Impact of cyclosporine 2-h level and mycophenolate mofetil dose on clinical outcomes in de novo heart transplant patients receiving anti-thymocyte globulin induction.
BACKGROUND
Cyclosporine (CsA) 2-h post-dose level (C2) correlates better than trough levels (C0) with the area under the curve. We evaluated the clinical impact of C2 and mycophenolate mofetil (MMF) dose in adult heart transplant patients receiving anti-thymocyte globulin (ATG) induction.


METHODS
Two immunosuppressive strategies were sequentially evaluated. In Group 1 (13 patients), simultaneous C0/C2 (ng/mL) were analyzed. CsA dose monitoring was initially based on C0 : <3 months: 200-300, 4-6 months: 150-250, 6-9 months: 100-200, and on C2 thereafter (as in Group 2). In Group 2 (nine patients), C2 monitoring was implemented: <3 months: 600-800, 4-6 months: 500-700, >6 months: 400-600. All patients received ATG induction, corticosteroids, and MMF (1.0 g b.i.d. in Group 1 and 1.5 g b.i.d. in Group 2).


RESULTS
Patients in Group 2 received higher MMF doses during the first trimester. C2 at 1, 3, 6, 12, 24, and 36 months was, respectively, 1199 +/- 476, 1202 +/- 587, 999 +/- 467, 664 +/- 203, 593 +/- 208, and 561 +/- 147 in Group 1, and 809 +/- 160 (p = 0.02), 644 +/- 178 (p = 0.003), 664 +/- 169 (p = 0.02), 616 +/- 221, 464 +/- 234, and 451 +/- 165 in Group 2. The incidence of acute rejection (grade > or =3A) at 6, 12, 24, and 36 months was, respectively, 38.5, 38.5, 46, and 54% in Group 1, and 11, 44, 56, and 56% in Group 2 (p = NS). At 3 months, the creatinine clearance was 25% lower in Group 1. Thereafter, renal function remained stable in both groups.


CONCLUSIONS
Our results suggest that heart transplant patients receiving ATG induction may experience similar outcomes with either a higher C2 and a lower MMF dose or a lower C2 and a higher MMF dose. These results could be considered to design prospective studies to optimize C2 monitoring, to reduce the incidence of acute rejection without increasing the risk of renal dysfunction.
Cantarovich
Marcelo
M
Department of Medicine, Division of Transplantation, Royal Victoria Hospital, McGill University Health Center, Montreal, Quebec, Canada. marcelo.cantarovich@muhc.mcgill.ca
Giannetti
Nadia
N
Cecere
Renzo
R
D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D003404:Creatinine / Q000652:urine; D016572:Cyclosporine / Q000008:administration & dosage* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection; D016027:Heart Transplantation; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives; D011446:Prospective Studies; D016896:Treatment Outcome
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid