T-Cell Lymphoma

T-cell lymphoma is a rare form of cancer that develops when T-cells, a type of white blood cell that fights infection, grow out of control. This disease makes up only about 7% to 15% of all non-Hodgkin lymphomas and includes many different subtypes, each with distinct characteristics and treatment approaches.

Table of contents

• What is T-cell lymphoma?
• Types of T-cell lymphoma
• Symptoms and signs
• Causes and risk factors
• Diagnosis
• Treatment options
• Prognosis and outlook
• Living with T-cell lymphoma

What is T-cell lymphoma?

T-cell lymphomas are forms of non-Hodgkin lymphoma, a type of cancer that affects the lymphatic system^[1]. The lymphatic system is part of your body’s immune system and includes organs, glands, vessels, and clusters of cells called lymph nodes that help fight infections^[2].

This condition happens when abnormal T-cells multiply and become cancer^[2]. T-cells, also called T-lymphocytes, are white blood cells that play a crucial role in protecting your body from disease. T-cell lymphomas can develop in lymphoid tissues such as the lymph nodes and spleen, or outside of lymphoid tissues in areas like the gastrointestinal tract, liver, nasal cavity, and skin^[1].

T-cell lymphomas account for about 7% of all non-Hodgkin lymphomas in the United States, though this figure varies by region—accounting for 2% in North America, 1% in Europe, and 25% in Asia^[1][4]. Each particular subtype is very uncommon^[1].

• Lymph nodes
• Spleen
• Skin
• Gastrointestinal tract
• Liver
• Nasal cavity
• Bone marrow

Types of T-cell lymphoma

There are many types of T-cell lymphoma, and healthcare providers often group them based on whether they are aggressive (fast-growing) or indolent (slow-growing)^[2]. A similar white blood cell called a natural killer (NK) cell shares many features with T-cells. When NK cells become cancerous, the cancer is called NK or NK/T-cell lymphoma and is generally grouped with other T-cell lymphomas^[1].

Lymphomas that arise from mature T-cells are sometimes categorized together under the general term peripheral T-cell lymphoma (PTCL), which distinguishes them from lymphomas that arise from immature T-cells. Under this broad meaning, almost all types of T-cell lymphoma fall under the category of PTCL^[1].

Aggressive T-cell lymphomas

This group includes fast-growing subtypes^[2]:

• Peripheral T-Cell Lymphoma, Not Otherwise Specified (PTCL-NOS): This refers to a group of diseases that do not fit into any of the other PTCL subtypes. PTCL-NOS accounts for about 20% of T-cell lymphomas and is the most common PTCL subtype. Although most patients are diagnosed with disease confined to the lymph nodes, sites outside the lymph nodes such as the liver, bone marrow, gastrointestinal tract, and skin may also be involved. Patients frequently have constitutional symptoms including fevers, serious night sweats, and unexplained weight loss^[1].
• Anaplastic Large Cell Lymphoma (ALCL): This describes several types of T-cell lymphomas and accounts for approximately 1% of all non-Hodgkin lymphomas and 11% of all T-cell lymphomas. Initial symptoms can include fever, backache, painless swelling of lymph nodes, loss of appetite, itching, skin rash, and tiredness. ALCL can be either systemic (occurring throughout the body) or cutaneous (limited to the skin). The systemic subtype is further classified as ALK-positive or ALK-negative, depending on whether it contains an abnormal anaplastic lymphoma kinase (ALK) fusion protein^[1]. Rarely, a specific subtype can be associated with breast implants^[2].
• Angioimmunoblastic T-cell Lymphoma (AITL): This may cause symptoms similar to autoimmune disorders^[2].
• Adult T-cell Lymphoma/Leukemia: This form is associated with human T-cell lymphotropic virus type I (HTLV-1) and often affects the skin and bones^[2].
• Enteropathy-associated T-cell Lymphoma: This type affects the intestines and is seen in association with celiac disease^[2][4].
• Hepatosplenic Gamma/Delta T-cell Lymphoma: This condition affects the liver and spleen^[2].
• Nasal NK/T-cell Lymphoma: This typically affects the lining of the nose and upper airway but may develop in the skin or gastrointestinal tract. It is usually associated with Epstein-Barr virus (EBV)^[2].

