title: Prognostic relevance of 'early-onset' graft-versus-host disease following non-myeloablative haematopoietic cell transplantation.
abstract: We retrospectively analysed outcomes among 395 patients with haematologic malignancies who underwent non-myeloablative haematopoietic cell transplantation (HCT) from human leucocyte antigen (HLA)-matched related (n = 297) or unrelated donors (n = 98) in order to identify a possible correlation between the time of onset of graft-versus-host disease (GVHD) and survival. The non-myeloablative regimen consisted of 2 Gy total body irradiation with or without fludarabine, followed by postgrafting immunosuppression with mycophenolate mofetil and cyclosporine. The cumulative incidences of grades II-IV acute GVHD and extensive chronic GVHD were 45% and 47%, respectively, with related donors, and 68% and 68%, respectively, with unrelated donors. High-dose corticosteroid treatment for acute or chronic GVHD was started at a median of 79 (range, 8-799) days and 30 (range, 5-333) days after transplantation from related and unrelated donors respectively. With related donors, the cumulative incidence of non-relapse mortality among patients with GVHD was 55% at 4 years when prednisone was started before day 50 (n = 72), compared with 29% when treatment was started after day 50 (n = 115) (P < 0.001). With unrelated donors, time to onset of treatment for GVHD was not associated with survival. Patients with early-onset GVHD after non-myeloablative HCT from HLA-identical related donors might benefit from intensified primary immunosuppressive treatment.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. mmielcar@fhcrc.org
authors.forename: Marco
authors.initials: M
authors.lastname: Mielcarek
authors.forename: Lauri
authors.initials: L
authors.lastname: Burroughs
authors.forename: Wendy
authors.initials: W
authors.lastname: Leisenring
authors.forename: Razvan
authors.initials: R
authors.lastname: Diaconescu
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.forename: Michael B
authors.initials: MB
authors.lastname: Maris
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Chauncey
authors.forename: Judith A
authors.initials: JA
authors.lastname: Shizuru
authors.forename: Karl G
authors.initials: KG
authors.lastname: Blume
authors.forename: Ute
authors.initials: U
authors.lastname: Hegenbart
authors.forename: Dietger
authors.initials: D
authors.lastname: Niederwieser
authors.forename: Stephen
authors.initials: S
authors.lastname: Forman
authors.forename: Benedetto
authors.initials: B
authors.lastname: Bruno
authors.forename: Ann
authors.initials: A
authors.lastname: Woolfrey
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D004334:Drug Administration Schedule; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology*; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007223:Infant; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D012737:Sex Factors; D016019:Survival Analysis; D013997:Time Factors; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
chemical_list: D005938:Glucocorticoids; D011241:Prednisone