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Ocular Gvhd: Epidemiology, Risk Factors and Impact on Quality of Life-a Chronic Gvhd Consortium Study
Background:
Ocular GVHD (o-GVHD) is a known manifestation of chronic GVHD (cGVHD). There are no prospective studies of factors associated with o-GVHD or its impact on quality of life (QOL). We analyzed the above endpoints using the cGVHD consortium database; a prospective multi-center longitudinal observational study.
Methods:
The study included patients with cGVHD requiring systemic treatment and enrolled within 3 months of diagnosis. O-GVHD was defined as NIH eye score > 0 and patient reported symptoms (> 1 on 0-10 eye related symptoms or >20 on Lee symptom eye score). Variables associated with o-GVHD at enrollment and subsequent new onset o-GVHD, and the associations with QOL were studied.
Results:
The cumulative incidence of o-GVHD at 2 y after cGVHD diagnosis was 58%. Of the 290 patients with o-GVHD, 117 (40%) had it within 3 months of cGVHD diagnosis (“early o-GVHD”). Chronic GVHD characteristics associated with early o-GVHD included: more severe global cGVHD (P<0.001), and greater severity of mouth (P=0.001), esophagus (P=0.002), and liver (P<0.001) involvement. In a multivariable analysis, female sex (OR 2.0, P=0.01) and higher prednisone dose at enrollment (P=0.04) were associated with o-GVHD. Early o-GVHD was not associated with subsequent non-relapse mortality (HR 1.2, P=0.53) or survival (HR 1.1, P=0.85).
Late o-GVHD (new onset > 3 months after cGVHD diagnosis) occurred in 68 patients. The cumulative incidence of late o-GVHD at 2-y post enrollment was 39%. In multivariable modeling, presence of prior grade I-IV aGVHD (HR 1.8, P=0.03) was associated with shorter time to late o-GVHD, while female donor into male recipient (HR 0.5, P=0.05) was associated with longer time to late o-GVHD onset.
The Table shows the association of o-GVHD with QOL metrics, using all available visit data adjusted for center effect, months since enrollment, platelet count, NIH severity, bilirubin, prior aGVHD, and overlap vs. classic cGVHD.
Conclusion:
This large multicenter, prospective study shows that o-GVHD affects 58% of patients at 2 y after a diagnosis of cGVHD and is statistically associated with worse QOL and more cGVHD symptoms compared to patients with cGVHD without ocular involvement. Since o-GVHD may be due to permanent destruction of lacrimal glands, prophylactic or pre-emptive clinical trial strategies prior to onset of irreversible dry eye syndrome are needed. Women, patients on higher doses of prednisone, and those with a history of acute GVHD seem to be at higher risk for o-GVHD.
QOL Metric
| O-GVHD | Estimate
| P
| NIH Eye score | Estimate | P
|
FACT-G
| No | 0* | 0.006 | 0 | 0* | 0.05^ |
Yes
| -2.1
| 1 | -0.7 | 0.40 | ||
2 or 3 | -2.5 | 0.01 | ||||
FACT-TOI | No | 0* | <0.001 | 0 | 0* | 0.03^ |
Yes
| -2.6
| 1 | -1.5 | 0.04 | ||
2 or 3 | -2.4 | 0.01 | ||||
FACT-BMT
| No | 0* | 0.002 | 0 | 0* | 0.08^ |
Yes
| -3.0
| 1 | -1.3 | 0.19 | ||
2 or 3 | -3 | 0.03 | ||||
Lee Score**
| No | 0* | <0.001 | 0 | 0* | 0.01^ |
Yes
| 2.8
| 1 | 1.7 | 0.01 | ||
2 or 3 | 2.1 | 0.02 |
^overall P value; *Estimate 0-reference category; **Lee symptom score-eye component excluded
Pfizer: Research Funding