Indolent T-cell lymphomas

This group includes less aggressive subtypes that grow more slowly^[2]:

• Cutaneous T-cell Lymphoma (CTCL): This is the most common type of T-cell lymphoma. It starts in the skin and includes mycosis fungoides and Sézary syndrome^[2].
• T-cell Prolymphocytic Leukemia
• Subcutaneous Panniculitis-like T-cell Lymphoma: This condition affects tissues under the skin^[2].

Symptoms and signs

T-cell lymphomas may affect different areas of your body, and symptoms vary based on where the condition started^[2]. For example, patches of reddish skin are common symptoms of cutaneous T-cell lymphoma^[2].

Common symptoms may include^[2]:

• Heavy night sweats: This is sweating so intense that it drenches your sheets.
• Pain in your belly, bones, or chest.
• Persistent fatigue: This is feeling much more tired than usual for at least several days and for no apparent reason.
• Swollen lymph nodes: You may have painless swelling in your neck, armpits, or groin.
• Unexplained fever: A fever that stays above 103 degrees Fahrenheit (39.5 degrees Celsius) for two or more hours after home treatment or lasts longer than two days may be a sign of a serious problem.
• Unexplained weight loss: This is losing body weight without trying. Losing 10% of your total body weight over six months is a sign of unexplained weight loss.

T-cell lymphomas cause many symptoms that are similar to other, less serious issues. Experiencing one or more of these symptoms doesn’t mean you have T-cell lymphoma^[2]. However, you should contact your healthcare provider if you have persistent symptoms such as fevers or swollen lymph nodes.

Causes and risk factors

The cause of the majority of T-cell lymphomas remains unexplained^[4]. However, several factors have been associated with an increased risk of developing these conditions.

Infectious agents, particularly viruses, have been linked to certain types of T-cell lymphoma. There is a specific association of HTLV-1 with adult T-cell leukemia/lymphoma and EBV with natural killer/T-cell lymphoma^[4]. The virus HTLV-1 is transmitted by blood transfusion, sharing of needles, sexual intercourse, and breastfeeding^[13].

Cutaneous T-cell lymphoma is considered to arise secondary to the dysregulation of genes and signaling pathways. There have been reports suggesting an association between chronic cutaneous inflammation and CTCL development^[4].

Other risk factors include^[4]:

• T-cell activating autoimmune disease
• Family history of myeloma
• Celiac disease (for enteropathy-associated T-cell lymphoma)

The incidence of T-cell lymphoma increases with advancing age. Geographic location and ethnic variability have an impact on the distribution of the disease^[4]. Infections with HTLV-1 and cases of adult T-cell leukemia/lymphoma are endemic in several regions of the world, including southwestern Japan, the Caribbean basin, and Central Africa^[13].

Diagnosis

Diagnosis of T-cell lymphomas often begins with a physical exam. The exam checks for swollen lymph nodes in the neck, underarms, and groin, and an enlarged spleen or liver^[15]. Other tests and procedures are then used to confirm the diagnosis.

Blood tests

Blood tests can sometimes show whether lymphoma cells are present. Blood tests may be used to test for viruses, including Epstein-Barr virus and human T-cell lymphotrophic virus. Blood tests also measure levels of lactate dehydrogenase (LDH), which is often higher in people with lymphoma^[15].

Imaging tests

Imaging tests make pictures of the body and can show the location and extent of a T-cell lymphoma. Tests might include MRI (magnetic resonance imaging), CT (computed tomography), and PET (positron emission tomography) scans^[15].

Biopsy

Your healthcare professional may suggest a lymph node biopsy or a biopsy of other tissue to look for cancer cells. A biopsy is a procedure to remove a sample of tissue for testing in a lab. A lymph node biopsy involves removing all or part of a lymph node. A sample may be taken from other parts of the body depending on symptoms and imaging test results. In the lab, tests may show whether you have a T-cell lymphoma^[15].

T-cell lymphoma may be hard to diagnose because the symptoms are like those of other conditions. Getting the right diagnosis may take time^[11].

Bone marrow aspiration and biopsy

Bone marrow aspiration and biopsy are procedures to collect cells from the bone marrow for testing. Bone marrow is the soft matter inside bones where blood cells are made. Most often, the samples are taken from the hip bone. The samples go to a lab for testing^[15].

Treatment options

Since there are so many different types of T-cell lymphoma, treatment varies widely^[9]. Standard lymphoma therapies may include chemotherapy, immunotherapy, radiation, stem cell transplantation, and surgery. Treatment varies depending on the T-cell lymphoma subtype^[2].

