Higher cyclosporine-A concentration increases the risk of relapse in AML following allogeneic stem cell transplantation from unrelated donors using anti-thymocyte globulin

Abstract

Cyclosporine-A (CsA) is used to prevent acute graft-versus-host disease (aGvHD). European Society for Blood and Marrow transplantation (EBMT) recommends a CsA target serum concentration of 200–300 µg/L during the first month after allogeneic hematopoietic stem cell transplantation (HSCT). With this study, we investigated whether a median CsA concentration > 200 µg/L (CsAhigh) the first month after HSCT, compared to ≤ 200 µg/L (CsAlow), increased the relapse risk of acute myloid leukemia (AML), using unrelated donors (URD) and antithymocyte globulin (ATG). Data was collected from 157 patients with AML, transplanted 2010–2016. The cumulative incidence of relapse (CIR) at 60 months was 50% in the CsAhigh versus 32% in the CsAlow group (p = 0.016). In univariate analysis, CsAhigh versus CsAlow (p = 0.028), 10-unit increase of CsA as a continuous variable (p = 0.017) and high risk disease (p = 0.003) were associated with higher CIR. The results remained after adjusting for disease risk. Death following relapse occurred more frequently in the CsAhigh group (p = 0.0076). There were no significant differences in rates of aGvHD, chronic GvHD (cGvHD), EBV/CMV-infections or overall survival (OS) between the two groups. In conclusion, we found that a median CsA concentration > 200 µg/L, the first month after HSCT, results in higher CIR of AML when combined with ATG.