Topical Cyclosporine Vs Tacrolimus for Ocular GVHD Prophylaxis after Allogeneic Hematopoietic Stem Cell Transplantation: A Phase I–II Trial

Ocular graft-versus-host disease (oGVHD) is a frequent complication after allogeneic hematopoietic stem cell transplantation (alloHCT), with dry eye symptoms affecting up to 90% of patients, often beginning within 3 months post-transplant and persisting indefinitely. Current treatments target established disease, and evidence for prophylactic approaches is limited. This study evaluated the safety, tolerability, and early efficacy of topical tacrolimus (Tac) versus cyclosporine (Cys) for oGVHD prevention in the outpatient alloHCT setting. Objective Primary endpoint: safety/tolerability. Secondary endpoints: oGVHD prevention, ocular symptoms, quality of life (QoL), and graft-versus-relapse-free survival (GFRS). Methods Non-blinded phase I–II trial (NCT06348602) including adults (>18 y) undergoing outpatient peripheral blood alloHCT from matched sibling or haploidentical donors. Exclusion criteria: active ocular infection or intolerance to Tac/Cys. After engraftment, patients were randomized to Tac 0.03% ointment or Cys 0.1% solution, twice daily in both eyes for 12 months. Artificial tears were allowed. Systemic GVHD prophylaxis included post-transplant cyclophosphamide, a calcineurin inhibitor, and mycophenolate. Ophthalmologic exams were performed every 3 months NIH/ICCGVHD criteria. Statistical analysis used IBM SPSS v27, with p < 0.05 considered significant. Twenty-two patients were enrolled (54.2% Cys, 45.8% Tac); median age 35 y; 70% male. Haploidentical donors 75%; reduced-intensity conditioning 50%. Median CD34⁺ dose 8.94 × 10⁶/kg; neutrophil and platelet recovery at 13 and 12.9 days. Acute GVHD occurred in 62.5% (grade 3–4 in 20.8%), chronic in 37.5% (moderate-severe 16.7%). Relapse 33.3%, mortality 20.8%. Median event-free survival 66.4 weeks; GFRS 6.2 months. Confirmed oGVHD occurred in 2 patients (1 per group) and probable in 2 Cys All were mild (median onset 18.3 weeks). Dry eye symptoms were more frequent in Cys (61.5% vs 18.2%), with Schirmer <5 mm only in Cys 33.3% vs 0%. Both treatments were well tolerated: burning 70% Cys vs 55% Tac; pruritus 15% vs 45%; blurred vision 30.7% vs 36.4%. No discontinuations occurred. Adherence was high (Tac 81.8%, Cys 76.9%). NEI VFQ-25 scores were similar: baseline 79.7 ± 16.0 vs 74.9 ± 23.9; engraftment 78.3 ± 15.5 vs 74.3 ± 14.5; 3 months 79.3 ± 14.5 vs 79.0 ± 7.5; p > 0.05. QoL remained stable at 12 months, Wilcoxon p = 0.93 Cys; p = 0.50 Tac Both topical Tac and Cys were safe, well tolerated, and associated with high adherence in outpatient alloHCT. Tac showed a trend toward fewer dry eye symptoms and lower ocular toxicity, though not statistically significant. Ocular QoL remained preserved in both groups, supporting the feasibility of topical immunomodulator prophylaxis for oGVHD. Longer follow-up is warranted to confirm sustained benefit.