Blood, 15 May 2003, Vol. 101, No. 10, pp. 3759-3759
Small steps to improve outcome in ALL
Small steps for small kids can result in big leaps. Advancing
by incremental steps in the past 40 years, the curability of childhood
acute lymphoblastic leukemia (ALL) stands as one of modern medicine's
crowning achievements. For children with standard-risk ALL, a cure can
be obtained in more than 80% of the cases. This achievement poses 2 difficult questions: (1) How can we reach 100%? (2) How can we
improve on the worse prognosis for adolescents and adults? The answer
is simply to perform well-designed, narrowly focused randomized
clinical trials built upon previous regimens and to follow the
protocols religiously.
In this issue, Bostrom and colleagues (page 3809) report a Children's
Cancer Group (CCG) trial for children with standard-risk ALL. Two
hypotheses were posed: substitution of dexamethasone for prednisone
reduces central nervous system (CNS) relapse, and the
substitution of intravenous for oral administration of 6-mercaptopurine improves event-free survival by improving drug bioavailability. While
the second hypothesis was not supported, the first was. Dexamethasone
was associated with a 50% reduction in the incidence of CNS relapse
and an increase in the 6-year event-free survival from 77% to
85%. Overall toxicity was comparable, although myopathy and
hyperglycemia were increased in the dexamethasone group. Most patients,
parents, and oncologists would gladly tolerate these side effects in
lieu of leukemic relapse. Results may have been biased in favor of
dexamethasone because its dose was not bioequivalent to prednisone. The
strengths of this study were that the study population was large (more
than 1000 patients), it was built on previous CCG ALL protocols, it
incorporated new strategies based on smaller studies, and it was
hypothesis driven. Now, investigators can move on and ask whether
another of the antileukemic drugs can be better used or whether a new
agent can be added to the old.
Seth J. Corey
M. D. Anderson Cancer
Center
