Acute lymphoblastic leukemia (ALL) 3

Because a blood-brain barrier exists that prevents most 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. Five to 10 percent
of children experience seizures from intrathecal medications.
Standard-risk patients receive intrathecal methotrexate, or triple intrathecal therapy—
methotrexate, hydrocortisone, and cytarabine—for CNS prophylaxis. Whether chil-
dren with a high-risk of CNS relapse (e.g., T-cell ALL with a high white cell count)
require cranial radiation is controversial. In some protocols, these children receive
1200 to 1800 cGy of cranial radiation as well as intrathecal chemotherapy, although
those with a rapid early response to therapy are sometimes treated with intrathecal
therapy alone.
CNS prophylaxis has decreased the risk of CNS relapse from 65 percent to only 5
percent, and is partially responsible for the huge 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.
Consolidation
Consolidation therapy consists of new combinations of drugs to destroy any cancer
cells that survived induction. It includes high doses of previously used or new drugs
and central nervous system prophylaxis.
In 2002, the most common drugs used in consolidation are: methotrexate, cyclo-
phosphamide (Cytoxan), cytosine arabinoside (ARA-C), 6-mercaptopurine (6-MP),
dexamethasone (Decadron), asparaginase, and thioguanine. See Chapter 10 for detailed
descriptions of these drugs.
Reinduction and reconsolidation
A second induction (commonly called delayed intensification or reinduction) and a
second consolidation may be administered prior to maintenance in some protocols.
Children who were slow to respond to induction treatment may benefit from a second
delayed intensification.
More intensive regimens
Protocols for high-risk ALL usually contain more drugs at higher doses, and some-
times involve cranial radiation. This treatment has increased toxicity, but is more
effective for the small percentage of children with high-risk features.
Researchers studying childhood cancer are increasing their understanding of what
types and subtypes of ALL require more intensive therapy and for which ones therapy
can be less aggressive.
Maintenance
Maintenance (also called continuation therapy) is the final phase of treatment for
ALL. It consists of lower-dose chemotherapy given for two to three years to kill any
remaining leukemia cells. This portion of treatment is less toxic and easier to tolerate
than induction and consolidation.
In most clinical trials, mercaptopurine (6-MP) is administered every evening and
methotrexate is given weekly. In addition, other drugs such as vincristine, prednisone,
or dexamethasone may be included. Many protocols also give intrathecal metho-
trexate during maintenance therapy. During maintenance, children are monitored for
drug-related toxicities as well as for compliance (making sure they are taking the drugs
as directed).
Some children have an inherited trait (deficiency of thiopurine methyltransferase)
that makes it difficult for them to break down mercaptopurine. These children can
only tolerate small doses of mercaptopurine; at conventional doses they will have
profound and life-threatening drops in their blood counts.
Stem cell transplantation
Stem cell transplants may be recommended after first remission in some children at
extremely high risk of relapse. These may include infants less than one year old with
MLL gene rearrangements or those with the Philadelphia chromosome. Transplanta-
tion may be recommended for children with ALL who relapsed and then achieved a
second remission (see Chapter 20, Stem Cell Transplantation).
Newest treatment options
To learn more about ALL, call (800) 422-6237 (800-4-CANCER) and ask for the PDQ
(Physician Data Query) for ALL. 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.