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What Is the Optimal Therapy for Childhood AML?

What Is the Optimal Therapy for Childhood AML?

The past 30 years have seen tremendous advances in the treatment of pediatric
leukemia. What was once an invariably fatal diagnosis is now quite curable in
close to 80% of cases. Unfortunately for children with acute myelogenous
leukemia (AML), most of these developments have been in the treatment of acute
lymphoblastic leukemia (ALL); even today, nearly half of all children diagnosed
with AML will die of the disease.

In their excellent and comprehensive article, Loeb and Arceci review the
current state of therapies for pediatric AML throughout the world, summarizing
the approaches taken by the various major cooperative groups. In essence, these
strategies have involved the intensification of either the dosages or timing of
the few chemotherapeutic agents active against AML.

Distinct Disease Entities

Several themes running through the review are worth emphasizing. First, it
has become increasingly clear that, despite their common CD34-positive
hematopoietic stem cell origin, AML and ALL are biologically quite distinct, and
the successful treatment of AML hinges upon differing treatment strategies than
those used for ALL. While ALL initially responds rapidly to a number of agents,
even when they are used alone, AML is resistant to all but a few drugs. Whereas
regimens involving intensive but short remission induction and consolidation
phases and prolonged low-intensity maintenance cycles have been effective in the
treatment of ALL, this approach has not been successful in the treatment of AML.

Rather, it was found in early Children’s Cancer Group (CCG) studies that
survival was significantly improved by intensive but short courses of therapy,
when directly compared against prolonged ALL-style maintenance treatments.[1] In
fact, it was later shown in the Medical Research Council (MRC) AML9 study that
extended maintenance therapy might be detrimental to survival because of
protracted periods of immunosuppression.[2]

Timed Sequential Therapy

In contrast to the rapid proliferation characteristic of ALL blasts, the
percentage of AML cells in cycle is typically quite low because of the presence
of a secreted hematopoietic inhibitory factor. This factor is no longer present
following a single cycle of chemotherapy but is replaced by a factor that
stimulates proliferation.[3] These insights into the biology of AML led the CCG
to adopt "timed sequential therapy" as its overall strategy in the
treatment of AML, the second major theme of this review.

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