Improvement of signs and symptoms of vulvovaginal chronic graft-versus-host disease with non-ablative radiofrequency therapy

Abstract Introduction: Chronic graft-versus-host disease (cGVHD) is a major cause of late morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). Gynecological complications following allo-HCT include female vulvovaginal cGVHD, premature ovarian insufficiency, and genital atrophy. Non-ablative radiofrequency (NARF) therapy has documented beneficial effects on oral and skin cGVHD and genital atrophy, but there are no reports of its use in vulvovaginal manifestations of chronic GVHD. Our aim wasto report a case series using NARF in female patients genital cGVHD. Methods: Data were retrieved from electronic medical records of patients who underwent allo-HCT from 2005 to 2023. We included female patients diagnosed with cGVHD according to the 2014 National Institutes of Health (NIH) Consensus Criteria with vulvovaginal involvement along with or without vulvovaginal atrophy. These patients were treated with at least three NARF sessions from January 2019 to June 2024. The device used was Tonederm®, with intervals of 30 to 45 days and a temperature of 40 to 45°C (vagina) and 35°C (vulvar region). Results:Ten patients with a median age of 42 years (range 37-51) were included. Of these, nine patients had received an HLA-identical sibling donor and one a matched unrelated donor graft. The primary cell source was peripheral blood (8/10) followed by bone marrow (2/10). The conditioning regimen intensity was myeloablative in 6/10 cases, reduced intensity in 3/10, and unknown in 1/10. The GVHD prophylaxis used in 9/10 cases was calcineurin inhibitor and methotrexate, and only one patient received post-transplant cyclophosphamide-based prophylaxis. Regarding vulvovaginal cGVHD at the time of the first session of NARF, 1/10 patients had an NIH genital score of 1, 5/10 had a score of 2, and 4/10 had a score of 3. Nine out of 10 patients underwent three sessions of therapy, while 1/10 received 4 sessions. Regarding systemic therapy, 6/9 patients received concomitant systemic immunosuppressive therapy, while all patients received topical hormonal therapy concurrently with NARF therapy. After three or four NARF therapy sessions, 5/10 patients improved from NIH score 2 to 1, 2/10 patients from 3 to 2, 2/10 patients from 3 to 1, and 1/10 maintained an NIH score of 2. Regarding adverse effects, one patient experienced a local thermal injury just in her last session and another presented genital herpes simplex reactivation; the remaining eight patients did not have adverse side effects attributable to the therapy. Conclusion:NARF therapy for vulvovalginal cGVHD appears to be promising. Prospective studies are needed to ascertain the efficacy and safety of this therapy modality.