How Leukemia Is Treated

The treatment for leukemia depends on many factors, including the type, subtype, and stage of the disease, and a person’s age and general health. Treatment typically involves powerful chemotherapy, bone marrow/stem cell transplant, targeted therapy (tyrosine kinase inhibitors), monoclonal antibodies, and immunotherapy—used alone or in combination.

In some cases, a period of watchful waiting may be appropriate. Leukemia is a cancer of blood cells that travels throughout the body, and local treatments such as surgery and radiation therapy are not used frequently.

Most people with leukemia will have a team of medical professionals caring for them, with a hematologist/oncologist (a doctor specializing in blood disorders and cancer) leading the group.

Approaches by Disease Type

Before discussing the different types of treatments, it’s helpful to understand common approaches to treatment for the different types of leukemia. You may find it useful to zero in on the type you have been diagnosed with, then jump ahead to the in-depth descriptions of each option.

Acute Lymphocytic Leukemia (ALL)

Treatment of acute lymphocytic leukemia (ALL) can take several years. It begins with induction treatment, with the goal of remission. Then, consolidation chemotherapy in several cycles is used to treat any remaining cancer cells and reduce the risk of relapse. Alternatively, some people may receive a hematopoietic stem cell transplant (though less commonly than with AML).

• After consolidation therapy, you may have maintenance chemotherapy (usually a lower dose) to further reduce the risk of relapse, with the goal being long-term survival.
• If leukemia cells are found in the central nervous system, chemotherapy is injected directly into the spinal fluid (intrathecal chemotherapy).
• Radiation therapy may also be used if leukemia has spread to the brain, spinal cord, or skin.
• If you have Philadelphia chromosome-positive ALL, the targeted therapy imatinib or another tyrosine kinase inhibitor may also be used.

Chemotherapy drugs do not penetrate well into the brain and spinal cord due to the blood-brain barrier, a tight network of capillaries that limits the ability of toxins (such as chemotherapy) to enter the brain. For this reason, many people are given treatment to prevent leukemia cells from remaining behind in the central nervous system.

Acute Myelogenous Leukemia (AML)

Treatment for acute myelogenous leukemia (AML) usually begins with induction chemotherapy. After remission is achieved, you might have further chemotherapy. People who have a high risk of relapse might have stem cell transplantation.

Among the treatments for leukemia, those for AML tend to be the most intense and suppress the immune system to the greatest degree. If you are over age 60, you may be treated with less intense chemotherapy or palliative care, depending on the subtype of your leukemia and your general health.

Chronic Lymphocytic Leukemia

In the early stages of chronic lymphocytic leukemia (CLL), a period of watchful waiting without treatment is often recommended as the best treatment option. This is often the best choice, even if the white blood cell count is very high.

If certain symptoms, physical findings, or changes in blood tests develop, treatment is often started with a BTK inhibitor, such as Imbruvica (ibrutinib) or Calquence (acalabrutinib), or a BCL-2 inhibitor, such as Venclexta (venetoclax).

Chronic Myelogenous Leukemia

Tyrosine kinase inhibitors (TKIs, a type of targeted therapy) have revolutionized the treatment of chronic myelogenous leukemia (CML) and resulted in a dramatic improvement in survival over the past two decades. These drugs target the BCR-ABL protein that causes the cancer cells to grow.

For those who develop resistance or can’t tolerate two or more of these drugs. Pegylated interferon (a type of immunotherapy) may be used.

Watchful Waiting

Most leukemias are treated aggressively when diagnosed, with the exception of CLL. Many people with this type of leukemia do not require treatment in the early stages of the disease, and a period of surveillance is considered a viable standard treatment option.

Watchful waiting does not mean the same thing as foregoing treatment and does not reduce survival when used appropriately. Blood counts are done every few months, and treatment is initiated if constitutional symptoms (fever, night sweats, fatigue, weight loss greater than 10 percent of body mass), progressive fatigue, progressive bone marrow failure (with a low red blood cell or platelet count), painfully enlarged lymph nodes, a significantly enlarged liver and/or spleen, or a very high white blood cell count develop.

