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Blood, Vol. 93 No. 9 (May 1), 1999:
pp. 3140-3147
Prevention of Transfusion-Associated Graft-Versus-Host Disease by
Photochemical Treatment
Joshua A. Grass,
Tamim Wafa,
Aaron Reames,
David Wages,
Laurence Corash,
James L.M. Ferrara, and
Lily Lin
From the Cerus Corporation Concord, CA; the University of
Michigan Cancer Center Ann Arbor, MI; and the Baxter Healthcare
Corporation, Fenwal Division, Viral Inactivation, Round Lake, IL.
Photochemical treatment (PCT) with the psoralen S-59 and long
wavelength ultraviolet light (UVA) inactivates high titers of contaminating viruses, bacteria, and leukocytes in human platelet concentrates. The present study evaluated the efficacy of PCT to
prevent transfusion-associated graft-versus-host disease (TA-GVHD) in
vivo using a well-characterized parent to F1 murine
transfusion model. Recipient mice in four treatment groups were
transfused with 108 splenic leukocytes. (1) Control group
mice received syngeneic splenic leukocyte transfusions; (2) GVHD group
mice received untreated allogeneic splenic leukocytes; (3) gamma
radiation group mice received gamma irradiated (2,500 cGy) allogeneic
splenic leukocytes; and (4) PCT group mice received allogeneic splenic
leukocytes treated with 150 µmol/L S-59 and 2.1 J/cm2
UVA. Multiple biological and clinical parameters were used to monitor
the development of TA-GVHD in recipient mice over a 10-week posttransfusion observation period: peripheral blood cell levels, spleen size, engraftment by donor T cells, thymic cellularity, clinical
signs of TA-GVHD (weight loss, activity, posture, fur texture, skin
integrity), and histologic lesions of liver, spleen, bone marrow, and
skin. Mice in the control group remained healthy and free of detectable
disease. Mice in the GVHD group developed clinical and histological
lesions of TA-GVHD, including pancytopenia, marked splenomegaly,
wasting, engraftment with donor derived T cells, and thymic hypoplasia.
In contrast, mice transfused with splenic leukocytes treated with
(2,500 cGy) gamma radiation or 150 µmol/L S-59 and 2.1 J/cm2 UVA remained healthy and did not develop detectable
TA-GVHD. Using an in vitro T-cell proliferation assay, greater than
105.1 murine T cells were inactivated by PCT. Therefore, in
addition to inactivating high levels of pathogenic viruses and bacteria in PC, these data indicate that PCT is an effective alternative to
gamma irradiation for prevention of TA-GVHD.
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