Cyclosporine levels > 195μg/L on day 10 post-transplant was associated with significantly reduced acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation.

Abstract

Acute graft-versus-host disease (aGvHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Prophylaxis with cyclosporine A (CsA) is the backbone of GvHD prevention. In a retrospective analysis of patients treated with allo-HSCT, we correlated CsA levels on the day of transplantation (day 0) and on day + 10 with the incidence of acute and chronic GvHD. We assessed 660 patients with either AML n = 248, lymphoma/myeloma n = 127, MDS/MPN n = 124, ALL n = 79, CLL n = 36, CML n = 23, or bone marrow failure n = 22. In patients with clinically relevant aGvHD grade ≥ 2, mean CsA levels was lower on day 0 and day + 10 (142 ± 88μg/L and 183 ± 64μg/L, respectively) compared to patients without aGvHD (156 ± 81μg/L and 207 ± 67μg/L, respectively; day 0: p = 0.003; day + 10: p = 7.57 × 10-9). In patients with CsA level < 200μg/L, the incidence of aGvHD was significantly more frequent compared to patients with CsA levels > 200μg/L [(234/356 (66%) versus 91/248 (37%); p = 1.34 × 10-12]. In patients with cGvHD, there was no significant difference between CsA levels < 200μg/L (128/330) compared to CsA levels > 200μg/L (96/233; p = 0.312). The optimal CsA cutoff level for the prevention (i.e., roughly 50% incidence reduction) of aGvHD was > 201μg/L at day 0 and > 195μg/L at day + 10. In a competing risk analysis, time to aGvHD grade ≥ 2 (using death of other causes as competing risk) was associated with CsA levels > 200μg/L on day 0 and on day 10, unrelated donors, myeloablative conditioning (MAC), and for the diagnosis lymphoma/myeloma. Our data support close monitoring with active adjustments of CsA dosing to maintain therapeutic CsA levels above 195μg/L in the first 10days of allo-HCST to reduce aGvHD.