title: Late Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.
abstract: There are little data regarding the incidence, clinical manifestations, risk factors, and outcomes of late acute graft-versus-host disease (aGVHD). We evaluated patients with late aGVHD after allogeneic hematopoietic cell transplantation (HCT) between 2007 and 2012 and compared their outcomes to patients with early-onset aGVHD. Of the 511 allogeneic HCT recipients, 75 developed late aGVHD (cumulative incidence: 14.7% (95% confidence interval [CI], 11.6% to 17.8%) versus 248 with early-onset aGVHD (cumulative incidence: 49% [95% CI, 45% to 53%]). Among those with late aGVHD, 52% had persistent, 39% had recurrent, and 9% had de novo late aGVHD. Advanced (grades III and IV) early-onset aGVHD was associated with a higher risk of developing late aGVHD (hazard ratio [HR], 1.9; 95% CI, 1.2 to 3.1; P = .01). Forty-eight percent (95% CI, 36% to 60%) of late aGVHD versus only 31% (95% CI, 26% to 37%) of early-onset aGVHD progressed to chronic GVHD by 2 years. Higher proportion of persistent (53%) as compared to recurrent (39%) and de novo (46%) late aGVHD progressed to cGVHD at 2 years. The overall survival was 59% (95% CI, 49% to 72%) in late aGVHD and 50% (95% CI, 44% to 57%) in early-onset aGVHD. Persistent late aGVHD had worse overall survival and nonrelapse mortality (45% and 39%, respectively) than recurrent (74% and 18%, respectively) and de novo (83% and 0%, respectively) late aGVHD. Compared with HLA-identical sibling HCT, unrelated donor transplantations were associated with a higher risk of mortality in patients developing late aGVHD (HR, 6.1; 95% CI, 2.3 to 16.2; P < .01). In a landmark analysis (evaluating 100-day survivors among early-onset aGVHD), no difference was seen in late mortality (after 100 days) between early-onset and late aGVHD (HR, .96; 95% CI, .59 to 1.55; P = .85); however, the risk of cGVHD was nearly doubled (HR, 1.81; 95% CI, 1.16 to 2.82; P = .01) in patients with late aGVHD. Late aGVHD is a relatively common complication after allogeneic HCT. Poorer outcomes in those with persistent late aGVHD imply need for more effective therapy in this group to improve transplantation outcomes. A higher risk of subsequent chronic GVHD needs further evaluation and close monitoring.
authors.affiliation: Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: Aazim K
authors.initials: AK
authors.lastname: Omer
authors.affiliation: Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.affiliation: Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Lazaryan
authors.affiliation: Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: Ryan
authors.initials: R
authors.lastname: Shanley
authors.affiliation: Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.affiliation: Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: Margaret L
authors.initials: ML
authors.lastname: MacMillan
authors.affiliation: Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: Claudio
authors.initials: C
authors.lastname: Brunstein
authors.affiliation: Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: Nelli
authors.initials: N
authors.lastname: Bejanyan
authors.affiliation: Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota. Electronic address: arora005@umn.edu.
authors.forename: Mukta
authors.initials: M
authors.lastname: Arora
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality*; D019337:Hematologic Neoplasms / Q000401:mortality* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D015996:Survival Rate
keywords: Allogeneic hematopoietic stem cell transplantation; Early onset acute graft-versus-host disease; Late acute graft-versus-host-disease