Chemotherapy

For most subtypes of peripheral T-cell lymphoma, the initial treatment is typically a combination chemotherapy regimen. Common regimens include CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), CHOEP (CHOP plus etoposide), or EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone)^[9][14].

Targeted therapy and immunotherapy

For CD30-expressing peripheral T-cell lymphomas, brentuximab vedotin (Adcetris) is now approved for use in combination with cyclophosphamide, doxorubicin, and prednisone as initial treatment^[14]. Treatments may also involve other forms of immunotherapy, including antibody drug conjugates^[9].

Skin-directed therapies

Treatments aimed at the skin are effective for many of the slow-growing T-cell lymphomas that appear in the skin. These include topical corticosteroids, topical retinoids, topical chemotherapy, ultraviolet light therapy, or electron beam therapy (a type of radiation that does not penetrate to internal organs)^[9].

A procedure called extracorporeal photopheresis (ECPP) is approved to treat people with cutaneous T-cell lymphoma. For this procedure, blood is removed from the patient and treated with ultraviolet light and with drugs that become active when exposed to ultraviolet light. Once the blood has been treated, it is returned back into the patient’s body^[9].

Stem cell transplantation

Because many patients with peripheral T-cell lymphoma will relapse, some physicians recommend high-dose chemotherapy followed by an autologous stem cell transplant (a type of stem cell transplant in which the patient receives his or her own stem cells, collected several weeks before the transplant)^[14]. In specific cases, it may be determined that transplantation is the most appropriate approach to treatment^[9].

Clinical trials

Patients diagnosed with rare forms of lymphoma should consult their medical team to find new promising therapies or to enroll in clinical trials^[9]. Treatment options for the different types of T-cell lymphomas are expanding as new treatments are discovered and current treatments are improved^[9].

Prognosis and outlook

T-cell lymphomas are rare and aggressive malignancies associated with poor outcome^[13]. The prognosis and treatment of T-cell lymphoma can vary drastically based on the specific type of lymphoma and its growth patterns^[6].

Most T-cell lymphoma subtypes are associated with worse outcomes than those of B-cell lymphomas^[12]. In general, peripheral T-cell lymphoma is associated with a poor prognosis, with a 5-year survival rate of approximately 30% to 40%^[12].

However, outcomes are better for patients with ALK-positive anaplastic large cell lymphoma, with a median 5-year overall survival closer to 70% to 80%^[12]. Cutaneous T-cell lymphoma is considered indolent and has a longer disease course^[4].

The effectiveness of treatments is often varied between subtypes, with most receiving a poor outcome with high relapse rates^[6]. Due to their rarity and high variability between the different subtypes, the prognosis of T-cell lymphoma is significantly worse than other non-Hodgkin lymphomas^[6].

Living with T-cell lymphoma

Any chronic disease changes your life significantly, and T-cell lymphoma is no different. You may face physical, logistical, and emotional hurdles because of your disease^[17].

Managing physical symptoms

You may experience discomfort or pain at times from the illness itself or from treatment methods. Common physical problems patients experience include^[17]:

• Severe itching that may affect sleep
• Hot and sore skin, which can be a sign of infection
• Flaking or burning skin
• Inflamed skin tumors
• Difficulty sleeping because of itching or discomfort
• Trouble finding comfortable clothes

Emotional support

You have cancer. Those three words can unleash a wave of emotions, from disbelief to anger to sadness to fear. All those emotions and more are normal and can be eased by asking questions, gaining information, and talking with individuals who have either experienced the disease or understand its course^[17].

Be prepared for a roller coaster of emotions and physical feelings. The reality is that T-cell lymphoma is a chronic disease with a high survival rate but no cure—at least not yet. Over the course of your disease, there may be times when symptoms are present and quite intense and other times when you may experience a period of remission, sometimes many years long^[17].

Talking with trusted friends and family, your healthcare team, and others close to you can ease the challenges and make it easier for you to manage your disease^[17].

Healthy living

A healthy lifestyle has many benefits, both physically and emotionally. It can help prepare you for treatment, reduce the risk of side effects, and lower the likelihood of developing other illnesses in the future. Although it takes time and can involve making some changes to your everyday life, most people adjust well to life after a diagnosis of lymphoma and find a “new normal”^[16].