Mucositis during Allogeneic Transplantation Determines Post-Transplant Serum Cyclosporin Levels

Introduction

Intestinal mucosal injury is a common complication following allogeneic stem cell transplant (alloHSCT), especially with myeloablative and TBI-based (total body irradiation) conditioning regimens¹. Prospective evaluation studies have shown that intestinal malabsorption persists for several weeks following conditioning, beyond visible resolution of mucositis and bowel integrity². Serum cyclosporin levels in the post-transplant period (when patients are taking oral cyclosporin) may be affected by reduced gut absorption and could influence early transplant related outcomes.

Aim

To determine the relationship between mucositis severity, cyclosporin 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 cyclosporin 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. 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 disease relapse (<6m versus >6m) were compared with patients without.

Results

Linear regression analysis showed an inverse correlation between days requiring TPN with the post SCT 100-day median cyclosporin level (p<0.0001, R²=0.23).

Higher median cyclosporin 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 cyclosporin levels. CMV reactivation was associated with higher cyclosporin levels (p<0.0001). There was no significant difference in cyclosporin levels according to viral copy number (p=0.067). There was no significant difference in cyclosporin levels between disease-relapsed groups and non-relapsed groups (p=0.33).

Conclusion

Our data suggest that patients who have significant mucositis have lower serum cyclosporin levels with oral cyclosporin dosing, which in turn impact upon post-transplant outcomes, in particular renal impairment and CMV reactivation.

References

1. Chaudhry, Hafsa M. et al. "The Incidence And Severity Of Oral Mucositis Among Allogeneic Hematopoietic Stem Cell Transplantation Patients: A Systematic Review." Biology of Blood and Marrow Transplantation 22.4 (2016): 605-616. Web.

2. Blijlevens, N M A, J P Donnelly, and B E de Pauw. "Prospective Evaluation Of Gut Mucosal Barrier Injury Following Various Myeloablative Regimens For Haematopoietic Stem Cell Transplant." Bone Marrow Transplantation 35.7 (2005): 707-711.