Incidence of ocular graft-versus-host disease during tapering of immunomodulatory therapy following allogeneic hematopoietic stem cell transplantation

Purpose : Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapeutic intervention in patients with hematologic malignancy. Ocular graft versus host disease (oGVHD) is a common and potentially severe complication of allo-HSCT. In this study, we assessed the incidence of oGVHD upon tapering of immunomodulatory (IM) drugs in patients following allo-HSCT. Methods : We performed a retrospective study including patients who underwent allo-HSCT and developed oGVHD during the IM dose tapering. We assessed the incidence, oGVHD event rate and ocular surface disease parameters including corneal fluorescein staining, tear break-up time (TBUT), and Schirmer’s test results. All calculations were performed with 95% confidence (95% CI) and p-value <0.05 was considered statistically significant. Results : A total of 77 patients (62% male) with oGVHD for whom we had comprehensive information on the timing of their IM therapy were included in the analysis. The mean time to develop oGVHD was 17.2± 15.16 months (range: 1- 126 months) post- transplantation. The event rate of oGVHD increased overtime on tapering all IM drugs except Methotrexate (p<0.05). The risk of oGVHD was significantly higher after the fourth tapering of IM drugs; patients receiving Sirolimus were at the highest risk of oGVHD (odds ratio: 6.42, P<0.0001), followed by Cyclosporine (odds ratio: 5.00, P<0.0001), Tacrolimus (odds ratio: 4.05, P<0.0001), and Mycophenolate (odds ratio: 2.44, P=0.03). Schirmer scores were significantly decreased after the fourth tapering of Tacrolimus and Cyclosporine [odds ratio: 3.72 (p=0.002) and 3.65 (p=0.032)] compared to the values reported at previous tapering timepoints. Similarly, TBUT was significantly reduced in patients receiving Tacrolimus. (odds ratio: 3.41, P<0.0001). The CFS scores were moderately increased following each tapering of the IM drugs. Conclusions : IM tapering following allo-HSCT increases the risk of developing oGVHD, especially following the fourth tapering. Close observation and adequate patient education about the early signs of oGVHD for these patients should be kept in mind to prevent severe complications of oGVHD.