Tacrolimus: The good, the bad, and the ugly

Abstract

The aim of this study was to evaluate the efficacy and side‐effects of tacrolimus in pediatric transplant patients previously receiving cyclosporin A (CsA). This study was a retrospective chart review strengthened by a concomitant patient interview. Eleven pediatric cardiac or renal transplant patients, who had been converted from CsA to tacrolimus from October 1995 to January 1999 at The Cleveland Clinic Foundation, were included; there were six renal and five cardiac transplant patients. Each chart was reviewed to assess transplanted organ function pre‐ and post‐conversion. For the six renal transplant patients, creatinine levels and biopsy findings were evaluated. For the five cardiac transplant patients, cardiac catheterization and routine biopsy data were analyzed likewise. Epstein–Barr virus (EBV) status was also evaluated in each patient. In addition, each parent or patient was interviewed to ascertain dates of transplant, current medications, and side‐effects. The patients' ages ranged from 6 to 20 yr (mean age 14.6 yr). All patients had been converted to tacrolimus. Eight patients were converted for treatment of refractory rejection, two were converted because of CsA‐associated side‐effects, and one patient was converted empirically for a history of multiple previous transplant rejections. Seven out of eight patients who received tacrolimus for rejection therapy improved. One patient had complete resolution of gingival hyperplasia. Another patient who previously developed hemolytic uremic syndrome on CsA had no further evidence of hemolysis. Four patients were weaned off steroid therapy. Despite conversion, two renal transplant patients progressed to chronic rejection. Five patients exhibited no side‐effects. Side‐effects experienced included transient hyperglycemia in conjunction with steroid use, headaches, and tremors that subsided rapidly. Four of 11 patients developed post‐transplant lymphoproliferative disease (PTLD). Fortunately, reducing the dose of tacrolimus and/or surgical resection of the mass (if present), eradicated the disease. In conclusion, conversion therapy successfully provides an alternate treatment for acute rejection. It also enabled some patients to discontinue steroid therapy, maximizing growth potential. PTLD is a severe, potentially life‐threatening complication that needs to be recognized and monitored closely. In conclusion, tacrolimus has been shown to be a very effective agent for the treatment of refractory organ rejection, but must be used cautiously.

Neuropsychologic side‐effects of tacrolimus in pediatric renal transplantation

“…One study reported severe neurotoxicity in one of 14 children undergoing RTPL (7). headache and tremor in two of 11 patients switched over to tacrolimus (17). Another publication described only mild neurologic symptoms, i.e.…”

Epstein-Barr virus nuclear antigen-2 detection and typing in immunocompromised children correlated with lymphoproliferative disorder biopsy findings

“…Immunosuppressive drugs such as cyclosporine A and tacrolimus seem to act synergistically with EBV as tumor inducing factors [2].…”

Pulmonary re-occurrence of post-transplant lymphoproliferative disease with hypogammaglobulinaemia

“…Compared with CsA, FK506 is associated with an increased risk for development of PTLD [2,3,5]. Typically, B-lymphocytes are latently infected by EBV and so the virus is hidden from the immune system.…”