Abstract
In everyday gynecological practice, there is an unmet need to manage survivors after allogeneic hematopoietic cell transplantation (allo-HCT). The major gynecological complications include premature ovarian insufficiency (POI), chronic graft-versus-host disease (cGVHD) of the anogenital zone (cGVHDgyn), and secondary neoplasms. Aiming to assess a real-life scale of problems associated with HCT, we performed a detailed analysis of a consecutive series of females after allo-HCT who were referred for a routine gynecological evaluation. The study includes 38 females after allo-HCT in whom gynecological examination with cervical smear and USG were performed, followed by colposcopy according to NCCN guidelines. NIH scoring system was used to classify a grade of cGVHDgyn. The incidence of cGVHD was 71% whereas GVHDgyn was 29%, including 5 patients with score 3 at the time of diagnosis. The other manifestations (frequently noted) included the skin, mucosa, eyes, and liver. Menopause was diagnosed in 93% females, and in 81% of them, POI criteria were fulfilled. Ovarian function resumed in 2 cases. The rate of abnormal cytology was 26%: 4 ASCUS, 1 AGUS, 1 LSIL, 3 HSIL/ASC-H, and one cytological suspicion of cervical cancer. GVHDgyn was documented in 10 patients, and 6 of them had abnormal cervical cytology. Early topical estrogen therapy led to a significant reduction in vaginal dryness (p < 0.05), dyspareunia (p < 0.05), and less frequent cGVHDgyn (p < 0.05). GVHDgyn develops in about 30% of long-term allo-HCT survivors. Topical estrogens and hormonal replacement therapy alleviate symptoms and prevent the occurrence of severe consequences of menopause.
Highlights
The management of gynecological complications in long-term survivors after allogeneic hematopoietic cell transplantation remains still an unmet need in daily practice
The most specific and often unrecognized complication is chronic graft-versus-host disease of the anogenital zone that was reported for the first time in 1982 [3]
Four patients had score 1, two score 2, and the rest (45%) score 3, which defines the severe form of chronic graft-versus-host disease (cGVHD) according to the National Institute of Health (NIH) classification
Summary
The management of gynecological complications in long-term survivors after allogeneic hematopoietic cell transplantation (allo-HCT) remains still an unmet need in daily practice. The most specific and often unrecognized complication is chronic graft-versus-host disease (cGVHD) of the anogenital zone (cGVHDgyn) that was reported for the first time in 1982 [3]. Donor-derived immunocompetent cells can become intolerant to host tissues and recognize them as their targets, leading to the development of a unique complication called graft-versus-host disease (GVHD) [4]. The acute form (aGVHD) that occurs typically up to 100 days post-allo-HCT does not affect the genitourinary tract. Chronic GVHD which develops more than 50% of patients can involve every organ and tissue, including genital zone, with the symptomatology often mimicking autoimmune disorders. The diagnosis of cGVHD is based on the clinical
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