Photochemotherapy of Cutaneous Graft-versus-Host Disease May Reduce Concomitant Visceral Disease

Abstract

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.

Photochemotherapy and Graft-versus-Leukemia Reaction in Acute Leukemia: Tumor Immunity and Survival Are Dependent on Timing of Photochemotherapy of the Skin

“…This is supported by our previous report of patients with acute GVHD both in the skin and viscera, where the time to treatment by photochemotherapy after acute-GVHD diagnosis was a median 21 days (interquartile range 12-28, min.-max. 1-43 days), in the group of patients who reached CR of acute GVHD of the liver and the gastrointestinal channel, a CR that was associated with conditioning with TBI and long-term survival [27]. In the present report, no adverse synergy of TBI on tumor immunity was found.…”

“…In mice, photochemotherapy may suppress DTH in the skin distant from the area treated, and this distant effect may be blocked by ketanserin, an unspecific serotonin inhibitor, which blocks the migration of not only mast cells [25], but also the dendritic cell migration and T-cell priming [26]. Yet, the systemic effect of photochemotherapy remains disputed, and the mediation thereof is not clearly chartered, but we have found that photochemotherapy of the skin may suppress acute GVHD of the internal organs in patients who had received total body irradiation (TBI) [27]. The experimental acute-GVHD reaction and the DTH reaction may both elicit effector cells within a week [28], and a week is what is needed to induce GVL in animal models [29,30].…”

Xanthotoxin (8‐methoxypsoralen): A review of its chemistry, pharmacology, pharmacokinetics, and toxicity

“…PUVA not only interferes with DNA synthesis and affects fibroblast activity (Cruz, Guecheva, Bonato, & Henriques, 2012; Wang, Liu, Gu, & Zhang, 2011), but also scavenges ROS through malate dehydrogenase (MD), succinate dehydrogenase (SD), and ubiquitin oxidoreductase thereby protecting normal cells. In general, photochemotherapy represented by PUVA is one of the more effective ways to treat skin diseases (Feldreich, Ringden, Emtestam, & Omazic, 2016).…”

Ultraviolet phototherapy for treatment of various dermatoses

“…However, the evidence are limited to retrospective studies or case reports (LoE IV), thus there are no phototherapy guidelines for these dermatoses. [67][68][69][70][71][72]…”