Chemotherapy

Chemotherapy is the mainstay of treatment for acute leukemias and is often combined with a monoclonal antibody for CLL. It may also be used for CML that has become resistant to targeted therapy.

Chemotherapy works by eliminating rapidly dividing cells such as cancer cells, but can also affect normal cells that divide rapidly, such as those in the hair follicles. It is most often given as combination chemotherapy (two or more drugs), with different drugs working at different places in the cell cycle.

Induction Chemotherapy

Induction chemotherapy is often the first therapy that is used when a person is diagnosed with acute leukemia. The goal of this treatment is to reduce the leukemia cells in the blood to undetectable levels. This does not mean that the cancer is cured, but only that it can’t be detected when looking at a blood sample.

The other goal of induction therapy is to reduce the number of cancer cells in the bone marrow so that normal production of the different types of blood cells can resume. Further treatment is needed after induction therapy so that cancer does not recur.

With AML, the 7+3 protocol is used. This includes three days of an anthracycline, either Idamycin (idarubicin) or Cerubidine (daunorubicin), along with seven days of a continuous infusion of Cytosar U or Depocyt (cytarabine). These drugs are often given through a central venous catheter in the hospital (people are usually hospitalized for the first four to six weeks of treatment). For younger people, the majority will achieve remission.

People with Philadelphia chromosome-positive ALL may also be treated with a tyrosine kinase inhibitor, such as Sprycel (dasatinib). After remission is achieved, treatment is used to prevent leukemia cells from remaining in the brain and spinal cord.

With acute promyelocytic leukemia (APL), induction therapy also includes the medication ATRA (all-trans retinoic acid) combined with Trisenox (arsenic trioxide).

While induction therapy often achieves a complete remission, further therapy is needed so that leukemia does not recur.

Consolidation and Intensification Chemotherapy

With acute leukemias, options after induction chemotherapy and remission include either further chemotherapy (consolidation chemotherapy) or high-dose chemotherapy plus stem cell transplantation.

• With AML, the most common treatment is three to five courses of further chemotherapy, though, for people with high-risk disease, a stem cell transplant is often recommended.
• With ALL, consolidation chemotherapy is usually followed by maintenance chemotherapy, but a stem cell transplant may also be recommended for some people.

Maintenance Chemotherapy (for ALL)

With ALL, further chemotherapy after induction and consolidation chemotherapy is often needed to reduce the risk of relapse and to improve long-term survival. Drugs used often include methotrexate or 6-MP (6-mercaptopurine).

Chemotherapy for CLL

When symptoms occur in CLL, a BTK inhibitor or a BCL-2 inhibitor may be used.

Chemotherapy for CML

The mainstay of treatment for CML is tyrosine kinase inhibitors, but chemotherapy may occasionally be recommended. Drugs such as Hydrea (hydroxyurea), cytarabine, cyclophosphamide, vincristine, or Myleran (busulfan) may be used to lower a very high white blood cell count or enlarged spleen.

Side Effects

Common side effects of chemotherapy can vary with the different drugs used but may include:

• Tissue damage: Anthracyclines are vesicants and can cause tissue damage if they leak into the tissues surrounding the infusion site.
• Bone marrow suppression: Damage to rapidly dividing cells in the bone marrow often results in low levels of red blood cells (chemotherapy-induced anemia), white blood cells such as neutrophils (chemotherapy-induced neutropenia), and platelets (chemotherapy-induced thrombocytopenia). Due to a low white blood cell count, taking precautions to reduce the risk of infections is extremely important.
• Hair loss: Hair loss is common—not just on the top of the head—you can expect to lose hair from your eyebrows, eyelashes, and pubic hair.
• Nausea and vomiting: Medications to both treat and prevent chemotherapy-associated vomiting can reduce this significantly.
• Mouth sores: Mouth sores are common, though dietary changes, as well as mouth rinses, can improve comfort. Taste changes may also occur.
• Red urine: Anthracycline medications have been coined the “red devils” for this common side effect. Urine may be bright red to orange in appearance, beginning shortly after the infusion and lasting for a day or so after it’s complete. Though perhaps startling, it’s not dangerous.
• Peripheral neuropathy: Numbness, tingling, and pain in a stocking and glove distribution (both the feet and the hands) may occur, especially with drugs such as Oncovin.
• Tumor lysis syndrome: The rapid breakdown of leukemia cells can result in a condition known as tumor lysis syndrome. Findings include high potassium, uric acid, blood urea nitrogen (BUN), creatinine, and phosphate levels in the blood. Tumor lysis syndrome is less problematic than in the past and is treated with intravenous fluids and medications to lower the uric acid level.
• Diarrhea

