Severity of Mucositis Determines Cyclosporine Levels after Allogeneic Transplantation

Abstract

Introduction Intestinal mucosal injury is a common complication following allogeneic stem cell transplant (alloHSCT), especially with myeloablative and TBI-based (total body irradiation) conditioning regimens. Prospective evaluation studies have shown that intestinal malabsorption persists for several weeks following conditioning, beyond visible resolution of mucositis and bowel integrity. Serum cyclosporine levels in the early to intermediate post-transplant period (when patients are taking oral cyclosporine) may be affected by reduced gut absorption and could influence early transplant related outcomes. Objective To determine the relationship between mucositis severity, cyclosporine levels, and post-transplant outcomes. Methods 169 patients who received myeloablative (BuCy, CyTBI, EtoTBI) or reduced-intensity (FluMel) allo-HSCT at the Royal Melbourne Hospital were studied. Serum cyclosporine levels were measured at 2 hours post oral dosing. Days of post-transplant total parental nutrition (TPN) were used as a surrogate for severity of gastrointestinal mucositis. To determine degree of renal impairment, creatinine values were recorded at baseline, D+30, D+60 and D+100. Percentage increase of mean creatinine above baseline was taken as an index of renal impairment. The incidence and severity of acute graft-versus-host disease (aGVHD) was recorded before D+100. The incidence of CMV viraemia before D+100 was recorded and analysed according to serum viral load. Patients with recurrence of disease were compared with patients without recurrence ( 6 months). Results Linear regression analysis showed an inverse correlation between days requiring TPN with the post SCT 100-day median cyclosporine level (p Higher median cyclosporine level was associated with a greater percentage increase of creatinine above baseline (p=0.004, R2= 0.051). There was no significant correlation between incidence (p=0.05) and severity (p=0.47) of aGVHD with lower cyclosporine levels. CMV reactivation was associated with higher cyclosporine levels (p Conclusion Our data suggest that patients who have significant mucositis have lower serum cyclosporine levels with oral cyclosporine dosing, which in turn impact upon post-transplant outcomes, in particular renal impairment and CMV reactivation.