Ethnic Variation in Chronic Graft-Versus-Host Disease (cGVHD) Manifestations

Risk of acute GVHD varies among different ethnic population. Thus, we evaluated potential differences in cGVHD manifestations in two ethnic distinct cohorts. The study included a Brazilian cohort diagnosed with cGVHD by 2005 NIH criteria who were enrolled in a prospective multicenter longitudinal study at 5 centers in Brazil and compared with a North American cohort reported by the cGVHD consortium (Arai S. et al. Blood 2011). Pts. were assessed using standardized clinical data forms every 3 months (124 visits). Any elevation of liver function tests was scored as cGVHD.  The Brazilian study cohort included 36 pts. with a median age of 44 (13-64) years and 21 (58%) were male. At study enrollment, 24 (67%) had classic cGVHD, and 12 (33%) pts. had overlap subtype (with feature of both acute and chronic).  Distribution of organ involvement attributed to cGVHD for the Brazilian and the North American cohorts at study enrollment is shown in the Figure. Liver severity scores at study enrollment was mild in 10 (34%), moderate in 12 (40%) and severe in 8 (26%) pts. among Brazilian cohort, and it was mild in 113 (76%), moderated in 36 (24%) and none severe in the North American cohort. Overall, cGVHD global severity at study enrollment was calculated from reported data as mild in 2 (5.5%), moderate in 17 (47%) and severe in 17 (47%) of Brazilian cohort compared to 32 (10%), 175 (59%) and 91(31%) in the North American cohort, respectively.  Similar to North American cohort, distribution of global severity was similar in the Brazilian cohort across 22 incident (enrollment < 3 months of cGVHD diagnosis) and 14 prevalent cases (enrollment 3 or 6 months after cGVHD diagnosis) and, between pts. with classic and overlap cGVHD. Prevalence of organs involvement at study enrollment was significant different between the two population. Compared to the North American cohort, the Brazilian cohort had higher rates of liver involvement (83% vs. 50%; p <0.001) and lower rate of lung (8% vs. 50%; p <0.001), respectively. The cause for the high incidence and severity scores in the liver among the Brazilian cohort is unknown, but we speculated potential contributors. For instance, 100% of Brazilian cohort was CMV positive and pre-emptive treatment for CMV reactivation is not used after day 100 posttransplant, thus reactivation of CMV may have contributed to the elevation of liver function tests. Moreover, it is not standard practice in Brazil to add ursodiol to treat elevation of liver tests attributed to GVHD, thus allowing for further potential increase in liver severity score. The lower rates of lung in the Brazilian cohort may reflect non-standardization of pulmonary function test in Brazil. In conclusion, prevalence of organ manifestations in cGVHD varied between the two ethnic distinct cohort studied. Attention should be taken into consideration when evaluating prognosis and outcomes in cGVHD in different ethnic population.