Late follow-up of genital and ophthalmologic chronic graft-vs-host disease in females after allogeneic stem cell transplantation.

INTRODUCTION: Genital chronic graft-vs-host disease (cGvHD) is a common late effect after allogeneic stem cell transplantation. In a previous cross-sectional study, prevalence, signs and symptoms of genital and extra-genital cGvHD were accounted for in a cohort of 42 women. Classifications of cGvHD were performed as per the National Institutes of Health (NIH) 2005 criteria. In this follow-up study on surviving women, the aim was to assess genital and extra-genital cGvHD status after long period of time. Our hypothesis was that signs and symptoms of cGvHD alleviate over time. MATERIAL AND METHODS: All surviving women (n = 38) were re-examined by an ophthalmologist, a gynecologist and a hematologist. Signs and symptoms were classified according to the NIH 2014 criteria. Clinical scorings of affected organs were combined for estimating global score of cGvHD. To make possible comparisons between the two studies, data from the original study were re-classified as per the NIH 2014 criteria, and the four dead women were excluded. The same questionnaires were completed. Cervical smear, human papilloma virus test and vulvar photo-documentation were performed. RESULTS: Median time after original study was 8.4 (5.8-12) years and after transplant 14.5 (10-19.3) years. The prevalence of genital cGvHD was similar in the original (50%) and follow-up (58%) studies (p = 0.646) as well as extra-genital cGvHD. Systemic corticosteroid treatment of cGvHD was ongoing in 34% and 29%, respectively (p = 0.805). Ocular cGvHD was found in 24 of 37 examined women (65%) in the follow-up study. Genital cGvHD had disappeared in three women and developed in two women 5-12 and 9-17 years, respectively, after transplantation. The severity of global cGvHD changed over time in 14 women, but was the same on group level (p = 0.345). Atrophic mucous membranes as in estrogen deficiency were seen in 66%. Three women had human papilloma virus genotypes associated with the risk of developing cervical cancer. CONCLUSIONS: Chronic GvHD did not alleviate over time. Allotransplanted women require early and continuous life-long contact with a gynecologist and an ophthalmologist for the detection of cGvHD. Specific attention should be given to the need for local estrogen and the risk of genital epithelial malignancies.

A prospective study of female genital chronic graft-versus-host disease symptoms, signs, diagnosis and treatment.

INTRODUCTION: Female genital chronic graft-versus-host disease (cGvHD) is a complication of allogeneic hematopoietic cell transplantation (alloHCT) for blood malignancies. Unattended inflammation and fibrosis in the vulva and vagina may lead to total vaginal stenosis. The course and treatment of genital cGvHD was observed in this population-based prospective study. MATERIAL AND METHODS: Women (n = 41) receiving alloHCT in 2005-10 were examined before and at 3, 6, 9, 12, 18, 24, 30 and 36 months post-transplant. Vulvovaginal signs were documented, National Institutes of Health clinical scores were calculated, and women completed questionnaires on symptoms, the Female Sexual Distress Scale and the Beck Depression Inventory. Local immunosuppressive treatment was given weekly. RESULTS: Genital cGvHD was diagnosed in 27 women (incidence 56% at 12 months; 66% at 36 months); extragenital cGvHD was found in 21/27. The most common signs at diagnosis were red and white spots, reticular white lines, fissures, synechiae and telangiectasia; symptoms included dryness, itching, dyspareunia, pain or no symptoms. Thirteen women were treated on a schedule of tacrolimus and clobetazol ointments. Although some signs progressed during treatment, only two women developed total stenosis. At 36 months, 12 women still had genital cGvHD. CONCLUSIONS: Genital cGvHD develops mainly in the first year after alloHCT. Early intervention may halt its progress to severe fibrosis, but despite correct diagnosis and treatment, symptoms and signs may become chronic. Women who develop genital cGvHD following alloHCT require life-long gynecological supervison and care.

Genital chronic graft-versus-host disease in females: a cross-sectional study.

Using the National Institutes of Health (NIH) consensus criteria for chronic graft-versus-host disease (cGVHD), we assessed the prevalence, symptoms, and clinical signs of female genital cGVHD in a cross-sectional population-based study. Forty-two women were evaluated at a median of 80 months (range, 13 to 148 months) after undergoing hematopoietic stem cell transplantation (HSCT). Medical history, ongoing medications, and genital signs and symptoms were recorded. Gynecologic examination for the diagnosis and clinical scoring of genital cGVHD was combined with clinical scoring of extragenital cGVHD for the estimation of each patient's global cGVHD score. Biopsy specimens from the genital mucosa were obtained from 38 patients. Genital cGVHD was diagnosed in 22 of 42 patients (52%). Its presence was associated with systemic corticoid steroid treatment of extragenital cGVHD (P = .001), older age (P = .07), and HSCT from a sibling donor (P = .002). Five patients had isolated genital cGVHD. Dryness, pain, smarting pain (P < .05 for all), and dyspareunia (P = .001) were observed more frequently in the women with genital cGVHD. Twelve patients had advanced genital cGVHD (clinical score 3), which was the main factor explaining the high rate (15 of 42) of severe global cGVHD. The rate of genital cGVHD was similar (P = .37) in patients with a follow-up of ≥80 months (10 of 22) and those with a follow-up of <80 months (12 of 20). We found no convincing relationship between clinical diagnosis and histopathological assessment of mucosal biopsy specimens. In our group of women with a long follow-up after HSCT, genital cGVHD was common and in many cases incorrectly diagnosed. Genital cGVHD causes genital symptoms and affects sexual life, and may present without any other cGVHD, warranting early and continuous gynecologic surveillance in all women after HSCT.

Partially erupted third molars as a potential source of infection in patients receiving peripheral stem cell transplantation for malignant diseases: a retrospective study.

Forty-four patients with malignant diseases for which they received peripheral stem cell transplant therapy (PSCT) were retrospectively studied regarding local and systemic infection originating from around partially erupted third molars (PEMs). Twenty-two patients had one or more PEMs, while 22 patients had none. Data were retrieved from medical and dental records. Systemic and local signs of infection and treatment were assessed. We recorded the number of transplanted CD34(+) blood stem cells, days with white blood cell counts < 0.5 x 10(9) l(-1), days until engraftment, maximum level of C-reactive protein (CRP), days with fever, positive blood cultures, days taking antibiotics, days drinking < 0.5 l, days of total parenteral nutrition, days receiving intravenously administered analgesics, and number of admission days. No statistically significant difference was detected between patients with PEMs and those without PEMs regarding any of the studied parameters. Of patients with PEMs, 36% (8 of 22) developed local infections around PEMs during the PSCT period. The study indicates that PEMs pose no significant risk of causing systemic infection in patients receiving PSCT for malignant diseases but increase the risk of developing a local infection, justifying close supervision and early treatment in cases of local infection during PSCT treatment.