Graft versus Host Disease (GVHD) is one of the serious complications of allogeneic stem cell transplantation used in the treatment of many hematological malignancies. Skin, liver, and eyes are frequently affected areas. In addition to frequently affected areas, genital region involvement can also be seen. Allogeneic stem cell transplantation is one of the definitive treatments for hematological malignancies seen in the young age group. And its use for therapeutic purposes in young patients is increasing day by day. Vulvovaginal GVHD is a disease type that concerns female patients of reproductive age. In this case report, we wanted to include in the literature a case that underwent allogeneic stem cell transplantation after CML diagnosis and TKI resistance and then developed vulvovaginal GVHD. In vaginal disease involvement; in addition to many genitourinary complaints, many negativities in sexual life and deterioration in quality of life are experienced. The chronic GVHD patient we treated is currently continuing her treatment response follow-ups. Our aim in presenting this case to the literature is to emphasize that GVHD should be included in the differential diagnosis in female patients with hematological disease and vaginal involvement.

42 years old female patient was diagnosed as chronic phase chronic myeloid leukemia in 2015. She was treated with imatinib 400 mg/day. After 6 months molecular response not obtained and treatment changed to dasatinib 100 mg/day, but after 3 months of dasatinib treatment molecular and hematologic progression occurred and treatment changed to nilotinib and bone marrow transplantation planned. After 4 months the patient transplanted succesfully with HLA matched sibling stem cell donor. Tyrosine Kinase inhibitory used till 1 years after transplantation, Bcr/abl was negative after transplantation and until now.

At 2 months of transplantation acute GvHD occurred and healed without any serious complication, but after 10 months symptoms and signs of chronic GvHD developed. Dry skin, itching, dark hyperpigmentation occurred in generalized of the body especially in the upper extremities and ocular GvHD was the main symptoms of the patient. She was used siklosporin and steroids for prophylaxis and treatment of GvHD, also she use ursodeoxycholic acid for liver protection.

Chronic GvHD sustained more than 2 years especially ocular findings (drying, itching and scarring of conjunctiva and eyelid). After 5 years of transplantation she told to our nurse some symptoms such as vulvodinia, pain during sexual intercourse and decreased sexual function. She has problems with her husband for this reason. She applied on october 2023 for gynecological examination, there were findings consistent with vulvodynia, but there was no genital atrophy. We prescribed 2% amitriptyline + 2% baclofen cream two times a day for the treatment of vulvodynia

When she came for a check-up 1 month later of local treatment, she stated that she was better in terms of sexual function but could not urinate completely. Bacteriuria, pyuria and hematuria was observed in urinalysis. Since there was not much residual urine in the pelvic ultrasonography. We treat her for urinary tract infection. Since the patient's genital atrophy was not evident, we did not prescribe vaginal estrogen during both examinations. If she came for a checkup, we was planning to re-evaluate and treat her if necessary.

Hematopoietic stem cell transplantation (HSCT) is a treatment method for malignant and benign hematological diseases as well as in the treatment of some non-hematological disorders such as autoimmune diseases (1). Graft-versus-host disease (GVHD) is an immunity related disease which affects 30-70% of patients after hematopoietic stem cell transplantation (alloHSCT) and is a significant contributor of morbidity and non relapse mortality (NRM) is the reason (2). Chronic GVHD is a mucosal disease of the mouth, eyes, genitals, intestines, and lungs. It includes inflammation and fibrosis of membranes. There are some evidences which indicates clinical symptoms and pathogenesis of GVHD is similar to various autoimmune disorders such as Scleroderma, Sjögren's syndrome and lichen planus. (3,4). Female genital GVHD was first described by Corson et al. By observing Sclerosing vaginitis and structure problems in 5 women in 1982 (5). Nowadays, it is an underdiagnosed condition and affects the quality of life which occurs in one quarter of long-term surviving women after allogeneic stem cell transplantation (6). The rates of genital GVHD vary widely, with rates ranging from 24.9-69% (7).

The wide variation in the incidence of genital GVHD is due to a variety of abnormalities, including the time at which incidence is calculated, the systematic and time-dependent gynecological evaluations, and the diagnostic criteria used (findings of examination with or without symptoms, etc.) (8). The main risk factor for the development of chronic genital GVHD issuing of peripheral blood as a source of progenitor cells; It represents a risk of three times higher than that obtained from bone marrow cells (9-11). The presence of GvHD in another organ is also considered one of the risk factors (12) . While one study found that 79% of patients with VVGvHD were treated for GvHD in a different organ, another study reported that almost all patients with VVGvHD had active chronic GvHD in the skin, mouth, and eyes (13-14). Our patient was receiving treatment for skin and liver involvement caused by chronic GVHD . It is supported by various studies that it develops after an average of 10.2 months after transplantation (6). In our patient, this condition was detected approximately 5 years after allogeneic transplantation. Clinic may be asymptomatic; The main signs and symptoms are vulvar tenderness to palpation of openings of the mucosa, erosion of the mucosa, cracks, leukokeratosis, labial or clitoral fusion, fibrous vaginal ring, vaginal shortening, vaginal adhesions and complete vaginal stenosis. Other symptoms include dryness, burning, itching, pain to touch, dysuria, dyspareunia and resulting sexual dysfunction takes place (5).

She has vulvodynia, pain during sexual intercourse and decreased sexual function. Although symptoms are similar to primary ovarian insufficiency which occurs after allogeneic stem cell transplantation, synechia and adhesive bands are not encountered in primary ovarian failure. In addition, studies have shown that hormone replacement therapy is used for the prophylaxis of this condition does not effects development rate of vulvo vaginal GVHD (11). The National Institutes of Health (NIH) Consensus Development Project proposed guidelines for screening, diagnosing, and preventing genital GVHD in HSCT survivors. Treatment goals for Female genital GVHD include symptom relief, disease control and prevention of further damage (7). In its treatment various patient-specific treatment modalities are advocated such as topical estrogens, topical steroids, topical immunosuppressive agents (such as cyclosporine, tacrolimus), vaginal dilators and surgicallysis (9,16). Diagnosis and treathment of post-transplant genital GVHD requires a systematic approach and collaboration between bone marrow transplant pyhsicians and coordinators and gynecologists. A systematic approach is required, requiring close cooperation between gynecologists. Incidence and severity of genital GVHD in women should be included in GVHD intervention studies.