Tajana Klepac Pulanic

Female Long-Term Survivors After Allogeneic Hematopoietic Stem Cell Transplantation: Evaluation and Management

Female long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) incur a significant burden of late effects. Genital graft-versus-host disease (GVHD), human papillomavirus (HPV) reactivation, ovarian failure and infertility, sexual dysfunction, and osteoporosis are concerns that can significantly impact quality of life. This review examines the risk, pathogenesis, clinical presentation, and implications of these common complications. Recommendations are provided for evaluation and management of these late effects and other obstetric and gynecologic issues that may arise in this patient population.

Magnetic Resonance Imaging–guided Volumetric Ablation of Symptomatic Leiomyomata: Correlation of Imaging with Histology

PURPOSE To describe the preliminary safety and accuracy of a magnetic resonance (MR) imaging-guided high-intensity-focused ultrasound (HIFU) system employing new technical developments, including ablation control via volumetric thermal feedback, for the treatment of uterine leiomyomata with histopathologic correlation. MATERIALS AND METHODS In this phase I clinical trial, 11 women underwent MR-guided HIFU ablation (Sonalleve 1.5T; Philips Medical Systems, Vantaa, Finland), followed by hysterectomy within 30 days. Adverse events, imaging findings, and pathologic confirmation of ablation were assessed. The relationship between MR imaging findings, thermal dose estimates, and pathology and HIFU spatial accuracy were assessed using Bland-Altman analyses and intraclass correlations. RESULTS There were 12 leiomyomata treated. No serious adverse events were observed. Two subjects decided against having hysterectomy and withdrew from the study before surgery. Of 11 women, 9 underwent hysterectomy; all leiomyomata demonstrated treatment in the expected location. A mean ablation volume of 6.92 cm(3) ± 10.7 was observed at histopathologic examination. No significant differences between MR imaging nonperfused volumes, thermal dose estimates, and histopathology ablation volumes were observed (P > .05). Mean misregistration values perpendicular to the ultrasound beam axis were 0.8 mm ± 1.2 in feet-head direction and 0.1 mm ± 1.0 in and left-right direction and -0.7 mm ± 3.1 along the axis. CONCLUSIONS Safe, accurate ablation of uterine leiomyomata was achieved with an MR-guided HIFU system with novel treatment monitoring capabilities, including ablation control via volumetric thermal feedback.

Human papillomavirus reactivation following treatment of genital graft-versus-host disease.

Vaginal chronic graft‐versus‐host disease (cGVHD) is a common complication of stem cell transplantation. Human papillomavirus (HPV) disease can reactivate after transplantation, presumably because of immune factors affecting systemic immunity, such as waning antibody titers, impaired T‐ and B‐lymphocyte responses, and the use of immunosuppressive therapies. However, a relationship between the use of local immunosuppressive agents and HPV reactivation and spread has not been previously described, to our knowledge. A 30‐year‐old woman, 2 years post transplant receiving systemic cyclosporine for cGVHD, was treated with vaginal dilators, topical corticosteroids, and estrogen for vaginal cGVHD. Colposcopy and biopsy for abnormal cytology revealed condylomatous cervicitis. Over the next 4 months, while continuing dilator therapy, linear verrucous lesions developed in the vagina and vulva, and were successfully treated with laser therapy. Use of local immunosuppression and dilators for genital GVHD can enhance spread of HPV infection. Integration of HPV screening and treatment into the care of women with genital cGVHD and development of strategies to manage both conditions simultaneously are warranted.

High frequency of cutaneous manifestations including vitiligo and alopecia areata in a prospective cohort of patients with chronic graft-vs-host disease.

Aim To determine the frequency and the characteristics of cutaneous manifestations, especially vitiligo and alopecia areata, in patients with chronic graft-vs-host disease (cGVHD). Methods 50 patients with cGVHD were prospectively enrolled in the observational study protocol and evaluated by an experienced dermatologist. The evaluation was focused on the clinical spectrum of skin and adnexal involvement, and the cutaneous GVHD score was determined according to National Institutes of Health (NIH) Consensus criteria. The presence of vitiligo, alopecia, xerosis, nail changes, and dyspigmentation was also assessed. Results Out of 50 cGVHD patients, 28 (56%) had skin involvement, and 27 of them (96%) had hypo and/or hyperpigmentations. 11 patients (39%) had a mild cutaneous NIH cGVHD score, 22% moderate, and 39% severe. 15 (30%) patients had nail changes and 10 (20%) had vitiligo or alopecia areata. Univariate analysis showed that patients with vitiligo/alopecia areata received more lines of prior systemic immunosuppressive therapy (P = 0.043), had lower Karnofsky performance status (P = 0.028), and had a higher B-cell number (P = 0.005), platelet count (P = 0.022), and total protein (P = 0.024). Vitiligo and alopecia areata were associated with higher NIH skin score (P = 0.001), higher intensity of immunosuppressive treatment (P = 0.020), and total body irradiation conditioning (P = 0.040). Multivariate regression model showed that patients with higher NIH skin scoring were 3.67 times more likely to have alopecia and/or vitiligo (odds ratio 3.67; 95% confidence interval 1.26-10.73), controlled for all other factors in the model (age at study entry, number of B-cells, platelet count, and global NIH score). Conclusion These data indicate that vitiligo and alopecia areata occur more frequently in cGVHD than previously reported.

