Supplementary Material for: Photochemotherapy of Cutaneous Graft-versus-Host Disease May Reduce Concomitant Visceral Disease

Background: Photochemotherapy may be used to treat cutaneous graft-versus-host disease (GvHD). Animal models show that in the days after photochemotherapy and antigen provocation, cells with an antigen-specific suppressive phenotype are elicited in the lymphoid organs. In GvHD, host antigens are present not only in the skin treated by photochemotherapy but also in the visceral tissues. Objective: The aim of this paper was to evaluate the effect on visceral acute GvHD (aGvHD) of photochemotherapy of the skin. Methods: We retrospectively evaluated 33 patients with aGvHD of the skin, the liver, and/or the gastrointestinal tract treated with photochemotherapy for their aGvHD of the skin and did a long-term follow-up of 10 years on survival. Results: The complete response (CR) to photochemotherapy was 39%, the complete and partial response was 64% and the 6-month survival was 64%. Total body irradiation (TBI) before hematopoietic stem cell transplantation predisposed for CR of aGvHD of the liver and the gastrointestinal tract (p = 0.045). In the TBI group, the accumulated dose (numbers of treatments) for CR of visceral aGvHD increased with the body surface area affected by disease, from 8 (min-max: 5-14) for skin disease stage 1 to 10.5 (6-33) for stage 2 and 13 (11-21) for stage 3 (p = 0.04). Skin disease stage 1 showed a trend to be associated with CR in visceral disease at 28, 56, and 100 days (p = 0.07). Overall CR in visceral disease predicted a better 10-year overall survival (p = 0.0036). Finally, after TBI aGvHD of the gastrointestinal tract without anti-thymocyte globulin (ATG), clearance of T cells and dendritic cells responded better than aGvHD of the liver and aGvHD of the gastrointestinal tract with ATG (p = 0.01). Conclusion: Photochemotherapy after ionizing irradiation regulates the cell-mediated immunity in the viscera, and the systemic efficacy increases when the skin itself is less affected by disease. ATG modulates the regulatory effect of the gastrointestinal tract.研究背景：光化学疗法（photochemotherapy）可用于治疗皮肤移植物抗宿主病（cutaneous graft-versus-host disease, GvHD）。动物模型研究显示，在光化学疗法与抗原激发后的数日内，淋巴器官中可诱导出抗原特异性抑制表型的细胞。在移植物抗宿主病中，宿主抗原不仅存在于接受光化学疗法治疗的皮肤组织中，也存在于内脏组织中。 研究目的：本研究旨在评估皮肤光化学疗法对内脏急性移植物抗宿主病（visceral acute graft-versus-host disease, aGvHD）的治疗效果。 研究方法：我们回顾性分析了33例因皮肤急性移植物抗宿主病接受光化学疗法治疗的患者，这些患者同时合并肝脏、胃肠道的急性移植物抗宿主病，并对其进行了长达10年的生存随访。 研究结果：皮肤光化学疗法的完全缓解（complete response, CR）率为39%，完全缓解联合部分缓解率为64%，6个月生存率为64%。造血干细胞移植前接受全身照射（total body irradiation, TBI）的患者，其肝脏与胃肠道急性移植物抗宿主病的完全缓解率更高（p=0.045）。在接受全身照射的患者中，内脏急性移植物抗宿主病达到完全缓解所需的累计治疗次数随受累体表面积增加而升高：皮肤病变1期患者为8次（最小值-最大值：5~14），2期患者为10.5次（6~33），3期患者为13次（11~21），差异具有统计学意义（p=0.04）。皮肤病变1期患者在第28、56、100天时的内脏病变完全缓解率呈现升高趋势（p=0.07）。内脏病变的整体完全缓解可预测更好的10年总生存率（p=0.0036）。最后，在接受全身照射且未使用抗胸腺细胞球蛋白（anti-thymocyte globulin, ATG）的胃肠道急性移植物抗宿主病患者中，经T细胞与树突状细胞清除治疗的亚组，其治疗反应优于使用抗胸腺细胞球蛋白的肝脏急性移植物抗宿主病及胃肠道急性移植物抗宿主病患者（p=0.01）。 研究结论：电离辐射后的光化学疗法可调节内脏的细胞介导免疫反应，且当皮肤本身受累程度较轻时，其全身治疗效果更佳。抗胸腺细胞球蛋白可调节胃肠道的免疫调节效应。