Overview

Leukemia is a cancer of the blood cells. Types of leukemia are named after the specific blood cell that becomes cancerous, such as the lymphocytic cells (white blood cells) or the myeloid cells (cells of the bone marrow, the spongy, red tissue in the inner part of large bones). There are four main types of leukemia in adults:

• Acute lymphocytic leukemia (ALL)
• Chronic lymphocytic leukemia (CLL)
• Acute myeloid leukemia (AML)
• Chronic myeloid leukemia (CML)

There are other, less common types of leukemia, but they are generally subcategories of one of the four main categories. This section focuses on different types of chronic T-cell lymphocytic leukemia. T cells are a type of white blood cell that directly participates in the immune defenses.

Large granular lymphocytic leukemia (LGLL). LGLL is a slow-growing leukemia of the T cells and is more common in women than in men. The cause of LGLL is unknown, although approximately 30% of people with LGLL have rheumatoid arthritis (a chronic, progressive disease in which inflammatory changes occur throughout the connective tissues of the body, mostly in the joints of the hands, feet, wrists, knees, hips, or shoulders).

T-cell prolymphocytic leukemia (T-PLL). T-PLL is an aggressive subtype of CLL that has only been defined recently. It occurs more often in older men, but women may also be affected. It can affect the skin, but in a different way than Sezary syndrome (see below).

Adult T-cell leukemia/lymphoma (ATLL). ATLL has four clinical subtypes. Depending on the clinical features, it is subclassified into smoldering, chronic, acute, and adult T-cell lymphoma (cancer of the lymph system, part of the body's immune system). The acute and the adult T-cell lymphoma subtypes are rapidly progressing diseases. ATLL is caused by a retrovirus called the human T-cell leukemia virus (HTLV).

Sezary syndrome. Sezary syndrome is an advanced form of mycosis fungoides, a T-cell lymphoma that occurs in or on the skin. Sezary syndrome is usually slow growing and takes years to develop from mycosis fungoides, which is limited to the skin. Sezary syndrome is generally diagnosed when large numbers of the lymphoma cells are found in the blood, often in association with erythroderma (reddening of the skin).

Risk Factors

A risk factor is anything that increases a person's chance of developing cancer. Some risk factors can be controlled, such as smoking, and some cannot be controlled, such as age and family history. Although risk factors can influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do. However, knowing your risk factors and communicating them to your doctor may help you make more informed lifestyle and health-care choices.

Leukemia can be caused by a hereditary genetic mutation or environmental factors (including smoking, chemical, or radiation exposure). However, there are many cases of leukemia that have unknown causes.

Symptoms

People with T-cell leukemia may experience the following symptoms. Sometimes, people with T-cell leukemia do not show any of these symptoms. Or, these symptoms may be caused by a medical condition that is not cancer. If you are concerned about a symptom on this list, please talk with your doctor.

• Recurrent infections, due to low numbers of neutrophils (infection-fighting white blood cells)
• Bleeding easily
• Bruising easily
• Tiredness
• Persistent, unexplained abdominal pain on the left side, due to an enlarged spleen (LGLL, T-PLL)
• Enlarged lymph nodes (T-PLL, ATLL)
• Rash or skin lesions (T-PLL), ATLL, Sezary syndrome)
• Frequent urination and/or constipation, due to high levels of calcium in the blood (ATLL)

Diagnosis

Doctors use many tests, such as blood tests and bone marrow tests, to diagnose leukemia and determine if it has metastasized (spread). Although a patient's signs and symptoms may cause a doctor to suspect leukemia, it is diagnosed only by blood tests and bone marrow evaluations. Some tests may also determine which treatments may be the most effective. Your doctor may consider these factors when choosing a diagnostic test:

• Age and medical condition
• The type of cancer
• Severity of symptoms
• Previous test results

The following tests may be used to diagnose T-cell leukemia:

Blood tests. A doctor will do a routine blood test to measure the counts of different types of cells in the blood. If the blood contains high levels of white blood cells, T-cell leukemia may be present.

Bone marrow biopsy. In a bone marrow biopsy, a doctor takes a sample of marrow, usually from the back of the hipbone, with a needle. The cells from the marrow, along with the cells from the blood, are analyzed by a pathologist (a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease).

Immunophenotyping. Immunophenotyping is the examination of antigens, a specific type of protein, on the surface of the leukemic cells. Immunophenotyping allows the doctor to confirm the exact type of leukemia.

Cytogenetics. Cytogenetics is the examination of the leukemic cells for chromosomal abnormalities. It assists in confirming the diagnosis and may help the doctor determine the person's prognosis (chance of recovery).

