Efficacy and tolerability of high-dose methotrexate in central nervous system positive or relapsed lymphoproliferative disease following liver transplant in children

Childhood post-transplant lymphoproliferative disease (PTLD) is a heterogeneous condition in which treatment varies, from the reduction of immunosuppression to moderately intensive chemotherapy. While low-dose chemotherapy/rituximab has been found to be effective, moderately intensive chemotherapy is required for patients who relapse, have classic non-Hodgkin lymphoma or have fulminant PTLD. Methotrexate (Mtx) is highly effective in lymphomas and crosses the blood-brain barrier. However, there are no data in the literature regarding its safety in post-liver transplant patients. We describe four cases of high-grade lymphomas (three diffuse large B cell and one T-cell lymphoblastic), post-liver transplant, for which chemotherapy including high-dose Mtx (HDMTX) was the treatment of choice. In total, 20 doses of HDMTX (1-5 g/m(2)) were given. The treatment was well tolerated and all four patients had a good response. One case of central nervous system (CNS) diffuse large B-cell lymphoma was treated with HDMTX alone. We conclude that, in the absence of significant organ damage, HDMTX can safely be given to liver transplant patients, but should only be administered in specialist oncology units. Proof of effectiveness as a single agent in CNS lymphoma needs further studies.