Leukemia Treatment, Diagnosis, Causes, Symptoms & Prognosis

Leukemia facts

Picture of white blood cells.

Leukemia is a cancer of the blood and blood-forming cells, such as white blood cells.

Leukemia is a cancer of blood or blood-forming cells (and therefore sometimes referred to as blood cancer).
While the exact cause(s) of leukemia is not known, risk factors have been identified, including radiation exposure, certain chemotherapy for cancer, smoking, family history of leukemia, and exposure to certain chemicals such as benzene.
Common symptoms of chronic or acute leukemia may include
- pain in the bones or joints,
- swollen lymph nodes that usually don't hurt,
- fevers or night sweats,
- feeling weak or tired,
- bleeding and bruising easily,
- frequent infections,
- discomfort or swelling in the abdomen,
- weight loss or loss of appetite.
Leukemias are grouped by how quickly the disease develops (acute or chronic) as well as by the type of blood cell that is affected (lymphocytes or myelocytes). The four main types of leukemia include acute lymphocytic leukemia or acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myelocytic leukemia (AML), and chronic myelocytic leukemia (CML) or chronic myelogenous leukemia (CML).
People with leukemia are at significantly increased risk for developing infections, anemia, and bleeding. Other symptoms and signs include easy bruising, weight loss, night sweats, and unexplained fevers.
The diagnosis of leukemia is supported by findings of the medical history and examination, and examining blood and bone marrow samples under a microscope.
Leukemia treatment choices depend on the type of leukemia, certain features of the leukemia cells, the extent of the disease, and prior history of treatment, as well as the age and health of the patient.
Most people with leukemia are treated with chemotherapy. Some also may have radiation therapy and/or bone marrow transplantation.
There is no known way to prevent leukemia.
The prognosis of leukemia depends upon several factors, including the patient's age, the type of leukemia, and the extent to which the cancer has spread.

woman swollen lymph nodes, leukemia symptoms and signs

Leukemia Symptoms

Signs of cancers of the blood cells

Leukemia is actually a group of different cancers of the blood cells. Leukemias can be acute or chronic, and people with chronic leukemias may not notice any symptoms before the condition is diagnosed with a blood test. Acute leukemias are more likely to cause symptoms. Symptoms of all forms of leukemia are related to the proliferation of abnormal blood cells and replacement of the bone marrow by the cancerous cells.

Symptoms of leukemia include fevers, night sweats, and swollen lymph nodes that are typically not painful or tender. Fatigue, weight loss, and bone or joint pain are other potential symptoms. Easy bruising and bleeding tendencies may result in bleeding from the gums, purplish patches on the skin, or small red spots under the skin.

What is leukemia? What are the different types of leukemia?

Leukemia is a malignancy (cancer) of blood cells. In leukemia, abnormal blood cells are produced in the bone marrow. Usually, leukemia involves the production of abnormal white blood cells — the cells responsible for fighting infection. However, the abnormal cells in leukemia do not function in the same way as normal white blood cells. The leukemia cells continue to grow and divide, eventually crowding out the normal blood cells. The end result is that it becomes difficult for the body to fight infections, control bleeding, and transport oxygen.

There are different types of leukemia, based upon how quickly the disease develops and the type of abnormal cells produced. Leukemia is called an acute leukemia if it develops rapidly. Large numbers of leukemia cells accumulate very quickly in the blood and bone marrow, leading to symptoms such as tiredness, easy bruising, and susceptibility to infections. Acute leukemia requires fast and aggressive treatment.

There are around 60,000 new cases of leukemia each year in the U.S. and over 24,000 deaths due to leukemia. Leukemia makes up about 3.7% of all new cancer cases.

Chronic leukemias develop slowly over time. These leukemias may not cause specific symptoms at the beginning of their course. If left untreated, the cells may eventually grow to high numbers, as in acute leukemias causing similar symptoms.

