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Distinctive Demography, Biology, and Outcome of Acute
Myeloid Leukemia and Myelodysplastic Syndrome in Children With Down
Syndrome: Children's Cancer Group Studies 2861 and 2891
Beverly J. Lange,
Nathan Kobrinsky,
Dorothy R. Barnard,
Diane C. Arthur,
Jonathan D. Buckley,
William B. Howells,
Stuart Gold,
Jean Sanders,
Steven Neudorf,
Franklin O. Smith, and
William G. Woods
From The Children's Hospital of Philadelphia and the University of
Pennsylvania School of Medicine, Philadelphia PA; the Children's
Cancer Group, Arcadia, CA; Roger Maris Cancer Center, Fargo, ND; Izaak
W. Killam Hospital for Children, Halifax, Nova Scotia, Canada;
University of Minnesota, Minneapolis, MN; University of Southern
California School of Medicine, Los Angeles, CA; University of North
Carolina, Chapel Hill, NC; Fred Hutchinson Cancer Research Center,
Seattle, WA; Children's Hospital of Pittsburgh, Pittsburgh, PA; and
Riley Hospital for Children, Indianapolis, IN.
In recent pediatric trials of acute myeloid leukemia (AML), children
with Down syndrome (DS) have had significantly more megakaryoblastic leukemia and have experienced better outcome than other children. To
further characterize AML in DS, Children's Cancer Group Studies 2861 and 2891 prospectively studied demography, biology, and response in AML
and myelodysplastic syndrome (MDS) of children with and without DS.
These studies evaluated timing of induction therapy and compared
postremission chemotherapy with marrow transplantation in 1,206 children. One-hundred eighteen (9.8%) had DS, a fourfold increase in
20 years. DS patients were younger, had lower white blood cell and
platelet counts, more antecedent MDS, acute megakaryoblastic leukemia
or undifferentiated AML, and an under-representation of chromosomal
translocations (P < .001 for each variable). Four-year event-free survival in DS was 69% versus 35% in others (P < .001). Intensively timed induction conferred significantly higher
mortality in DS patients; bone marrow transplantation offered no
advantage. Conventional induction followed by chemotherapy achieved an
88%, 4-year, disease-free survival in DS patients versus
42% in others (P < .001). Megakaryoblastic
leukemia was unfavorable in others but prognostically neutral in DS.
AML in DS is demographically and biologically distinct from AML in
other children. It is singularly responsive to conventional
chemotherapy and may warrant even less therapy. The increasing
proportion of DS patients with AML most likely reflects changes in
attitudes about entering DS patients on AML trials and possibly
increasing ability to distinguish megakaryoblastic leukemia from
lymphoid leukemia.
Blood, Vol. 91 No. 2 (January 15), 1998:
pp. 608-615
© 1998 by The American Society of Hematology.
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