T-cell lymphoma

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T-cell lymphoma
Enteropathy-associated T cell lymphoma - low mag.jpg
Micrograph of an enteropathy-associated T-cell lymphoma (upper right of image), a type of T-cell lymphoma. H&E stain.
Specialty Hematology and oncology
Symptoms swollen lymph nodes, fevers, enlarged liver or spleen, liver dysfunction, rash
Risk factors Autoimmune disorders, Epstein–Barr virus (EBV), Human T-cell leukemia virus-1 (HTLV1), Organ transplants, immunosuppressant therapy
Treatment chemotherapy, radiotherapy, stem cell transplant

T-cell lymphoma is a rare form of cancerous lymphoma affecting T-cells. [1] Lymphoma arises mainly from the uncontrolled proliferation of T-cells and can become cancerous. [2]

Contents

T-cell lymphoma is categorized under Non-Hodgkin lymphoma (NHL) and represents less than 15% of all Non-Hodgkin's diseases in the category. [3] T-cell lymphomas are often categorised based on their growth patterns as either; aggressive (fast-growing) or indolent (slow-growing). [1] Although the cause of T-cell lymphoma is not definitive, it has been associated with various risk factors and viruses such as Epstein–Barr virus (EBV) and Human T-cell leukemia virus-1 (HTLV1). [2]

The prognosis and treatment of T-cell lymphoma can vary drastically based on the specific type of lymphoma and its growth patterns. Due to their rarity and high variability between the different subtypes, the prognosis of T-cell lymphoma is significantly worse than other Non-Hodgkin lymphoma. [1] The treatment of T-cell lymphoma is often similar to other Non-Hodgkin lymphomas with early-stage treatments consisting of chemotherapy and/or radiotherapy. [2] The effectiveness of these treatments is often varied between subtypes with most receiving a poor outcome with high relapse rates. [4]

Types

There are many types and variations of T-cell lymphoma, each with vastly different symptoms, survival, and prognosis. The classification of T-cell lymphoma has been difficult to accomplish due to the lack of understanding of their biology. [4] Most classifications are basic with many still under the title of ‘provisional categories’ in the World Health Organization Classification of disease. [5]

Common

Rare

Symptoms and signs

Symptoms of Mycosis fungoide Mycosis fungoide.JPG
Symptoms of Mycosis fungoide

Differences in T-cell lymphoma subtypes extend to the clinical characteristics and symptoms of the disease with each varying drastically. As a result, there is almost no universally known symptom that can be applied to all T-cell lymphoma subtypes. [4]

The hemophagocytic syndrome (HPS)

Hemophagocytic syndrome has been associated with most T-cell lymphoma subtypes, and is commonly characterized by fevers, reduction of lymphocytes numbers, enlarged liver or spleen, and liver dysfunction. [2] These symptoms are especially common in Extranodal T cell lymphoma subtypes which develop outside the lymph nodes, these can include; Extranodal NK/T-cell lymphoma, nasal type, Cutaneous T-cell lymphoma (CTCL), etc. [5]

Swollen lymph nodes

T-cell lymphoma which develops from the lymph nodes commonly causes symptoms as such swollen lymph nodes. [6] The swelling normally will not cause any pain and can be felt or seen as lumps on the surface of the skin. Nodal T-cell lymphoma subtypes such as peripheral T-cell lymphoma will often develop this symptom.[ citation needed ]

Skin infections

T-cell lymphoma can cause eczema or rash-like symptoms where small red patches will appear around the skin. These patches will often be irritated and may appear slightly lighter in colour compared to the rest of the skin. Occasionally, small lumps will develop which may rupture and cause the surface layer of the skin to break open. This is especially common in Cutaneous T-cell lymphoma subtypes. [4]

Cause

Although there is no definitive cause for most T-cell lymphoma subtypes, a series of risk factors have been linked and associated with the increased likelihood of contracting the disease.

Risk factors

Family history: A family history of hematopoietic malignancies has been linked to an increased association with most T-cell lymphoma subtypes. This link is especially elevated among individuals 50 years or younger. [2] However, the link is still considered as a hypothesised risk meaning that research conducted on this link have been insufficient or inconclusive.

