Monday, March 30, 2009

Acute myeloid leukemia (AML) 2

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 success-
ful 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 com-
ponent 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 treat-
ment 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