Treatment for AML

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Treatment for AML lasts for six to twelve months and is very intense. Acute complications of treatment are common. Children with this disease need to be treated at a major pediatric hospital with expertise in treating acute leukemias. The goal of treatment is to achieve a complete remission by obliterating all cancer cells as quickly as possible and to prevent the disease from returning. Complete remission occurs when all signs and symptoms of leukemia disappear; blood counts are rising towards normal; and abnormal cells are no longer found in the blood, bone marrow (less than 5 percent blasts), and cerebrospinal fluid.

Chemotherapy is the primary treatment to induce remission in children with AML. Radiation of the brain and sometimes the spinal cord is used infrequently. Stem cell transplantation (see Chapter 20) is frequently used to treat childhood AML in first or second remission.

Certain groups of children with AML (those with Down syndrome and those with M3 t(15;17) APL) are treated on different protocols to address their unique disease. Children with subtype M3 are given all-trans-retinoic acid (ATRA) in addition to chemotherapy.

For most children, treatment usually consists of two or three parts: induction (to achieve remission), postremission consolidation, and/or postremission intensification.

Induction

Induction is the most intense part of treatment; its purpose is to quickly kill as many cancer cells as possible. As with ALL, chemotherapy drugs for AML are more successful if two or three are used simultaneously. The most common drugs used to treat AML are: ARA-C (cytarabine), daunomycin (daunorubicin), etoposide, and thiogua-nine. Children with acute promyelocytic leukemia (M3) receive all-trans-retinoic acid (ATRA) in addition to chemotherapy. Recently, it has been discovered that arsenic is also a very effective drug in the treatment of this particular type of AML. However, arsenic is not currently used for newly diagnosed children.

Chemotherapy can be administered by mouth (orally), intravenously (through a needle placed in a vein), intramuscularly (injection in the muscle), or intrathecally (through a needle in the lower part of the back). Most AML chemotherapy is given intravenously. See Chapter 10 for an in-depth discussion of each drug, possible side effects, and parent suggestions.

Recent studies have shown that induction therapy for AML is most successful if given on a timed basis, that is, giving a second treatment without waiting for full recovery from the first treatment. Because of the intensive nature of this treatment, several weeks of hospitalization are usually required during induction, as the chemotherapy drugs damage normal cells as well as leukemic cells, leaving the child susceptible to infections and excessive bleeding. Bone marrow growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF) are sometimes used to shorten the duration of neutropenia (low white cell counts). Transfusions (blood and platelets) and intravenous feeding (hyper-alimentation) are often necessary.

If the disease has spread to the brain, the child is given intrathecal chemotherapy (cytarabine or methotrexate). Radiation therapy may also be used in these children.

Children with M4 and M5 AML are most likely to have CNS leukemia at diagnosis (especially those with inv 16 or 11q23 chromosomal abnormalities). Even if leukemia cells have not been found in the brain, most protocols for childhood AML use some form of CNS treatment, usually intrathecal chemotherapy with or without cranial radiation.

During induction, a majority of children go into remission, and then enter the second phase of treatment.

CNS prophylaxis

The central nervous system (CNS) is composed of the brain and spinal cord, which are bathed in a fluid called cerebrospinal fluid (CSF). When cancer invades the CNS, cancer cells are found in the cerebrospinal fluid. In most cases of childhood AML, leukemia cells are not visible in the CSF. However, before it became standard practice to use radiation or inject chemotherapy drugs directly into the cerebrospinal fluid, nervous system leukemia developed in 30 to 40 percent of children with AML. This suggests that at the time of diagnosis, microscopic amounts of leukemia are already present in the CNS. Therefore, CNS prophylaxis (prevention) is an essential component of treatment for AML. Children with M4 or M5 subtypes and very high white blood cell counts at diagnosis are at the highest risk for developing CNS leukemia.

Because a blood-brain barrier exists that prevents many chemotherapy drugs from crossing into the CNS to destroy leukemic cells, chemotherapy drugs are injected directly into the cerebrospinal fluid (called intrathecal medication) during spinal taps. Intrathecal medication is given periodically throughout treatment.

CNS prophylaxis has decreased the risk of developing leukemia in the nervous system to about 5 percent and is partially responsible for the overall increase in cure rates. Unfortunately, the treatments can sometimes cause long-term disabilities such as decreased attention span, short-term memory problems, and lower ability in spatial and mathematical skills, particularly when radiation is used (see Chapter 15, School). Current clinical trials are attempting to determine how much and what type of treatment is necessary to prevent CNS relapse while minimizing the chances for long-term side effects.

Postremission therapy

Even when a child is in complete remission, residual cancer cells multiply rapidly without additional treatment. Consequently, after a short period of recuperation from induction, children with AML receive further intensive treatment with an allogeneic bone marrow transplant (if a matched sibling donor is available) or more chemotherapy, called postremission therapy.

Postremission chemotherapy may include: cytosine arabinoside (in high or standard doses), etoposide, an anthracycline (doxorubicin, daunorubicin or idarubicin), thioguanine, amsacrine, azacytidine, and cyclophosphamide. Children with APL also get ATRA (and in some cases, 6-mercaptopurine and methotrexate) during postremission therapy.

In the past, another phase of treatment, called maintenance, was used. This phase consisted of low-dose chemotherapy given for a number of years. Studies have shown that additional therapy after intensive induction and consolidation does not lengthen remission for children with AML.

Bone marrow transplantation (BMT)

BMT is being used increasingly to treat children with AML in first remission. Highdose chemotherapy, with or without total body radiation, is used to destroy the childs bone marrow and any remaining cancer cells. Healthy, matched marrow or peripheral blood stem cells are taken from a compatible family member and dripped into the patients blood intravenously. The new marrow migrates to the bones and replaces the destroyed marrow. This is called an allogeneic transplant. Nearly 60 percent of children with AML with matched donors who undergo a BMT in first remission may be cured by transplantation from a closely matched family donor.

Another method sometimes used for children without a matched, or closely matched, donor is called autologous BMT. In this type of transplant, marrow is removed from the child, may be treated chemically to remove leukemia cells, and frozen. After the child's own diseased marrow has been destroyed, the frozen marrow is thawed and returned to the patient intravenously. The data so far indicate that this is no better than conventional chemotherapy and is inferior to matched allogeneic bone marrow transplantation.

The role of transplants using bone marrow, peripheral blood, or cord blood from unrelated donors for childhood AML in first remission has not yet been established. These are sometimes used to treat AML in second remission or AML that occurs as a second cancer.

Chapter 20 discusses in detail the types of transplants, procedures, side effects, and coping suggestions from parents and survivors.

Treatment for chloromas

Chloromas are most commonly found in children with M4 and M5 AML. They occur in approximately 10 percent of all AML patients. Chloromas usually disappear with standard AML treatment. However, if the location of a chloroma may cause a serious problem such as vision loss or spinal cord damage, radiation therapy may be given.

Newest treatment options

To learn more about AML, call (800) 422-6237 (800-4-CANCER) and ask for the PDQ (Physician Data Query) for AML. These free statements, also available on the Internet at http://www.cancer.gov/cancer_information/pdq/, explain the disease, state-of-the-art treatments, and ongoing clinical trials. There are two versions available: the version designed for patients uses simple language and contains no statistics; the version for professionals is technical, thorough, and includes citations to the scientific literature.

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