MYCOPHENOLATE MOFETIL (MMF) IN PAEDIATRIC LIVER TRANSPLANTATION

Abstract

146 MMF is a new non-nephrotoxic immunosuppressant. We report our experience of using MMF in 18 children (age 9 months - 15 years, median 2.5 yr). Ten had refractory acute rejection (AR), defined as histologic persistence of changes of ongoging cellular rejection following bolus methylprednisolone and 2 weeks of Tacrolimus blood levels 10-15 ng/dl ug/L (IMx II assay), and would have been candidates for OKT3 or ATG treatment; two had persistent chronic rejection (CR), defined as >25% duct loss on two or more biopsies; two were converted from Tacrolimus to Neoral and MMF for suspected EBV related lymphoproliferative disease (PTLD), but developed acute cellular rejection; four had severe nephrotoxicity (mean GFR 43.5ml/min/1.73m2, range 28-65) while on cyclosporin. MMF was started at 20 mg/kg/day bid and increased after 1 week to 40 mg/kg/day bid. Following addition of MMF no child with AR has experienced relapse (median follow up 5 months, range2-16 months). Median interval from initiation of therapy to normal transaminases was 15 days and range 10-28 days. Neither patient with CR had sustained improvement of liver function: MMF was discontinued in one after 3 weeks because of leucopenia and the other received 3 months therapy when tuberculosis was diagnosed. Both patients with suspected PTLD are well 13 and 15 months after Tacrolimus withdrawal, without evidence of PTLD or rejection. Both children with CR have died. The children with nephrotoxicity have tolerated a mean reduction of trough cyclosporin levels of 50% (pre MMF mean trough level 143 ug/l to 73ug/l monoclonal TDX method) after 6 weeks of MMF treatment, and remain rejection free, median 5 months, (range 1-9months) with improvement in GFR from 65 to 115ml/min/1.73m2 in one when tested after 6 months. 3 others are awaiting repeat GFR studies. Transient diarrhoea was observed in 4 patients and leucopenia in 3 which responded to transient dose reduction with restarting full dose in 3 weeks. Conclusion: MMF should be considered in the treatment of AR and in the presence of cyclosporin or Tacrolimus induced nephrotoxicity. Prospective trials are indicated to see whether earlier introduction of MMF and maintaining lower trough cyclosporin or Tacrolimus levels could avoid the nephrotoxicity.