Discussion
This case is unique because the cervical cytology changed in a short time. The change in cervical and vaginal stump cytology without treatment is rare, so we speculate that this change was associated with allo-SCT.
GVHD is among the most potentially serious complications of allo-SCT, but patients who develop GVHD also have a low incidence of leukemia recurrence,1 suggesting a GVT effect due to the donor lymphocytes in association with GVHD.
Eibl et al. reported a breast cancer patient with liver and bone metastases who underwent allo-SCT and had complete resolution of the liver metastases on CT 27 days later.2 On the same day, the patient developed acute GVHD of the skin. Considering this clinical course, Eibl et al. attributed the resolution of the metastases to a GVT effect. Child et al. performed allo-SCT in 19 patients with refractory metastatic renal-cell carcinoma, of whom 3 had complete response and 7 had partial response. 3 They noted that regression of metastases occurred at a median of 129 days after transplantation, often following withdrawal of cyclosporine and the establishment of complete donor T cell chimerism. Cyclosporine suppresses the increase of T cells and the production of cytokines. This agrees with the previous study suggesting that the graft-versus-leukemia and GVT effect is caused by donor T cells.4
There are many reports of the GVT effect in patients with solid tumors. To our knowledge, however, this is the first report showing a GVT effect for only abnormal cytology. Some studies have reported that the cervical cytology after allo-SCT was affected by immune status.
Shanis et al. studied 82 women who underwent allo-SCT and found the cumulative incidence rate of any genital HPV infection at 20 years after transplantation to be 40.1%.5 Women who developed extensive and genital chronic GVHD had a cumulative HPV infection rate of 67.1%, compared with 18.4% in women without chronic GVHD. They also reported that the cumulative rate of severe dysplasia reached 19% at 20 years after transplantation, and the rate was significantly different between women with and without chronic GVHD (41.2% versus 2.5%). In contrast, there was no association between acute GVHD and the rate of HPV infection. Shanis et al. suggested that, since sexual activity after allo-SCT is generally decreased, the increased HPV infection rate was due to reactivation of HPV rather than new infection. Moreover, viral reactivation may have been influenced by chronic GVHD and/or immunosuppression. Similarly, Bipin et al. reported that genital HPV disease occurred in one-third of 38 patients.6 All of them were long-term survivors of allo-SCT on prolonged immunosuppressive therapy. Bipin et al. suggested that prolonged systemic immunosuppressive treatment for chronic GVHD was associated with a higher risk of developing genital HPV disease.
Our patient may have already been infected with HPV before she underwent the first allo-SCT considering her history of sexually transmitted infection. The abnormal cervical cytology may represent HPV reactivation due to prolonged immunosuppression.
We suggest that our patient developed a GVT effect associated with GVHD, which resulted in transient improvement of the cervical cytology after the second allo-SCT. This GVT effect may have been suppressed later by immunosuppressive therapy, resulting in worsening of her cervical cytology. As shown in Figure 10, the cervical cytology changed from NILM to HSIL. When GVHD recurred and the immunosuppressant dose was increased, the cervical cytology improved. When the immunosuppressant dose was again decreased because of improvement of GVHD, the cervical cytology worsened. Although we speculate that the cervical cytology was affected by a GVT effect mediated by the immunosuppressant dose, there is no direct evidence that the cervical cytology improved because of a GVT effect. However, transformation of the cervical cytology from NILM to HSIL without treatment is rare. Although the possibility of sampling error cannot be excluded, if it were to occur, then there would be no correlation between cytology, GVHD and the immunosuppressant dose.
The cervical cytology of patients after allo-SCT is likely to change depending on their immune status. Regular gynecologic follow-up is needed even after improvement of the cervical cytology to monitor for changes.