Autoimmune conditions: Autoimmune conditions are commonly considered as a risk factor that has been associated with non-Hodgkin lymphomas, with coeliac disease having an established associated with an increased risk of Extranodal T-cell lymphoma subtypes. [2]

Organ transplants and immunosuppressant: Organ transplants and immunosuppressant therapy is considered an established risk factor for all Non-Hodgkin lymphoma, including T-cell lymphoma. This risk factor elevates the risk of contracting T-cell lymphoma. [2]

Infectious Agents: Several infectious agents have been linked to a higher risk of T-cell lymphoma by providing a compromised immune function allowing the establishment of lymphomas. Of these Epstein–Barr virus (EBV) and Human T-cell leukemia virus-1 (HTLV1) are considered established risks. [7]

Epstein–Barr virus is a largely common virus with more than 90% of individuals exposed to the virus in their lifetime. EBV has been consistently associated with many lymphoproliferation disorders, of these EBV-associated T-cell lymphomas include Epstein–Barr virus–associated lymphoproliferative diseases, angioimmunoblastic T-cell lymphoma (AITL), extranodal NK/T-cell lymphoma, nasal type, and Peripheral T-cell lymphoma not otherwise specified (PTCL, NOS). [8]

The human T-cell leukemia virus-1 is endemic in regions such as Japan and the Caribbean and has been associated with the increased risk of T-cell lymphoma such as Adult T-cell leukemia/lymphoma (ATL). [9] HTLV-1 has been attributed to 56% and 78% of all ATL cases in Japan and the Caribbean respectively. [8]

Diagnosis

Biopsy Procedure Skin Punch Biopsy.png
Biopsy Procedure

The diagnosis of T-cell lymphoma varies largely between the subtypes. Some subtypes like anaplastic large-cell lymphoma have an exceptional diagnostic rate however, [4] for a majority of T-cell lymphoma subtypes the diagnosis is often flawed due to the difficulty to culture damaged lymphoma cells and the overall low frequency of cases compared to other Non-Hodgkin lymphoma. [6] The current and most accurate diagnosis used across most subtypes is a biopsy in which fresh tissue that is suspected to be affected by the lymphoma is collected from the patient to be closely examined by pathology laboratories. [2] Other diagnostic methods are specific to the type of T-cell lymphoma, physical examination of skin or lymph nodes is common for cutaneous subtypes of T-cell lymphoma whilst others may be diagnosed using blood tests. Series of scans such as CT scan, MRI, ultrasounds, and even X-rays may also be used for diagnostic purposes. [1]

Treatment

Stem cell Transplant Bone Marrow Transplant.png
Stem cell Transplant

Treatment for T-cell lymphoma varies widely due to the large variability in the subtypes. Due to the lack of research performed in understanding the nature of T-cell lymphoma pathogenesis, a majority of cases will often have poor outcomes for the treatment or will relapse. [3] However, new research into new therapy methods have been made to help reduce the mortality rates and risk of relapse. [10] [2]

Chemotherapy

Chemotherapy is a drug treatment that involves the use of one or more anti-cancer drugs and is currently the most common treatment method used across all subtypes. [8] T cell lymphoma is typically treated using the CHOP regimen in which four anti-cancer drugs; cyclophosphamide, doxorubicin, vincristine, and prednisone are used in combination at a relatively high dosage. However, outcomes of the CHOP regimen are often poor with high relapse rates. [3] Other less common chemotherapy regime which can also be used include; DHAP (dexamethasone, high-dose cytarabine, and cisplatin) and ICE (ifosfamide, carboplatin, etoposide), however, the outcomes of these treatments are often similar to or worse than the CHOP regimen. [6] In order to improve these outcomes chemotherapy has often been used in conjunction with radiotherapy followed by stem cell transplants. [2]

Radiotherapy

Radiotherapy is the use of radiation to eradicate cancer. [2] As the electron beams in radiotherapy only penetrate to the level of the dermis, it is a common method of treatment for skin lymphoma which may only occur locally such as Cutaneous T-cell lymphoma, however, it is not recommended for patients with systemic lymphoma conditions. [6]

Stem cell transplant

Stem Cell Transplants are a common method of treatment which can either be used in conjunction with chemotherapy to improve remission and effectiveness or it can be used with relapsed lymphoma patients. [6] Stem cell transplants can either be an autologous stem cell transplant (ASCT) in which the patient donates their own stem cells or an allogeneic stem cell transplant (alloHCT) in which a related or unrelated healthy donor will donate their stem cells to the patient. [3] Stem cells are collected from the bone marrow and are a type of cell capable of self-renewal and can differentiate into all types of cells, [2] this can be utilised for patients with T-cell lymphoma and has seen effective results in treating some subtypes, especially Angioimmunoblastic T-cell lymphoma. [8]