Computed tomography (CT or CAT) scan. A CT scan creates a three-dimensional picture of the inside of the body with an x-ray machine. A computer then puts these images into a detailed, cross-sectional view that shows any abnormalities or tumors. Sometimes, a contrast medium (a special dye) is injected into a vein to provide better detail. A CT scan also shows enlarged lymph nodes or a swollen spleen.

Treatment

The treatment of T-cell leukemia depends on the development of the disease, whether the cancer has spread, and the person's overall health. In many cases, a team of doctors will work with the patient to determine the best treatment plan.

The goal of treatment for blood cancers is to bring about a remission of the disease. A complete remission means the doctor can find no evidence of the disease.

Watch and wait

This approach does not mean that the doctor is doing nothing, but that the disease is being actively observed. Patients are monitored using blood and other tests at regularly scheduled checkups to track blood cell counts and look for other symptoms that the leukemia is progressing. Studies have shown that, in people with certain disease characteristics, no harm comes from the watch-and-wait approach versus offering early treatment. Treatment begins when people develop signs that the disease is worsening, such as increasing fatigue, night sweats, enlarged lymph nodes, or falling red blood cell or platelet counts. People with leukemia are encouraged to talk with their doctors about whether their symptoms need treatment, including the balancing of the benefits of treatment with side effects that might result.

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy travels through the bloodstream to cancer cells throughout the body. Chemotherapy can be given by mouth or injection.

Because chemotherapy affects normal cells as well as cancer cells, many people experience side effects from treatment. Side effects depend on the drug and the dosage. Common side effects include nausea and vomiting, loss of appetite, diarrhea, fatigue, low blood count, bleeding or bruising after minor cuts or injuries, numbness and tingling in the hands or feet, headaches, hair loss, and darkening of the skin and fingernails. Side effects usually go away when treatment is complete.

The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications you've been prescribed, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions through PLWC's Drug Information Resources, which provides links to searchable drug databases.

Radiation therapy

Radiation therapy uses x-rays or other high-energy particles to kill cancer cells. Radiation therapy for leukemia usually comes from a machine outside the body and is called external-beam radiation therapy.

Side effects from radiation therapy include fatigue, mild skin reactions, upset stomach, and loose bowel movements. Most side effects go away soon after treatment is finished.

Surgery

A splenectomy (surgery to remove the spleen) may be appropriate for some people.

Stem cell transplantation

Hematopoietic stem cells are special cells that can develop into different kinds of blood cells, such as red blood cells, white blood cells, or platelets. Stem cells are found both in the circulating blood and in the bone marrow. In a stem cell transplantation (SCT), the person is first treated with high doses of chemotherapy and/or radiation therapy to get rid of as many cancer (leukemic) cells as possible and to prevent the immune system from reacting to and rejecting the donated stem cells. After the high-dose therapy is given, stem cells obtained from a healthy donor (usually a sibling) are infused into the patient's bloodstream. Within two to three weeks, these cells will mature into healthy, blood-producing tissue. Until that time, people may need antibiotics to prevent and treat infection, as well as transfusions of red blood cells and platelets.

This type of SCT is called an allogeneic SCT, because the new stem cells came from a donor. Allogeneic transplantation may be a considered a good treatment option in some patients, especially those who are younger. More recently, some transplants have been carried out using less intensive therapies (so-called reduced intensity conditioning or "mini" transplants) which have fewer short-term side effects, allowing transplants to be done in some older individuals.

An autologous transplantation is the use of the person's own stem cells. The blood or bone marrow stem cells are removed from the person when he or she is in complete remission and then frozen. The person then receives the same treatment given for an allogeneic transplantation, and the frozen stem cells are thawed and injected back into the bloodstream to replace the destroyed marrow. Autologous SCT is rarely considered for patients with T-cell leukemia.

SCT is a higher-risk procedure and is not used frequently in people with T-cell leukemia because it is not a consistently effective therapy and because many patients with this disease are older and may not tolerate the therapy well.

Learn more by reading the PLWC Feature series, Understanding Bone Marrow and Stem Cell Transplantation.

Biologic therapy

Biologic therapy or immunotherapy is the use of substances (made by the body or created in a laboratory) to support or stimulate the body's own immune system to fight the cancer. Of these, interferon alpha (Roferon, Intron A) has been found to be an effective therapy in ATLL. Interferon is a natural protein present in the body that stimulates immunity.

Monoclonal antibodies

Monoclonal antibodies are antibodies directed against specific proteins on the leukemic cell surface. When the antibody attaches to their antigen, some leukemic cells die.

