T-cell lymphomas are much less common than b-cell lymphomas, particularly in the United States. They develop from abnormal t-lymphocytes and account for approximately 15 percent of all non-Hodgkin lymphoma cases in the United States. There are many different types of t-cell lymphomas, some of which are very rare. Among the more common t-cell lymphomas are peripheral t-cell lymphoma not otherwise specified (PTCL-NOS), which accounts for about a quarter of all t-cell lymphomas. These lymphomas are often aggressive and may show up in lymph nodes, skin, or other organs of the body.
Anaplastic large cell lymphoma describes several types of t-cell lymphoma and accounts for approximately 15 percent of all t-cell lymphomas in adults. It is subdivided into three subtypes: ALK positive, ALK negative, or a skin only type called primary cutaneous anaplastic large cell lymphoma. The systemic types are usually fast-growing while the skin only type is usually more slow-growing.
Angioimmunoblastic lymphoma is a fast-growing t-cell lymphoma accounting for more than 15 percent of all t-cell lymphomas in the Unted States. It often presents with swollen lymph nodes and systemic symptoms such as fever and rash. It is generally treated like other fast-growing t-cell lymphomas, but can be managed sometimes with milder therapies.
Cutaneous t-cell lymphoma accounts for 2 percent to 3 percent of all NHL cases and mostly affects adults. These are slow-growing cancers that start, and are most often confined, to the skin. Mycosis fungoides is the most common type of cutaneous t-cell lymphoma. It appears as skin patches or plaques, and is often controlled over many years.
Less common forms include Sezary syndrome, primary cutaneous anaplastic large cell lymphoma and lymphomatoid papulosis among others.
Even rarer t-cell lymphomas include adult t-cell leukemia/lymphoma, which is caused by the HTLV virus. This virus is more commonly found in people from the Caribbean, southern Japan, and central Africa. The virus often is acquired from breast feeding, but only about 2 percent who carry the virus will develop lymphoma. The great majority will remain asymptomatic carriers throughout their life.
Blastic NK-cell lymphoma is a very rare cancer that only impacts a small number of people each year. This lymphoma is fast-growing and can be difficult to treat. It can arise anywhere in the body. Dark red or purple skin lesions are a common feature.
Enteropathy-type t-cell lymphoma is an extremely rare subtype of t-cell lymphoma that appears in the intestines and is strongly associated with celiac disease.
Hematosplenic gamma-delta t-cell lymphoma is an extremely rare and aggressive disease that starts in the liver or spleen. It may occur in those with inflammatory bowel disease who are immunosuppressed.
Lymphoblastic lymphoma can appear in both b-cells and t-cells, but is much more common in t-cells, comprising 80 percent of all lymphoblastic lymphomas. This lymphoma is most often diagnosed in children. With intensive chemotherapy, the complete remission rate can be very high.
Nasal NK/t-cell lymphomas are relatively rare in the United States, but are fast-growing and typically originate in the lining of the nose or upper airway. They are treated with radiation and various combinations of chemotherapy. Treatment-related t-cell lymphomas sometimes appear after solid organ or bone marrow transplantation. The immune system suppression that is required to transplant patients can put them at risk for developing post-transplant lymphoproliferative disorders, certain unusual forms of peripheral t-cell lymphoma and other types of NHL.
Treatments depend upon the type and other factors. Due to the rarity of t-cell lymphomas, most treatments are borrowed from other types of lymphoma. Treatments include chemotherapy, radiation, stem cell transplantation and surgery. Treatments aimed at the skin, such as ultraviolet light therapy or electron beam therapy are effective for many slow-growing t-cell lymphomas that appear in the skin.
For most subtypes of PTCL, the frontline treatment regimen is typically a combination chemotherapy, such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide, prednisone) or other multi-drug regimens. Drugs that have been approved specifically for t-cell lymphomas of the skin include: bexarotene (Targretin); denileukin diftitox (Ontak); romidepsin (Isotodax); and vorinostat (Zolinza).
