Prevalence of genital graft-versus-host disease after allogeneic stem cell transplantation

Objectives: Chronic Graft-versus-Host Disease (cGvHD) is a recognized but unsatisfactorily described cause of genital complications in female patients after allogeneic stem cell transplantation (SCT). In a population-based study, we have assessed the prevalence, clinical features and histopathology of genital cGvHD. Methods: All women alive after allo-SCT 1996-2005 (n=53) in the Western region of Sweden were invited to participate in a study comprising (i) gynaecological examination including photo-documentation for the clinical diagnosis of genital cGvHD, (ii) biopsies for pathological examination and (iii) structured anamnesis and validated questionnaires for assessment of depression and sexual dysfunction. To exclude estrogen deficiency, all pts recevied local estrogen before cGvHD diagnosis. Results: Of 53 consecutive pts, 44 (83%) were examined with a minimal follow-up of 3 years post-transplant. Median age was 47 (26-72) yrs and post-SCT 6 (3-12) yrs. Symptoms of genital cGvHD included dryness, smart, pain and dyspareunia; signs were dry, thin, sore mucosa, local white and red spots, lichenoid patterns, synechiae, stenosis and painful vaginal strings. Clinical signs were categorized as probable, possible or unlikely cGvHD. Probable genital cGvHD was diagnosed in 17 pts (39%) of whom 13 had vaginal stenosis or adhesions and 3 women had vulvar synechiae. Possible cGvHD was observed in another 14 pts. Biopsies were obtained from 34 pts and histopathological diagnosis of cGvHD was made in accordance with NIH criteria (ref). Histopathological findings included lichenoid inflammation, epithelial apoptosis, ulceration and fibrosis. The clinical diagnosis of probable cGvHD was confirmed as probable or possible in biopsies of 15/17 cases, whereas in the group of pts clinically cathegorized as possible cGvHD 8/14 were graded as probable or possible. Depression as assessed by Beck Depression Inventory and sexual dysfunction as estimated by Female Sexual Distress Scale were established in 29% and 45% of pts, respectively. Conclusion: The prevalence of genital cGvHD after allo-grafting is unexpectedly high and appears to be associated with sexual dysfunction and mental depression. We hypothesize that early gynecological intervention may reduce the risk of severe symptoms and sequelae, and propose that gynecological expertise should be part of the team around the allografted woman.