Blood, Vol. 92 No. 3 (August 1), 1998:
pp. 765-769
RAPID COMMUNICATION
FLT-3 Ligand Provides Hematopoietic Protection From Total Body
Irradiation in Rabbits
A. Gratwohl,
L. John,
H. Baldomero,
J. Roth,
A. Tichelli,
C. Nissen,
S.D. Lyman, and
A. Wodnar-Filipowicz
From the Division of Hematology, the Department of Research,
Hematology Laboratory, and the Department of Radiation Physics,
Kantonsspital, Basel, Switzerland; and Immunex Corp, Seattle, WA.
Several hematopoietic cytokines have been investigated for their
potential to provide protection from the lethal consequences of bone
marrow aplasia after total body irradiation (TBI). Some can increase
the dose of irradiation tolerated by the animals; none allow endogenous
recovery after doses such as administered in clinical blood or marrow
transplantation. We tested the radioprotective potential of FLT-3
ligand, an early acting hematopoietic cytokine, alone and in
combination with a late acting cytokine, granulocyte-colony stimulating
factor (G-CSF). Adult outbred New Zealand White rabbits were submitted
to TBI of 1,200 or 1,400 cGy by a Co60 source. Recombinant
human (rh) FLT-3 ligand at a dose of 500 µg/kg and/or rhG-CSF
at a dose of 10 µg/kg were administered for 14 days subcutaneously daily, beginning either 2 days before or the day after TBI. All control
animals given no growth factors died of aplasia at day 10 (range, 5 to
16). All 8 animals given G-CSF had severe aplasia and 7 died at day 8 (range, 5 to 10); 1 animal survived, with G-CSF being administered
before TBI. In contrast, 11 of 12 animals given FLT-3 ligand, with or
without G-CSF, survived. Radioprotection was best in the group given
FLT-3 ligand together with G-CSF before TBI. In these animals median
platelet counts were never <10 × 109/L and median white
blood cell counts never <0.5 × 109/L. These data show
that hematopoietic recovery can occur after 1,400 cGy TBI in rabbits,
if protected by FLT-3 ligand, and suggest a radioprotective clinical
potential of this cytokine.
© 1998 by The American Society of Hematology.