Since many people who develop leukemia are young and are expected to survive treatment, the late effects of treatment that may occur years or decades after treatment are of particular concern.

Targeted Therapy

Targeted therapies are medications that work by specifically targeting cancer cells or pathways involved in the growth and division of cancer cells. Unlike chemotherapy drugs, which can affect both cancer cells and normal cells in the body, targeted therapies focus on mechanisms that specifically support the growth of the diagnosed type of cancer. For this reason, they may have fewer side effects than chemotherapy (but not always).

In addition to the targeted therapies mentioned below, there are a number of drugs that may be used for leukemia that has relapsed or leukemias that harbor specific genetic mutations.

Tyrosine Kinase Inhibitors (TKIs) for CML

Tyrosine inhibitors (TKIs) are medications that target enzymes called tyrosine kinases to interrupt the growth of cancer cells.

With CML, TKIs have revolutionized treatment and have vastly improved survival over the past two decades. Continued use of the drugs can often result in long-term remission and survival with CML.

Medications currently available include:

• Gleevec (imatinib)
• Bosulif (bosutinib)
• Sprycel (dasatinib)
• Tasigna (nilotinib)
• Iclusig (ponatinib)

Kinase Inhibitors for CLL

In addition to monoclonal antibodies, which are the mainstay of treatment, kinase inhibitors may be used for CLL.

Drugs include:

• Imbruvica (ibrutinib): This drug inhibits Bruton’s tyrosine kinase (BTK) and may be effective for difficult-to-treat CLL.
• Calquence (acalabrutinib): This drug also inhibits BTK, preventing B-cell activation and B-cell-mediated signaling, and is used to treat CLL and mantle cell lymphoma.
• Zydelig (idelalisib): This drug blocks a protein (P13K) and may be used when other treatments are not working.
• Copiktra (duvelisib): This drug inhibits phosphoinositide-3 kinases and is used to treat relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.
• Venclextra (venetoclax): This drug blocks a protein (BCL-2) and may be used to treat CLL.

Copiktra comes with a warning regarding a possible increased risk of death and serious side effects. If you are taking Copiktra, talk with your healthcare provider about the risks and benefits of treatment with Copiktra. In addition, discuss any questions or concerns you may have, including possible alternative treatments.

Monoclonal Antibodies

Monoclonal antibodies are similar to the natural antibodies that your body makes to fight infections. These are synthetic versions that are designed to attack cancer cells.

For CLL, monoclonal antibodies are a mainstay of treatment, often combined with chemotherapy. These drugs target a protein (CD20) found on the surface of B cells.

Drugs currently approved include:

• Rituxan (rituximab)
• Gazyva (obinutuzumab)
• Arzerra (ofatumumab)

These drugs can be very effective, though they do not work as well for people who have a mutation or deletion in chromosome 17.

For refractory B cell ALL, the monoclonal antibodies Blincyto (blinatumomab) or Besponsa (inotuzumab) may be used.

Proteasome Inhibitors

For refractory ALL in children, the proteasome inhibitor Velcade (bortezomib) may be used.

Immunotherapy

There is a wide range of treatments that fall under the general category of immunotherapy. These drugs work by directing your own immune system to fight cancer.

CAR T-Cell Therapy

CAR T-cell therapy (chimeric antigen receptor T-cell therapy) uses a person’s own (T cells) to fight cancer. It starts with a procedure in which T cells are collected from the body and modified in a laboratory to target a protein on the surface of leukemia cells. They are then allowed to multiply before being injected back into the body, where they often eliminate leukemia cells within a few weeks.

