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.

Background: Cure of acute leukemia after transplantation is mediated by the grafted cells. We investigated the graft-versus-leukemia effect (GVL) in patients with cutaneous acute graft-versus-host disease (GVHD) treated with photochemotherapy (psoralen and ultraviolet light type A). Method: Forty-seven patients with acute leukemia were followed 5,000 days after transplantation to assess survival and GVL by multivariate analysis. The primary predictor was time to treatment of cutaneous acute GVHD by photochemotherapy separated into treatment start during the first week of acute GVHD versus after the first week of acute GVHD. Results: Photochemotherapy started after the first week of acute GVHD predicted GVL with a hazard ratio (HR) of 3.94 (95% confidence interval, CI, 1.67-9.33, p = 0.0018) and survival with preserved GVL with an HR of 2.63 (95% CI 1.30-5.32, p = 0.007). The effects on GVL and survival with preserved GVL were present regardless of whether the patients were transplanted in remission or relapse (p < 0.05). Chronic GVHD came earlier in the group that started photochemotherapy after 1 week of acute GHVD, but chronic GVHD did not increase the GVL. Conclusion: The timing of photochemotherapy after cutaneous acute GVHD may direct the GVL and predict long-term leukemia-free survival.

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