title: Tacrolimus-related encephalopathy following allogeneic stem cell transplantation in children.
abstract: Tacrolimus is a potent immunosuppressive drug widely used to prevent and treat graft-versus-host disease (GVHD) in stem cell transplantation (SCT). Among 49 patients receiving tacrolimus who underwent SCT from January 2000 to July 2003, 10 patients (20%) developed encephalopathy. The commonly observed symptoms were convulsions and drowsiness, and most patients complained of signal symptoms such as headache, nausea, and cortical blindness before onset. The most common abnormality on neuroimages was high-intensity lesions in white matter on magnetic resonance imaging T2-weighted or fluid-attenuated inversion recovery images. At onset, all patients were receiving treatment for acute GVHD (grade II/III) or extensive chronic GVHD and demonstrated an abrupt increase in blood pressure from baseline levels. The serum tacrolimus concentration was generally within acceptable levels at onset. Symptoms gradually improved in all patients when the blood pressure was lowered with antihypertensive medication, regardless of continued tacrolimus administration following a short-term suspension. The pathogenesis of tacrolimus-related encephalopathy is multifactorial, although refractory GVHD and a sudden increase in blood pressure seem to be major predisposing factors. Because the withdrawal of tacrolimus or switching to less potent anti-GVHD agents usually worsens the GVHD, the administration of tacrolimus should be managed by closely monitoring serum levels and controlling blood pressure.
authors.affiliation: Department of Developmental Medicine, Osaka University, Graduate School of Medicine, Japan. tkhsknky@ped.med.osaka-u.ac.jp
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kanekiyo
authors.forename: Junichi
authors.initials: J
authors.lastname: Hara
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Matsuda-Hashii
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujisaki
authors.forename: Sadao
authors.initials: S
authors.lastname: Tokimasa
authors.forename: Akihisa
authors.initials: A
authors.lastname: Sawada
authors.forename: Keiko
authors.initials: K
authors.lastname: Kubota
authors.forename: Kuriko
authors.initials: K
authors.lastname: Shimono
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imai
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ozono
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000150:complications / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000959:Antihypertensive Agents; D007166:Immunosuppressive Agents; D016559:Tacrolimus