Drugs currently approved include:

• Kymriah (tisagenlecleucel)
• Tecartus (brexucabtagene autoleucel)

Interferon

Interferons are substances made by the human body that function to control the growth and division of cancer cells, among other immune functions. In contrast to the CAR T-cell therapy, which is designed to attack particular markers on leukemia cells, interferons are non-specific and have been used in many settings, including cancer to chronic infections.

Interferon alpha, a synthetic interferon, was once commonly used for CML but is now used more often for people with CML who can’t tolerate other treatments. It can be given by injection (either subcutaneously or intramuscularly) or intravenously and is given for a long period of time.

Bone Marrow/Stem Cell Transplants

Hematopoietic cell transplants, or bone marrow and stem cell transplants, work by replacing the hematopoietic cells in the bone marrow that develop into the different types of blood cells. Before these transplants, a person’s bone marrow cells are destroyed. They are then replaced with donated cells that restock the bone marrow and eventually produce healthy white blood cells, red blood cells, and platelets.

Types

While bone marrow transplants (cells harvested from the bone marrow and injected) were once more common, peripheral blood stem cell transplants are now used. Stem cells are harvested from the blood of a donor (in a procedure similar to dialysis) and collected. Medications are given to the donor prior to this procedure to increase the number of stem cells in the peripheral blood.

Types of hematopoietic cell transplants include:

• Autologous transplants: Transplants in which a person’s own stem cells are used
• Allogeneic transplants: Transplants in which stem cells are derived from a donor, such as a sibling or unknown but matched donor
• Transplants from umbilical cord blood
• Non-ablative stem cell transplant: These transplants are less invasive “mini-transplants” that do not require obliterating the bone marrow prior to the transplant. They work by a graft versus malignancy process in which the donor cells help fight off the cancer cells rather than by replacing the cells in the bone marrow.

Uses

A hematopoietic cell transplant may be used after induction chemotherapy with both AML and ALL, especially for high-risk disease. The goal of treatment with acute leukemia is long-term remission and survival. With CLL, stem cell transplantation may be used when other treatments do not control the disease. Stem cell transplants were once the treatment of choice for CLL, but are now used much less often.

Non-ablative transplants may be used for people who would not tolerate the high-dose chemotherapy required for a traditional stem cell transplant (for example, people over the age of 50). They may also be used when leukemia recurs after a previous stem cell transplant.

Side Effects and Complications

Stem cell transplants are major procedures that can sometimes bring about a cure. But they can have significant mortality. This is primarily due to the absence of infection-fighting cells between conditioning and the time it takes the donated cells to develop in the marrow, during which there are few white blood cells left to fight infections.

A few possible complications include:

• Immunosuppression: A severely suppressed immune system is responsible for the relatively high mortality rate of this procedure.
• Graft-versus-host disease: Graft-versus-host disease occurs when the donated cells attack a person’s own cells and can be both acute and chronic.

Complementary Medicine

There are currently no alternative treatments that are effective in treating leukemia, though some integrative cancer treatments such as meditation, prayer, yoga, and massage may help you cope with the symptoms of leukemia and its treatments.

It’s important to note that some vitamins may interfere with cancer treatments.

The general uncertainty in this area is a good reminder to talk to your oncologist about any vitamins, dietary supplements, or over-the-counter medications you consider taking.

Clinical Trials

There are many different clinical trials in progress looking at more effective ways to treat leukemia or methods that have fewer side effects. With treatments for cancer rapidly improving, the National Cancer Institute recommends that people talk with their oncologist about the option of a clinical trial.

Some of the treatments being tested combine therapies mentioned above, whereas others are looking at unique ways to treat leukemia, including many next-generation drugs. The science is changing rapidly. For example, the first monoclonal antibody was only approved in 2002, and since then, second- and third-generation drugs have become available. Similar progress is being made with other types of targeted therapies and immunotherapy.