Higher therapeutic CsA levels early post transplantation reduce risk of acute GVHD and improves survival

Abstract

We studied whether early cyclosporine A (CsA) trough levels were associated with the risk of acute graft-vs.-host disease (GVHD) in 337 patients after either sibling peripheral blood stem cell or double umbilical cord blood transplantation. All patients, regardless of donor type, started CsA at a dose of 5 mg/kg IV divided twice daily, targeting trough concentrations 200–400 ng/ml. The CsA level was studied by a weighted average method calculated by giving 70% of the weight to the level that was measured just prior to the onset of the event or day +30. We found that higher weighted average CsA trough levels early post-transplantation contributed to lower risk of acute GVHD, and lower non-relapse and overall mortality. Thus, our data support close monitoring with active adjustments of CsA dosing to maintain therapeutic CsA levels in the first weeks of allo-HCT. In patients who are near or even modestly above the CsA target trough level, in the absence of CsA related toxicity, dose reduction should be cautious in order to avoid subtherapeutic drug levels resulting in higher risks for acute GVHD.