High prevalence of small- and large-fiber neuropathy in a prospective cohort of patients with moderate to severe chronic GvHD

High prevalence of small- and large-fiber neuropathy in a prospective cohort of patients with moderate to severe chronic GvHD

Treatment of Multifocal Bowen’s Disease in Immunocompromised Women With Surgery and Topical Imiquimod

BACKGROUND: In human immunodeficiency virus (HIV)-infected women, Bowens disease may be difficult to treat successfully with surgery alone. Imiquimod cream, effective in treating Bowens disease in healthy women, may be a useful postsurgical treatment in immunocompromised women. CASES: Two HIV-infected women had both Bowens disease and severe cervical dysplasia. In both cases, Bowens disease, but not cervical dysplasia, recurred after surgical treatment. When treated with topical 5% imiquimod cream twice weekly for 4 months, 70–80% reduction in lesions were observed in both patients. Follow-up biopsies of remaining lesions were vulvar intraepithelial neoplasia 1. CONCLUSION: Imiquimod cream, in combination with surgical treatment, may be an appropriate strategy for treatment of Bowens disease in HIV-infected and other immunocompromised women.

Early Diagnosis of Labial Fusion in Women After Allogeneic Hematopoietic Cell Transplant Enables Outpatient Treatment

Objective The aim of the study was to describe the presentation and successful treatment of labial fusion in women after allogeneic hematopoietic cell transplantation (HCT). Materials and Methods During routine posttransplant gynecologic evaluation, labial fusion was identified in 5 female patients. Clinical data were collected regarding underlying disease, transplant regimen, genital symptoms, systemic sites of chronic graft-versus-host disease (cGvHD) and treatment, and follow-up. Results At presentation, women had a median age of 40 years (range = 35–50) and were 23-month to 8-year post-HCT. Four of the 5 patients with labial fusion had evidence of active cGvHD; 3 patients had severe sclerotic cGvHD, and 1 patient had bronchiolitis obliterans. One had rheumatoid arthritis and had recently stopped taking etanercept, but had no sites of cGvHD. One patient presented with only a pinpoint opening for passage of urine. Her complete labial fusion was lysed under general anesthesia. Three of the 4 others presented with dyspareunia. Their labia were fused between the clitoris and urethra narrowing the vaginal opening without obstructing the urethra. These labial adhesions were successfully lysed during an office procedure. Once the labial mucosa healed, the patients applied topical clobetasol and estrogen to prevent reagglutination. On follow-up, 1 month to 1 year later, all women were significantly improved. Conclusions These patients highlight the importance of asking women who have undergone allogeneic HCT, especially those with severe cGvHD, about dyspareunia and dysuria. Those with genital symptoms warrant referral to a gynecologist. These cases illustrate that labial fusion, if diagnosed early enough, may be treated successfully with an office procedure and medical therapy.

Vaginal Pessary for Uterine Repositioning during High-Intensity Focused Ultrasound Ablation of Uterine Leiomyomas

In order to ensure safe magnetic resonance-guided, high-intensity focused, ultrasound ablation of uterine leiomyomas, the ultrasound beam path should be free of intervening scar and bowel. Pre-treatment MRI of a 9-cm long and 7.7-cm wide leiomyomatous uterus in a 39-year-old woman with menorrhagia and abdominopelvic pain initially demonstrated a focused ultrasound treatment path without a bowel between the uterus and the abdominal wall. On the day of ablation, however, multiple loops of bowel were observed in the ultrasound beam path by MRI. Uterine repositioning was accomplished with a 76-mm donut vaginal pessary, which anteverted the fundus and successfully displaced the bowel. A vaginal pessary may aid in repositioning an axial or retroverted uterus to enable ablation of uterine leiomyomas.