Treatment of Pancreas Allograft Rejection?

Robert J. Stratta, MD

Disclosures

July 22, 2002

Question

What are the drug recommendations for treatment of pancreas rejection, with special reference to corticosteroid dosage and the role of intravenous immunoglobulin (IVIG)?

Response from Robert J. Stratta, MD

My bias is that any/all pancreas allograft rejection (biopsy-proven) should be treated with anti-T-cell therapy rather than corticosteroids alone, particularly since bolus corticosteroid therapy results in hyperglycemia. In general, the exocrine pancreas tends to reject before the endocrine pancreas, so one might make a case that "mild" exocrine rejection alone can be treated with corticosteroids alone. However, any rejection episode associated with hyperglycemia implies endocrine involvement with islet-cell injury, and I would recommend treatment with an anti-T-cell agent. My preferred agent is Thymoglobulin 1.5 mg/kg (up to a maximal dose of 150 mg) daily x 3 days, then every other day for a total of 5-10 doses, depending on clinical response, adverse effects, tolerability, and grade of rejection. A follow-up biopsy of the pancreas is recommended within 2-3 weeks of the final Thymoglobulin dose in order to document histologic clearing. I specifically try to avoid OKT3 because of the concern about side effects, although it has efficacy comparable to Thymoglobulin. I am unaware of any data or role for IVIG in the treatment of pancreas rejection, although we use CytoGam prophylaxis on occasion during the treatment of rejection, particularly if the donor/recipient CMV serologic status is +/- or the biopsy shows an antibody-mediated process.

Conversely, if a kidney-pancreas transplant recipient has biopsy-proven mild renal allograft rejection without clinical or histological evidence of pancreas rejection, then corticosteroid therapy alone is a reasonable option. We use bolus methylprednisolone 500 mg IV on alternate days for 3 doses in conjunction with an increase in the maintenance immunosuppression. If the patient is on cyclosporine (CsA), we switch to tacrolimus (unless the CsA level was subtherapeutic). If the patient appeared to have adequate calcineurin inhibitor levels, then we increase the mycophenolate mofetil (MMF) dosage to 3 gm/day (or switch to MMF if the patient was on azathioprine). For moderate-to-severe kidney rejection, or any pancreas rejection, we treat with Thymoglobulin as above. Again, a follow-up kidney biopsy is recommended to document histologic resolution of the immunologic process.

Whenever we treat for rejection, we initiate (or continue) anti-infective prophylaxis with valganciclovir (3-6 months), fluconazole (2-3 months), and Septra/Bactrim (12-month minimum).

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