<p class="first" id="P1">There is little data regarding the incidence, clinical manifestations,
risk factors
and outcomes of late acute GVHD (aGVHD). We evaluated patients with late aGVHD after
allogeneic 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% CI: 11.6-17.8) versus 248 with early onset aGVHD (cumulative
incidence: 49% (95% CI: 45-53). Amongst those with late aGVHD, 52% had persistent,
39% recurrent and 9% de-novo late aGVHD. Advanced (grade III-IV) early onset aGVHD
was associated with a higher risk of developing late aGVHD (HR 1.9, 95% CI: 1.2 −3.1,
p= 0.01). 48% (95% CI: 36-60%) of late aGVHD versus only 31% (95% CI: 26-37%) 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: 49-72) in late aGVHD and 50% (95%
CI: 44-57%) in early onset aGVHD. Persistent late aGVHD had worse OS and NRM (45%
and 39%) as compared to recurrent (74% and 18%) and de-novo (83% and 0%) late aGVHD.
Compared to HLA-identical sibling HCT, unrelated donor transplants were associated
with a higher risk of mortality in patients developing late aGVHD (HR 6.1, 95% CI:
2.3-16.2, p<0.01). 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 0.96, 95% CI: 0.59-1.55, p= 0.85), however the risk of cGVHD
was nearly doubled (HR 1.81, 95% CI: 1.16-2.82, p=0.01) in patients with late aGVHD.
Conclusions: 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 transplant outcomes. A higher risk of subsequent
chronic GVHD needs further evaluation and close monitoring.
</p>