title: Dismal response to high-dose methylprednisolone after failure to respond to standard dose in patients with acute GVHD.
abstract: Corticosteroids such as methylprednisolone (MP) remain the primary therapy for acute GVHD (aGVHD). Patients who are refractory to standard treatment (MP 2 mg/kg/day) may be treated with high-dose MP. This study evaluated the response to high-dose MP in children with aGVHD refractory to standard dose MP. Children who underwent hematopoietic SCT (HSCT) at our hospital between 1 June 2002 and 31 July 2006 and were treated with high-dose MP upon developing steroid-refractory aGVHD were included. Response to aGVHD therapy, adverse effects attributed to MP and overall outcomes were documented. Ten children received high-dose MP (≥ 20mg/kg/day) on 3-5 consecutive days followed by a tapering dose for steroid-refractory aGVHD, at a median of 12 days after starting standard treatment. Nine patients had ≥ grade III aGVHD. Only one patient with grade III aGVHD had a complete response. Two patients had a partial response but flared when MP was tapered. Complications included hypertension (100%), hyperglycemia requiring insulin therapy (33%) and four documented severe infections. Five children (50%) died (median follow-up: 5.9 years). Salvage therapy other than high-dose MP should be considered in children who fail to respond to MP 2 mg/kg/day.
authors.affiliation: Department of Haematology/Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada. tal.finkelstein-schechter@sickkids.ca
authors.forename: T
authors.initials: T
authors.lastname: Schechter
authors.forename: C
authors.initials: C
authors.lastname: Macartney
authors.forename: Y
authors.initials: Y
authors.lastname: Finkelstein
authors.forename: A
authors.initials: A
authors.lastname: Gassas
authors.forename: M
authors.initials: M
authors.lastname: Husain
authors.forename: J
authors.initials: J
authors.lastname: Doyle
authors.forename: L L
authors.initials: LL
authors.lastname: Dupuis
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006086:Graft vs Host Disease / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*
chemical_list: D005938:Glucocorticoids; D008775:Methylprednisolone