Impact of Ethnicity and Socioeconomic Status on Outcome of Unrelated Donor (URD) Hematopoietic Cell Transplantation (HcT).
Authors: Baker K. Scott , Hassebroek Anna , Ballen Karen , Bigelow Carolyn , Frangoul Haydar , Hardy Cheryl , Lee Stephanie , Switzer Galen , Rizzo J. Douglas , Klein John P. , Majhail Navneet , Davies Stella 
Published: October 2019

Abstract
Prior studies suggest that success of HCT varies by race and ethnicity. This study examined whether disparate outcomes in URD-HCT are explained by socioeconomic status (SES), HLA disparity or other factors. Patients (n=6207) with acute or chronic leukemia or MDS, receiving myeloablative conditioning and URD HCT in the U.S., with available valid ZIP code, and reported to the CIBMTR between 1995–2004 were included. Patients were reported by the transplant center to be Caucasian (CC, n=5253), African American (AA, n=368), Asian/Pacific Islander (AP, n=141), or Hispanic (HS, n=445). We used 3 distinct HLA groupings with significantly different outcomes identified in another study to adjust for HLA disparity while accounting for best available resolution of typing. Well matched patients had no identified mismatches at HLA-A,B,C and DRB1 with low/intermediate or high resolution data available at HLA-A,B and high resolution DRB1. Partial matched patients had a single locus mismatch at any of the 4 loci and/or missing HLA-C data. Mismatched included any patient with 2 or more allele or antigen mismatches. Ethnic minorities were more likely than CC to have partially matched or mismatched donors. Patient income was estimated from reported residential ZIP code. The median follow-up of survivors ranged from 48 (AA and HS) to 66 months (CC). By Kaplan-Meier estimate, 1-year overall survival (OS) was 47% in CC, 32% in AA, 43% in AP, and 41% in HS (p<.001), and disease free survival (DFS) was 42% in CC, 28% in AA, 36% in AP, and 39% in HS (p<.001). These differences were sustained through 5 years post-HCT. Cox regression was used to examine the effect of study variables (age, performance status, income, co-morbidities, diagnosis, disease status, CMV status, stem cell source, HLA match, donor age and gender, year of HCT, conditioning regimen, cell dose, time from diagnosis to HCT, distance from patient ZIP code to transplant center) on the outcomes of interest between the 4 racial/ethnic groups. After adjusting for other significant factors, compared to CC, AA (but not AP or HS) were independently associated with worse OS (relative risk [RR] 1.46 (95% CI 1.28–1.66), P<.0001) and with worse DFS (RR 1.45 (1.27–1.64), P<.0001). The risk of treatment related mortality was higher in AA (RR 1.54, (1.33–1.79), P<.0001) and in HS (RR 1.23, (1.06–1.42), p=.005). HS had an increased risk of chronic GVHD (RR 1.24, (1.06–1.45), P=.008) compared to CC, otherwise there was no difference in the risk of acute or chronic GVHD among the racial groups. Race/ethnicity, median income and distance from transplant center were not associated with the risk of disease relapse. Greater distance to the transplant center (>175 miles) and higher median incomes (>$35,500) were associated with higher DFS (p=0.006, p=0.0002) and OS (p=0.001, p<0.0001) in all racial/ethnic groups. While this study is limited by the use of surrogate markers of SES and relatively small numbers of ethnic minority patients, the results suggest that the inferior outcomes after URD HCT detected primarily in AA patients are not fully explained by HLA disparity or SES indicators. Potential other mechanisms such as genetic polymorphisms that impact drug metabolism or the risk of TRM, as well as other pre- or post-transplant factors may be important.