Leukemias are further classified as myeloid or lymphoid, depending upon the type of white blood cell that makes up the leukemia cells. A basic understanding of the normal development of blood cells is needed to understand the different types of leukemia. Normal blood cells develop from stem cells that have the potential to become many cell types. Myeloid stem cells mature in the bone marrow and become immature white cells called myeloid blasts. These myeloid blasts further mature to become either red blood cells, platelets, or certain kinds of white blood cells. Lymphoid stem cells mature in the bone marrow to become lymphoid blasts. The lymphoid blasts develop further into T or B lymphocytes (T-cells or B-cells), special types of white blood cells. Myeloid or myelogenous leukemias are made up of cells that arise from myeloid cells, while lymphoid leukemias arise from lymphoid cells. Knowing the type of cell involved in leukemia is important in choosing the appropriate treatment.

Common types of leukemia

The four most common types of leukemia are acute lymphocytic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, and chronic myeloid leukemia.

Acute lymphocytic leukemia (ALL, also known as acute lymphoblastic leukemia) is the most common type of leukemia in children, but it can also affect adults. In this type of leukemia, immature lymphoid cells grow rapidly in the blood. It affects almost 6,000 people per year in the U.S.
Acute myeloid leukemia (AML, also called acute myelogenous leukemia) involves the rapid growth of myeloid cells. It occurs in both adults and children and affects about 19,500 people each year in the U.S.
Chronic lymphocytic leukemia (CLL) is a slow-growing cancer of lymphoid cells that usually affects people over 55 years of age. It is estimated to affect about 21,000 people in the U.S. every year. It almost never occurs in children or adolescents.
Chronic myeloid leukemia (CML, also known as chronic myelogenous leukemia) is a type of chronic myeloproliferative disorder that primarily affects adults and occurs in about 8,400 people every year in the U.S.

Less common types of leukemia account for about 6,000 cases of leukemia each year in the U.S.

Hairy cell leukemia is an uncommon type of chronic leukemia.
Chronic myelomonocytic leukemia (CMML) is another type of chronic leukemia that develops from myeloid cells.
Juvenile myelomonocytic leukemia (JMML) is a type of myeloid leukemia that usually occurs in children under 6 years of age.
Large granular lymphocytic leukemia (LGL leukemia) is a type of chronic leukemia that develops from lymphoid cells. It can be slow- or fast-growing.
Acute promyelocytic leukemia (APL) is a subtype of AML.

What causes leukemia? Is leukemia hereditary?

The exact cause of leukemia is not known, but it is thought to involve a combination of genetic and environmental factors. Leukemia cells have acquired mutations in their DNA that cause them to grow abnormally and lose functions of typical white blood cells. It is not clear what causes these mutations to occur. One type of change in the cells' DNA that is common in leukemias is known as a chromosome translocation. In this process, a portion of one chromosome breaks off and attaches to a different chromosome. One translocation seen in almost all cases of CML and in sometimes in other types of leukemia is an exchange of DNA between chromosomes 9 and 22, which leads to what is known as the Philadelphia chromosome. This creates an oncogene (cancer-promoting gene) known as BCR-ABL. This change in DNA is not inherited but occurs sometime in the life of the affected individual.

Most cases of leukemia are not believed to be hereditary, but certain genetic mutations and conditions can be passed along to offspring that increase the chances of developing leukemia. A condition known as Li-Fraumeni syndrome is characterized by an inherited mutation in a tumor suppressor gene known as TP53, and individuals with this condition have an increased risk of leukemia and other cancers. Other hereditary conditions that can increase the risk of developing leukemia include Down syndrome, neurofibromatosis type 1, ataxia telangiectasia, and Noonan syndrome.

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What are leukemia risk factors?

Exposure to radiation is known to increase the risk of developing AML, CML, or ALL. Increases in leukemia were observed in people surviving atomic bombs. Radiation therapy for cancer can also increase the risk of leukemia. Exposure to certain chemicals, including benzene (used commonly in the chemical industry), increases the risk of leukemia. Cigarette smoking is known to increase the risk of developing AML.