Allogenic stem cell transplants are mainly used when the patient lacks adequate healthy stem cells for an autologous stem cell transplant or has relapsed after prior autologous stem cell transplant treatments. [8] However, allogenic transplants pose a risk as it may be toxic to the patient. Proposed solution include improved donor selection and the use of a conditioning regime in which a high dose of a myeloablative treatment is given alongside stem cell transplants to reduce the immune response. [2]

Monoclonal antibodies

Monoclonal antibodies (mAb) utilizes antibodies to target tumours, it induces apoptosis of the tumour through the obstruction of survival pathways. [11] Monoclonal antibodies can be used as a single treatment agent, however, are more effective when used concurrently with chemotherapy to improve survival and remission. [2] Most commonly used monoclonal antibody used to treat T cell lymphoma include; alemtuzumab and denileukin difititox. [3]

Nucleoside analogs

Nucleoside analogs are a type of antiviral cytotoxic drug used to treat various cancer related diseases. It possesses highly immunosuppressive abilities and acts by inhibiting viral replication and prevent the spread of the cancerous growth. [3] Nucleoside analogs are one of the most active class of drug used to treat T-cell lymphoma.

Other

Other non-tradition or new treatment options include: targeted therapy, [10] protease inhibitors, signalling inhibitors, and HDAC inhibitors.

Epidemiology

While the incidence of Non-Hodgkin's lymphoma has plateaued, the rate of T-cell lymphomas has gradually increased over the past few years. However, due to the low frequency and lack of research performed on the disease, the number of cases is relatively underrepresented compared to other non-Hodgkin lymphomas. [3]

Cases are more common in those of Native American descent followed by Caucasian ancestry, [2] however, the epidemiology can vary greatly between the different subtypes. The incidences[ spelling? ] of T-cell lymphoma are slightly higher in men than in women in all categories of race [6] with cases increasing in frequency with age for most subtypes. [2]

In Asia, T/NK-cell neoplasms are more common as a result of host factors and the higher prevalence of human T-cell leukemia virus-1 (HTLV1) and Epstein–Barr virus (EBV). While enteropathy-associated T-cell lymphoma (EATCL) is more common among Irish and Welsh populations. [2]

See also

Related Research Articles

<span class="mw-page-title-main">Non-Hodgkin lymphoma</span> Type of cancer of lymph nodes

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.

<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">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">Intravascular lymphomas</span> Medical condition

Intravascular lymphomas (IVL) are rare cancers in which malignant lymphocytes proliferate and accumulate within blood vessels. Almost all other types of lymphoma involve the proliferation and accumulation of malignant lymphocytes in lymph nodes, other parts of the lymphatic system, and various non-lymphatic organs but not in blood vessels.

<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 NK-cell leukemia</span> Medical condition

Aggressive NK-cell leukemia is a disease with an aggressive, systemic proliferation of natural killer cells and a rapidly declining clinical course.

Angioimmunoblastic T-cell lymphoma is a mature T-cell lymphoma of blood or lymph vessel immunoblasts characterized by a polymorphous lymph node infiltrate showing a marked increase in follicular dendritic cells (FDCs) and high endothelial venules (HEVs) and systemic involvement.

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.

<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.

Subcutaneous T-cell lymphoma is a cutaneous condition that most commonly presents in young adults, and is characterized by subcutaneous nodules. Common symptoms include fever, fatigue, and pancytopenia.

<span class="mw-page-title-main">Extranodal NK/T-cell lymphoma, nasal type</span> Medical condition

Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT) is a rare type of lymphoma that commonly involves midline areas of the nasal cavity, oral cavity, and/or pharynx At these sites, the disease often takes the form of massive, necrotic, and extremely disfiguring lesions. However, ENKTCL-NT can also involve the eye, larynx, lung, gastrointestinal tract, skin, and various other tissues. ENKTCL-NT mainly affects adults; it is relatively common in Asia and to lesser extents Mexico, Central America, and South America but is rare in Europe and North America. In Korea, ENKTCL-NT often involves the skin and is reported to be the most common form of cutaneous lymphoma after mycosis fungoides.

<span class="mw-page-title-main">Peripheral T-cell lymphoma not otherwise specified</span> Medical condition

Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), is a subtype of peripheral T-cell lymphoma. Peripheral T-cell lymphoma (PTCL) is defined as a diverse group of aggressive lymphomas that develop from mature-stage white blood cells called T-cells and natural killer cells. PTCL is a type of non-Hodgkin's lymphoma (NHL). PTCL specifically affects T-cells rather than B-cells, and results when T-cells develop and grow abnormally.

