TY - JOUR
T1 - Late Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation
AU - Omer, Aazim K
AU - Weisdorf, Daniel J
AU - Lazaryan, Aleksandr
AU - Shanley, Ryan M
AU - Blazar, Bruce R
AU - MacMillan, Margaret L
AU - Brunstein, Claudio G
AU - Bejanyan, Nelli
AU - Arora, Mukta
N1 - Publisher Copyright:
© 2016 American Society for Blood and Marrow Transplantation.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
KW - Allogeneic hematopoietic stem cell transplantation
KW - Early onset acute graft-versus-host disease
KW - Late acute graft-versus-host-disease
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U2 - 10.1016/j.bbmt.2015.12.020
DO - 10.1016/j.bbmt.2015.12.020
M3 - Article
C2 - 26743342
AN - SCOPUS:84960824733
SN - 1083-8791
VL - 22
SP - 879
EP - 883
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 5
ER -