Certain genetic disorders can increase the risk; Down syndrome, Li-Fraumeni syndrome, and other medical conditions can increase the risk of developing leukemia. Blood disorders known as myelodysplastic syndromes confer an increased risk of developing AML. Human T-cell leukemia virus type 1 (HTLV-1) is a virus that causes a rare type of leukemia. Certain chemotherapy drugs for cancer can increase the risk for AML or ALL.

Having risk factors does not mean that a person will definitely get leukemia, and most people with risk factors will not develop the disease. Likewise, not everyone who develops leukemia has an identifiable risk factor.

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What is leukemia?
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What are leukemia symptoms and signs?

The symptoms and signs of leukemia depend upon the type of leukemia. As stated earlier, slow-growing or chronic leukemia may not cause any symptoms at the outset, while aggressive or rapidly growing leukemia may lead to severe symptoms. The symptoms of leukemia arise from a loss of function of the normal blood cells or from accumulation of the abnormal cells in the body.

Signs and symptoms of leukemia typically include the following:

Fevers
Night sweats
Swollen lymph nodes that are usually painless
Feelings of fatigue, tiredness
Easy bleeding or bruising, causing bluish or purplish patches on the skin or tiny red spots on the skin, or recurring nosebleeds
Frequent infections
Bone or joint pain
Weight loss that is unintentional and otherwise unexplained, or loss of appetite
Enlargement of the spleen or liver, which can lead to abdominal pain or swelling
Red spots on the skin (petechiae)

If leukemia cells have infiltrated the brain, symptoms such as headaches, seizures, confusion, loss of muscle control, and vomiting can occur.

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How do physicians diagnose leukemia?

Hematologists are specialist physicians who diagnose and treat blood diseases, including leukemia; hematologist-oncologists treat blood diseases like leukemia, as well as other types of cancers.

In addition to a medical history (asking about symptoms and risk factors) and a physical exam to look for signs of leukemia (lymph node enlargement, enlargement of spleen), the diagnosis of leukemia typically involves laboratory studies of a blood sample. Abnormal numbers of blood cells may suggest a diagnosis of leukemia, and the blood sample may also be examined under the microscope to see if the cells appear abnormal. A sample of the bone marrow may also be obtained to establish the diagnosis. For a bone marrow aspirate, a long, thin needle is used to withdraw a sample of bone marrow from the hip bone, under local anesthesia. A bone marrow biopsy involves insertion of a thick, hollow needle into the hip bone to remove a sample of the bone marrow, using local anesthesia.

Cells from the blood and bone marrow are further tested if leukemia cells are present. These additional tests look for genetic alterations and expression of certain cell surface markers by the cancer cells (immunophenotyping). The results of these tests are used to help determine the precise classification of the leukemia and to decide on optimal treatment.

Other tests that may be useful include a chest X-ray to determine if there are enlarged lymph nodes or other signs of disease and a lumbar puncture to remove a sample of cerebrospinal fluid to determine if the leukemia cells have infiltrated the membranes and space surrounding the brain and spinal cord.

Imaging tests such as MRI and CT scanning can also be useful for some patients to determine the extent of disease.

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What are leukemia treatment options?

There are a number of different medical approaches to the treatment of leukemia. Treatment will typically depend upon the type of leukemia, the patient's age and health status, as well as whether or not the leukemia cells have spread to the cerebrospinal fluid. The genetic changes or specific characteristics of the leukemia cells as determined in the laboratory can also determine the type of treatment that may be most appropriate.

Watchful waiting may be an option for some people with a chronic leukemia who do not have symptoms. This involves close monitoring of the disease so that treatment can begin when symptoms develop. Watchful waiting allows the patient to avoid or postpone the side effects of treatment. The risk of waiting is that it may eliminate the possibility of controlling the leukemia before it worsens.

Treatments for leukemia include chemotherapy (major treatment modality for leukemia), radiation therapy, biological therapy, targeted therapy, and stem cell transplant. Combinations of these treatments may be used. Surgical removal of the spleen can be a part of treatment if the spleen is enlarged.

Acute leukemia needs to be treated when it is diagnosed, with the goal of inducing a remission (absence of leukemia cells in the body). After remission is achieved, therapy may be given to prevent a relapse of the leukemia. This is called consolidation or maintenance therapy. Acute leukemias can often be cured with treatment.

