Therapeutic Drug Monitoring (TDM) of Cyclosporine Using the Area Under the Curve in Children Undergoing Hematopoietic Stem Cell Transplant (HSCT)

Introduction: The controversy surrounding cyclosporine TDM is still ongoing. In HSCT practice, the C0 method (or trough) is the one most commonly employed. At the CHU Sainte-Justine, the AUC method has been used for cyclosporine TDM in HSCT patients since October 2009. The aim of this study was to evaluate the correlation between cyclosporine levels (AUC or C0) with nephrotoxicity and GVHD in a pediatric population.

Methods: Forty-seven patients treated by IV cyclosporine for a first HSCT and having at least two AUCs were included in this retrospective study. Our protocol stipulates that a complete AUC (9 samples) must be done seven days after the beginning of the intravenous cyclosporine and partial AUCs (3 samples) once a week. All AUCs also include a C0. GVHD was defined as acute or chronic GVHD of any grade for the duration of the post-transplant follow-up. The patients were evaluated for the occurrence of nephrotoxicity according to the AKIN criteria.

Results: Median age of patients was 10.4 years (0.19-20.9). A total of 176 AUC samples were included (55 complete and 121 partial). Fourteen patients (30%) were diagnosed with GVHD and 23 (49%) with nephrotoxicity (AKIN stage 1, 2 or 3 at least one day for the duration of the IV cyclosporine).

	Mean AUC24h 21 days (ng.h/mL)			Mean C0 21 days (ng/mL)
All patients	12 581	Minimum 6531	Maximum 20 168	202	Minimum 78	Maximum 430
With GVHD	12 561	p = 0.98		193	p = 0.64
No GVHD	12 590			205
With nephrotoxicity	12 345	p = 0.611		214	p = 0.360
No nephrotoxicity	12 765			193

Conclusion: No correlation was found between the cyclosporine levels (AUC or C0) and the occurrence of GVHD or nephrotoxicity. Many confounding factors can influence theses issues and the small number of patients limits the extent of these findings.