Defining a critical therapeutic window: cyclosporine exposure in months 1-2 as a determinant of acute graft-versus-host disease in patients with acute leukemia undergoing allogeneic hematopoietic stem cell transplantation from matched related donors.

Acute graft-versus-host disease (aGVHD) is one of the most fatal yet preventable complications of hematopoietic stem cell transplantation (HSCT). Identifying optimal cyclosporine (CsA) blood level thresholds is particularly important in patients receiving CsA-based prophylaxis; however, cut-off values remain unclear. This retrospective study evaluated 120 patients with acute leukemia (64% acute myeloid leukemia [AML], 36% acute lymphoblastic leukemia [ALL]) who underwent allogeneic HSCT (AHSCT) between June 2011 and March 2021. CsA combined with methotrexate was used for GVHD prophylaxis. Statistical analyses included ROC analysis to determine optimal cut-off values and logistic regression to identify independent risk factors for aGVHD. aGVHD developed in 34 patients (28%), with a median onset at day 48. ROC curve analysis identified a CsA cut-off level of 274 µg/L during months 1-2, with an AUC of 0.697 (95% Confidence Interval [CI]: 0.574-0.820, p = 0.005), sensitivity of 77.3%, and specificity of 63%. In multivariate analysis, higher CsA levels during months 1-2 (Odds Ratio [OR] = 0.990, 95% CI 0.981-1.000; p = 0.039) and pre-transplant steroid use (OR = 0.284, 95% CI 0.094-0.860; p = 0.026) were independently associated with reduced risk of aGVHD. No universally accepted cut-off value of CsA levels has been defined to date, and our findings suggest that maintaining levels above 274 µg/L during the first 1-2 months post-transplant is critical to reduce aGVHD risk.