Brentuximab vedotin, sold under the brand name Adcetris, is an antibody-drug conjugate medication used to treat relapsed or refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), a type of T cell non-Hodgkin lymphoma. It selectively targets tumor cells expressing the CD30 antigen, a defining marker of Hodgkin lymphoma and ALCL. The drug is being jointly marketed by Millennium Pharmaceuticals outside the US and by Seagen in the US.

<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.

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.

Monomorphic epitheliotropic intestinal T cell lymphoma (MEITL) is an extremely rare peripheral T-cell lymphoma that involves the malignant proliferation of a type of lymphocyte, the T cell, in the gastrointestinal tract. Over time, these T cells commonly spread throughout the mucosal lining of a portion of the GI tract, lead to GI tract nodules and ulcerations, and cause symptoms such as abdominal pain, weight loss, diarrhea, obstruction, bleeding, and/or perforation.

<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.

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.

Mature T-cell lymphoma, also called peripheral T-cell lymphoma, is a group of rare, aggressive lymphomas that develop from mature white blood cells and originate from lymphoid tissues outside of the bone marrow. Mature T-cell lymphoma is under the category of non-Hodgkin lymphoma. Mature T-cell lymphomas account for 10% to 15% of all lymphomas and is more common in Asia than in Europe and America. Its common subtypes include angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma and peripheral T-cell lymphoma not otherwise specified. While different subtypes have variable symptoms, common symptoms include enlarged painless lymph nodes, fever, weight loss, rash and night sweats.

Tabelecleucel, sold under the brand name Ebvallo, is a medication used for the treatment of Epstein-Barr virus positive post-transplant lymphoproliferative disease. Tabelecleucel is an allogeneic, EBV-specific T-cell immunotherapy which targets and eliminates EBV-infected cells in a human leukocyte antigen (HLA)-restricted manner. It is made of cells of the immune system called T-cells that have been taken from the recipient (allogeneic) and are then mixed with EBV-infected B-cells from the same donor.

References

  1. 1 2 3 4 Quesenberry, Peter J.; Castillo, Jorge J. (2013). Non-Hodgkin Lymphoma Prognostic Factors and Targets. NY: Humana Press.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Foss, Francine (2013). T-cell Lymphomas. Totowa, NJ: Humana Press.
  3. 1 2 3 4 5 6 7 Querfeld, Christiane; Zain, Jasmine; Rosen, Steven T (2019). T-Cell and NK-Cell Lymphomas From Biology to Novel Therapies. Cham: Springer International Publishing.
  4. 1 2 3 4 5 Ansell, Stephen M (2015). "Non-Hodgkin Lymphoma: Diagnosis and Treatment". Mayo Clinic Proceedings. 90 (8): 1152–63. doi: 10.1016/j.mayocp.2015.04.025 . PMID   26250731.
  5. 1 2 World Health Organization. "International Classification of Diseases 11th Revision". World Health Organization. Retrieved 5 October 2020.
  6. 1 2 3 4 5 6 Younes, Anas; Coiffier, Bertrand (2013). Lymphoma Diagnosis and Treatment. NY: Humana Press. ISBN   978-1-62703-407-4.
  7. ↑ Shankland, Kate R; Armitage, James O; Hancock, Barry W (2012). "Non-Hodgkin lymphoma". The Lancet. 380 (9844): 848–57. doi:10.1016/S0140-6736(12)60605-9. PMID   22835603. S2CID   44302140.
  8. 1 2 3 4 5 Evens, Andrew M.; Blum, Kristie A. (2015). Non-Hodgkin Lymphoma Pathology, Imaging, and Current Therapy. Cham: Springer International Publishing.
  9. ↑ Watanabe, Toshiki; Fukushima, Takuya (2017). Adult T-cell Leukemia/Lymphoma. Japan: Springer Japan. ISBN   978-4-431-56523-9.
  10. 1 2 Cordo V, Meijerink J (January 2021). "T-cell Acute Lymphoblastic Leukemia: A Roadmap to Targeted Therapies". Blood Cancer Discovery. 2 (1): 19–31. doi: 10.1158/2643-3230.BCD-20-0093 . PMC   8447273 . PMID   34661151.
  11. ↑ Cheng, Liu; Morrow, John (2017). Biosimilars of Monoclonal Antibodies: A Practical Guide to Manufacturing, Preclinical, and Clinical Development. New Jersey: John Wiley & Sons, Inc. ISBN   978-1-118-66231-1.
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