Impact of Donor-Recipient Ethnicity On Risk of Acute Graft-Versus-Host Disease, Leukemia Relapse and Survival in Hematopoietic Stem Cell Transplantation From HLA-Compatible Unrelated Donors. A Report From the International Histocompatibility Workshop Group.
Authors: Morishima Yasuo , Kawase Takakazu , Morishima Satoko , Malkki Mari , Spellman Stephen R , Velardi Andrea , Petersdorf Effie W 
Published: October 2019

Abstract
Abstract 871

Introduction:
The association of ethnicity with the incidence of acute graft-versus-host disease (aGVHD) after HLA identical sibling bone marrow transplantation is well documented. However, there has been no international analysis for the association of ethnicity in hematopoietic stem cell transplantation (HSCT) from unrelated donors. The large scale international unrelated HSCT International Histocompatibility Workshop Group (IHWG) dataset provides a unique opportunity to compare the clinical outcomes according to donor-recipient ethnicity.

Patients and methods:
Of the 16,198 pairs in the IHWG database, 5543 patient/donor pairs met the following 3 criteria and were included in this analysis: (1) HLA-A, B, C, DRB1 and DQB1 allele matched donor; (2) diagnosis of leukemia or myelo-dysplastic syndrome, and (3) non-T cell depleted GVHD prophylaxis. Multivariable Cox regression analyses were conducted to evaluate the impact of the ethnicity on clinical outcomes considering factors as confounders including HLA-DPB1 matching, disease, leukemia risk, donor age, patient age, gender, GVHD prophylaxis and conditioning regimen. A subset of pairs who shared HLA alleles with those of common European or Japanese HLA-A, -C, -B, -DRB1 and -DQB1 haplotype were further analyzed for transplant outcomes.

Results:
The number of pairs and hazard risk (HR) of aGVHD, leukemia relapse and overall survival (mortality) after transplantation by ethnic group are shown in the table. Asian/Pacific pairs (n=2062) showed lower incidence of acute GVHD (39.2% of grade 2-4 and 15.0% of grade 3-4) than that of Caucasian pairs (55.2% of grade 2-4 and 21.9% of grade 3-4) significantly (p<0.001). Multivariate analysis revealed that HR of aGVHD, leukemia relapse and mortality in Caucasian pairs was significantly higher compared with Asian/Pacific pairs. Although the number of Hispanic pairs and Black pairs is small, the HR of mortality in these pairs is significantly higher than Asian/Pacific pairs. The incidence of aGVHD in pairs sharing HLA alleles with either 2 common Japanese HLA haplotypes was significantly lower than that in pairs sharing HLA alleles with any 4 common European HLA haplotypes.

Conclusion and discussion:
As clinical factors and HLA matching were adjusted statistically, these different outcomes between ethnic groups might be attributable to the genetic background of ethnic group. As most Asian/Pacific pairs (2039 out of 2062) were Japanese registered from the Japan Marrow Donor Program, the data is representative of the Japanese population rather than Asian/Pacific ethnicities as a whole. The results from this analysis provide a platform for future international analyses of unrelated HSCT outcomes and for the international exchange of unrelated donors.

Disclosures:
No relevant conflicts of interest to declare.