CSA-ASSOCIATED NEUROTOXICITY AND INEFFECTIVE PROPHYLAXIS WITH CLONAZEPAM IN PATIENTS TRANSPLANTED FOR THALASSEMIA MAJOR - ANALYSIS OF RISK-FACTORS

Cyclosporin A (CsA) has been shown to be useful in the prophylaxis of acute graft-versus-host-disease (GVHD). However, this immunosuppressiv e agent produces multiple side-effects including nephrotoxicity, hyper tension, hypertricosis, gum hyperplasia, infections, and neurotoxicity . We report a retrospective analysis of neurotoxicity in 625 recipient s transplanted for thalassemia and given CsA as part of GVHD prophylax is. Neurotoxicity consisted in mental status changes, tremor, headache (grade 1), visual disturbance and cortical blindness (grade 2) and se izures and coma (grade 3). The overall toxicity was 28.8 % and the inc idence of convulsions was 10.1%. Neurological findings were reversible after temporary reduction or discontinuation of CsA, Class 3 patients , when prepared with protocol 6 (Bu 14 + Cy 200 and CsA for GVHD) or w hen they developed acute GVHD, had the highest risk of convulsions. Ag e, sex, different conditioning regimens, different anticonvulsive prop hylaxis, liver damage due to iron-overload and/or to chronic inflammat ion did not influence the occurrence of CsA-related CNS toxicity, The occurrence of acute GVHD with concomitant use of high-dose corticoster oids is the single significant predisposing factor in the occurrence o f convulsions, Grades 1 and 2 of neurotoxicity occurred earlier and we re not influenced even by acute GVHD.