Chronic leukemias are unlikely to be cured with treatment, but treatments are often able to control the cancer and manage symptoms. Some people with chronic leukemia may be candidates for stem cell transplantation, which does offer a chance for cure.

Many patients opt to receive a second opinion before beginning treatment for leukemia. In most cases, there is time to receive a second opinion and consider treatment options without making the treatment less effective. However, in rare cases of very aggressive leukemias, treatment must begin immediately. One should discuss with a doctor the possibility of obtaining a second opinion and any potential delays in treatment. Most doctors welcome the possibility of a second opinion and should not be offended by a patient's wish to obtain one.

Chemotherapy

Chemotherapy is the administration of drugs that kill rapidly dividing cells such as leukemia or other cancer cells. Chemotherapy may be taken orally in pill or tablet form, or it may be delivered via a catheter or intravenous line directly into the bloodstream. Combination chemotherapy is usually given, which involves a combination of more than one drug. The drugs are given in cycles with rest periods in between.

Sometimes, chemotherapy drugs for leukemia are delivered directly to the cerebrospinal fluid (known as intrathecal chemotherapy). Intrathecal chemotherapy is given in addition to other types of chemotherapy and can be used to treat leukemia in the brain or spinal cord or, in some cases, to prevent spread of leukemia to the brain and spinal cord. An Ommaya reservoir is a special catheter placed under the scalp for the delivery of chemotherapy medications. This is used for children and some adult patients as a way to avoid injections into the cerebrospinal fluid.

Side effects of chemotherapy depend on the particular drugs taken and the dosage or regimen. Some side effects from chemotherapy drugs include hair loss, nausea, vomiting, mouth sores, loss of appetite, tiredness, easy bruising or bleeding, and an increased chance of infection due to the destruction of white blood cells. There are medications available to help manage the side effects of chemotherapy.

Some adult men and women who receive chemotherapy sustain damage to the ovaries or testes, resulting in infertility. Most children who receive chemotherapy for leukemia will have normal fertility as adults, but depending on the drugs and dosages used, some may have infertility as adults.

Biological therapy

Biological therapy is any treatment that uses living organisms, substances that come from living organisms, or synthetic versions of these substances to treat cancer. These treatments help the immune system recognize abnormal cells and then attack them. Biological therapies for various types of cancer can include antibodies, tumor vaccines, or cytokines (substances that are produced within the body to control the immune system). Monoclonal antibodies are antibodies that react against a specific target that are used in the treatment of many kinds of cancer. An example of a monoclonal antibody used in the treatment of leukemia is alemtuzumab, which targets the CD52 antigen, a protein found on B-cell chronic lymphocytic leukemia (CLL) cells. Interferons are cell signaling chemicals that have been used in the treatment of leukemia.

Side effects of biological therapies tend to be less severe than those of chemotherapy and can include rash or swelling at the injection site for IV infusions of the therapeutic agents. Other side effects can include headache, muscle aches, fever, or tiredness.

Targeted therapy

Targeted therapies are drugs that interfere with one specific property or function of a cancer cell, rather than acting to kill all rapidly growing cells indiscriminately. This means there is less damage to normal cells with targeted therapy than with chemotherapy. Targeted therapies may cause the target cell to cease growing rather than to die, and they interfere with specific molecules that promote growth or spread of cancers. Targeted cancer therapies are also referred to as molecularly targeted drugs, molecularly targeted therapies, or precision medicines.

Monoclonal antibodies (described above in the section on biologic therapy) are also considered to be targeted therapies since they specifically interfere and interact with a specific target protein on the surface of cancer cells. Imatinib (Gleevec) and dasatinib (Sprycel) are examples of targeted therapies that are used to treat CML, some cases of ALL, and some other cancers. These drugs target the cancer-promoting protein that is formed by the BCR-ABL gene translocation.

Targeted therapies are given in pill form or by injection. Side effects can include swelling, bloating, and sudden weight gain. Other side effects can include nausea, vomiting, diarrhea, muscle cramps, or rash.

