Acute Myeloid Leukemia

Patients with acute myeloid leukemia undergo an extensive initial work-up including:

The leukemia doctors and pathologist review this material and confirm the specific subtype of acute myeloid leukemia (AML). Then, treatment is started as soon as possible.

The treatment of AML varies according to one's age, general condition at diagnosis and the results of the cytogenetics. For most patients age 65 or younger, an autologous transplant will be recommended as part of the initial consolidation therapy. Overall, typical AML therapy includes three phases:

One AML subtype, called acute promyelocytic leukemia (APL), has a unique biology and is treated differently. This type of leukemia can be treated with a vitamin pill called altransretinoic acid (ATRA) together with chemotherapy. Most people undergo multiple cycles of this therapy. Sometimes, bone marrow transplantation is preferred.

The goals of induction chemotherapy are to eliminate leukemia cells from the blood and bone marrow and to induce a remission. A complete remission is defined as having no visible leukemia cells in the blood or bone marrow and having normal blood counts without the need of transfusions.

Induction therapy for patients age 65 or younger typically includes high doses of ARA-C and daunorubicin chemotherapy. The medications are given over a six-day period. Although side effects are expected and can be severe, our team is very skilled at caring for patients undergoing induction therapy for AML, administering all needed supportive care measures, such as transfusions, antibiotics and medications.

Chemotherapy is usually given over approximately five to seven days. During most of the hospital stay, patients receive intensive supportive care to protect them during their period of very low blood counts, including transfusions of red blood cells and platelets to correct anemia and to prevent bleeding. Antibiotics are used both preventatively and to treat bacteria and fungal infections. Additional antibiotics may be needed if other infections occur. Growth factors such as G-CSF (Neupogen) can help bring the patient's white blood count back more quickly and may help prevent infections. The chemotherapy agents also are associated with complete but temporary hair loss, sores in the mouth, and throat and skin rashes. Other support care measures include anti-nausea drugs to prevent or decrease nausea, anti-diarrheals to decrease diarrhea, eye drops to prevent irritation and nutrient-rich beverages to improve nutrition.

Patients are expected to be hospitalized for four to five weeks. Once the blood counts have returned to normal and the bowels function normally, patients may be discharged from the hospital. At the end of the induction therapy, a bone marrow biopsy is performed to see if a complete remission has been achieved. Approximately 70 percent to 80 percent of patients are expected to enter complete remission. If a complete remission is achieved, patients are then given a one-month break to prepare for the second (consolidation) treatment cycle.

Once a patient achieves a complete remission more chemotherapy is needed to destroy any residual leukemia in the body. Consolidation chemotherapy can consist of the following:

The type of consolidation therapy offered to any particular patient depends on the subtype of leukemia, the initial cytogenetics and the expertise of the leukemia doctor and center.

This second phase of treatment likely will include similar chemotherapy medications including the drug ARA-C (cytarabine). The actual number of chemotherapy cycles required during consolidation as well as the need for a stem cell transplant varies from case to case.

In general, consolidation treatment has similar toxicities as induction therapy and also requires intensive supportive care. At some institutions, the consolidation treatments can be done as an outpatient, but most patients are treated in the hospital and require a four to five week hospitalization. Overall, approximately 30 percent to 40 percent of patients receiving consolidation chemotherapy are cured of their AML.

If a patient is going to have an autologous stem cell transplantation, his or her stem cells are collected after the consolidation chemotherapy stage is complete and once their blood counts recover. A process called "mobilization" enables the collection of stem cells from the blood. When the white blood cell counts are more than 10,000 cells/uL, a large IV catheter called a Quentin catheter is inserted into one of the large veins in the neck. This catheter is connected to an "apheresis" machine that separates the blood into individual components allowing the collection of only the white blood cells. All the other cells, including red blood cells and platelets, are given back to the patient. Each apheresis procedure takes four hours, and two to three procedures are usually necessary to collect enough stem cells.

Once the stem cells are collected, and all other toxicities have resolved, the patients may be discharged from the hospital. The stem cells are frozen and saved for future use. Patients are then given a one-month break to prepare for high-dose chemotherapy and the re-infusion of the stem cells.

Stem cell transplantation, also called bone marrow transplantation, is often recommended for both intermediate- and poor-risk AML. UCSF Medical Center has an expertise in autologous stem cell transplantation for AML. Autologous stem cell transplantation -- using cells collected from the patient's own bone marrow after they have achieved complete remission -- appears to produce a cure approximately 50 percent to 55 percent of the time for intermediate-risk AML.

This stage of treatment is both the most important and most dangerous. This therapy requires a one-month hospitalization. The goal of this therapy is to utilize much higher doses of chemotherapy to completely destroy any residual leukemia cells. The side effects are rather severe and the chances of dying from complications associated with high-dose chemotherapy are approximately 2 percent to 5 percent.

The chemotherapy medications include Busulfan and etoposide, which are administered over five days. After two days of chemotherapy, the frozen stem cells will be re-infused into an IV catheter. The rest of the hospitalization consists of waiting for the new stem cells to grow, and during this time supportive care is administered as needed. Once the blood counts have improved and the other side effects have resolved, patients may be discharged. Patients are followed closely in the outpatient clinic for approximately three months. Most Patients are able to return to work within three to six months of transplantation.

The preferred treatment for patients with good or intermediate-risk cytogenetics is autologous stem cell transplantation, while allogeneic transplantation is favored for those with bad cytogenetics.

Allogeneic transplantation using stem cells or bone marrow from a matched brother or sister produces cure rates of approximately 50 percent to 60 percent. However, allogeneic transplantation is significantly more difficult and dangerous than either chemotherapy or autologous transplantation, and 20 percent to 30 percent of patients do not survive the first three months of treatment. For this reason, it is often reserved for more difficult cases. Poor-risk AML patients are best treated with allogeneic transplant despite its difficulties and dangers. Cure rates of 20 percent to 25 percent may be achieved. For patients with poor-risk leukemia who do not have a matched sibling donor, an unrelated donor may be sought through the National Marrow Donor Program (NMDP).

Mylotarg is a new treatment for leukemia that combines an antibody that specifically targets leukemia cells and then inserts them with a toxin. This treatment is beneficial because it does not cause hair loss, mouth sores or disturbance of the intestinal tract. However, it does produce long periods of low blood counts. Also, the chance of reaching a remission is not as strong as with chemotherapy. Further work still needs to be done to determine the best role of this agent in the treatment of AML.