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Blood, 15 July 2002, Vol. 100, No. 2, pp. 427-434
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Acute myeloid leukemia and myelodysplastic syndrome
in children treated for cancer: comparison with primary
presentation
Dorothy R. Barnard,
Beverley Lange,
Todd A. Alonzo,
Jonathan Buckley,
J. Nathan Kobrinsky,
Stuart Gold,
Steven Neudorf,
Jean Sanders,
Laura Burden, and
William G. Woods
From Dalhousie University, Halifax, NS; Children's
Hospital of Philadelphia, PA; Keck School of Medicine, University of
Southern California, Los Angeles; Roger Maris Cancer Center, Fargo, ND;
University of North Carolina, Chapel Hill; Children's Hospital Orange
County, Orange, CA; Fred Hutchinson Cancer Research Center, Seattle,
WA; Children's Oncology Group, Arcadia, CA; and Emory University,
Atlanta, GA.
There has not been a reported series of children with
therapy-induced myelodysplastic syndrome/acute myeloid leukemia
(tMDS/tAML) who were treated systematically. This paper describes 24 children with tMDS/tAML who were assigned randomly to standard- or
intensive-timing induction on protocol CCG 2891. Presenting features
and outcomes of those children were compared with those of 960 patients
with de novo MDS (62 patients) or AML (898 patients). Children with tMDS/tAML were older at presentation (P = .015), had
lower white blood cell counts (P = .01), and were more
likely to have MDS (21% vs 7%) (P = .02) and trisomy 8 (P = .06). Fewer had hepatomegaly (P = .02), splenomegaly (P = .03),
hepatosplenomegaly (P = .02), or classic AML
translocations [t(8;21), t(15;17), 16q22; P = .02]. They had a poorer induction rate (50% vs 72%,
P = .016), overall survival (26% vs 47% at 3 years,
P = .007), and event-free survival (21% vs 39% at 3 years, P =.023). Disease-free survival after achieving
remission was similar (45% vs 53%, P = .868). Children with tMDS/tAML who received intensive-timing induction had better outcomes than those who received standard-timing induction (overall survival 32% vs 0%, P = .54). In this study, the
latency period to development of tMDS/tAML was the same for presumed
alkylator-induced as for topoisomerase-induced myeloid leukemia. The
findings of this study confirm that most children with tMDS/tAML have
disease resistant to current therapies. Standard-timing induction
appears less effective for this population.
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