Radiation therapy

Radiation therapy uses high energy radiation to target cancer cells. Radiation therapy may be used in the treatment of leukemia that has spread to the brain, or it may be used to target the spleen or other areas where leukemia cells have accumulated.

Radiation therapy also causes side effects, but they are not likely to be permanent. Side effects depend on the location of the body that is irradiated. For example, radiation to the abdomen can cause nausea, vomiting, and diarrhea. With any radiation therapy, the skin in the area being treated may become red, dry, and tender. Generalized tiredness is also common while undergoing radiation therapy.

Stem cell transplant

In stem cell transplantation, high doses of chemotherapy and/or radiation are given to destroy leukemia cells along with normal bone marrow. Then, transplant stem cells are delivered by an intravenous infusion. The stem cells travel to the bone marrow and begin producing new blood cells. Stem cells may come from the patient or from a donor.

Autologous stem cell transplantation refers to the situation in which the patient's own stem cells are removed and treated to destroy leukemia cells. They are then returned to the body after the bone marrow and leukemia cells have been destroyed.

An allogeneic stem cells transplant refers to stem cells transplanted from a donor. These may be from a relative or an unrelated donor. A syngeneic stem cell transplant uses stem cells taken from a healthy identical twin of the patient.

Stem cells may be removed (harvested) in different ways. Typically, they are taken from the blood. They can also be harvested from the bone marrow or from umbilical cord blood.

Stem cell transplantation is done in a hospital, and it is necessary to remain in the hospital for several weeks. Risks of the procedure include infections and bleeding due to the depletion of normal blood cells. A risk of stem cell transplant with donor cells is known as graft-versus-host disease (GVHD). In GVHD, the donor white blood cells react against the patient's normal tissues. GVHD can be mild or very severe, and often affects the liver, skin, or digestive tract. GVHD can occur at any time after the transplant, even years later. Steroids or medications that suppress the immune response may be used to treat this complication.

Chimeric antigen receptor (CAR) T-cell treatment

Chimeric antigen receptor (CAR) T-cell treatment is a new form of treatment in which a patient's own normal T lymphocytes are re-engineered in a laboratory to attack the leukemia cells and are then reintroduced into the patient's bloodstream. This treatment has been used for people with B-cell lymphomas that have relapsed or are refractory to treatment. It is also an approved treatment option for certain cases of leukemia. The U.S. FDA approved tisagenlecleucel (Kymriah) in 2018 for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.

CAR-T therapy is also available in clinical trials. Cytokine-release syndrome (CRS) is a potentially serious side effect frequently associated with CAR T-cell therapy. Cytokines are chemical messengers produced when the CAR T-cells multiply in the body and kill cancer cells. CRS may cause a range of symptoms from mild flu-like symptoms to more serious symptoms including fast heart rate, low blood pressure, and heart problems. Other side effects can include nerve damage, suppressed immune function, and a condition known as tumor lysis syndrome that results when cancer cells are rapidly destroyed.

Because CAR T-cell therapy is so new, the patients who have had this treatment have not been followed over the long term. Studies are under way to determine whether CAR-T treatment may be useful in other types of leukemia.

Supportive treatments

Because many of the treatments for leukemia deplete normal blood cells, increasing the risk for bleeding and infection, supportive treatments may be needed to help prevent these complications of treatment. Supportive treatments may also be needed to help minimize and manage unpleasant side effects of medical or radiation therapy.

Types of supportive and preventive treatments that can be used for patients undergoing treatment for leukemia include the following:

Vaccines against the flu or pneumonia
Blood or platelet transfusions
Anti-nausea medications
Antibiotics or antiviral medications to treat or prevent infections
White blood cell growth factors to stimulate white blood cell production (such as granulocyte-colony stimulating factor [G-CSF], made up of filgrastim [Neupogen] and pegfilgrastim [Neulasta] and granulocyte macrophage-colony stimulating growth factor [GM-CSF], made up of sargramostim [Leukine])
Red cell growth factors to stimulate red blood cell production (darbepoetin alfa [Aranesp] or epoetin alfa [Procrit])
Intravenous injections of immunoglobulins to help fight infection

What are complications of leukemia?