A procedure called extracorporeal photopheresis, which involves removing a patient’s blood and treating it with ultraviolet light and drugs that become active when exposed to light is approved to treat the blood of people with mycosis fungoides or Sezary syndrome. Pralatrexate (Folotyn) has been approved for relapsed and refractory peripheral T-cell lymphoma. Relapsed PTCL patients may also be treated with combination chemotherapy programs such as ICE (ifosfamide, carboplatin, etoposide), followed by an autologous or allogeneic stem cell transplant. Gemcitabine (Gemzar) appears effective against some forms of relapsed PTCL and is often given in combination with other chemotherapies, including vinorelbine (Navelbine) and doxorubicin (Doxil) in a regimen called GND. Other chemotherapy regimens include DHAP (dexamethasone, cytarabine, cisplatin) and ESHAP (etoposide, methylprednisolone, cytarabine and cisplatin). In June 2011, the U.S. Food and Drug Administration (FDA) granted accelerated approval of romidepsin (Istodax) for injection for the treatment of peripheral t-cell lymphoma (PTCL) in patients who have received at least one prior therapy. In 2011, the U.S. Food and Drug Administration (FDA) granted accelerated approval of brentuximab vedotin (Adcetris), an antibody-drug conjugate which targets CD30, for the treatment of patients with relapsed or refractory systemic anaplastic large cell lymphoma (ALCL). Many drugs are being studied in clinical trials for the treatment of PTCL, including: ABT-262; AT-101; bortezomib (Velcade); decapeptide; obatoclax; (GX15-070); panobinostat (Faridak); PXD101 (Belinostat); romidepsin (Istodax); vorinostat (Zolinza); lenalidomide (Revlimid); zanolimumab; and brentuximab vedotin (Adcetris)
ALCL appearing in multiple sites on the body may require systemic treatment such as mild chemotherapy (single agents or mild combinations); bexarotene (Targretin) pills; CVP (cyclophosphamide, vincristine, prednisone) chemotherapy; or methotrexate (Trexall). There are several drugs now in clinical trials that are showing promising results, including pralatrexate (Folotyn). Novel combination chemotherapy regimens are also being studied in ongoing trials for patients with systemic t-cell lymphomas such as CHOP plus bevacizumab (Avastin) and PEGS (cisplatin, etoposide, gemcitabine and solumedrol).
Angioimmunoblastic t-cell lymphoma is usually first treated with chemotherapy regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), dose intense regimens such as Hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone), or non-adriamycin based chemotherapy, radiation or high-dose chemotherapy followed by an autologous stem cell transplant (stem cell transplant in which a patient receives their own stem cells). Once a patient has disease that has relapsed, alternative therapies are indicated such as pralatrexate (Folotyn). Other salvage chemotherapies such as a gemcitabine (Gemzar) containing regimen, or an allogeneic stem cell transplant (stem cell transplant in which a patient receives stem cells from a donor). Several drugs currently being tested in clinical trials are showing promise. For example, a new class of drugs, known as histone deacetylase inhibitors, which include the drugs suberoylanilide hydroxamic acid (SAHA) and vorinostat (Zolinza), have been effective in the treatment of a variety of t-cell lymphomas.
For mycosis fungoides, treatment is either directed at the skin or the entire body (systemic). Because Sezary syndrome is chronic and systemic (affecting the entire body), it is usually not treated with skin-directed therapies alone. Treatments may be prescribed alone or in combination to achieve the best long-term benefit. Other treatments include: ultraviolet light (PUVA, UVB); denileukin diftitox (Ontak); narrow-band UVB); extracorporeal photopheresis; topical steroids; gemcitabine (Gemzar); nitrogen mustard; interferon; liposomal doxorubicin (Doxil); retinoids (bexarotene gel); mMethotrexate (Trexall); local radiation; oral retinoids (bexarotene capsules); total skin electron beam therapy; romidepsin (Istodax); vorinostat (Zolinza). Some second-line therapies include the above or bortezomib (Velcade), chlorambucil (Leukeran), cyclophosphamide (Cytoxan), etoposide (Toposar), pentostatin (Nipent), and temozolomide (Temodar). There are several treatments being tested in clinical trials for cutanious t-cell, including allogeneic stem cell transplant; lenalidomide (Revlimid); autologous dendritic cell vaccine; mogamulizumab (KW-0761); bortezomib (Velcade); pralatrexate (Folotyn); enzastaurin; vorinostat (Zolinza); forodesine (BCX-1777); and zanolimumab (HuMax-CD4).
T-cell leukemias are a poorly defined group of diseases that show up in the blood. These include slow-growing diseases such as t-cell granular lymphocytic leukemia, or faster-growing diseases such as aggressive NK-cell leukemia. There are other rare cancers of the immune system that are neither b-cell nor t-cell lymphomas, but involve other types of white blood cells such as histiocytic and dendritic cell neoplasms.