Safety, efficacy, and cost analysis of thymoglobulin induction therapy with intermittent dosing based on CD3+ lymphocyte counts in kidney and kidney-pancreas transplant recipients.
BACKGROUND
In view of the superior T-cell depletion and prolonged half-life of thymoglobulin, we initiated a protocol to administer thymoglobulin intermittently based on peripheral blood CD3+ lymphocyte counts.


METHODS
In this prospective study, 41 consecutive high-risk cadaver transplant recipients (panel reactive antibody level >30%, repeat transplant recipients, simultaneous pancreas and kidney or pancreas after kidney recipients, prolonged cold-ischemia time, prolonged donor hypotension, non-heart-beating donors) who received thymoglobulin induction therapy were included. The first dose (1.5 mg/kg) of thymoglobulin was administered intraoperatively. CD3+ lymphocyte count in the peripheral blood was determined daily and repeat doses were administered when the CD3+ count was >20 cells/mm3. Calcineurin inhibitors (CI) in low doses were introduced when the allograft function recovered and the serum creatinine level dropped by at least 25% from the pretransplant level. Thymoglobulin treatment was discontinued once therapeutic CI drug levels were achieved. Concomitant immunosuppression consisted of mycophenolate mofetil and prednisone.


RESULTS
The mean individual thymoglobulin dose was 104 mg (1.4 mg/kg), and the total cumulative dose per patient was 318 mg (4.2 mg/kg). Patients received an average of three doses and a mean of six CD3 counts were obtained per patient. Introduction of CI was delayed for an average of 6 days posttransplantation. At a mean follow-up of 340 days, two (4.9%) patients died; three (7.3%) renal allografts and two (18.2%) pancreas allografts were lost. Five (12.2%) patients developed a total of six acute rejection episodes. The mean serum creatinine in the 38 patients with a functioning kidney was 1.47 mg/dl, and the mean blood glucose in the 9 pancreas allograft recipients was 89 mg/dl. Cytomegalovirus (CMV) infection occurred in one (2.4%) patient. No posttransplant lymphoproliferative disorders were seen in this patient cohort. The hospital pharmacy charge for a 100-mg dose of thymoglobulin at this center was $2,165, and the laboratory charge for a single CD3 determination was $70. In this study, the average charges per patient for the total dose of thymoglobulin and six CD3 determinations were $7305. In comparison, the charge for daily administration of 104 mg of thymoglobulin (which was the mean dose) for 6 days (mean time to CI therapy initiation) would be $13,510 and for 10 days (mean time to therapeutic CI levels) would be $22,516. This represents a savings of 46% and 68%, respectively.


CONCLUSIONS
Intermittent thymoglobulin therapy, based on peripheral blood CD3+ lymphocyte counts, is safe and associated with low acute rejection rate in high-risk kidney and kidney-pancreas transplant recipients. A mean of three doses resulted in adequate suppression of CD3+ lymphocytes permitting delayed introduction of CI in low doses until recovery of renal function occurred. When compared to traditional daily administration, intermittent therapy results in significant cost savings and reduces the total cumulative dose of this potent immunosuppressive agent.
Peddi
V Ram
VR
University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0585, USA. ram.peddi@uc.edu
Bryant
Margaret
M
Roy-Chaudhury
Prabir
P
Woodle
E Steve
ES
First
M Roy
MR
D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use*; D001773:Blood Cells / Q000276:immunology; D017252:CD3 Complex / Q000032:analysis*; D065095:Calcineurin Inhibitors; D015331:Cohort Studies; D004334:Drug Administration Schedule; D017048:Health Care Costs; D006801:Humans; D016030:Kidney Transplantation; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology*; D008875:Middle Aged; D016035:Pancreas Transplantation; D011446:Prospective Studies; D012449:Safety; D016019:Survival Analysis; D016896:Treatment Outcome
D000961:Antilymphocyte Serum; D017252:CD3 Complex; D065095:Calcineurin Inhibitors