Many of the challenges of leukemia relate to the depletion of normal blood cells as well as the side effects of treatments as described in the previous section, such as frequent infections, bleeding, and GVHD in recipients of stem cell transplants. Weight loss and anemia are further complications of leukemia and its treatment. Complications of any leukemia also include a relapse or a progression of the disease after a remission has been achieved with treatment.

Other complications of leukemia relate to the specific type of leukemia. For example, in 3% to 5% of cases of CLL, the cells change characteristics and transform into an aggressive lymphoma. This is known as a Richter transformation. Autoimmune hemolytic anemic, in the body attacks and destroys red blood cells, is another potential complication of CLL. People with CLL are also more likely to develop second cancers and other blood disorders and blood cancers.

Tumor lysis syndrome is a condition caused by the rapid death of cancer cells during acute treatment. It can occur in almost any type of cancer, and it is seen with some cases of leukemia, particularly when large numbers of leukemia cells are present such as with AML or ALL. The rapid destruction of the leukemia cells leads to the release of large amounts of phosphate, which further causes metabolic abnormalities and can lead to kidney failure.

Children who receive therapy for ALL may experience late adverse effects including central nervous system (CNS) impairment, slowing of growth, infertility, cataracts, and an increased risk for other cancers. The incidence of these late effects varies depending upon the age at treatment and the type and strength of therapies.

What is the prognosis of leukemia?

The prognosis of leukemia depends upon the type of leukemia that is present and the age and health status of the patient. Mortality (death) rates for leukemia are higher in the elderly than in younger adults and children. In many cases, leukemia can be managed or cured with treatments available today. In particular, childhood ALL has a very high 5-year survival rate.

Modern treatments have led to a greater than fourfold increase since 1960 in five-year survival rates for leukemia. Five-year survival rates for different types of leukemia from 2007-2013 are approximately:

CML: 68%

CLL: 86%

AML: 27% overall, 66% for children and teens younger than 15

ALL: 71% overall, over 90% for children

How often does leukemia recur?

The likelihood that leukemia will recur (come back after successful treatment) depends upon the type of leukemia including the specific molecular characteristics of the cancer cells and the patient's response to initial treatment. Some acute leukemias are successfully treated, and the patient never experiences a recurrence. In chronic leukemias, such as CML, ongoing symptoms and recurrences are common, and treatments may be directed at keeping the leukemia under control.

Is it possible to prevent leukemia?

Most people who develop leukemia do not have a known risk factor, and it is generally not possible to prevent leukemia. Certain risk factors, such as exposure to radiation or benzene, may be minimized, but this does not guarantee prevention of leukemia.

What support groups are available for people with leukemia?

Support groups for people with leukemia and their families offer a variety of resources.

The Leukemia and Lymphoma Society (http://www.lls.org/#/diseaseinformation/
getinformationsupport/) offers information for patients and families, discussion boards, online chats, support groups, and 1:1 support from information specialists. They also offer family support groups.

Information specialists at 1-800-4-CANCER and at LiveHelp (http://www.cancer.gov/help) can help someone locate programs, services, and publications.

Throughout the U.S., hospitals and health systems offer support groups and resources for people living with leukemia. A doctor or other members of a patient's treatment team can provide information about support groups in the area. The National Cancer Institute has publications for patients on coping with leukemia and other cancers (http://www.cancer.gov/publications/patient-education#coping-and-support).

What research is being done on leukemia?

Leukemia is an active area of biomedical research. Ongoing studies are examining the risk factors and causes of leukemia, as well as examining new and improved treatment options.

Clinical trials are studies that examine new drugs or new combinations of drugs and existing treatments. Trials are under way to test new targeted therapy, biological therapy, and chemotherapy regimens. Patients should discuss their situation and care with their doctor if they are interested in being part of a clinical trial. The NCI's web site includes a section on clinical trials at https://clinicaltrials.gov.

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