Grass J A, Wafa T, Reames A, Wages D, Corash L, Ferrara J L, Lin L
Cerus Corporation Concord, CA; the University of Michigan Cancer Center Ann Arbor, MI, USA.
Blood. 1999 May 1;93(9):3140-7.
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 10(8) 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 micromol/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 micromol/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 10(5.1) 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.
使用补骨脂素S - 59和长波紫外线（UVA）进行光化学处理（PCT）可使人类血小板浓缩物中高滴度的污染病毒、细菌和白细胞失活。本研究使用特征明确的亲代到F1代小鼠输血模型评估了PCT在体内预防输血相关移植物抗宿主病（TA - GVHD）的效果。四个治疗组的受体小鼠均输注10⁸个脾白细胞。（1）对照组小鼠接受同基因脾白细胞输血；（2）GVHD组小鼠接受未处理的异基因脾白细胞；（3）γ射线辐射组小鼠接受γ射线照射（2500 cGy）的异基因脾白细胞；（4）PCT组小鼠接受用150 μmol/L S - 59和2.1 J/cm² UVA处理的异基因脾白细胞。在输血后10周的观察期内，使用多种生物学和临床参数监测受体小鼠TA - GVHD的发展情况：外周血细胞水平、脾脏大小、供体T细胞植入情况、胸腺细胞数量、TA - GVHD的临床体征（体重减轻、活动、姿势、皮毛质地、皮肤完整性）以及肝脏、脾脏、骨髓和皮肤的组织学病变。对照组小鼠保持健康且未发现疾病。GVHD组小鼠出现了TA - GVHD的临床和组织学病变，包括全血细胞减少、明显的脾肿大、消瘦、供体来源T细胞植入以及胸腺发育不全。相比之下，输注经（2500 cGy）γ射线辐射或150 μmol/L S - 59和2.1 J/cm² UVA处理的脾白细胞的小鼠保持健康，未出现可检测到的TA - GVHD。使用体外T细胞增殖试验，PCT可使超过10⁵·¹个小鼠T细胞失活。因此，除了使血小板浓缩物中的高水平致病病毒和细菌失活外，这些数据表明PCT是预防TA - GVHD的γ射线辐射的有效替代方法。
