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Inactivation of Leukocytes in Platelet Concentrates by Photochemical
Treatment With Psoralen Plus UVA
Joshua A. Grass,
Derek J. Hei,
Ken Metchette,
George D. Cimino,
Gary P. Wiesehahn,
Laurence Corash, and
Lily Lin
From the Cerus Corp, Concord, CA.
A photochemical treatment (PCT) process using a novel psoralen and
long wavelength ultraviolet light (UVA, 320-400 nm) has been developed
to inactivate bacteria and viruses in platelet concentrates. This study evaluated the efficacy of PCT for
inactivation of leukocytes that contaminate platelet preparations.
Three psoralens, 8-methoxypsoralen (8-MOP), 4 -aminomethyl
4,5,8-trimethylpsoralen (AMT), and the novel psoralen S-59, were
compared using the following four independent but complementary
biological and molecular assays. (1) T-cell viability: Treatment with
150 µmol/L S-59 and 1.0 to 3.0 Joules/cm2 UVA inactivated
>5.4 ± 0.3 log10 of T cells in full-sized single-donor plateletpheresis units. Using 1.0 Joule/cm2 UVA, the lowest
dose of S-59, AMT and 8-MOP required to reduce the number of T cells to
the limit of detection was 0.05 µmol/L, 1.0 µmol/L, and 10.0 µmol/L, respectively. (2) Cytokine synthesis: Treatment with 1.9 Joules/cm2 UVA and 150 µmol/L S-59 or AMT completely
inhibited synthesis of the cytokine IL-8 by contaminating leukocytes
during 5 days of platelet storage. After treatment with 75 µmol/L
8-MOP and 1.9 Joules/cm2 UVA, only low levels of IL-8 were
detected. (3) Psoralen-DNA adduct formation: The combination of 1.9 Joules/cm2 UVA and 150 µmol/L S-59, AMT, or 8-MOP induced
12.0 ± 3.0, 6.0 ± 0.9, and 0.7 psoralen adducts per 1,000 bp DNA,
respectively. (4) Replication competence: Polymerase chain reaction
(PCR) amplification of small genomic DNA sequences (242-439 bp) after
PCT was inhibited. The degree of PCR amplification inhibition
correlated with the level of adduct formation
(S-59 > AMT > 8-MOP). In contrast, 2,500 cGy gamma radiation, a
dose that inactivates >5 log10 of T cells in blood
products, had minimal effect on cytokine synthesis and did not induce
sufficient DNA strand breaks to inhibit PCR amplification of the same
small DNA sequences. These results demonstrate that leukocytes are
sensitive to PCT with psoralens and among the psoralens tested S-59 is
the most effective. Therefore, PCT has the potential to reduce the
incidence of leukocyte-mediated adverse immune reactions associated
with platelet transfusion.
Blood, Vol. 91 No. 6 (March 15), 1998:
pp. 2180-2188
© 1998 by The American Society of Hematology.
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