Thymoglobulin, sirolimus, and reduced-dose cyclosporine provides excellent rejection prophylaxis for pancreas transplantation.
BACKGROUND
We investigated a novel immunosuppressive protocol including thymoglobulin induction in combination with sirolimus and corticosteroids, followed by introduction of markedly reduced exposures to cyclosporine to prevent pancreas-transplant rejection.


METHODS
A 7-day course of thymoglobulin (1.5 mg/kg per day) was begun on postoperative day (POD) 0, together with 15 mg of sirolimus on POD 1, and followed by 5 mg per day, targeting these doses to achieve a trough of 10 to 20 ng/mL. When the serum creatinine was below 2.5 mg/dL, cyclosporine was introduced at 50 mg twice daily with dose adjustment to maintain a trough concentration of 100 to 125 ng/mL.


RESULTS
The 18 patients included 14 simultaneous pancreas-kidney and 4 pancreas-after-kidney transplant recipients. Two patients were African-American, three patients had a pretransplant panel reactive antibody greater than 20%, and the human leukocyte antigen (HLA) mismatch was 4.5+/-1 (mean+/-standard deviation). With a mean follow-up of 13.6+/-4.7 months, patient, kidney, and pancreas graft survivals are 100%, 100%, and 94%, respectively. A single pancreas graft was lost to thrombosis. There were no acute rejection episodes and no opportunistic infections. Mean hospital stay was 9+/-3 days. At 3 months posttransplantation, the mean value of serum creatinine was 1.2+/-0.3 mg/dL, fasting glucose was 88+/-15 mg/dL, and sirolimus dose at month 3 was 6.3+/-3 mg per day and at month 12 2.7+/-1 mg per day. The average total daily cyclosporine A dose at month 3 was 208+/-62 mg per day and 133+/-13 mg per day at 1 year.


CONCLUSIONS
This immunosuppressive regimen provided excellent prophylaxis against acute rejection with no opportunistic infections. We believe that careful monitoring of sirolimus and cyclosporine levels was critical to success of this protocol.
Knight
Richard J
RJ
Division of Immunology and Organ Transplantation, The University of Texas Health Science Center at Houston, Texas 77030, USA.
Kerman
Ronald H
RH
Zela
Scott
S
Podder
Hemangshu
H
Van Buren
Charles T
CT
Katz
Stephen
S
Kahan
Barry D
BD
D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D016572:Cyclosporine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D006547:Hernia / Q000209:etiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D007668:Kidney / Q000503:physiopathology; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000503:physiopathology; D016035:Pancreas Transplantation / Q000009:adverse effects; D011446:Prospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D013530:Surgical Wound Infection / Q000209:etiology; D013601:T-Lymphocytes / Q000276:immunology*
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D008055:Lipids; D016572:Cyclosporine; D020123:Sirolimus