Treatments specific to T-cell leukemia type

LGLL. LGLL sometimes requires no treatment during its early stages, but treatment may begin once symptoms develop. Sometimes, infections occur because of the limited numbers of neutrophils, and these need treatment. When treatment for the disease does become necessary, LGLL is treated with immunosuppressant drugs, such as cyclosporine (Neoral, Sandimmune, SangCya), cyclophosphamide (Cytoxan, Neosar), or low-dose methotrexate (Rheumatrex, Trexall). Treatment with oral cyclosporine, a drug that suppresses the immune system, can be effective in some people in whom low levels of neutrophils or platelets represent the major problem. Treatment with combination chemotherapy is occasionally used if the disease is advancing rapidly. Combination chemotherapy is similar to that used in aggressive lymphoma. For more information, see the PLWC Guide: Non-Hodgkin Lymphoma.

T-PLL. T-PLL may be treated with drugs that include chlorambucil (Leukeran), cyclophosphamide, doxorubicin (Adriamycin, Rubex), vincristine (Oncovin), and prednisone. Newer drugs, such as pentostatin (Nipent) and alemtuzumab (Campath), have also shown promising results.

Sezary syndrome. Sezary syndrome may be treated using therapies focused on the skin and systemic therapies. Skin therapies include topical agents (skin creams); phototherapy (the use of light to kill cancer cells); and radiation therapy, including total skin electron-beam radiation therapy, which can treat the entire body. Other systemic therapies for Sezary syndrome include chemotherapy, oral bexarotene (a drug that is similar to vitamin A), and occasionally, STC. Alemtuzumab is a monoclonal antibody directed against a protein (CD52) that is present on the leukemic cells and has shown to be somewhat effective for treating this disease. Recently, a new drug, vorinostat (Zolinza), was approved by the U.S. Food and Drug Administration (FDA) for patients with cutaneous T-cell lymphoma. This drug is thought to change the expression of certain genes.

Adult T-cell leukemia/lymphoma (ATLL). ATLL may be treated with zidovudine (Retrovir) and interferon if it is in the chronic or acute phase. Zidovudine is an antiviral therapy used in the treatment of human immunodeficiency virus (HIV). This therapy aims at strengthening the immune system and treating the human T-cell leukemia virus (HTLV). The lymphoma phase is best treated with combination chemotherapy.

Side Effects of Cancer and Cancer Treatment

Cancer and cancer treatment can cause a variety of side effects; some are easily controlled and others require specialized care. Below are some of the side effects that are more common to T-cell leukemia and its treatments. For more detailed information on managing these and other side effects of cancer and cancer treatment, visit the PLWC Managing Side Effects section.

Constipation. Constipation is the infrequent or difficult passage of stool. About 40% of patients in palliative care (care given to improve a patient's quality of life) experience constipation, and about 90% of patients taking opioid medications (such as morphine) experience constipation. Constipation includes fewer bowel movements, stools that are abnormally hard, discomfort, or a feeling of incomplete rectal emptying. Patients with constipation can experience pain, swelling in the abdomen, loss of appetite, nausea and/or vomiting, inability to urinate, and confusion.

Fatigue (tiredness). Fatigue is extreme exhaustion or tiredness, and is the most common problem that people with cancer experience. More than half of patients experience fatigue during chemotherapy or radiation therapy, and up to 70% of patients with advanced cancer experience fatigue. Patients who feel fatigue often say that even a small effort, such as walking across a room, can seem like too much. Fatigue can seriously affect family activities and other daily activities, can make patients avoid or skip cancer treatments, and may even affect the will to live.

Hair loss (alopecia). A potential side effect of radiation therapy and chemotherapy is hair loss. Radiation therapy and chemotherapy cause hair loss by damaging the hair follicles responsible for hair growth. Hair loss may occur throughout the body, including the head, face, arms, legs, underarms, and pubic area. The hair may fall out entirely, gradually, or in sections. In some cases, the hair will simply thin-sometimes unnoticeably-and may become duller and dryer. Losing one's hair can be a psychologically and emotionally challenging experience and can affect a patient's self-image and quality of life. However, the hair loss is usually temporary, and the hair often grows back.

Hypercalcemia. Hypercalcemia is an unusually high level of calcium in the blood. Hypercalcemia can be life threatening and is the most common metabolic disorder associated with cancer, occurring in 10% to 20% of patients with cancer. While most of the calcium in the body is stored in the bones, about 1% of the body's calcium circulates in the bloodstream. Calcium is important for many bodily functions, including bone formation, muscle contractions, and nerve and brain function. Patients with hypercalcemia may experience loss of appetite, nausea and/or vomiting; constipation and abdominal pain; increased thirst and frequent urination; fatigue, weakness, and muscle pain; changes in mental status, including confusion, disorientation, and difficulty thinking; and headaches. Severe hypercalcemia can be associated with kidney stones, irregular heartbeat or heart attack, and eventually loss of consciousness and coma.

