcoma-associated herpesvirus. Plasmablasts are immature plasma cells, i.e. lymphocytes of the B-cell type that have differentiated into plasmablasts but because of their malignant nature do not differentiate into mature plasma cells but rather proliferate excessively and thereby cause life-threatening disease. In PEL, the proliferating plasmablastoid cells commonly accumulate within body cavities to produce effusions, primarily in the pleural, pericardial, or peritoneal cavities, without forming a contiguous tumor mass. In rare cases of these cavitary forms of PEL, the effusions develop in joints, the epidural space surrounding the brain and spinal cord, and underneath the capsule which forms around breast implants. Less frequently, individuals present with extracavitary primary effusion lymphomas, i.e., solid tumor masses not accompanied by effusions. The extracavitary tumors may develop in lymph nodes, bone, bone marrow, the gastrointestinal tract, skin, spleen, liver, lungs, central nervous system, testes, paranasal sinuses, muscle, and, rarely, inside the vasculature and sinuses of lymph nodes. As their disease progresses, however, individuals with the classical effusion-form of PEL may develop extracavitary tumors and individuals with extracavitary PEL may develop cavitary effusions.

<span class="mw-page-title-main">T-cell lymphoma</span> Medical condition

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.

<span class="mw-page-title-main">Acute myeloid leukemia</span> Cancer of the myeloid line of blood cells

Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may include feeling tired, shortness of breath, easy bruising and bleeding, and increased risk of infection. Occasionally, spread may occur to the brain, skin, or gums. As an acute leukemia, AML progresses rapidly, and is typically fatal within weeks or months if left untreated.

<span class="mw-page-title-main">Platelet transfusion</span> Treatment for bleeding irregularities

Platelet transfusion, also known as platelet concentrate, is used to prevent or treat bleeding in people with either a low platelet count or poor platelet function. Often this occurs in people receiving cancer chemotherapy. Preventive transfusion is often done in those with platelet levels of less than 10 x 109/L. In those who are bleeding transfusion is usually carried out at less than 50 x 109/L. Blood group matching (ABO, RhD) is typically recommended before platelets are given. Unmatched platelets, however, are often used due to the unavailability of matched platelets. They are given by injection into a vein.

<span class="mw-page-title-main">Diffuse large B-cell lymphoma</span> Type of blood cancer

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.

<span class="mw-page-title-main">Aggressive lymphoma</span> Medical condition

Aggressive lymphoma, also known as high-grade lymphoma, is a group of fast growing non-Hodgkin lymphoma.

<span class="mw-page-title-main">Hodgkin lymphoma</span> Type of blood and immune-system cancer

Hodgkin lymphoma (HL) is a type of lymphoma in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells are present in the patient's lymph nodes. The condition was named after the English physician Thomas Hodgkin, who first described it in 1832. Symptoms may include fever, night sweats, and weight loss. Often, nonpainful enlarged lymph nodes occur in the neck, under the arm, or in the groin. Persons affected may feel tired or be itchy.

<span class="mw-page-title-main">Plasmablastic lymphoma</span> Type of large B-cell lymphoma

Plasmablastic lymphoma (PBL) is a type of large B-cell lymphoma recognized by the World Health Organization (WHO) in 2017 as belonging to a subgroup of lymphomas termed lymphoid neoplasms with plasmablastic differentiation. The other lymphoid neoplasms within this subgroup are: plasmablastic plasma cell lymphoma ; primary effusion lymphoma that is Kaposi's sarcoma-associated herpesvirus positive or Kaposi's sarcoma-associated Herpesvirus negative; anaplastic lymphoma kinase-positive large B-cell lymphoma; and human herpesvirus 8-positive diffuse large B-cell lymphoma, not otherwise specified. All of these lymphomas are malignancies of plasmablasts, i.e. B-cells that have differentiated into plasmablasts but because of their malignant nature: fail to differentiate further into mature plasma cells; proliferate excessively; and accumulate in and injure various tissues and organs.

Large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease is a type of large B-cell lymphoma, recognized in the WHO 2008 classification. It is sometimes called the plasmablastic form of multicentric Castleman disease. It has sometimes been confused with plasmablastic lymphoma in the literature, although that is a dissimilar specific entity. It has variable CD20 expression and unmutated immunoglobulin variable region genes.

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.

<span class="mw-page-title-main">Indolent lymphoma</span> Medical condition

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.

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