Acute myeloid leukemia (AML) accounts for about 20% of
cases of acute leukemia in children and 80% of cases of
acute leukemia among adults. Further, although AML is significantly
less common than acute lymphoblastic leukemia (ALL) in childhood,
the survival for children with AML is current between 50% and
60% compared to nearly 85% of children with ALL.
In addition, the treatment for children with AML remains particularly
toxic and includes multiple, near myeloablative courses of treatment with
chemotherapeutic agents and often hematopoietic stem cell transplantation (HSCT).
As chemotherapeutic regimens have achieved higher cure rates in
selected patients with good prognostic characteristics, HSCT is currently
recommended primarily for patients with very high-risk disease characteristics
or those who relapse and achieve a second remission. Insights into
stem cell physiology and the molecular basis of AML have demonstrated
some of the fundamental molecular changes driving the behavior of
the leukemia, revealed their extensive heterogeneity, and have begun
to provide new therapeutic targets and strategies.
The chronic myeloid forms of leukemia are extremely rare in children.
These myeloproliferative syndromes most commonly include the adult
type of Philadelphia-chromosome-positive (Ph+), chronic
myelogenous leukemia (CML), and juvenile myelomonocytic leukemia
(JMML). The clinical course, biologic characteristics, and molecular
pathogenesis of CML and JMML are quite different. Until recently,
allogeneic bone marrow transplant (BMT) from either a related or
an unrelated donor was the management of choice for children with
Ph + CML but the kinase inhibitor imatinib has changed
the treatment paradigm for that disease in both children and adults,
although hematopoietic stem cell transplantation (HSCT) is still
the only know curative therapy for CML. An allogeneic HSCT remains
the only know curative option for children with JMML.
The annual incidence of acute myeloid leukemia (AML) in children
remains constant, with the exception of a slight peak in infants
and during adolescence. After age 20 years, the incidence of AML
slowly increases with age. Infants with congenital leukemia are
more likely to have AML than acute lymphoblastic leukemia (ALL). Although
the incidence of AML in children in the United States is approximately
7 cases per million children per year or approximately 600 new cases
per year, there is a slightly higher incidence in Hispanic children
of 9 per million per year. The incidence also appears slightly higher in
Japan, Australia, and Zimbabwe. Of note, the incidence of AML has
been increasing slightly although steadily.
The cause of AML is unknown, and most children have no known
predisposing factors. Known risk factors include exposure to high-dose
ionizing radiation, previous chemotherapy (especially with alkylating
agents and epipodophyllotoxins), Down syndrome, congenital bone
marrow failure syndromes (Diamond-Blackfan anemia and Kostmann agranulocytosis;
see Chapter 430), chromosome fragility and
impaired DNA repair mechanisms (such as Fanconi anemia), and inherited
disorders, such as neurofibromatosis type I (NF1), which is due
to mutations in neurofibromin, a RAS-directed GTPase (see Chapter 182). Children with NF1 are ...