Infection. An infection occurs when harmful bacteria, viruses, or fungi (such as yeast) invade the body and the immune system is not able to destroy them quickly enough. Patients with cancer are more likely to develop infections because both cancer and cancer treatments (particularly chemotherapy and radiation therapy to the bones or extensive areas of the body) can weaken the immune system. Symptoms of infection include fever (temperature of 100.5°F or higher); chills or sweating; sore throat or sores in the mouth; abdominal pain; pain or burning when urinating or frequent urination; diarrhea or sores around the anus; cough or breathlessness; redness, swelling, or pain, particularly around a cut or wound; and unusual vaginal discharge or itching.

Mouth sores (mucositis). Mucositis is an inflammation of the inside of the mouth and throat, leading to painful ulcers and mouth sores. It occurs in up to 40% of patients receiving chemotherapy treatments. Mucositis can be caused by chemotherapy directly, the reduced immunity brought on by chemotherapy, or radiation therapy to the head and neck area.

Nausea and vomiting. Vomiting, also called emesis or throwing up, is the act of expelling the contents of the stomach through the mouth. It is a natural way for the body to rid itself of harmful substances. Nausea is the urge to vomit. Nausea and vomiting are preventable, treatable side effects. They are common in patients receiving chemotherapy for cancer and in some patients receiving radiation therapy. Many patients with cancer say they fear nausea and vomiting more than any other side effects of treatment. When it is minor and treated quickly, nausea and vomiting can be quite uncomfortable but cause no serious problems. Persistent vomiting can cause dehydration, electrolyte imbalance, weight loss, depression, and avoidance of chemotherapy.

Neutropenia. Neutropenia is an abnormally low level of neutrophils, a type of white blood cell. All white blood cells help the body fight infection. Neutrophils fight infection by destroying bacteria. Patients who have neutropenia are at increased risk for developing serious bacterial infections because there are not enough neutrophils to destroy harmful bacteria. Neutropenia occurs in about 50% of patients receiving chemotherapy and is common in patients with leukemia.

Skin problems. The skin is an organ system that contains many nerves. Because of this, skin problems can be very painful. Because the skin is on the outside of the body and visible to others, many patients find skin problems especially difficult to cope with. Because the skin protects the inside of the body from infection, skin problems can often lead to other serious problems. As with other side effects, prevention or early treatment is best. In other cases, treatment and wound care can often improve pain and quality of life. Skin problems can have many different causes, including chemotherapeutic drugs leaking out of the intravenous (IV) tube, which can cause pain or burning; peeling or burned skin caused by radiation therapy; pressure ulcers (bed sores) caused by constant pressure on one area of the body; and pruritus (itching) in patients with cancer, most often caused by leukemia, lymphoma, myeloma, or other cancers.

Thrombocytopenia. Thrombocytopenia is an unusually low level of platelets (thrombocytes) in the blood. Platelets are the blood cells that stop bleeding by plugging damaged blood vessels and helping the blood to clot. Patients with low levels of platelets bleed more easily and are prone to bruising. Certain types of chemotherapy can damage the bone marrow so that it does not make enough platelets. Thrombocytopenia caused by chemotherapy is usually temporary. Other medications used to treat cancer may also lower the number of platelets. In rare instances, a patient's body can make antibodies to the platelets, lowering the number of platelets.

After Treatment

After treatment for T-cell leukemia ends, talk with your doctor about developing a follow-up care plan. This plan may include regular physical examinations, blood tests, bone marrow biopsies, and possibly scans or other imaging studies to monitor your recovery for the coming months and years. People experiencing a long-term remission are encouraged to follow cancer screening recommendations for the general population.

Several long-term side effects from leukemia treatment may occur:

• People who have received certain chemotherapy or radiation therapy to the lungs may develop lung damage.
• Cardiac damage in the form of a weakened heart muscle may occur in people who have received a higher dose of doxorubicin or radiation therapy to the chest.
• Infertility or premature menopause can occur in people who have received high-dose cyclophosphamide or other chemotherapy.
• People treated with chemotherapy and specifically with alemtuzumab are at higher risk for infection even after the end of therapy.
• Secondary leukemia and secondary cancers (cancers that develop because of the treatment for another type of cancer) are more common in people who were treated with chemotherapy and radiation therapy.