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In vitro and in vivo effects of deferoxamine in neonatal acute leukemia
Z Estrov, A Tawa, XH Wang, ID Dube, H Sulh, A Cohen, EW Gelfand and MH Freedman
A six week old infant with acute leukemia failed to attain remission with
chemotherapy. Because we previously demonstrated that the iron chelator
deferoxamine (DFO) has antiproliferative properties and modulatory effects
on cell differentiation, a protocol was designed for in vitro study and for
clinical use in the patient. At diagnosis, blast cells were morphologically
undifferentiated, had nondiagnostic cytochemistry, showed an abnormal
karyotype (t[4;11]), expressed markers of B cell lineage, and demonstrated
C mu gene rearrangement. Tissue culture of marrow or blood cells yielded
colonies of leukemic blasts. Increasing concentrations of DFO produced a
dose-dependent suppression of patient's blast colony growth in vitro, and
blasts within colonies showed a marked change in surface antigen expression
from lymphoid to myelomonocytic markers, became monocytic in appearance,
and developed intense staining for nonspecific esterase. When DFO was given
intravenously to the patient as a single agent for 48 hours, blasts no
longer expressed lymphoid antigens and became strongly positive for
myelomonocytic markers, identical to the in vitro findings. Intravenous DFO
halted rising peripheral blood blast cell numbers and allowed a
several-fold increase in normal hematopoietic progenitor colony growth.
When combined with low-dose cytosine arabinoside in the treatment protocol,
DFO caused striking leukemic cytoreduction. Our findings indicate that DFO
has antileukemic properties by virtue of its effects on proliferation and
differentiation, and they prompt further experimental and clinical studies
with this agent.
Volume 69,
Issue 3,
pp. 757-761,
03/01/1987
Copyright © 1987 by The American Society of Hematology
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